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The distinctive low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) of the stomach has been well characterized in recent years, but its relationship with the more commonly occurring large B-cell gastric lymphoma has not been clarified. This study aimed to elucidate their relationship. Among 48 consecutive cases of primary malignant lymphoma found in gastrectomy specimens, there were 10 cases showing coexistence of these two elements, which were further studied in detail. The high-grade component predominated in six cases, the low-grade component predominated in two cases, and the two components were intermingled in two cases. In the low-grade component, the small neoplastic cells possessed irregular nuclei (centrocytelike), and glandular invasion was a prominent feature. In the high-grade component, the blasts occurred in clusters or sheets, and often possessed plasmacytoid cytoplasm; glandular invasion was a rare event. In both components, the neoplastic cells frequently showed formation of nodules suggestive of colonization of reactive lymphoid follicles. Immunohistochemical studies showed that the neoplastic cells in the low- and high-grade components expressed the same class of immunoglobulin light chain in eight of the nine cases studied; staining in one case was unsatisfactory. Their intimate relationship as well as identical light chain restriction suggests that the high-grade component arises through blastic transformation of the low-grade component. Images Figure 7 Figure 6 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2349966
Chan, J. K.; Ng, C. S.; Isaacson, P. G.
Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy
Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up.
Seo, Sang-Wook; Lee, Seung-Hwa; Lee, Duck-Joo; Kim, Kwang-Min; Kang, Joon-Koo; Kim, Do-Wan; Lee, Jeong-Hun
Colonic mucosa-associated lymphoid tissue lymphoma identified by chromoendoscopy.
Colonic mucosa-associated lymphoid tissue (MALT) lymphomas are a rare occurrence and the definitive treatment has not been established. Solitary or multiple, elevated or polypoid lesions are the usual appearances of MALT lymphoma in the large intestine and sometimes the surface may reveal abnormal vascularity. Herein, we report a case of MALT lymphoma and review the relevant literature. Upon colonoscopy, a suspected pathologic lesion was observed in the proximal transverse colon. The lesion could be distinguished more prominently after using narrow-band imaging mode and indigo carmine-dye spraying chromoendoscopy. Histopathologic examination of this biopsy specimen revealed lymphoepithelial lesions with diffuse proliferation of atypical lymphoid cells effacing the glandular architecture and centrocyte-like cells infiltrating the lamina propria. Immunohistochemical analyses showed that tumor cells were positive for CD20 and Bcl-2e, and negative for CD10, CD23, and Bcl-6. According to Ann-Arbor staging system, the patient had stage IIE. A partial colectomy with dissection of the paracolic lymph nodes was performed. Until now, there is no recurrence of lymphoma at follow-up. PMID:25561821
Seo, Sang-Wook; Lee, Seung-Hwa; Lee, Duck-Joo; Kim, Kwang-Min; Kang, Joon-Koo; Kim, Do-Wan; Lee, Jeong-Hun
Botryomycosis is an unusual chronic suppurative disease characterized by the histological finding of sulphur granules containing the causative bacteria in an abscess. We describe a previously healthy 14-year-old girl who presented with chronic productive cough. Chest computed tomography (CT) revealed a right lower mass with involvement of the parietal pleura, chest wall, diaphragm, liver and costovertebral junction. Thoracostomy biopsy was performed due to suspicion of low-grade mucosa-associated lymphoid tissue lymphoma. However, histological analysis revealed a pulmonary botryomycosis. The right lower lung mass completely resolved after 3 months of antibiotics treatment. This case emphasizes that primary pulmonary botryomycosis with extensive contiguous involvement may not be distinguishable from lung cancer, lymphoma or fungal infection on chest CT. PMID:16385377
Leong, Yew-Loong; Liaw, Yuang-Shuang; Chang, Yih-Leong; Lee, Yung-Chie
[Mucosa-associated lymphoid tissue lymphoma of the larynx].
A 63-year-old female suffering from hepatitis C virus infection and manic depression was admitted with a 4-month history of hoarseness. Endoscopic examination revealed the presence of a neoplasm with a smooth surface in the left supraglottic region extending to the left false vocal cord. Based on the histological findings, together with the results of systemic evaluation, the patient was diagnosed as having a mucosa-associated lymphoid tissue (MALT) lymphoma in clinical stage IE, according to the Ann Arbor classification. After one month of follow-up, the patient presented with involvement of multiple subcutaneous regions in the left neck area, etc. Biopsies revealed the same type of lymphoma as that in the supraglottis. The disease was considered to have progressed to clinical stage IV. Six courses of R-CVP (rituximab, cyclophosphamide, vincristine and prednisolone) treatment resulted in complete remission of all lesions. Primary MALT lymphoma in the larynx is extremely rare. Since the first description by Diebold et al in 1990, only 43 cases have been reported. Among these reported cases, only 7 (16%) with progressive stages were described. The R-CVP regimen appears to be effective for the treatment of progressive primary MALT lymphoma of the larynx. Furthermore, hepatitis C virus infection is thought to be closely associated with the aggressive malignant process and subcutaneous dissemination. PMID:24681938
Hua, Jian; Iwaki, Yasunobu; Inoue, Morihiro; Takiguchi, Yoichiro; Ota, Yasunori; Hagihara, Masao
The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma
Purpose To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications. Materials and Methods Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received radiotherapy alone. Ten patients received chemotherapy before radiotherapy, and three patients underwent surgery followed by chemotherapy and radiotherapy. One patient received surgery followed by radiotherapy. All patients received radiotherapy of median dose of 30.6 Gy. Results The duration of follow-up ranged from 6 to 158 months (median, 48 months). Five-year overall survival and cause-specific survival rates were 90.3% and 100%. All patients treated with radiotherapy alone achieved pathologic complete remission (pCR) in 31 of the low-grade and in three of the mixed-grade patients. All patients treated with chemotherapy and/or surgery prior to radiotherapy achieved pCR except one patient who received chemotherapy before radiotherapy. During the follow-up period, three patients developed diffuse large B-cell lymphoma in the stomach, and one developed gastric adenocarcinoma after radiotherapy. No grade 3 or higher acute or late complications developed. One patient, who initially exhibited gastroptosis, developed mild atrophy of left kidney. Conclusion These findings indicate that a modest dose of radiotherapy alone can achieve a high cure rate for low-grade and even mixed-grade gastric MALT lymphoma without serious toxicity. Patients should be carefully observed after radiotherapy to screen for secondary malignancies. PMID:24520221
Nam, Taek-Keun; Ahn, Jae-Sook; Choi, Yoo-Duk; Jeong, Jae-Uk; Kim, Yong-Hyeob; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja
Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma
Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma. Despite its increasing incidence, diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings, and, thus, a high index of suspicion, and multiple, deep, repeated biopsies at abnormally and normally appearing sites in the stomach are needed. In addition, testing for Helicobacter pylori (H. pylori) infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H. pylori eradication and for assessment of disease progression. In addition, H. pylori infection and MALT lymphoma development are associated, and complete regression of low-grade MALT lymphomas after H. pylori eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used in cases that show poor response to H. pylori eradication, negativity for H. pylori infection, or high-grade lymphoma. PMID:24659867
Park, Jeong Bae; Koo, Ja Seol
Primary malignant lymphoma of the salivary gland: a tumor of mucosa-associated lymphoid tissue.
The clinical, morphologic and immunohistochemical features of 10 cases of the low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of salivary glands are described. Although the initial histologic diagnosis in nine of these cases was myoepithelial sialadenitis, the diagnosis of primary salivary gland MALT lymphoma was based on the demonstration of light chain restriction and on morphologic characteristics. Histologic study showed a characteristic cytology, which included centrocytoid cells (composed of small centrocytes and monocytoid B cells) and a varying degree of plasma cell differentiation; the occurrence of epithelial or acinar invasion by neoplastic centrocytoid cells; and the presence of reactive lymph follicles among the neoplastic cells. Furthermore, multinucleate giant cells resembling Warthin-Finkeldey cells were detected in seven cases. In the light of these findings, cases previously diagnosed as myoepithelial sialadenitis require careful assessment and nine out of 32 cases are, in reality, examples of primary salivary gland MALT lymphomas. Immunohistochemical analysis of paraffin sections revealed the following characteristic immunophenotype of MALT lymphoma: L26, KiB3 and LN2 positive, and a monotypic immunoglobulin pattern (predominantly IgM/kappa). It was of interest that salivary gland parenchyma, infiltrated by neoplastic centrocytoid cells, reacted with LN3 for cells expressing human leukocyte antigen-DR (HLA-DR) antigens. Whereas salivary gland epithelia devoid of a neoplastic invasion were invariably negative for LN3. This suggests a lymphocyte-mediated role in salivary epithelial HLA-DR expression. It appears that HLA-DR expression is an inducible phenomenon in MALT lymphomas of salivary gland. PMID:1522534
Takahashi, H; Cheng, J; Fujita, S; Tsuda, N; Tezuka, F; Liu, A R; Okabe, H
Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or association with Helicobacter pylori infection. This report describes the case of a 76-year-old man with a polypoid mass in the duodenal bulb, diagnosed as low-grade MALT lymphoma. H. pylori infection in the duodenal mucosa was confirmed by histology with silver stain. Endoscopic examination showed that the gross lesion regressed after the eradication of H. pylori despite its histopathologic persistence. Ten months later, however, cervical and intraperitoneal lymphadenopathy and bone marrow involvement was observed, and the pathologic diagnosis of the cervical lymph node was identical with that of the duodenal lesion. PMID:10192204
Kim, J S; Jung, H C; Shin, K H; Song, I S; Kim, C W; Kim, C Y
Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas
Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract's unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care. PMID:24574742
Pereira, Marta-Isabel; Medeiros, José Augusto
Primary hepatic lymphoma is a rare disorder representing less than 1% of all extranodal lymphomas. Histological examination of a primary hepatic lymphoma usually reveals a diffuse large B-cell lymphoma; there have been few reports of primary hepatic mucosa-associated lymphoid tissue (MALT) lymphomas. A 67-year-old man was being treated for a duodenal ulcer; while receiving therapy for the ulcer, a liver mass was incidentally found on abdominal ultrasonography. The pathologic diagnosis of the hepatic mass was an extranodal marginal zone B-cell lymphoma of MALT. The patient underwent radiotherapy with a total of 4,140 cGy delivered. The patient achieved complete remission and has been followed for 6 years with no recurrence of the disease. This report reviews the case of a primary hepatic extranodal marginal zone B-cell lymphoma of MALT successfully treated by radiotherapy alone. PMID:16913444
Shin, Sang Yun; Kim, Jin Seok; Lim, Jong Keun; Yang, Woo Ick; Suh, Chang Ok
Technology Transfer Automated Retrieval System (TEKTRAN)
This report summarizes the comparative diagnostic performance of postmortem rectoanal mucosa-associated lymphoid tissue (RAMALT) sampling in four white-tailed deer test populations: from Wisconsin, a sample of free-ranging deer and a captive herd; and from Saskatchewan, Canada, two captive herds. Th...
Catastrophic antiphospholipid antibody syndrome (CAPS) is characterized by fulminant thrombosis of the arterial and venous beds of multiple organ systems over a relatively short period of time and with a high mortality rate. Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung has never been reported as a causative or precipitating factor for CAPS in the CAPS registry database. The present study describes a rare case of pulmonary MALT lymphoma of the lung that presented as CAPS. A 19-year-old Hispanic female presented with shortness of breath and abdominal pain. Computed tomography (CT) scans of the chest and abdomen revealed multiple portal vein thromboses and bilateral pulmonary nodules. Within one week of presentation, the patient developed a straight sinus thrombosis and upper extremity deep vein thrombosis, which led to shortness of breath. A biopsy of the lung nodule revealed MALT lymphoma. The present case illustrates a rarely reported pulmonary MALT lymphoma presenting as CAPS in a young female. The patient was successfully treated with 90 mg/m2 bendamustine on days one and two and rituximab 375 mg/m2 on day one of each 28-day cycle. Complete remission of the lung nodules was observed following three cycles of treatment, as visualized by positron emission tomography (PET)/CT scan. Fondaparinux was identified as a feasible anticoagulation drug of choice for this case. At seven months post-treatment, the patient continues to be stable with no further evidence of thrombosis and is currently undergoing rituximab maintenance therapy every six months for two years. A repeat lupus anticoagulant antibody assay turned and remained negative during the clinical follow-up period. A prompt diagnosis and early aggressive treatment is potentially curative and may dramatically decrease the mortality risk. Future studies should explore the role of rituximab in the management of CAPS-associated B-cell lymphoid malignancies. PMID:24179505
Recent reports have suggested an association between Helicobacter pylori infection and both gastric mucosa associated lymphoid tissue (MALT) lymphoma and thrombocytopenic purpura. Although treatments eradicating H pylori lead to regression of these diseases in some cases, the exact mechanisms are still controversial. This case report describes a patient with thrombocytopenic purpura accompanied by an early stage gastric MALT lymphoma. Endoscopic mucosal resection of the lesion in this patient led to dramatic regression of thrombocytopenic purpura, and t(11;18)(q21;q21), which means resistance more likely to H pylori eradication therapy, was confirmed by fluorescence in situ hybridisation. There is no evidence of recurrence and his platelet count is within normal limits after 24 months of follow up. This is the first case report describing regression of thrombocytopenic purpura after mucosal resection of a gastric MALT lymphoma. We suggest that while some cases of thrombocytopenic purpura may be induced by H pylori, others may be due to an autoreactive antibody produced by MALT lymphoma B cells. PMID:15479694
Noda, M; Mori, N; Nomura, K; Kojima, K; Mitsufuji, S; Yamane, I; Misawa, S; Okanoue, T
Crystal-storing histiocytosis is an uncommon form of nonneoplastic histiocytic proliferation that in most patients complicates an underlying lymphoproliferative or plasma cell disorder. Lung is a common site of involvement in patients with localized disease. We present an illustrative example from a 54-year-old woman with an asymptomatic solitary lung nodule. The tumor was characterized by sheets of histiocytes with abundant cytoplasm expanded by distinctive eosinophilic inclusions. Focal necrosis was present. Aggregates of monocytoid lymphocytes and clusters of peribronchiolar plasma cells were overshadowed by the histiocytic infiltrate. Immunohistochemical stains showed CD68 staining in nonneoplastic histiocytes and CD20 staining in monocytoid lymphocytes. In situ hybridization studies showed ? light-chain restriction in plasma cells. These results, combined with the histologic findings, supported the diagnosis of crystal-storing histiocytosis complicating marginal zone lymphoma of mucosa-associated lymphoid tissue. We review the literature pertaining to pulmonary crystal-storing histiocytosis, highlighting the differential diagnosis for this rare phenomenon. PMID:23991730
Zhang, Chen; Myers, Jeffrey L
Recent progress in the research regarding the molecular pathogenesis and management of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is reviewed. In approximately 90% of cases, Helicobacter pylori (H. pylori) infection plays the causative role in the pathogenesis, and H. pylori eradication is nowadays the first-line treatment for this disease, which leads to complete disease remission in 50%-90% of cases. In H. pylori-dependent cases, microbe-generated immune responses, including interaction between B and T cells involving CD40 and CD40L co-stimulatory molecules, are considered to induce the development of MALT lymphoma. In H. pylori-independent cases, activation of the nuclear factor-?B pathway by oncogenic products of specific chromosomal translocations such as t(11;18)/API2-MALT1, or inactivation of tumor necrosis factor alpha-induced protein 3 (A20) are considered to contribute to the lymphomagenesis. Recently, a large-scale Japanese multicenter study confirmed that the long-term clinical outcome of gastric MALT lymphoma after H. pylori eradication is excellent. Treatment modalities for patients not responding to H. pylori eradication include a "watch and wait" strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and a combination of these. Because of the indolent behavior of MALT lymphoma, second-line treatment should be tailored in consideration of the clinical stage and extent of the disease in each patient. PMID:24363507
Nakamura, Shotaro; Matsumoto, Takayuki
Radioimmunotherapy using (90)Y-ibritumomab tiuxetan has predominantly been used in patients with follicular lymphoma, but little is known about its activity in patients with extranodal marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT). A total of six patients progressing/relapsing following conventional therapy for MALT lymphoma were treated with (90)Y-ibritumomab tiuxetan at our institution. Two patients had gastric MALT lymphoma, one suffered from orbital MALT lymphoma, and two had cutaneous MALT lymphoma, while one patient had a widely disseminated lymphoma involving the stomach, lungs, lymph nodes, and salivary glands. All patients were at least in third relapse following various forms of therapy including Helicobacter pylori-eradication, radiation, chemotherapy, and application of rituximab. Following two doses of rituximab at 250?mg/m(2) at an interval of 1 week, (90)Y-ibritumomab tiuxetan was given immediately at a dose of 0.4?mCi/kg body weight. Treatment was well tolerated apart from one episode of pneumonia requiring hospitalization. Four patients developed a complete remission (ongoing now for 4, 16, 23, and 24 months), one patient had a partial response lasting for 5 months, and one patient had stable disease for 13 months. After a follow-up of 9-29 months, all patients are alive. Application of (90)Y-ibritumomab tiuxetan is active and safe in heavily pretreated patients with MALT lymphoma. PMID:21133720
Hoffmann, Martha; Troch, Marlene; Eidherr, Harald; Traub-Weidinger, Tatjana; Jonak, Constanze; Muellauer, Leonhard; Raderer, Markus
Purpose: Among extranodal lymphomas, orbital mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare presentation. We performed a review to ascertain treatment efficacy and toxicity of radiation therapy for orbital MALT lymphoma. We also evaluated changes in visual acuity after irradiation. Methods and Materials: Thirty patients with orbital MALT lymphoma underwent radiation therapy with curative intent. Clinical stages at diagnosis were stage I{sub E}A in 29 patients and stage II{sub E}A in 1 patient. Total doses of 28.8 to 45.8 Gy (median, 30 Gy) in 15 to 26 fractions (median, 16 fractions) were delivered to the tumors. Results: All irradiated tumors were controlled during the follow-up period of 2 to 157 months (median, 35 months) after treatment. Two patients had relapses that arose in the cervical lymph node and the ipsilateral palpebral conjunctiva outside the radiation field at 15 and 67 months after treatment, respectively. The 5-year local progression-free and relapse-free rates were 100% and 96%, respectively. All 30 patients are presently alive; the overall and relapse-free survival rates at 5 years were 100% and 96%, respectively. Although 5 patients developed cataracts of grade 2 at 8 to 45 months after irradiation, they underwent intraocular lens implantation, and their eyesight recovered. Additionally, there was no marked deterioration in the visual acuity of patients due to irradiation, with the exception of cataracts. No therapy-related toxicity of grade 3 or greater was observed. Conclusions: Radiation therapy was effective and safe for patients with orbital MALT lymphoma. Although some patients developed cataracts after irradiation, visual acuity was well preserved.
Hata, Masaharu, E-mail: firstname.lastname@example.com [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Omura, Motoko; Koike, Izumi [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tomita, Naoto [Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Iijima, Yasuhito [Department of Ophthalmology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Tayama, Yoshibumi; Odagiri, Kazumasa; Minagawa, Yumiko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan); Ogino, Ichiro [Department of Radiation Oncology, Yokohama City University Medical Center, Yokohama, Kanagawa (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa (Japan)
Mucosa-associated lymphoid tissue (MALT) lymphoma is the third most common non-Hodgkin lymphoma, and it is strongly associated with helicobacter pylori infection of the stomach. MALT lymphoma of the lacrimal gland usually presents as a localized disease process in extranodal tissues. The treatment options of MALT lymphoma of the lacrimal gland chiefly include radiation of the tumor, chemotherapy, surgical removal, or a combination of these strategies. We report a case of localized MALT lymphoma of the lacrimal gland, with prolonged sustained remission after eradication of gastric Helicobacter pylori (H. Pylori) infection. He sustains in remission of lacrimal MALT lymphoma for four years without chemotherapy or radiotherapy. PMID:22606434
Hasosah, Mohammed; Baothman, Abdullah; Satti, Mohamed; Kutbi, Suzanne; Alghamdi, Khaled; Jacobson, Kevan
Mucosa-associated lymphoid tissue (MALT) lymphoma of the ocular adnexae is rare. A 39-year-old woman presenting with proptosis was diagnosed to have non-Hodgkin's lymphoma with intermediate-sized cells and lymphoepithelial lesion. Unlike most MALT lymphomas, this lymphoma was found to be CD5-positive. Small lymphocytic lymphoma/chronic lymphocytic leukemia and lymphoplasmacytic lymphoma are two other entities that are CD5-positive and have a morphological pattern similar to MALT lymphoma. The case report and approach to the diagnosis is discussed. PMID:25473357
Mulay, Kaustubh; Honavar, Santosh G
Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer. PMID:25400790
Matsuda, Ikuo; Watanabe, Takahiro; Enomoto, Yukie; Takatsuka, Yuichi; Miyoshi, Yasuo; Hirota, Seiichi
The structure and distribution of the mucosa-associated lymphoid tissue (MALT) throughout the large intestine of 10 Bactrian camels were comparatively studied by anatomical and histological methods. The results showed that Peyer's patches (PPs) were mainly located on the mucosal surfaces of the entire ileocecal orifice, the beginning of the cecum and the first third of the colon. The shape of PPs gradually changed from "scrotiform" to "faviform" along the large intestine with the scrotiform PP as the major type in the ileocecal orifice. The distribution density also gradually decreased from the ileocecal orifice to the colon. The histological observations further revealed that the MALT in the form of PPs or isolated lymphoid follicles (ILF) and lamina propria lymphocytes was mainly present in the lamina propria and submucosa from the entire ileocecal orifice, where the muscularis mucosa is usually incomplete, to the colonic forepart. In addition, lymphoid tissue was much more abundant in the lamina propria and submucosa of the ileocecal orifice as compared to the cecum and colon. Statistically, the MALT of the ileocecal orifice contained a higher number of lymphoid follicles (37.7/10 mm(2) ) than that of the cecum, colon, or rectum (P?0.05). The germinal centers of the lymphoid follicles were clearly visible. Together, our data suggest that the ileocecal orifice constitutes the main inductive site for the mucosal immunity in the large intestine of the Bactrian camel; and that scrotiform PPs are likely to the result of long-term adaptation of the Bactrian camel to the harsh living environment. PMID:24820911
ZhaXi, Yingpai; Wang, Wenhui; Zhang, Wangdong; Gao, Qiang; Guo, Minggang; Jia, Shuai
Mucosa-associated lymphoid tissue (MALT) lymphoma is a radiosensitive malignancy. We report on a case of severe retinopathy following radiation therapy with a moderate dose for orbital MALT lymphoma. A 69-year-old woman with orbital MALT lymphoma received definitive radiation therapy with a total dose of 36 Gy in 18 fractions. The patient showed complete response but had severe retinopathy along with marked deterioration in visual acuity at 2 years after irradiation. Although the patient underwent treatments for retinopathy, including laser photocoagulation and steroid injection, improvement of the visual acuity was modest. This case developed severe radiation-induced retinopathy after radiation therapy with the moderate dose of 36 Gy that is considered to be usually safe. PMID:25471380
Hata, Masaharu; Kaneko, Akihiro; Tomita, Naoto; Inoue, Tomio
A 57-year-old woman presented with cough and dyspnea for 2 months. Computed tomography of the chest showed diffuse ground-glass opacities in both lungs. Histologic examination via thoracoscopic lung biopsy revealed atypical lymphoproliferative lesion. Her symptoms and radiologic findings of the chest improved just after lung biopsy without any treatment. Therefore, she was discharged and monitored at an outpatient clinic. Two months later, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection of API2-MALT1 translocation in fluorescent in situ hybridization analysis. Although the lung lesions resolved spontaneously, she received chemotherapy due to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is rare. Nodular or consolidative patterns are the most frequent radiologic findings. Although the disease has an indolent growth, it rarely resolves without treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse interstitial abnormalities on image and spontaneous regression on clinical course. PMID:25381826
Kang, Hye Seon; Lee, Hea Yon; Kim, Seung Joon; Kim, Seok Chan; Kim, Young Kyoon; Park, Gyeong Sin; Lee, Kyo Young; Jung, Jung Im; Kang, Ji Young
Synchronous occurrence of adenocarcinoma and mucosa associated lymphoid tissue (MALT) lymphoma of colon is rare, and its presence with coexisting tuberculosis is still rarer. To our knowledge, this may be the first case report. In the present report, we describe a 43-year-old female who presented with a history of abdominal pain, fever, loss of weight and loss of appetite. Colonoscopy showed a large ulceroproliferative mass arising from the caecum, biopsy of which showed it to be adenocarcinoma of the colon. A right hemicolectomy was performed and microscopic study of the colon revealed tuberculosis and synchronous adenocarcinoma with lymphoma. Eight of sixteen lymph nodes showed tuberculosis and three of sixteenpericoloniclymphnodes showed metastatic deposits. Immunostains further confirmed the tumour to be adenocarcinoma with MALT lymphoma. We would like to highlight the diagnostic challenges arising from the multi-faceted presentations of these three conditions. PMID:25232463
Velu, Ambedkar Raj Kulandai; Srinivasamurthy, Banushree C; Nagarajan, Krishnan; Sinduja, Ilavarasi
We present the complete genome sequence of Helicobacter pylori strain Hp238, isolated from a Taiwanese patient with gastric mucosa-associated lymphoid tissue lymphoma. Importantly, H. pylori strain Hp238 can multiply in THP-1 cells after internalization through the induction of autophagosome formation. These genome data will help to identify genes associated with H. pylori intracellular multiplication and pathogenesis.
Kao, Cheng-Yen; Chen, Jenn-Wei; Huang, Yi-Ting; Sheu, Shew-Meei; Sheu, Bor-Shyang
We report a case of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT) that presented as multiple pulmonary nodules and masses. Lung lesions were found incidentally on a chest radiograph in an asymptomatic patient. Abdominal CT scan was obtained that showed asymmetric gastric mucosal thickening. Biopsy of lung masses and gastric mucosa confirmed the diagnosis of MALT
Bobbak Vahid; Bernadette Wildmore; Paul Marik
Primary mucosa-associated lymphoid tissue lymphoma of the esophagus masquerading as a benign tumor
We report a case of primary esophageal low-grade B-cell lymphoma of MALT type in a 50-year-old Saudi male patient who presented to our hospital with a history of dysphagia and heartburn for more than 2 years. Endoscopy showed a large esophageal mass with an intact mucosa located in the distal esophagus, 28 cm–35 cm from the incisor teeth. Endoscopic ultrasonography (EUS) showed a large well demarcated sub-epithelial lesion 4 cm in width and 10 cm in length arising from the muscularis mucosa with mixed echogenicity consistent with benign leiomyoma. Subsequently, the patient underwent surgical resection of the tumor; the histopathology confirmed the diagnosis of esophageal lymphoma. The tumor was considered to be completely resected and therefore additional treatment was not administered. The patient was doing well on follow up after treatment. Clinically and radiologically he did not reveal any signs of recurrence. Surgical resection is beneficial as a primary treatment option in incipient primary low grade MALT esophageal lymphomas.
Bardisi, Ekhlas S.; Alghanmi, Najla; Merdad, Adnan A.
Low-grade B cell non-Hodgkin lymphomas typically arise from the marginal zone of the secondary lymphatic follicles. Their intracranial expression is very rare, most frequently affecting the dura mater and the choroid plexus glomi in the lateral ventricles. Their initial evaluation requires the exclusion of more common extra-axial lesions, such as meningiomas, dural metastasis, granulomatous lesions or secondary lymphoproliferative dural extension from body lymphomas. Whenever a ventricular lesion is present, the patient's age and lesion location help narrow the differential diagnosis. Dural-based lymphomas and ventricular/choroid plexus lymphomas are slow-growing lesions with imaging features similar to meningiomas, which is typically their main differential consideration. Diffusion-weighted images frequently show restricted diffusion behaviour on lymphomas, helping to differentiate them from the typical meningiomas. PMID:25196615
Sebastián, Cristina; Vela, Ana Carmen; Figueroa, Ramón; Marín, Miguel Ángel; Alfaro, Jorge
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies. PMID:24372375
Adam, Patrick; Czapiewski, Piotr; Colak, Seba; Kosmidis, Perikles; Tousseyn, Thomas; Sagaert, Xavier; Boudova, Ludmila; Oko?, Krzysztof; Morresi-Hauf, Alicia; Agostinelli, Claudio; Pileri, Stefano; Pruneri, Giancarlo; Martinelli, Giovanni; Du, Ming-Qing; Fend, Falko
Helicobacter pylori (H. pylori) infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue (MALT). Increasing evidence shows that eradication of H. pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission. The eradication of H. pylori is the standard care for patients with gastric MALT lymphoma. Cytotoxin-associated gene A (CagA) protein, one of the most extensively studied H. pylori virulence factors, is strongly associated with the gastric MALT lymphoma. CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races. After being translocated into B lymphocytes via type IV secretion system, CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and -independent manners and/or some other pathways, and thereby promotes lymphomagenesis. A variety of proteins including p53 and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA. Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma. PMID:24363512
Wang, Hong-Ping; Zhu, Yong-Liang; Shao, Wei
Purpose To elucidate risk potentiality of frontline radiotherapy associated cataracts in primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML). Methods Data from eight consecutive patients of 41 total OAML patients who had undergone cataract surgery after frontline radiotherapy were analyzed. Results The median patient age was 46 years (range, 36 to 69 years). The median total radiation dose was 3,780 cGy (range, 3,060 to 4,500 cGy), and the mean duration from radiation irradiation to cataract surgery was 36.60 ± 8.93 months. Preoperative lens opacification was primarily at the posterior lens subcapsule, and best-corrected visual acuity (BCVA) was 0.43 ± 0.21. Patients underwent the phacoemulsification surgical procedure with posterior chamber intraocular lens insertion. The average BCVA improved to 0.90 ± 0.14 after cataract surgery. Two patients underwent posterior continuous curvilinear capsulorhexis, and one had posterior capsule rupture. For posterior capsule opacification (PCO), three patients received Nd:YAG laser posterior capsulotomy after the initial surgery, and one patient is currently under consideration for laser posterior capsulotomy. Conclusions Radiotherapy increased posterior subcapsule opacification at a relatively young age in primary OAML. Phacoemulsification was a manageable procedure without severe complications, and final visual outcomes were good. However, because after-cataracts progressed earlier than did senile cataracts, close follow-up should be considered for PCO management. PMID:23908569
Cho, Won-Kyung; Lee, Sung-Eun; Paik, Ji-Sun; Cho, Seok-Goo
According to a previous review, multiple mucosa-associated lymphoid tissue (MALT)-organs involving marginal zone B cell lymphomas\\u000a (MZLs) are present in 10–30% of patients. However, the clinical features and specific relationships among involved organs\\u000a are yet to be clearly identified. In this study, we conducted retrospective analyses of multiple MALT organs involving MZLs\\u000a (MM-MZLs) to identify their clinical features, treatment, prognosis,
Sung Yong Oh; Won Seog Kim; Jin Seok Kim; Seok Jin Kim; Suee Lee; Dae Ho Lee; Jong-Ho Won; In Gyu Hwang; Min Kyoung Kim; Soon Il Lee; Yee Soo Chae; Deok-Hwan Yang; Hye Jin Kang; Chul Won Choi; Jinny Park; Hyo Jung Kim; Jung Hye Kwon; Ho Sup Lee; Gyeong-Won Lee; Hyeon Seok Eom; Jae-Yong Kwak; Won Sik Lee; Cheolwon Suh; Hyo-Jin Kim
Summary A case of small lymphocytic B-cell lymphoma with seropositivity for human T-cell leukemia virus type I (HTLV-I), whose clinical features were closely related to those of mucosa-associated lymphoid tissue (MALT) lymphoma, is presented. The neoplastic cells of the lymph node were immunologically positive for CD5, in addition to several B-cell markers, but negative for CD10, and cytogenetically carried a
K. Shibata; Y. Shimamoto; S. Nakano; M. Miyahara; H. Nakano; M. Yamaguchi
Plasmablastic lymphoma (PBL) is an uncommon malignancy which predominantly occurs in the oral cavity of human immunodeficiency virus (HIV)-positive patients. Sporadic cases have been published describing PBL in immunocompetent patients as well as in immunodeficient patients following immunosuppressive therapy or transplantation. We hereby reported a case of PBL in a 69-year-old, HIV-negative male subjected to combination treatment with fludarabine and rituximab for nongastric mucosa-associated lymphoid tissue (MALT) lymphoma. The diagnosis of PBL was made with tumor cells of immunoblasts or plasmablasts morphology strongly positive for MUM-1, EMA and CD138, and partly positive for CD38, and negative for CD20, BCL-6, and CD56, and approximately 80% of which were positive for Ki-67. The case presented PBL after MALT, and a history of chemotherapy including fludarabine and rituximab led to the potential immunocompromised state. The patient died 5 months after the diagnosis of PBL. PMID:25120825
Wu, Jia-Zhu; Min, Ke; Fan, Lei; Wang, Li; Xu, Ji; Li, Jian-Yong; Xu, Wei
The simultaneous presence of hematological malignancies and sarcoidosis, defined as sarcoidosis-lymphoma syndrome, has been reported in 79 patients in the literature to date. The majority of these patients were affected by sarcoidosis and developed non-Hodgkin lymphoma or acute leukemia after 1–2 years; however, in <20 cases the malignancy developed first. This report presents the case of an 83-year-old male with a clinical history of Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma. The patient developed sarcoidosis 10 years after the first diagnosis, which caused the diagnostic work-up and differential diagnosis between a lymphoma relapse and de novo sarcoidosis to be challenging. PMID:25120711
A 66-year-old man was admitted to our hospital because of an intra-abdominal tumor and pleural effusion (PE). Immunoelectrophoresis of the serum showed immunoglobulin M (IgM) kappa paraprotein (7330 mg/dL). Abnormal plasmacytoid cells were seen in both the peripheral blood (PB) and the bone marrow (BM). Computed tomography scans showed extensive thickening of the gastric wall and bilateral massive PE without lymph node or pulmonary involvement. A histologic examination of the gastric mucosa showed a diffuse infiltration of small- to medium-sized lymphoid CD20-bearing cells, some of which showed a plasmacytoid morphology. Lymphoepithelial lesions were demonstrated with an immunohistochemical stain. The diagnosis was gastric mucosa-associated lymphoid tissue (MALT) lymphoma infiltrating to the PE, PB, and BM. The PE contained numerous lymphoid cells with plasmacytoid morphology that Southern blotting analysis showed to have a monoclonal IgH gene rearrangement pattern. The cells seemed to be divided into two populations according to their surface markers: mature B-cells (CD19+CD20+CD22+CD21+CD38-) and secretory B-cells (CD19+CD20(dim)CD22-CD21-CD38+). The reverse transcriptase-polymerase chain reaction technique detected the API-2/MLT transcript in the PE and PB. The patient had a good response to fludarabine treatment, which was followed with rituximab therapy. In general, gastric MALT lymphoma cells have a tendency to differentiate into plasma cells. In this article, we show that the cell character of API-2/MLT-positive MALT lymphoma is preserved even when the cells are disseminated. This is the first published case, to our knowledge, in which two differentiation stages of MALT lymphoma cells infiltrating into PE have been confirmed by flow cytometric analysis. PMID:14686495
Kunisaki, Yuya; Muta, Tsuyoshi; Yamano, Yujiro; Kobayashi, Yukio
Purpose: To propose an alternative approach for treatment of pulmonary marginal zone lymphoma, using a very small radiation dose (2 Multiplication-Sign 2 Gy) delivered exclusively to tumor sites. Methods and Materials: Patients had localized pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma according to the World Health Organization classification. The 6-MV radiation treatments were delivered using tumor-limited fields, except in cases of diffuse bilateral involvement. Two daily fractions of 2 Gy were delivered to tumor-limited fields using a 6-MV linear accelerator. Results: Ten patients with pulmonary MALT lymphoma entered the study. All but 1 had localized tumor masses. The median follow-up was 56 months (range, 2-103 months). Complete remission or an unconfirmed complete remission was obtained in 60% of patients within the first 2 months, and two additional partial responses were converted into a long-term unconfirmed complete remission. All patients are well and alive, no local progression was observed, and the 5-year progression-free survival rate was 87.5% (95% confidence interval 49%-97%). Conclusions: Our results suggest that extremely low radiation doses delivered exclusively to tumor sites might be a treatment option in pulmonary MALT lymphoma.
Girinsky, Theodore, E-mail: email@example.com [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Paumier, Amaury [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France); Ferme, Christophe; Hanna, Colette; Ribrag, Vincent [Department of Hematology, Institut Gustave Roussy, Villejuif (France); Leroy-Ladurie, Francois [Department of Thoracic Surgery, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson (France); Ghalibafian, Mithra [Department of Radiation Oncology, Institut Gustave Roussy, Villejuif (France)
Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r2=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4+ T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIII? and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication. PMID:25303370
Liao, F; Hsu, Y-C; Kuo, S-H; Yang, Y-C; Chen, J-P; Hsu, P-N; Lin, C-W; Chen, L-T; Cheng, A-L; Fann, C S J; Lin, J-T; Wu, M-S
This study investigated expression profiles of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) pathway components and mechanisms underlying TRAIL-induced apoptosis in mucosa associated lymphoid tissue (MALT) lymphoma. Genetic aberrations including translocations and trisomies were assessed by reverse transcription polymerase chain reaction and fluorescence in situ hybridization. Expression of TRAIL, death receptors 4 and 5, decoy receptors 1 and 2, and FADD-like interleukin-1?-converting enzyme (FLICE) inhibitory protein was analyzed by immunohistochemistry. All 32 patients under study showed some alterations in TRAIL pathway mainly involving loss of death receptors (37.5%), gain of decoy receptors (3.1%) or both (59.4%). Decoy receptor 2 (DcR2) was highly expressed in patients with normal cytogenetic status as compared to those with cytogenetic aberrations (p = 0.005). Moreover, DcR2 expression correlated significantly with nuclear factor-?B (NF-?B) expression (R = 0.372, p = 0.047). High expression of DcR2 in patients with normal cytogenetic status and its significant correlation with NF-?B expression provides a potential clue to evasion of immune surveillance in cytogenetically normal MALT lymphomas. PMID:25248880
Anees, Mariam; Horak, Peter; Schiefer, Ana-Iris; Va?hara, Petr; El-Gazzar, Ahmed; Perco, Paul; Kiesewetter, Barbara; Müllauer, Leonhard; Streubel, Berthold; Raderer, Markus; Krainer, Michael
Primary indolent leptomeningeal lymphoma is a rare entity, and corresponds in most cases to mucosa-associated lymphoid tissue (MALT) type lymphoma. We are reporting a case of a 75 years old woman, who presented with a 2-year history of behavioral disorder, progressive memory loss and aphasia. Neuroimaging showed a mass infiltrating the frontal circumvolutions and the roof of the orbit. The biopsy revealed an infiltration of the dura by an indolent lymphoma, characteristic of a MALT-type lymphoma. Complete staging work-up did not show any evidence of systemic involvement. A treatment with systemic methotrexate, combined with intrathecal chemotherapy and followed by radiotherapy (30,6 Gy) of the primary site, was conducted. The 3-year follow-up confirms the persistent remission, the patient remaining well and free of symptoms. The review of the literature highlights the importance to recognize the indolent PLML as a distinct clinical entity, which exhibits a rather good prognosis following a relatively non-toxic therapy. PMID:16122999
George, Anne-Claude; Ozsahin, Mahmut; Janzer, Robert; Agassis, Siverio; Meuli, Reto; Baur, Audrey S; Frossard, Valérie; Leyvraz, Serge; Ketterer, Nicolas
Background: Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. Methods: Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migratory abilities of cells in response to MALT1 were determined by wound-healing assay and time-lapse analysis. Results: Totally, 2933 genes upregulated or downregulated in MALT1-expressing cells were identified. The subsequent pathway analysis implicated the inhibition of epidermal growth factor and transforming growth factor-? signalling gene expression, and highlighted the involvement in the cellular movement. Wound closure was suppressed by wild-type MALT1 (66.4%) and accelerated by dominant-negative MALT1 (218.6%), and the velocities of cell migration were increased 0.2-fold and 3.0-fold by wild-type and dominant-negative MALT1, respectively. Conclusion: These observations demonstrate that MALT1 represses genes activating the aggressive phenotype of carcinoma cells, and suggest that MALT1 acts as a tumour suppressor and that the loss of expression stimulates oral carcinoma progression. PMID:23778523
Ohyama, Y; Kawamoto, Y; Chiba, T; Maeda, G; Sakashita, H; Imai, K
Purpose: To evaluate the long-term treatment outcome and disease behavior of primary ocular adnexal MALT (mucosa-associated lymphoid tissue) lymphoma (POAML) after treatment with radiotherapy. Methods and Materials: Seventy-eight patients (42 male, 36 female) diagnosed with stage I POAML between 1991 and 2010 at Kobe University Hospital were included. The median age was 60 years (range, 22-85 years). The median radiation dose administered was 30.6 Gy. Rituximab-based targeted therapy and/or chemotherapy was performed in 20 patients (25.6%). Local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method. Results: The median follow-up duration was 66 months. Major tumor sites were conjunctiva in 37 patients (47.4%), orbita in 29 (37.2%), and lacrimal glands in 12 (15.4%). The 5- and 10-year OS rates were 98.1% and 95.3%, respectively. The 5- and 10-year LC rates were both 100%, and the 5- and 10-year RFS rates were 88.5% and 75.9%, respectively. Patients treated with a combination of radiotherapy and targeted therapy and/or chemotherapy had a trend for a better RFS compared with those treated with radiotherapy alone (p = 0.114). None developed greater than Grade 2 acute morbidity. There were 14 patients who experienced Grade 2 morbidities (cataract: 14; retinal disorders: 7; dry eye: 3), 23 patients who had Grade 3 morbidities (cataract: 23; dry eye: 1), and 1 patient who had Grade 4 glaucoma. Conclusions: Radiotherapy for POAML was shown to be highly effective and safe for LC and OS on the basis of long-term observation. The absence of systemic relapse in patients with combined-modality treatment suggests that lower doses of radiation combined with targeted therapy may be worth further study.
Hashimoto, Naoki [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Sasaki, Ryohei, E-mail: firstname.lastname@example.com [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Nishimura, Hideki; Yoshida, Kenji; Miyawaki, Daisuke; Nakayama, Masao; Uehara, Kazuyuki; Okamoto, Yoshiaki; Ejima, Yasuo [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan); Azumi, Atsushi [Division of Ophthalmology, Kobe University Graduate School of Medicine, Hyogo (Japan); Matsui, Toshimitsu [Division of Hematology, Kobe University Graduate School of Medicine, Hyogo (Japan); Sugimura, Kazuro [Division of Radiation Oncology, Kobe University Graduate School of Medicine, Hyogo (Japan)
Given the favorable immunologic effects of IL-2 post transplant, we conducted a feasibility study examining rIL-2 1.0×106 IU\\/m2\\/day (SQ) beginning on D+14 post-transplant and continuing for 90 days in 12 patients with low-grade lymphoproliferative disorders. Prior to high-dose chemotherapy and autologous peripheral blood stem cell transplantation (HDCT), 11 patients underwent cytoreduction with fludarabine and cyclophosphamide (Flu\\/Cy); 11 were in complete remission (CR)
Jamie K. Waselenko; Ann Burrows; Douglas A. Nelson; Margaret Lucas; John Ekstrand; William Jeffrey Edenfield; Rick C. Myhand
Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma
Cyclin D1 (Bcl-1, PRAD1) protein expression in low-grade B-cell lymphomas and reactive hyperplasia.
Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region. Recently it was shown that the key Bcl-1 region oncogene is cyclin D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin D1 protein expression in low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1 protein. Definite nuclear staining was seen in 15 of 15 MCLs, 1 of 7 B-SLL/CLLs, 0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin-embedded sections. Best results were obtained with the affinity-purified polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded tissue. MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL showed dot-like or globular nuclear staining. Nuclear cyclin D1 protein can be detected in all cases of MCL and in rare cases of B-SLL/CLL using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it does not appear to be detectable in reactive hyperplasias and other low-grade B-cell lymphomas. This protein may be useful in subclassification of low-grade B-cell lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:7518196
Yang, W. I.; Zukerberg, L. R.; Motokura, T.; Arnold, A.; Harris, N. L.
\\u000a Glial tumors constitute approximately 50% of newly diagnosed primary brain tumors, with low-grade gliomas (LGG) accounting\\u000a for approximately 15% of all brain tumors in adults [21]. The subset of tumors classified as LGG represents a heterogeneous\\u000a group of tumors with astrocytic, oligodendroglial, ependymal, or mixed cellular histologies. In the adult population, the\\u000a term LGG typically refers to the diffuse, infiltrating
Nader Sanai; Mitchel S. Berger
Marginal Zone Mucosa Associated Lymphoid Tissue Diffuse Large B Cell Lymphoma
Context: Non-Hodgkin's lymphomas (NHL) primarily involving the orbit, is relatively uncommon. Rarely two pathologically different NHL cell types have been found to be coexistent. Case Report: We report a case of orbital lymphoma in a 62-year-old male with rare histopathological findings secondary to transformation of once cell type into another. Tissue diagnosis and molecular studies led to revelation of diffuse large B cell lymphoma evolving from MALT lymphoma. Conclusion: Proliferation of two morphologically and phenotypically different B cells resulting in malignancy has not been found in the orbit so far. They are usually aggressive tumors and require chemo-immunotherapy. PMID:25210678
Aldave, Adrian Pedro Noriega; Jaiswal, Shikha; Davidson, Stephen L
Common variable immunodeficiency syndrome (CVID) is a primary immunodeficiency typically presenting with recurrent sinopulmonary infections. Non-Hodgkin's lymphoma and other secondary cancers are typical late complications of CVID. We report on a patient suffering from CVID with a history of recurrent sinopulmonary infections, interstitial pulmonary changes and hepatic granulomas. Despite treatment with intravenous immunoglobulin followed by a reduction in the number
F. Reichenberger; C. Wyser; M. Gonon; G. Cathomas; M. Tamm
in the pathogenesis of gastritis, peptic ulcer disease and gastric adenocarcinoma. In addition, a causal role of H oxidases. Indeed, Salles et al. showed that NOX family (NOX2 and NOX5) was expressed in human stomach
Paris-Sud XI, Université de
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma
Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia
Pediatric low-grade gliomas encompass a heterogeneous set of tumors of different histologies. Cerebellar pilocytic astrocytomas occur most frequently followed by supratentorial diffuse fibrillary astrocytomas. Recent research has implicated activation of the RAS/RAF/MEK pathway in tumorigenesis of these tumors. Surgery is the mainstay of therapy. Overall survival rates for patients whose tumors are completely resected are 90% or greater, 10 years from diagnosis. Conversely, most optic pathway/hypothalamic, deep midline, and brain stem gliomas have minimal potential for resection; these tumors can be difficult to treat and deserve special attention. Combination chemotherapy is currently recommended as front-line adjuvant treatment for progressive or recurrent tumors. Second-line radiotherapy can also improve overall survival but is associated with more frequent and significant neurocognitive, endocrine, and other long-term toxicities. PMID:19841428
Sievert, Angela J.; Fisher, Michael J.
Warthin's tumor is rarely associated with malignant lymphoma. Only 18 cases were reported in the literature so far. In most cases the latter is a low grade process, including Marginal zone/Mucosa associated lymphoid tissue (MALT) type lymphoma, follicular lymphoma, and rarely diffuse large cell lymphoma which may arise de novo or secondary to low grade lymphoma. This study was conducted to determine the prevalence of occult B cell monoclones and genetic alterations in Warthin's tumor. Fourteen cases of Warthin's tumor were stained with antibodies to CD3, CD20, kappa and lambda light chains. On six cases of randomly selected Warthin's tumor, polymerase chain reaction (PCR) of IgH gene rearrangement (IgH-GR) was performed on genomic DNA extracted from formalin-fixed paraffin embedded tissue. One case of primary salivary gland indolent B-cell lymphoma and 3 cases of sialadenitis were analyzed by the same methods for comparison. In all Warthin's tumor and sialadenitis cases most of lymphoid stroma was B cell phenotype and concentrated in germinal centers. T cells were mostly located between germinal centers. No light chain restriction was demonstrable by kappa and lambda immunostains. Molecular genetic studies failed to show IgH-GR by FISH and showed polyclonal by IgH PCR. In contrast, the lymphoma case showed a diffuse proliferation of small B cells with light chain restriction and a minor component of reactive T cells. FISH showed IgH-GR and bcl-2 gene translocation with monoclonality by IgH PCR. Our study concludes that the lymphoid stroma of Warthin's tumor is reactive. PMID:19956447
Song, Kunchang; Cotelingam, James D.; Lowery-Nordberg, Mary; Sun, Wei
Low grade chondrosarcoma of the nasal septum
Chondrosarcoma of the nasal septum is extremely rare. In some cases, it may be difficult to preoperatively differentiate low grade chondrosarcoma from benign cartilaginous tumors such as chondroma. We report a case of low grade chondrosarcoma of the nasal septum with characteristic radiologic findings. Characteristic radiologic findings such as calcifications on computed tomography scan and a ring-and-arc pattern on enhanced T1 weighted image were useful in the preoperative diagnosis of low grade chondrosarcoma of the septum. Awareness of radiologic findings of low grade chondrosarcoma can help to make an accurate diagnosis and perform appropriate excision, leading to successful local control. PMID:24303467
Lee, Dong Hoon; Jung, Se Hee; Yoon, Tae Mi; Lee, Joon Kyoo; Joo, Young Eun; Lim, Sang Chul
The criteria for distinguishing benign lymphoepithelial lesions (BLEL) from low grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type in salivary glands and the significance of genotypically documented clonality in this setting are controversial. In addition, the clinical implications of a neoplastic diagnosis are unclear. The histopathologic features of 68 specimens from 49 patients with at least one salivary gland biopsy with LEL together with available clinical data were, therefore, reviewed. Paraffin section immunohistochemical (IHC) stains for kappa, lambda, CD3, CD20, and CD43; in situ hybridization (ISH) for kappa and lambda; and polymerase chain reaction (PCR) for immunoglobulin (Ig) HC rearrangement were performed. The 61 salivary gland specimens were classified as BLEL-13, BLEL with monocytoid B-cell (MBC) halos (BLEL-halo-8), low grade B-cell lymphoma of MALT type with confluent zones of MBC or other atypical lymphocytes (ML-MALT-24), low grade B-cell lymphoma of MALT type with monoclonal plasma cells (ML-MALT-PC-12), and high grade B-cell lymphoma of MALT type (MALT-high grade-4). Soft tissue and perineural invasion was not observed in BLEL and was most common in the MALT lymphomas. Lymph node involvement was identified in six patients at the time of their salivary gland MALT lymphomas but in none with BLEL. CD43+ B cells were seen most commonly in ML-MALT but were present in all other categories except MALT-high grade. Clonal B cells were identified by PCR in 5 of 12 BLEL, 5 of 8 BLEL-halo, 17 of 22 ML-MALT, 6 of 10 ML-MALT-PC, and 3 of 3 MALT-high grade biopsies. All ML-MALT-PC were clonal by ISH or IHC. Repeat biopsies in 14 patients most commonly showed a BLEL/ML-MALT lesion in an ipsilateral or contralateral salivary gland with one transformation to a MALT-high grade. Although only a few patients are known to have received chemoradiation or radiation therapy, most patients with low-grade lesions have pursued an indolent course. These data show the presence of two types of borderline lesions within the spectrum of lymphoid proliferations associated with salivary gland LEL. One has clonal B cells without histological features of neoplasia and the other nonconfluent MBC extending beyond the confines of LEL ("halos"). They share some features with the infrequent nonneoplastic BLEL and others with the more common low-grade B-cell lymphomas of MALT. A few high-grade B-cell lymphomas of MALT were also identified including a rare example of transformation from a low- to high-grade lesion. The optimal therapeutic approach for the borderline and low-grade lesions and the reason why so many of the lymphoproliferative lesions associated with LEL remain localized to the neck remain to be defined. PMID:9224756
Quintana, P G; Kapadia, S B; Bahler, D W; Johnson, J T; Swerdlow, S H
Nodular lymphoid hyperplasia of the stomach in a patient with multiple submucosal tumors
Nodular lymphoid hyperplasia of the stomach is a rare lymphoproliferative disorder. Here, we report a 38-year-old man who presented with multiple submucosal tumors of the stomach. Histologically, the lesions were characterized by multiple discrete submucosal nodules of lymphoid cells. The infiltrates between the lymphoid follicles were composed mainly of medium-sized lymphoid cells with abundant clear cytoplasm, as well as a few large cells with vesicular nuclei. The gastric mucosa exhibited multifocal lymphoid aggregates and some of the epithelial cells were infiltrated by small lymphocytes mimicking lymphoepithelial lesions. Histopathology was consistent with mucosa-associated lymphoid tissue lymphoma. However, the infiltrating lymphoid cells were positive for CD2, CD3, CD5, and CD7. In addition, polymerase chain reaction analysis of the immunoglobulin heavy chain and T-cell receptor gene rearrangements demonstrated polyclonality. This case was diagnosed as reactive lymphoid hyperplasia of the stomach. PMID:24466554
Jeon, Ja Young; Lim, Sun Gyo; Kim, Jang Hee; Lee, Kee Myung; Cho, Sung Ran
Technology Transfer Automated Retrieval System (TEKTRAN)
Background and aims: Mucosa-associated E. coli are abundant in Crohn's disease (CD) but whether these bacteria gain intracellular access within the mucosa is less certain. If E. coli does gain intracellular access in CD, the contribution of bacterial pathogenicity as opposed to a defect in host inna...
Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma
Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia
Natural heterogeneity in the structure of the lipid A portion of lipopolysaccharide (LPS) produces differential effects on the innate immune response. Gram-negative bacterial species produce LPS structures that differ from the classic endotoxic LPS structures. These differences include hypoacylation and hypophosphorylation of the diglucosamine backbone, both differences known to decrease LPS toxicity. The effect of decreased toxicity on the adjuvant properties of many of these LPS structures has not been fully explored. Here we demonstrate that two naturally produced forms of monophosphorylated LPS, from the mucosa-associated bacteria Bacteroides thetaiotaomicron and Prevotella intermedia, function as immunological adjuvants for antigen-specific immune responses. Each form of mucosal LPS increased vaccination-initiated antigen-specific antibody titers in both quantity and quality when given simultaneously with vaccine antigen preparations. Interestingly, adjuvant effects on initial T cell clonal expansion were selective for CD4 T cells. No significant increase in CD8 T cell expansion was detected. MyD88/Toll-like receptor 4 (TLR4) and TRIF/TLR4 signaling pathways showed equally decreased signaling with the LPS forms studied here as with endotoxic LPS or detoxified monophosphorylated lipid A (MPLA). Natural monophosphorylated LPS from mucosa-associated bacteria functions as a weak but effective adjuvant for specific immune responses, with preferential effects on antibody and CD4 T cell responses over CD8 T cell responses. PMID:23798540
Chilton, Paula M.; Hadel, Diana M.; To, Thao T.
Conformal Proton Radiation Therapy for Pediatric Low-Grade Astrocytomas
Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at
Eugen B. Hug; Marc W. Muenter; John O. Archambeau; Alexander DeVries; Boleslaw Liwnicz; Lilia N. Loredo; Roger I. Grove; Jerry D. Slater
Helicobacter (H.) suis is capable of infecting various animals including humans, and H. suis infections can lead to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, we reported that interferon-? (IFN-?) was highly expressed in the stomachs of H. suis-infected mice, but the direct relationship between the upregulation of IFN-? expression and the formation of gastric lymphoid follicles after H. suis infection remains unclear. Here, we demonstrated that the IFN-? produced by B cells plays an important role in the formation of gastric lymphoid follicles after H. suis infection. In addition, IFN-?-producing B cells evoked gastric lymphoid follicle formation independent of T-cell help, suggesting that they are crucial for the development of gastric MALT induced by Helicobacter infection. PMID:25073677
Yang, L; Yamamoto, K; Nishiumi, S; Nakamura, M; Matsui, H; Takahashi, S; Dohi, T; Okada, T; Kakimoto, K; Hoshi, N; Yoshida, M; Azuma, T
MAPping the genomic landscape of low-grade pediatric gliomas.
Two recent large-scale sequencing studies have identified multiple genetic aberrations in pediatric low-grade gliomas. These findings offer substantial insights that may spur the development of new diagnostics and treatments for these cancers. PMID:23892663
Turcan, Sevin; Chan, Timothy A
Many colonic mucosal genes that are highly regulated by microbial signals are differentially expressed along the rostral-caudal axis. This would suggest that differences in regional microbiota exist, particularly mucosa-associated microbes that are less likely to be transient. We therefore explored this possibility by examining the bacterial populations associated with the normal proximal and distal colonic mucosa in context of host Toll-like receptors (TLR) expression in C57BL/6J mice housed in specific pathogen-free (SPF) and germ-free (GF) environments. 16S rRNA gene-based terminal restriction fragment length polymorphism (T-RFLP) and clone library analysis revealed significant differences in the community structure and diversity of the mucosa-associated microbiota located in the distal colon compared to proximal colon and stool, the latter two clustering closely. Differential expression of colonic TLR2 and TLR4 along the proximal-distal axis was also found in SPF mice, but not in GF mice, suggesting that enteric microbes are essential in maintaining the regional expression of these TLRs. TLR2 is more highly expressed in proximal colon and decreases in a gradient to distal while TLR4 expression is highest in distal colon and a gradient of decreased expression to proximal colon is observed. After transfaunation in GF mice, both regional colonization of mucosa-associated microbes and expression of TLRs in the mouse colon were reestablished. In addition, exposure of the distal colon to cecal (proximal) microbiota induced TLR2 expression. These results demonstrate that regional colonic mucosa-associated microbiota determine the region-specific expression of TLR2 and TLR4. Conversely, region-specific host assembly rules are essential in determining the structure and function of mucosa-associated microbial populations. We believe this type of host-microbial mutualism is pivotal to the maintenance of intestinal and immune homeostasis. PMID:21042588
Wang, Yunwei; Devkota, Suzanne; Musch, Mark W.; Jabri, Bana; Nagler, Cathryn; Antonopoulos, Dionysios A.; Chervonsky, Alexander; Chang, Eugene B.
Polyclonal Mucosa-Associated Invariant T Cells Have Unique Innate Functions in Bacterial Infection
Mucosa-associated invariant T (MAIT) cells are a unique population of ?? T cells in mammals that reside preferentially in mucosal tissues and express an invariant V? paired with limited V? T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using in vitro assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of Mycobacterium bovis BCG in macrophages (M?) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-?), and an innate interleukin 12 (IL-12) signal from infected M?. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected M? was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection. PMID:22778103
Chua, Wei-Jen; Truscott, Steven M.; Eickhoff, Christopher S.; Blazevic, Azra
Pathological and Molecular Advances in Pediatric Low Grade Astrocytoma
Pediatric low grade astrocytomas are the commonest brain tumors in children. They sometimes have similar microscopic and clinical features, making accurate diagnosis difficult. For patients whose tumors are in locations that do not permit full resection, or those with an intrinsically aggressive biology, more effective therapies are required. Until recently, little was known about the molecular changes that drive the initiation and growth of pilocytic and other low grade astrocytomas beyond the association of a minority of cases, primarily in the optic nerve, with neurofibromatosis type 1. Over the last several years, a wide range of studies have implicated the BRAF oncogene and other members of this signaling cascade in the pathobiology of pediatric low grade astrocytoma. In this review, we attempt to summarize this rapidly developing field, and discuss the potential for translating our growing molecular knowledge into improved diagnostic and prognostic biomarkers and new targeted therapies. PMID:23121055
Rodriguez, Fausto J.; Lim, Kah Suan; Bowers, Daniel; Eberhart, Charles G.
Dietary composition largely influences pig's gastrointestinal microbiota and represents a useful prophylactic tool against enteric disturbances in young pigs. Despite the importance for host-microbe interactions and bacterial colonization, dietary responses of the mucosa-associated bacterial communities are less well investigated. In the present study, we characterized the mucosa-associated bacterial communities at the Pars non-glandularis of the stomach, ileum and colon, and identified shifts in these communities in response to different dietary calcium-phosphorus (Ca-P) contents (100% versus 190% of the Ca and P requirements) in combination with two basal diets (wheat-barley- or corn-based) in weaned pigs. Pyrosequencing of 16S rRNA genes from 93 mucosal samples yielded 447,849 sequences, clustering into 997 operational taxonomic units (OTUs) at 97% similarity level. OTUs were assigned to 198 genera belonging to 14 different phyla. Correlation-based networks revealed strong interactions among OTUs at the various gastrointestinal sites. Our data describe a previously not reported high diversity and species richness at the Pars non-glandularis of the stomach in weaned pigs. Moreover, high versus adequate Ca-P content significantly promoted Lactobacillus by 14.9% units (1.4 fold change) at the gastric Pars non-glandularis (P?=?0.035). Discriminant analysis revealed dynamic changes in OTU composition in response to dietary cereals and Ca-P contents at all gastrointestinal sites which were less distinguishable at higher taxonomic levels. Overall, this study revealed a distinct mucosa-associated bacterial community at the different gut sites, and a strong effect of high Ca-P diets on the gastric community, thereby markedly expanding our comprehension on mucosa-associated microbiota and their diet-related dynamics in weaned pigs. PMID:24466298
Mann, Evelyne; Schmitz-Esser, Stephan; Zebeli, Qendrim; Wagner, Martin; Ritzmann, Mathias; Metzler-Zebeli, Barbara U.
Low-grade heat recuperation by the organic Rankine cycle
The use of an organic Rankine cycle engine in the conversion of low-grade industrial waste heat into mechanical energy is examined. The principles of a Rankine system using a vapor as the working fluid at operating temperatures from 100 to 500 C are presented, and the advantages of using organic vapors rather than water in the Rankine cycle are pointed
A. Verneau
Properties of concrete blocks prepared with low grade recycled aggregates.
Low grade recycled aggregates obtained from a construction waste sorting facility were tested to assess the feasibility of using these in the production of concrete blocks. The characteristics of the sorted construction waste are significantly different from that of crushed concrete rubbles that are mostly derived from demolition waste streams. This is due to the presence of higher percentages of non-concrete components (e.g. >10% soil, brick, tiles etc.) in the sorted construction waste. In the study reported in this paper, three series of concrete block mixtures were prepared by using the low grade recycled aggregates to replace (i) natural coarse granite (10mm), and (ii) 0, 25, 50, 75 and 100% replacement levels of crushed stone fine (crushed natural granite <5mm) in the concrete blocks. Test results on properties such as density, compressive strength, transverse strength and drying shrinkage as well as strength reduction after exposure to 800 degrees C are presented below. The results show that the soil content in the recycled fine aggregate was an important factor in affecting the properties of the blocks produced and the mechanical strength deceased with increasing low grade recycled fine aggregate content. But the higher soil content in the recycled aggregates reduced the reduction of compressive strength of the blocks after exposure to high temperature due probably to the formation of a new crystalline phase. The results show that the low grade recycled aggregates obtained from the construction waste sorting facility has potential to be used as aggregates for making non-structural pre-cast concrete blocks. PMID:19398196
Poon, Chi-Sun; Kou, Shi-cong; Wan, Hui-wen; Etxeberria, Miren
Physical activity, exercise and low-grade systemic inflammation.
Prospective studies have shown that chronic low-grade inflammation may contribute to the pathogenesis of the most common chronic diseases and in particular CVD. Obesity has repeatedly been associated with moderately raised levels of inflammation, and this observation has led to the view that obesity is characterised by a state of chronic low-grade inflammation. There is now great interest in elucidating how physical activity and exercise modulate inflammation. This review summarises the current research addressing the influence of physical activity and exercise in mitigating the risks of obesity and diseases such as type-II diabetes and CVD, through its action on the low-grade inflammatory state. Most research on this topic hypothesised that the association between physical activity and inflammatory markers is independent of fatness, but very few studies have proven this. Given that physical activity and obesity are often inversely related, it is not clear as to whether the anti-inflammatory health benefits of a physically active lifestyle are due to exercise per se or result from favourable changes in the body composition. PMID:20598198
Wärnberg, Julia; Cunningham, Karen; Romeo, Javier; Marcos, Ascension
Technology Transfer Automated Retrieval System (TEKTRAN)
The transmissible spongiform encephalopathies are a family of fatal neurodegenerative diseases characterized by accumulation of abnormal prion proteins in the brain. The abnormal prion protein is the major constituent of the infectious agent and is a reliable marker for disease. The occurrence of ...
A 71-year-old woman was referred to our hospital because of hyperproteinemia and serum M-protein (IgG-? type). Chest computed tomographic (CT) scan revealed a tumor in each lung and transbronchial lung biopsy was performed. Histopathological examination showed monotonous medullary proliferation of morphologically mature plasma cells. These cells were cIgG+, cIg-?+, CD20+, CD79a+, CD138+, cIg-??, and CD3?. Since there were very few
Nozomi Niitsu; Mika Kohri; Miyuki Hayama; Hirokazu Nakamine; Naoya Nakamura; Masami Bessho; Masaaki Higashihara
A 66-year-old man was admitted to our hospital because of an intra-abdominal tumor and pleural effusion (PE). Immunoelectrophoresis\\u000a of the serum showed immunoglobulin M (IgM) ? paraprotein (7330 mg\\/dL). Abnormal plasmacytoid cells were seen in both the peripheral\\u000a blood (PB) and the bone marrow (BM). Computed tomography scans showed extensive thickening of the gastric wall and bilateral\\u000a massive PE without
Yuya Kunisaki; Tsuyoshi Muta; Yujiro Yamano; Yukio Kobayashi
Background Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. Material and Methods We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999–2012. Median age at diagnosis was 64 years (IQR 51–75) and follow-up time 43 months (IQR 16–92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. Results The majority of patients presented with stage IE (n?=?40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9–39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p?=?0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. Conclusion Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML. PMID:25077481
Kiesewetter, Barbara; Lukas, Julius; Kuchar, Andreas; Mayerhoefer, Marius E.; Streubel, Berthold; Lagler, Heimo; Müllauer, Leonhard; Wöhrer, Stefan; Fischbach, Julia; Raderer, Markus
Stimulation of systemic low-grade inflammation by psychosocial stress.
Psychosocial stress is an important precursor of disease and reduced quality of life in humans. The biological pathways between stress exposure and pathophysiological processes underlying disease have received substantial scientific attention, although the roles of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system remain insufficiently understood. Recent attention has focused on chronic systemic low-grade inflammation as a promising pathway because elevated inflammation often accompanies chronic psychosocial distress. These alterations of inflammatory activity play a key role in the pathophysiology of diseases that are adversely affected by chronic distress, such as cardiovascular disease. Transient increases in systemic inflammation are observed in response to acute psychosocial stress, with larger responses among individuals reporting adverse psychosocial states or conditions such as depression, lower self-esteem, or lower self-compassion. Recent evidence shows that lower subjective social status and perceived purpose in life are associated with sensitization of inflammatory stress responses to repeated stress exposure. The aims of this selective review article are to summarize current knowledge of the role of acute and chronic psychosocial stress on low-grade inflammation in humans and to discuss potential relationships between inflammatory responses to acute psychosocial stress and long-term development of disease. PMID:24608036
Rohleder, Nicolas
Association of carcinoid tumor and low grade glioma
Background Lung carcinoid tumor and low grade glioma are two uncommon malignancies. Patients and methods We report the case of 24-year-old man who presented with respiratory disease. Imaging investigations showed a right lung tumor and histological analysis confirmed a typical carcinoid tumor. As part of initial staging, brain MRI revealed an asymptomatic right frontal lesion. First, a right pulmonary lobectomy was performed without adjuvant treatment. In second time, brain tumorectomy was performed. Histological examination confirmed the diagnosis of low grade glioma (LGG). The patient remained in complete remission 2.5 years after the initial diagnosis. Results This is the first case reporting the association between LGG and lung carcinoid tumor, while no association between LGG and a systemic tumor have been published to date. Association of lung carcinoid tumor with other malignant diseases has been reported but remained uncommon. Only minimal data support a potential molecular common origin. Conclusion This exceptional association may be fortuitous. However, their concomitant diagnoses suggest a potential association between both rare diseases. A genetic susceptibility remains possible. PMID:23137305
Examination of 50 autopsied cases of human poliomyelitis showed prominent hyperplastic and inflammatory changes in the lymphoid tissues of 41, the most frequent and severe lesions observed save those in the central nervous system. Histologically the germinal centers showed prominent degenerative and regenerative alterations, fluid transudation, giant cell formation, and rare inclusion bodies, all consistent with virus effects. Treatment of mice with x-rays, aminopterin, and adrenocorticotropic hormone increased poliomyelitis infections following intraperitoneal injection of MEF strain virus, potentiated by intracerebrally injected corn starch. This was ascribed to the damage to lymphoid tissues produced by these agents. On the basis of combined morphologic and virus studies, the presence of gastrointestinal, lymphoid, nervous tissue, and nerve cell defense barriers to poliomyelitis virus is suggested. Use of irradiated mice might prove useful in primary isolation of virus from human poliomyelitis. PMID:14832397
Sommers, Sheldon C.; Wilson, Joan C.; Hartman, Frank W.
Low-grade heat recuperation by the organic Rankine cycle
NASA Astrophysics Data System (ADS)
The use of an organic Rankine cycle engine in the conversion of low-grade industrial waste heat into mechanical energy is examined. The principles of a Rankine system using a vapor as the working fluid at operating temperatures from 100 to 500 C are presented, and the advantages of using organic vapors rather than water in the Rankine cycle are pointed out. Attention is then given to the Rankine cycle itself, the organic fluids employed, the multistage low-power turbines and the evaporator, which acts as a countercurrent heat exchanger. Economic aspects of the use of Rankine cycle systems for industrial waste heat recovery are then considered, and examples are presented of the calculation of power recovered and investment costs for the examples of heat recovery from diesel exhaust and from low-pressure steam.
Verneau, A.
Polymorphous low-grade adenocarcinoma: a 17 patient case series.
Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignancy most commonly seen in the minor salivary glands. First described in 1983, this entity has been recognized to have an indolent course with rare metastases or deaths. We describe our experience with 17 patients treated at our institution for PLGA from 1984 to 2012. All tumors were located in the oral cavity or soft palate. All patients were treated surgically, with the exception of one patient who declined therapy. No deaths or metastases have been identified in subsequent follow-up. Three patients in this series had undergone prior surgery up to 20 years previously and were treated for recurrences at our institution; no other recurrences have been noted. In summary, PLGA is best treated with wide excision to negative margins with excellent prognosis, but long-term follow-up is recommended given the propensity for late recurrences. PMID:23618791
Fife, Tim A; Smith, Brooks; Sullivan, Christopher A; Browne, J Dale; Waltonen, Joshua D
Interaction of low-grade metamorphic coals with methanol
How conditions of alkylation of low-grade metamorphic coals with methanol in the presence of benzenesulfonic acid influence the yield of extractable matter was experimentally studied and relevant regression equations were obtained. It was shown that catalytic methylation considerably increases the yield of the extractable matter, as well as reducing the thermal stability of modified samples and alters the elemental composition of the samples and their extracts. A possible mechanism of coal methylation is discussed on the basis of regression models and experimental results. The interaction of the coal matter with the alkylating agent presumably involves the formation of the carbocation and its reaction with the coal organic matter. Both depolymerization reactions and the addition reactions of a portion of extractable compounds, the alkylating agent, and the catalyst with the high-molecular mass coal matrix take place.
S.I. Zherebtsov [Russian Academy of Sciences, Kemerovo (Russian Federation). Institute of Coal and Coal Chemistry, Siberian Division
Low Grade Endometrial Stromal Sarcoma: A Case Report
Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the endometrium, occurring in the age group of 40–50 years. We report a case of low-grade ESS in a 39-year-old woman, presenting as rapid enlargement of a uterine fibroid polyp associated with irregular and excessive vaginal bleeding. Polypectomy followed by pan hysterectomy was performed. Histopathological examination and immunohistochemistry confirmed LGESS. As the tumor is rarely encountered, management protocols are still questionable. In our case, we tried a different post-surgical protocol and the patient is being closely followed up. Although rare, ESS should be considered in the differential diagnosis of all women who present with a rapid enlargement of a uterine leiomyoma.
Jain, Reena; Batra, Swaraj; Ahmad, Ayesha; Elahi, Arifa Anwar; Gupta, Monika; Saith, Poonam
Low-grade alimentary lymphoma: clinicopathological findings and response to treatment in 17 cases.
Low-grade alimentary lymphoma (LGAL) was diagnosed by histological and immunohistochemical evaluation of full-thickness biopsies from multiple regions of the gastrointestinal tract collected during exploratory laparotomy in 17 cats. The most common clinical signs were weight loss (n=17) and vomiting and/or diarrhoea (n=15). Clinical signs were chronic in 11 cases. Abdominal palpation was abnormal in 12 cats, including diffuse intestinal thickening (n=8), an abdominal mass due to mesenteric lymph node enlargement (n=5) and a focal mural intestinal mass (n=1). The most common ultrasonographic finding was normal or increased intestinal wall thickness with preservation of layering. Ultrasound-guided fine-needle aspirates of mesenteric lymph nodes (n=9) were incorrectly identified as benign lymphoid hyperplasia in eight cats, in which the histological diagnosis from biopsies was lymphoma. There was neoplastic infiltration of more than one anatomic region of the gastrointestinal tract in 16/17 cats. The jejunum (15/15 cats) and ileum (13/14 cats), followed by the duodenum (10/12 cats), were the most frequently affected sites. Twelve cats were treated with oral prednisolone and high-dose pulse chlorambucil, two with a modified Madison-Wisconsin multiagent protocol and three with a combination of both protocols. Thirteen of the 17 cats (76%) had complete clinical remission with a median remission time of 18.9 months. Cats that achieved complete remission had significantly longer median survival times (19.3 months) than cats that did not achieve complete remission (n=4) (4.1 months; P=0.019). The prognosis for cats with LGAL treated with oral prednisolone in combination with high-dose pulse chlorambucil is good to excellent. PMID:19576832
Lingard, Amy E; Briscoe, Katherine; Beatty, Julia A; Moore, Antony S; Crowley, Ann M; Krockenberger, Mark; Churcher, Richard K; Canfield, Paul J; Barrs, Vanessa R
Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas
Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.
Oh, Kevin S., E-mail: email@example.com [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Hung, Jonathan [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Robertson, Patricia L. [Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI (United States); Department of Neurology, University of Michigan Health System, Ann Arbor, MI (United States); Garton, Hugh J.; Muraszko, Karin M. [Department of Neurosurgery, University of Michigan Health System, Ann Arbor, MI (United States); Sandler, Howard M. [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Hamstra, Daniel A. [Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI (United States)
Low-grade albuminuria in children with obstructive sleep apnea.
Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1) ; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1) ; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes?h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea. PMID:23228180
Varlami, Vasiliki; Malakasioti, Georgia; Alexopoulos, Emmanouel I; Theologi, Vasiliki; Theophanous, Eleni; Liakos, Nikolaos; Daskalopoulou, Euphemia; Gourgoulianis, Konstantinos; Kaditis, Athanasios G
Characterization and Beneficiation Studies of a Low Grade Bauxite Ore
NASA Astrophysics Data System (ADS)
A low grade bauxite sample of central India was thoroughly characterized with the help of stereomicroscope, reflected light microscope and electron microscope using QEMSCAN. A few hand picked samples were collected from different places of the mine and were subjected to geochemical characterization studies. The geochemical studies indicated that most of the samples contain high silica and low alumina, except a few which are high grade. Mineralogically the samples consist of bauxite (gibbsite and boehmite), ferruginous mineral phases (goethite and hematite), clay and silicate (quartz), and titanium bearing minerals like rutile and ilmenite. Majority of the gibbsite, boehmite and gibbsitic oolites contain clay, quartz and iron and titanium mineral phases within the sample as inclusions. The sample on an average contains 39.1 % Al2O3 and 12.3 % SiO2, and 20.08 % of Fe2O3. Beneficiation techniques like size classification, sorting, scrubbing, hydrocyclone and magnetic separation were employed to reduce the silica content suitable for Bayer process. The studies indicated that, 50 % by weight with 41 % Al2O3 containing less than 5 % SiO2 could be achieved. The finer sized sample after physical beneficiation still contains high silica due to complex mineralogical associations.
Rao, D. S.; Das, B.
Low-grade myofibroblastic sarcomas of the maxilla
Low-grade myofibroblastic sarcoma (LGMS) is a distinct mesenchymal myofibroblastic malignancy. The tumor may occur at a variety of sites, but is particularly associated with the head and neck. Of the two maxillary sarcomas that were analyzed in the present study, one was misdiagnosed as an inflammatory myofibroblastic tumor during pre-operative excision biopsy, and later presented with a different immunophenotype upon recurrence. Representative paraffin blocks from formalin-fixed tissues were selected from each patient and designated as case 1 and case 2. Immunohistochemical studies were performed on 3-?m thick sections using primary antibodies against ?-smooth muscle actin (?-SMA), muscle-specific actin (MSA), desmin, vimentin, calponin, h-caldesmon, fibronectin, cytokeratin, cluster of differentiation 34 (CD34), S-100 protein, anaplastic lymphoma kinase (ALK), epithelial membrane antigen (EMA) and Ki-67. Immunohistochemistry was performed using the streptavidin-biotin-peroxidase complex method. The tumor cells from the two maxillary LGMSs, including the recurrent lesion, were positive for vimentin and fibronectin, and negative for S-100 protein, CD34, EMA, h-caldesmon, ALK, MSA and calponin. The tumor cells from case 1 demonstrated positive staining for ?-SMA protein and negative staining for desmin. By contrast, the tumor cells from the primary lesion in case 2 presented with negative staining for ?-SMA and positive staining for desmin, while the cells of the recurrent lesion were ?-SMA-positive and desmin-negative. The present study concluded that cases of LGMS with immunoprofile alterations are predictive of relatively poor prognoses. PMID:25624890
Genomic changes in progression of low-grade gliomas.
Using a one-megabase BAC-based array comparative genomic hybridization technique (aCGH), we have investigated a series of 16 low-grade gliomas (LGGs) and their subsequent progression to higher-grade malignancies. The most frequent chromosome imbalances in primary tumors were gains of chromosomes 7q, 8q, and 22q, and losses of chromosomes 1p, 13q, and 19q. In tumor progression, gains of chromosomes 11q, 7q, 20q, and 21q, and losses of chromosomes 9p, including CDKN2A locus, 19q, 14q, 1p, and 6q were the most frequent genomic disequilibria. Progressive tumors were more imbalanced than primary tumors in terms of altered chromosomal arms (3.8 vs. 6.6 in mean abnormal chromosomal arm) and altered BACs (17 vs. 21%). Interestingly, putative novel candidate genes associated with glioma progression were identified, in particular DOCK8, PTPRD, CER1, TPHO, DHFR, MSH3, ETS1, ACACA, and CSE1L. PMID:18618226
Idbaih, Ahmed; Carvalho Silva, Rosana; Criničre, Emmanuelle; Marie, Yannick; Carpentier, Catherine; Boisselier, Blandine; Taillibert, Sophie; Rousseau, Audrey; Mokhtari, Karima; Ducray, François; Thillet, Joelle; Sanson, Marc; Hoang-Xuan, Khę; Delattre, Jean-Yves
Warthin-Finkeldey-like cells in benign and malignant lymphoid proliferations.
Multinucleate giant cells resembling Warthin-Finkeldey cells have been described in various lymphoid disorders. These Warthin-Finkeldey-like cells (WFLC) with as many as 50 nuclei are of three main types: reticular, lymphocyte and intermediary. In reactive lymphoid proliferations (34 cases) WFLC were mainly observed inside germinal centres and to a lesser extent in the interfollicular zones. In neoplastic lymphoid proliferations (33 cases) WFLC were most commonly found in the lymphocytic predominance type of Hodgkin's disease (16/25 cases). All non-Hodgkin's lymphomas (13 cases) in which WFLC were detected proved to be of low grade malignancy (lymphocytic: one case, lymphoplasmacytic-plasmacytoid: six cases; and centroblastic-centrocytic, six cases). They were also found in two cases of angioimmunoblastic lymphadenopathy. Immunoperoxidase and electron microscopic studies could not elucidate the exact histogenesis of these cells, but it is assumed that they are associated with B cell proliferations. PMID:7118083
Delsol, G; Pradere, M; Voigt, J J; Nespoulous, M; Gorguet, B; Marty, C; Fabre, J
AMG 319 Lymphoid Malignancy FIH
Cancer; Chronic Lymphocytic Leukemia; Diffuse Large Cell Lymphoma; Hematologic Malignancies; Hematology; Leukemia; Low Grade Lymphoma; Lymphoma; Mantle Cell Lymphoma; Non-Hodgkin's Lymphoma; Oncology; Oncology Patients; T Cell Lymphoma; Tumors
The molecular profile of low-grade mucoepidermoid carcinomas remains to be clarified. In the present study, matrix metalloproteinase (MMP) expression was compared in low-grade mucoepidermoid carcinoma (MEC) and typical lung cancer. The expression of MMP-2, MMP-7 and MMP-9 was detected by immunohistochemistry in a cohort of 110 patients (34 with low-grade MEC and 76 with matched typical lung cancers). A positive MMP-2 expression was found to be 35.29 vs. 65.79% in low-grade MEC and typical NSCLCs (p=0.003); a positive MMP-7 expression was 41.18 vs. 55.26% (p=0.172); and a positive MMP-9 expression was 35.29 vs. 57.89% (p=0.028). In conclusion, the expression of MMP-2 and MMP-9 in low-grade MEC is lower than that in typical lung carcinomas. PMID:22848300
Protein ubiquitination in lymphoid malignancies.
Human lymphoid malignancies inherit gene expression networks from their normal B-cell counterpart and co-opt them for their own oncogenic purpose, which is usually governed by transcription factors and signaling pathways. These transcription factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. Protein ubiqutination plays a role in almost all cellular events and in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here, we discuss our current understanding of both proteolytic and non-proteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid-restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers. PMID:25510281
Yang, Yibin; Staudt, Louis M
Mutant BRAF in low-grade epilepsy-associated tumors and focal cortical dysplasia
BRAF alterations, namely BRAF fusion and BRAF V600E mutation, have been recently reported in low-grade epilepsy-associated tumors. Twenty low-grade epilepsy-associated tumors were retrieved to evaluate the BRAF mutational status. BRAF mutations were present in 10 tumors and concomitantly in associated dysplastic tissue of three patients. We here show for the first time that BRAF mutations are present not only in low-grade epilepsy-associated tumors but, in some cases, also in the associated focal cortical dysplasia. PMID:25356392
Marucci, Gianluca; de Biase, Dario; Visani, Michela; Giulioni, Marco; Martinoni, Matteo; Volpi, Llilia; Riguzzi, Patrizia; Rubboli, Guido; Michelucci, Roberto; Tallini, Giovanni
Mutant BRAF in low-grade epilepsy-associated tumors and focal cortical dysplasia.
BRAF alterations, namely BRAF fusion and BRAF V600E mutation, have been recently reported in low-grade epilepsy-associated tumors. Twenty low-grade epilepsy-associated tumors were retrieved to evaluate the BRAF mutational status. BRAF mutations were present in 10 tumors and concomitantly in associated dysplastic tissue of three patients. We here show for the first time that BRAF mutations are present not only in low-grade epilepsy-associated tumors but, in some cases, also in the associated focal cortical dysplasia. PMID:25356392
Marucci, Gianluca; de Biase, Dario; Visani, Michela; Giulioni, Marco; Martinoni, Matteo; Volpi, Llilia; Riguzzi, Patrizia; Rubboli, Guido; Michelucci, Roberto; Tallini, Giovanni
Introduction Colorectal lymphomas represent only 5% to 10% of gastrointestinal lymphomas, after the stomach and small intestine. Primary lymphoma of the colon and rectum is an unusual observation, constituting only 0.2% to 0.5% of all malignant tumors arising from the colorectal region. Very little is known about the correlation between adenoma and lymphoma in the colorectal tract. We report here a rare case of diffuse large B-cell lymphoma developing within a solitary tubular adenoma with low-grade dysplasia of the rectum. Case presentation An 83-year-old Caucasian man was referred to our hospital intermittent anal bleeding and irregular bowel. Colonoscopy revealed a 1cm solitary rectal polyp, which was completely removed by endoscopic resection. Histologic studies revealed low-grade intraepithelial dysplasia; the stroma of adenoma showed focal localization by highly proliferative lymphoid cells. Immunohistochemical analyses demonstrated that lymphoid cells were positive for CD20 and bcl2, whereas they were negative for CD3, CD5, CD10, CD23, CD30, CD138 and cyclin D1. Approximately 90% of the neoplastic cells reacted positively when stained with an antibody to Ki-67. Molecular studies showed the presence of a monoclonal immunoglobulin heavy chain gene rearrangement. To determine primary or secondary lymphoma localization, Dawson's criteria were applied to the case. A diagnosis of primary diffuse large B- lymphoma Ann Arbor stage 1A was established. Subsequently, the patient was referred to oncology to establish the stage and to select appropriate treatment. Conclusions The case of diffuse large B-cell lymphoma developing within a tubular adenoma, as reported here, is considered a rare event. Little about the prognosis of primary colorectal lymphomas is available and therapeutic treatment protocol is unclear. This case report provides more information on the history and macroscopic appearance of lymphomas presenting in an unusual location. To report additional cases in the future would be helpful in redefining the diagnostic, prognostic and therapeutic approach. PMID:24661491
Prospects for production of synthetic liquid fuel from low-grade coal
NASA Astrophysics Data System (ADS)
In the paper, we compare the energy costs of steam and steam-oxygen gasification technologies for production of synthetic liquid fuel. Results of mathematic simulation and experimental studies on gasification of low-grade coal are presented.
Shevyrev, Sergei; Bogomolov, Aleksandr; Alekssev, Maksim
Assessment of an Industrial Wet Oxidation System for Burning Waste and Low-Grade Fuels
"Stone & Webster Engineering Corporation, under Department of Energy sponsorship, is developing a wet oxidation system to generate steam for industrial processes by burning industrial waste materials and low-grade fuels. The program involves...
Bettinger, J.; Koppel, P.; Margulies, A.
Pediatric low-grade gliomas and the need for new options for therapy: why and how?
Pediatric low-grade gliomas are the most common tumors of the central nervous system in children, accounting for almost 50% of all childhood brain tumors. They are a heterogeneous group of tumors with different histologic subtypes. Most treatment studies address low-grade gliomas as a single entity, depriving us of histology-specific treatment outcomes. This is mostly due to a lack of understanding of tumor biology at the molecular level. Pediatric low-grade gliomas are not benign, and most incompletely resected tumors will progress and negatively affect quality of life. The advancements made in understanding sporadic pilocytic astrocytoma and neurofibromatosis 1-associated pilocytic astrocytoma in particular have paved the way for potential targeted therapy and biological stratification. Such progress in pilocytic astrocytoma needs to be consolidated and expanded to other histologic varieties of pediatric low-grade gliomas. PMID:19164945
Qaddoumi, Ibrahim; Sultan, Iyad; Broniscer, Alberto
An electrochemical system for efficiently harvesting low-grade heat energy
Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low ...
Lee, Seok Woo
Diagnostic value of fine motor deficits in patients with low-grade hepatic encephalopathy
Abstract Abstract Abstract Abstract AIM: The role of motor dysfunction in early diagnosis of low-grade hepatic encephalopathy remains uncertain. We performed a pilot study to comparatively investigate the kinematic characteristics of small and large rapid alternating movements in patients with liver cirrhosis and low-grade hepatic encephalopathy. METHODS: A kinematic analysis of alternating handwriting (7.5 mm) and large drawing movements (DM,
Sergei Mechtcheriakov; Ivo W. Graziadei; Maria Rettenbacher; Ingrid Schuster; Hartmann Hinterhuber; Wolfgang Vogel; Josef Marksteiner; Graziadei IW
Plasma-enhanced gasification of low-grade coals for compact power plants
A high temperature of a steam torch ensures an efficient gasification of low-grade coals, which is comparable to that of high-grade coals. Therefore, the coal gasification system energized by microwaves can serve as a moderately sized power plant due to its compact and lightweight design. This plasma power plant of low-grade coals would be useful in rural or sparsely populated areas without access to a national power grid.
Uhm, Han S. [Department of Electrophysics, Kwangwoon University, 447-1 Wolgye-Dong, Nowon-Gu, Seoul 139-701 (Korea, Republic of); Hong, Yong C.; Shin, Dong H.; Lee, Bong J. [Convergence Plasma Research Center, National Fusion Research Institute, 113 Gwahangno, Yuseong-Gu, Daejeon 305-333 (Korea, Republic of)
Thermoelectric energy converter for generation of electricity from low-grade heat
A thermoelectric energy conversion device which includes a plurality of thermoelectric elements is described. A hot liquid is supplied to one side of each element and a cold liquid is supplied to the other side of each element. The thermoelectric generator may be utilized to produce power from low-grade heat sources such as ocean thermal gradients, solar ponds, and low-grade geothermal resources. (WHK)
Jayadev, T.S.; Benson, D.K.
Active pipe-embedded structures in buildings for utilizing low-grade energy sources: A review
Low-grade energy sources such as geothermal energy, favorable ambient air and industrial waste heat etc. exist widely. Sufficient utilization of these low-grade energy sources may reduce our daily dependence on high-grade energy sources such as electricity resulting in reduced emission of green house gas for environmental conservation. Active pipe-embedded structure as floor\\/ceiling usually with water as the medium to carry
Xinhua Xu; Shengwei Wang; Jinbo Wang; Fu Xiao
NASA Astrophysics Data System (ADS)
Many ductile shear zones like ductile low-angle normal faults on top of, and oblique-slip faults bordering, metamorphic core complexes exhibit a regular pattern of fabrics which usually show decreasing temperature and pressure conditions during their formation. This is because the presence of rocks with a dominant but different mineralogy results in shear concentration in the rheological weakest layer. These dominant fabric-forming minerals are with decreasing temperature: feldspar at >450 °C, quartz at >300 °C and calcite <300 °C. Fabrics and textures formed at higher temperatures are preserved in microlithons surrounded by micro-shear zones. This allows determine semiquantitively the temperature and pressure of several fabric-forming events within one rock, where generally disequilibrium is present between micro-lithon and surrounding micro-shear zones. We tested this approach using the white mica barometry and chlorite on two shear zones bordering two distinct metamorphic core complexes. The low-grade Rechnitz metamorphic core complex at the eastern termination of the Eastern Alps, which formed within an extensional setting and is surrounded by a contemporaneously formed Neogene sedimentary basin. Microstructural and textural analysis has revealed the co-existence of microstructures ranging from middle-temperatures to low-temperatures, which overprinted deformation features within the Rechnitz metamorphic core complex. Quartz displays abundant evidence for early high-temperature plastic deformation (e.g. dynamic recrystallization, polygonal grains with straight grain boundaries forming 120° triple junctions) (D2). In some cases, preferred orientations of crystallographic axes are missing and white mica was overgrowing the penetrative foliation. These features suggest annealing during subsequent metamorphism and deformation at high temperature conditions. The high-temperature microstructures and textures are in part or entirely altered by subsequent late low-temperature shearing. Certain minerals such as white mica showed extensive grain-size reduction in mylonites and some are completely transformed into extremely fine grains. The later low-temperature deformational overprint during shearing was affected by ductile low-angle normal faulting. According to backscatter electron analysis (BSE), two microfabric types are observed in white mica and chlorite, (1) type I-microlithons, the older generation with coarse-grained white mica and chlorite occurring in the micro-lithons, where chlorite is sometimes associated with white mica, are seemingly in equilibrium with the surrounding mineral assemblage; and (2) type II-micro-shear zones. The sheared generation has very fine-grained sheared bands, which represent mixtures of white mica and chlorite with apparent disequilibrium boundaries. In most cases, the thermometry calculations from the coarse chlorite grains (microfabric type-I) yield a main result ranging from 328 to 376 °C. In the microfabric type II, the thermometry results from the sheared chlorite grains yield a temperature ranging from 305 to 132 °C. The later temperature is clearly sub-greenschist facies. The lower temperature group is interpreted to result from late-stage hydrothermal overprint, which affected older microfabrics. Chlorite is seemingly accessible to late-stage resetting. Phengitic compositions with high-Si white micas occur in the microfabric type I micro-lithons, however, some phengitic high-Si compositions are also from the micro-shear zone (micro-type II). We note that there is a continuous range of phengitic white mica to nearly pure muscovite. Phengitic white mica is common in all samples of the lower unit together with white mica of lower phengite content. The lower unit experienced, therefore, high-pressure metamorphism, and white mica grains are partly reset to low-pressure white mica indicating decompression. Decompression occurred during shearing and as a result of tectonic exhumation. Detailed microstructural and textural analysis reveals that the movement along the Mou
Cao, Shuyun; Neubauer, Franz; Bernroider, Manfred; Genser, Johann
Extraction of Copper from Malanjkhand Low-Grade Ore by Bacillus stearothermophilus.
Thermophilic bacteria are actively prevalent in hot water springs. Their potential to grow and sustain at higher temperatures makes them exceptional compare to other microorganism. The present study was initiated to isolate, identify and determine the feasibility of extraction of copper using thermophilic heterotrophic bacterial strain. Bacillus stearothermophilus is a thermophilic heterotrophic bacterium isolated from hot water spring, Atri, Orissa, India. This bacterium was adapted to low-grade chalcopyrite ore and its efficiency to solubilize copper from Malanjkhand low-grade ore was determined. The low-grade copper ore contains 0.27% Cu, in which the major copper-bearing mineral is chalcopyrite associated with other minerals present as minor phase. Variation in parameters such as pulp-density and temperatures were studied. After 30 days of incubation, it was found that Bacillus stearothermophilus solubilize copper up to 81.25% at pH 6.8 at 60°C. PMID:23024410
Singh, Sradhanjali; Sukla, Lala Behari; Mishra, Baroda Kanta
Gata3 drives development of ROR?t+ group 3 innate lymphoid cells.
Group 3 innate lymphoid cells (ILC3) include IL-22-producing NKp46(+) cells and IL-17A/IL-22-producing CD4(+) lymphoid tissue inducerlike cells that express ROR?t and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal ROR?t(+) ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut ROR?t(+) ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets. PMID:24419270
Serafini, Nicolas; Klein Wolterink, Roel G J; Satoh-Takayama, Naoko; Xu, Wei; Vosshenrich, Christian A J; Hendriks, Rudi W; Di Santo, James P
Gata3 drives development of ROR?t+ group 3 innate lymphoid cells
Group 3 innate lymphoid cells (ILC3) include IL-22–producing NKp46+ cells and IL-17A/IL-22–producing CD4+ lymphoid tissue inducerlike cells that express ROR?t and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal ROR?t+ ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut ROR?t+ ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets. PMID:24419270
Serafini, Nicolas; Klein Wolterink, Roel G.J.; Satoh-Takayama, Naoko; Xu, Wei; Vosshenrich, Christian A.J.; Hendriks, Rudi W.
The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic strategies for IBS. PMID:21607147
Akiho, Hirotada; Ihara, Eikichi; Nakamura, Kazuhiko
Atypical lymphoid hyperplasia mimicking lymphoma.
The distinction between reactive and neoplastic lymphoid infiltrates is a common problem in clinical practice and can be problematic. The clinical implications for both the patient and the treating clinician are profound. In this article, we discuss six of the common entities that can present as atypical lymphoid hyperplasia and thus can mimic malignant lymphomas, with emphasis on morphologic features, immunophenotypic findings, and molecular correlates that help distinguish these disorders from neoplastic conditions. The six conditions to be discussed in detail include reactive follicular hyperplasia versus follicular lymphoma; progressive transformation of germinal centers versus nodular lymphocyte predominant Hodgkin lymphoma; immunoblastic proliferations versus diffuse large B-cell lymphomas; variant forms of Castleman disease that may mimic a number of lymphoid cancers; Kikuchi's disease versus large cell lymphomas; and finally, dermatopathic lymphadenopathy and its distinction from lymph nodes showing early involvement by cutaneous T-cell lymphoma (Mycosis fungoides). PMID:19577167
Good, David J; Gascoyne, Randy D
Florid reactive lymphoid hyperplasia of terminal ileum
Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn's disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn's disease. In florid lymphoid hyperplasia limited resection may be curative. PMID:22242075
Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh
Complete surgical resection in children with low-grade astrocytomas after neoadjuvant chemotherapy
Introduction.. Low-grade astrocytomas constitute the majority of pediatric central nervous system neoplasms. Gross total resection is desirable as the initial therapeutic approach and is curative in most cases. In the past, radiation therapy was often recommended for patients in whom complete resection was not achieved, although there are special concerns about secondary malignancy and cognitive impairment. There has been increasing
Elvis Terci Valera; Luciano Neder Serafini; Hélio Rubens Machado; Luiz Gonzaga Tone
Organic Rankine cycles for low grade waste heat recovery are described with different working fluids. The effects of the thermodynamic parameters on the ORC performance are examined, and the thermodynamic parameters of the ORC for each working fluid are optimized with exergy efficiency as an objective function by means of the genetic algorithm. The optimum performance of cycles with different
Yiping Dai; Jiangfeng Wang; Lin Gao
Critical flicker frequency for quantification of low-grade hepatic encephalopathy
Subclinical hepatic encephalopathy (SHE) is currently diagnosed by psychometric tests or neurophysiologic techniques. In view of its sociomedical relevance, simple and reproducible tests for routine diagnosis are required. This study evaluates critical flicker-frequency thresholds for quantification of low-grade hepatic encephalopathy. A total of 115 patients (92 with cirrhosis, 23 controls) were analyzed for HE severity (mental state, computerized psychometric tests),
Gerald Kircheis; Matthias Wettstein; Lars Timmermann; Alfons Schnitzler; Dieter Häussinger
Organic nitrogen chemistry during low-grade metamorphism Jean-Paul Boudou
and to shed light on the subsurface biogeochemical nitrogen cycle and its participating organic and inorganic Earth's geochemical nitrogen cycle links the relatively small pool of organic nitrogen in living biomassOrganic nitrogen chemistry during low-grade metamorphism Jean-Paul Boudou a *, Arndt Schimmelmann b
Paris-Sud XI, Université de
Aerobic Training Improved Low-Grade Inflammation in Obese Women with Intellectual Disability
ERIC Educational Resources Information Center
Background: Obesity is a major health problem in people with intellectual disabilities. It is also widely accepted that low-grade systemic inflammation associated to obesity plays a key role in the pathogenic mechanism of several disorders. Fortunately, physical activity has shown to improve inflammation in people with metabolic syndrome and type…
Ordonez, F. J.; Rosety, M. A.; Camacho, A.; Rosety, I.; Diaz, A. J.; Fornieles, G.; Garcia, N.; Rosety-Rodriguez, M.
Study of Supercritical Carbon Dioxide Power Cycle for Low Grade Heat Conversion
Research on supercritical carbon dioxide power cycles has been mainly focused on high temperature applications, such as Brayton cycle in a nuclear power plant. This paper conducts a comprehensive study on the feasibility of a CO2-based supercritical power cycle for low-grade heat conversion. Energy and exergy analyses of the cycle were conducted to discuss the obstacles as well as the
Rachana Vidhi; Yogi D. Goswami; Huijuan Chen; Elias Stefanakos; Sarada Kuravi; Adrian S Sabau
Beneficiation and agglomeration process to utilize low-grade ferruginous manganese ore fines
Characterisation, beneficiation and agglomeration studies were carried out to develop a utilization strategy for typical Indian low grade manganese ore fines. The major mineral phases found are pyrolusite, hematite, goethite, clay, feldspar and quartz. QEMSCAN and Sink–Float studies suggested that 40% of manganese minerals are in liberated form, whereas 30% are locked with iron minerals. Classification followed by two-stage high
Veerendra Singh; Tamal K. Ghosh; Y. Ramamurthy; Vilas Tathavadkar
Approximately 15% of foster kittens die before 8 weeks of age, with most of these kittens demonstrating clinical signs or postmortem evidence of enteritis. While a specific cause of enteritis is not determined in most cases, these kittens are often empirically administered probiotics that contain enterococci. The enterococci are members of the commensal intestinal microbiota but also can function as opportunistic pathogens. Given the complicated role of enterococci in health and disease, it would be valuable to better understand what constitutes a "healthy" enterococcal community in these kittens and how this microbiota is impacted by severe illness. In this study, we characterized the ileum mucosa-associated enterococcal community of 50 apparently healthy and 50 terminally ill foster kittens. In healthy kittens, Enterococcus hirae was the most common species of ileum mucosa-associated enterococci and was often observed to adhere extensively to the small intestinal epithelium. These E. hirae isolates generally lacked virulence traits. In contrast, non-E. hirae enterococci, notably Enterococcus faecalis, were more commonly isolated from the ileum mucosa of kittens with terminal illness. Isolates of E. faecalis had numerous virulence traits and multiple antimicrobial resistances. Moreover, the attachment of Escherichia coli to the intestinal epithelium was significantly associated with terminal illness and was not observed in any kitten with adherent E. hirae. These findings identify a significant difference in the species of enterococci cultured from the ileum mucosa of kittens with terminal illness compared to the species cultured from healthy kittens. In contrast to prior case studies that associated enteroadherent E. hirae with diarrhea in young animals, these controlled studies identified E. hirae as more often isolated from healthy kittens and adherence of E. hirae as more common and extensive in healthy kittens than in sick kittens. PMID:23966487
Ghosh, Anuradha; Borst, Luke; Stauffer, Stephen H.; Suyemoto, Mitsu; Moisan, Peter; Zurek, Ludek
Objective To compare neurodevelopmental outcomes at 18–22 months corrected age for extremely low gestational age infants with low grade (Grade 1 or 2) periventricular-intraventricular hemorrhage to infants with either no hemorrhage or severe (Grade 3 or 4) hemorrhage on cranial ultrasound. Design Longitudinal observational study Setting Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Participants 1472 infants born at <27 weeks gestational age between 2006–2008 with ultrasound results within the first 28 days of life and surviving to 18–22 months with complete follow-up assessments were eligible. Main Exposure Low grade periventricular-intraventricular hemorrhage Outcome Measures Outcomes included cerebral palsy, gross motor functional limitation, Bayley III cognitive and language scores, and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. Results Low grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared to infants without hemorrhage. Compared with low grade hemorrhage, severe hemorrhage was associated with decrease in adjusted continuous cognitive (?3.91, [95% Confidence Interval [CI]: ?6.41, ?1.42]) and language (?3.19 [?6.19, ?0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (OR: 1.46 [0.74, 2.88]) and mild language impairment (OR: 1.35 [0.88, 2.06]). Conclusion At 18–22 months, the neurodevelopmental outcomes of extremely low gestational age infants with low grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. PMID:23460139
Payne, Allison H.; Hintz, Susan R.; Hibbs, Anna Maria; Walsh, Michele C.; Vohr, Betty R.; Bann, Carla M.; Wilson-Costello, Deanne E.
It is important to understand how low grade tumors recur and progress to malignant lesions since this dramatically shortens patient survival. Here, we evaluated the concept that malignant progression and poor prognosis of low grade astrocytic tumors are TP53 dependent through clonal expansion of mutated cells. TP53 status was established in primary and recurrent tumors from 36 patients with WHO
Nobuaki Ishii; Mitsuhiro Tada; Marie-France Hamou; Robert C Janzer; Kathleen Meagher-Villemure; Otmar D Wiestler; Nicolas de Tribolet; Erwin G Van Meir; EG Van Meir
Low-Grade Inflammation and Spinal Cord Injury: Exercise as Therapy?
An increase in the prevalence of obesity in people with spinal cord injury can contribute to low-grade chronic inflammation and increase the risk of infection in this population. A decrease in sympathetic activity contributes to immunosuppression due to the lower activation of immune cells in the blood. The effects of physical exercise on inflammatory parameters in individuals with spinal cord injury have not been well described. We conducted a review of the literature published from 1974 to 2012. This review explored the relationships between low-grade inflammation, spinal cord injury, and exercise to discuss a novel mechanism that might explain the beneficial effects of exercise involving an increase in catecholamines and cytokines in people with spinal cord injury. PMID:23533315
da Silva Alves, Eduardo; de Aquino Lemos, Valdir; Ruiz da Silva, Francieli; Lira, Fabio Santos; dos Santos, Ronaldo Vagner Thomathieli; Rosa, Joăo Paulo Pereira; Caperuto, Erico; Tufik, Sergio; de Mello, Marco Tulio
Survivin is a member of the inhibitor of apoptosis gene family, which is also implicated in mitosis regulation. Most reports in the literature impute poor prognosis to neoplasms with overexpression of this protein. The purpose of the present study is to validate and compare the immunohistochemical reactivity of malignant lymphomas and reactive lymphoid tissue using a new mouse monoclonal antibody to Survivin produced in our laboratory, 6-78. Survivin was detected by immunohistochemistry on tissue microarrays. It was shown that the antibody anti-Survivin 6-78 reliably stains formalin-fixed, paraffin-embedded reactive and neoplastic lymphoid tissues, mostly in a nuclear pattern. We confirmed using this novel antibody that Survivin immunostaining has a tendency to be lower in reactive lymphoid tissues and low-grade B cell lymphomas than in aggressive lymphomas. This antibody may represent a useful tool for standardizing the study of the immunoexpression of Survivin in neoplasms. PMID:21279158
Al Saati, Talal; Gascoyne, Randy D.; Welsh, Kathyrn; Reed, John C.; Brousset, Pierre; Delsol, Georges
Investigation on exergo-economic performance of evaporator in ORC recovering low-grade waste heat
Based on the perspective of exergy recovery (profit), an exergo-economic performance evaluation model of evaporator in ORC recovering low-grade waste heat is established. Selecting dry fluid R600a as a working fluid, an exergo-economic criterion was defined to estimate the effects of operating parameters and tube length on the performance of evaporator when the boiling temperature of evaporator is fixed. The
Shuang-Ying Wu; Liang Jiang; Lan Xiao; You-Rong Li; Jin-Liang Xu
Kinetics of sulfuric acid leaching of low-grade zinc silicate ore
The results of a leaching kinetics study of low-grade zinc silicate ore with sulfuric acid are presented. Effect of ore particle size, reaction temperature, and acid concentration on zinc dissolution rate were determined. The results obtained show that leaching of about 94% of zinc is achieved using ?200+270 mesh ore particle size at a reaction temperature of 70°C for 180
E. A Abdel-Aal
Somatic hypermutation signature in B-cell low-grade lymphomas
Background Immunoglobulin gene somatic hypermutation is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas, including chronic lympho- cytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. Design and Methods With the aim of identifying surrogate markers of somatic hypermutation, a combined investiga- tion of IgVH mutational status and expression profiles of 93
Lorraine Tracey; Mohit Aggarwal; Mónica García-Cosio; Raquel Villuendas; Patrocinio Algara; Margarita Sánchez-Beato; Abel Sánchez-Aguilera; Juan F. García; Antonia Rodríguez; Francisca I. Camacho; Nerea Martínez; Elena Ruiz-Ballesteros; Manuela Mollejo; Miguel Á
We report a rare tumor called low-grade renal collecting duct carcinoma. Grossly, the tumor consisted of multiple cysts and solid white nodules, measuring 10 cm in diameter and occupying most of the renal parenchyma.Histologically, the tumor was characterized by well-differentiated tubules lined by eosinophilic cells without papillary projections, abundant predominantly extracellular mucin, minimal cellular atypia, no desmoplasia, and rare mitoses.This
Raymond Farah; Ofer Ben-Izhak; Mariana Munichor; Hector Cohen
Existing acid leaching data for low-grade manganese ores are modeled using an evolving neural net. Three distinct cases of leaching in the presence of glucose, sucrose and lactose have been considered and the results compared with an existing analytical model. The neural models are then subjected to bi-objective optimization, using a predator–prey genetic algorithm, maximizing recovery in tandem with a
Frank Pettersson; Arijit Biswas; Prodip Kumar Sen; Henrik Saxén; Nirupam Chakraborti
Low Grade Glandular Lesions of the Sinonasal Tract: A Focused Review
The sinonasal tract is a complex anatomic site with an exhaustive list of possible diagnoses. While most biopsies or resections\\u000a encountered routinely consist of common diagnoses such as inflammatory polyps and papillomas, occasional cases are more difficult,\\u000a and separating reactive or benign from malignancy can be challenging. One of the most poorly understood and daunting categories\\u000a is low grade glandular
Ilan Weinreb
Characterization of poly(ethylene- co-vinyl acetate) (EVA) filled with low grade magnesium hydroxide
Low-grade magnesium hydroxide (LG-MH) is a solid by-product that undergoes an endothermic decomposition in the temperature range of 300–750°C. Due to its thermal behaviour and its lower cost relative to pure Mg(OH)2, it was studied as a non-halogenated flame retardant filler in a 28% vinyl acetate (VA) content poly(ethylene-co-vinyl acetate) matrix. The solid was characterized by XRF and the crystalline
A. I. Fernández; L. Haurie; J. Formosa; J. M. Chimenos; M. Antunes; J. I. Velasco
Revisiting the prognostic role of gallium scintigraphy in low-grade Non-Hodgkin's lymphoma
. The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin's\\u000a lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the\\u000a 67Ga uptake by the tumour, and to establish the contribution of 67Ga scan in defining the prognosis of LGNHL.
Andrea Gallamini; Alberto Biggi; Adriana Fruttero; Francesco Pugno; Giobatta Cavallero; Patrizia Pregno; Mariella Grasso; Chiara Farinelli; Alessandro Leone; Eugenio Gallo
Human papillomavirus infection in couples with female low-grade intraepithelial cervical lesion
Low-grade squamous intraepithelial lesions (LSIL) are frequently found during cervical cancer screening. Usually they are associated with a human papillomavirus (HPV) infection. Does the high-transmission rate of HPV infection to the male partner represent a clinical risk for him? Are preventive measures to be taken to prevent the occurrence of male diseases?More than 80% of all LSIL are associated with
Philippe Simon; Thierry Roumeguere; Jean Christophe Noël
Introduction Primary colorectal lymphomas are particularly rare and contribute to 0.2% of all colorectal malignancies. Gastroentrointestinal\\u000a (GI) tract is most commonly a secondary involvement site for non-Hodgkin's lymphoma (NHL). Primary NHL of GI tract are very\\u000a rare, constituting about 1–4% of all GI tract malignancies. In GI tract, two-thirds of all cases occur in stomach followed\\u000a by small intestine (9%). Clinical
Rohtesh S. Mehta; Niyati Modi; Nancy Sapanara; Prashanth Ramachandra; Michael Mikhail
The role of low-grade inflammation in the polycystic ovary syndrome.
PCOS is not only the most frequent cause of oligomenorrhea in young women, but also a metabolic disorder characterized by insulin resistance, glucose intolerance, dyslipidemia, and obesity, especially the visceral phenotype. PCOS represents a broad spectrum of endocrine and metabolic alterations which change with age and with increasing adiposity. In fact, during adolescence and youth the predominant clinical manifestations of PCOS are menstrual abnormalities, hirsutism and acne, whereas in peri-menopausal and post-menopausal periods metabolic disorders and an increased risk for cardiovascular diseases prevail. The pathogenetic links between PCOS and metabolic or cardiovascular complications are still debated. However, recent evidence has been focused on a condition of low-grade chronic inflammation as a potential cause of the long-term consequence of the syndrome. In this review we describe the state of low-grade inflammation observed in PCOS. In addition, we hypothesize the potential mechanisms responsible for the generation of this inflammatory state and the role played by low-grade inflammation in linking hyperandrogenism and insulin resistance with the metabolic and cardiovascular long-term complications of the syndrome. PMID:20708064
Repaci, Andrea; Gambineri, Alessandra; Pasquali, Renato
Low-grade extraskeletal osteosarcoma of the chest wall: case report and review of literature
Background Low-grade extraskeletal osteosarcomas (ESOS) are extremely rare. Case presentation We present the first case of low-grade ESOS of the chest wall, which occurred in a 30-year-old man. Because of initial misdiagnosis and patient's refusal of surgery, the diagnosis was done after a 4-year history of a slowly growing mass in soft tissues, leading to a huge (30-cm diameter) calcified mass locally extended over the left chest wall. Final diagnosis was helped by molecular analysis of MDM2 and CDK4 oncogenes. Unfortunately, at this time, no surgical treatment was possible due to loco-regional extension, and despite chemotherapy, the patient died one year after diagnosis, five years after the first symptoms. Conclusion We describe the clinical, radiological and bio-pathological features of this unique case, and review the literature concerning low-grade ESOS. Our case highlights the diagnostic difficulties for such very rare tumours and the interest of molecular analysis in ambiguous cases. PMID:21106072
Temozolomide after radiotherapy in recurrent "low grade" diffuse brainstem glioma in adults.
Diffuse brainstem glioma is a rare disease in adults. Radiotherapy (RT) is usually considered to be the standard treatment. However, the role of chemotherapy in treating relapses after RT is unclear, and this study aimed to assess the use of temozolomide (TMZ) in this situation. We conducted a retrospective analysis of patients from our database with "low grade" adult diffuse infiltrating brainstem glioma who received TMZ at relapse after failing RT. The patients were diagnosed by histology or MRI criteria compatible with a low-grade glioma. The tumors were localized in the pons, medulla oblongata or midbrain, excluding supratentorial or infratentorial tumors that had infiltrated the brainstem secondarily. The patients' clinical and radiological responses were assessed, and their progression free survival (PFS) and overall survival (OS) time were estimated. Fifteen adult patients (median age 34 years) fulfilled the inclusion criteria. Histological analysis was available in 5 cases and showed grade II oligodendroglioma (2 cases), grade II oligoastrocytoma (2 cases), and grade II astrocytoma (1 case). Ten patients were selected by MRI criteria only. All patients received RT as initial treatment and had a median PFS of 34.2 months (95 % CI 24.1-44.2). The median KPS at the time of relapse was 80. TMZ was administered orally at 150-200 mg/m(2) for 5 days, every 28 days. Clinical improvement after TMZ was observed in 9 cases (60 %), whereas radiological assessment detected responses in 6/15 cases, including 4 partial and 2 minor responses. The estimated median PFS after TMZ was 9.5 months (95 % CI 7.9-11), and the median OS was 14.4 months (95 % CI 10.5-18.2). Grade 3 thrombopenia was observed in 26 % of cases. TMZ could be useful after RT failure in adult patients with recurrent diffuse "low grade" brainstem glioma. PMID:25139026
Reyes-Botero, Germán; Laigle-Donadey, Florence; Mokhtari, Karima; Martin-Duverneuil, Nadine; Delattre, Jean-Yves
NASA Astrophysics Data System (ADS)
We report Mg isotope ratios for low-grade metamorphosed mudrocks from three lower Paleozoic basins (northern Lake District, southern Lake District and Southern Uplands) in the British Caledonides, previously analyzed for Li, Sr and Nd isotopes (Qiu et al., 2009, GCA), with the aim of understanding the behavior of Mg isotopes during subgreenschist-facies metamorphism, and the processes responsible for Mg isotopic variations in mudrocks. The ?26Mg of mudrocks varies greatly from -0.754 to 0.251, and displays no correlation with metamorphic grade, which ranges from diagenesis to subgreenschist-facies. Thus, low-grade metamorphism has no apparent influence on Mg isotopes. The variations instead likely reflect their provenance and mineralogical components. Samples from the northern Lake District, previously interpreted to derive from ancient, heavily weathered crust have ?26Mg (-0.06 × 0.11 on average) significantly heavier than that of average upper continental crust (~ -0.22), which is consistent with this interpretation. By contrast, mudrocks from the southern Lake District are characterized by low ?26Mg values (from -0.754 to -0.093) that require the presences of an unusually light component. The previously inferred provenance for these rocks of upper continental crust and arc volcanic detritus cannot explain such light isotopic compositions. Rather, such values may reflect the presence of carbonate in these samples and uptake of sea water Mg. Samples from the Southern Uplands, which contain the heaviest Li isotopes and ?Nd, and contain volcanic arc detritus, display Mg isotopic compositions divergent from a 'normal' mantle value (-0.25) towards both high and low ?26Mg values (from -0.742 to -0.079). Therefore, these mudrocks must contain a minimum of three end-members: mature felsic upper continental crust, arc lavas and carbonate. Given that limited Mg isotope fractionation occurs during low-grade metamorphism, Mg isotopes could be a potential tracer of provenance as well as carbonate involvement for fine-grained terrigenous sediments.
Wang, S.; Teng, F.; Rudnick, R. L.; Li, S.
Dietary Phthalates and Low-Grade Albuminuria in US Children and Adolescents
Summary Background Low-grade albuminuria is an indicator of endothelial dysfunction and is associated with an increased risk of cardiovascular disease. A graded level of exposure to bisphenol A was recently identified to be associated with increased risk of low-grade albuminuria in children and adults. Because bisphenol A and phthalates coexist as dietary contaminants, this study investigated whether exposure to phthalates is also associated with low-grade albuminuria. Design, setting, participants, & measurements Data were examined from 667 children who participated in the 2009–2010 National Health and Nutrition Examination Survey and who had results for urinary phthalate metabolites and albumin excretion. Urinary albumin and creatinine concentrations were measured in a first morning specimen using a solid-phase fluorescent immunoassay and a Roche/Hitachi Modular P Chemistry Analyzer with an enzymatic method, respectively. Phthalate metabolites were analyzed in a separate spot urine sample from each participant, using high-performance liquid chromatography and tandem mass spectroscopy. Results For each (roughly) 3-fold increase in metabolites of di-2-ethylhexylphthalate (a high molecular weight phthalate commonly found in foods), a 0.55 mg/g increase in albumin/creatinine ratio (ACR) was identified (P=0.02), whereas a 1.30-fold odds of a higher ACR quartile was also identified for each (roughly) 3-fold increase (P=0.02). Higher ACR was not identified in relationship to metabolites of lower molecular phthalates commonly found in lotions or shampoos, suggesting specificity. Conclusions Although reverse causation and unmeasured confounders represent alternative explanations, these findings, in conjunction with our earlier data on bisphenol A, indicate that a wide array of environmental toxins may adversely affect albuminuria and potentially increase the risk of cardiovascular disease. In view of the potential long-term health implications of ongoing exposure in this vulnerable subpopulation, our data support both further study and renewed regulatory efforts to limit exposure during childhood. PMID:24178978
Trasande, Leonardo; Sathyanarayana, Sheela
Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrP(d)). The distribution of PrP(d) within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrP(TME) and of which only the HY strain is associated with accumulation of PrP(TME) in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrP(TME) in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum, after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrP(TME) was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrP(TME) was detected readily in the brain and retropharyngeal lymph node during preclinical infection, with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrP(TME) in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrP(TME) accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrP(TME) in the lymphoid tissues of mink but not in hamsters. Thus, mink are a relevant animal model for further study of this unique strain, which ultimately may have been introduced through consumption of a TSE of ruminant origin. PMID:22595634
Schneider, D A; Harrington, R D; Zhuang, D; Yan, H; Truscott, T C; Dassanayake, R P; O'Rourke, K I
Current and Future Strategies inRadiotherapy of Childhood Low-Grade Glioma of theBrain
Background: For more than 60 years, radiation therapy has been an integral part in the management of childhood low-grade glioma. As this tumor carries an excellent long-term prognosis, the risk of late effects is of particular clinical importance and impinges upon radiotherapeutic treatment strategies. Material and Methods: Studies on the use of radiation therapy in children with low-grade glioma were
Rolf-Dieter Kortmann; Beate Timmermann; Roger E. Taylor; Giovanni Scarzello; Ludwig Plasswilm; Frank Paulsen; Branislav Jeremic; Astrid K. Gnekow; Karin Dieckmann; Sylvia Kay; Michael Bamberg
Summary.\\u000a Summary. \\u000a ?\\u000a \\u000a \\u000a \\u000a \\u000a Objective: With the aim to better evaluate the role of the insula in seizures and the therapeutic implications, we analyzed the rate\\u000a of insular low-grade gliomas (LGG) presenting with medically refractory epilepsy, detailed their ictal symptoms, and described\\u000a the epileptological results following their surgical resection.\\u000a \\u000a ?\\u000a \\u000a \\u000a \\u000a \\u000a Methods: Eleven patients (8 men, 3 women, mean age: 35 years)
H. Duffau; L. Capelle; M. Lopes; A. Bitar; J.-P. Sichez; R. van Effenterre
Low-grade myofibroblastic sarcoma of the maxillary region in a dog.
A subcutaneous tumour was identified in the maxillary region of a 14-year-old mixed breed dog. This tumour had grown rapidly over 2 weeks. Microscopically, the tumour had ill-defined borders and was composed of bundles and whorls of atypical spindle cells accompanied by abundant collagen fibres. Immunohistochemically, neoplastic cells were immunoreactive for vimentin, ?-smooth muscle actin and calponin and negative for S100 protein, von Willebrand factor, desmin and smoothelin. These results suggested that the neoplastic cells were derived from myofibroblasts and that the tumour was a low-grade myofibroblastic sarcoma. PMID:21996034
Tsuchiya, T; Suzuki, K; Hojo, Y; Shiraki, A; Imaoka, M; Shibutani, M; Mitsumori, K
The gut microbiota plays important roles in animal nutrition and health. This relationship is particularly dynamic in hibernating mammals where fasting drives the gut community to rely on host-derived nutrients instead of exogenous substrates. We used 16S rRNA pyrosequencing and caecal tissue protein analysis to investigate the effects of hibernation on the mucosa-associated bacterial microbiota and host responses in 13-lined ground squirrels. The mucosal microbiota was less diverse in winter hibernators than in actively feeding spring and summer squirrels. UniFrac analysis revealed distinct summer and late winter microbiota clusters, while spring and early winter clusters overlapped slightly, consistent with their transitional structures. Communities in all seasons were dominated by Firmicutes and Bacteroidetes, with lesser contributions from Proteobacteria, Verrucomicrobia, Tenericutes and Actinobacteria. Hibernators had lower relative abundances of Firmicutes, which include genera that prefer plant polysaccharides, and higher abundances of Bacteroidetes and Verrucomicrobia, some of which can survive solely on host-derived mucins. A core mucosal assemblage of nine operational taxonomic units shared among all individuals was identified with an average total sequence abundance of 60.2%. This core community, together with moderate shifts in specific taxa, indicates that the mucosal microbiota remains relatively stable over the annual cycle yet responds to substrate changes while potentially serving as a pool for 'seeding' the microbiota once exogenous substrates return in spring. Relative to summer, hibernation reduced caecal crypt length and increased MUC2 expression in early winter and spring. Hibernation also decreased caecal TLR4 and increased TLR5 expression, suggesting a protective response that minimizes inflammation. PMID:25130694
Dill-McFarland, Kimberly A; Neil, Katie L; Zeng, Austin; Sprenger, Ryan J; Kurtz, Courtney C; Suen, Garret; Carey, Hannah V
Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia
Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia
Obesity and Low-Grade Inflammation Increase Plasma Follistatin-Like 3 in Humans
Background. Rodent models suggest that follistatin-like 3 (fstl3) is associated with diabetes and obesity. In humans, plasma fstl3 is reduced with gestational diabetes. In vitro, TNF-? induces fstl3 secretion, which suggests a link to inflammation. Objective. To elucidate the association between plasma fstl3 and obesity, insulin resistance, and low-grade inflammation in humans. Study Design. Plasma fstl3 levels were determined in a cross-sectional study including three groups: patients with type 2 diabetes, impaired glucose tolerance, and healthy controls. In addition, lipopolysaccharide (LPS), TNF-?, or interleukin-6 (IL-6) as well as a hyperinsulinemic euglycemic clamp were used to examine if plasma fstl3 was acutely regulated in humans. Results. Plasma fstl3 was increased in obese subjects independent of glycemic state. Moreover, plasma fstl3 was positively correlated with fat mass, plasma leptin, fasting insulin, and HOMA B and negatively with HOMA S. Furthermore plasma fstl3 correlated positively with plasma TNF-? and IL-6 levels. Infusion of LPS and TNF-?, but not IL-6 and insulin, increased plasma fstl3 in humans. Conclusion. Plasma fstl3 is increased in obese subjects and associated with fat mass and low-grade inflammation. Furthermore, TNF-? increased plasma fstl3, suggesting that TNF-? is one of the inflammatory drivers of increased systemic levels of fstl3. PMID:25104880
Pedersen, Maria; Rinnov, Anders; Andreasen, Anne S.; Mřller, Kirsten; Pedersen, Bente K.
Canonical Nlrp3 inflammasome links systemic low grade inflammation to functional decline in aging
SUMMARY Despite a wealth of clinical data showing an association between inflammation and degenerative disorders in elderly, the immune sensors that causally link systemic inflammation to aging remain unclear. Here we detail a mechanism that the Nlrp3 inflammasome controls systemic low grade age-related 'sterile' inflammation in both periphery and brain independently of the non-canonical caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age-related increases in the innate immune activation, alterations in CNS transcriptome and astrogliosis. Consistent with the hypothesis that systemic low grade inflammation promotes age-related degenerative changes, the deficient Nlrp3 inflammasome mediated caspase-1 activity improved glycemic control and attenuated bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome dependent improvement in cognitive function and motor performance in aged mice. These studies reveal Nlrp3 inflammasome as an upstream target that controls age-related inflammation and offer innovative therapeutic strategy to lower Nlrp3 activity to delay multiple age-related chronic diseases. PMID:24093676
Youm, Yun-Hee; Grant, Ryan W.; McCabe, Laura R.; Albarado, Diana C.; Nguyen, Kim Yen; Ravussin, Anthony; Pistell, Paul; Newman, Susan; Carter, Renee; Laque, Amanda; Münzberg, Heike; Rosen, Clifford J.; Ingram, Donald K.; Salbaum, J. Michael; Dixit, Vishwa Deep
Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas
The commonest pediatric brain tumors are low-grade gliomas (LGGs). We utilized whole genome sequencing to discover multiple novel genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24/39 (62%) tumors. Intragenic duplications of the FGFR1 tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes containing TKD-duplicated FGFR1 into brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. TKD-duplicated FGFR1 induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs/LGGNTs. PMID:23583981
Zhang, Jinghui; Wu, Gang; Miller, Claudia P.; Tatevossian, Ruth G.; Dalton, James D.; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A.; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S.; Fulton, Lucinda L.; Dooling, David J.; Vadodaria, Bhavin; Mulder, Heather L.; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G.; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J.; Mardis, Elaine R.; Wilson, Richard K.; Downing, James R.; Baker, Suzanne J.; Ellison, David W.
Whole-genome sequencing identifies genetic alterations in pediatric low-grade gliomas.
The most common pediatric brain tumors are low-grade gliomas (LGGs). We used whole-genome sequencing to identify multiple new genetic alterations involving BRAF, RAF1, FGFR1, MYB, MYBL1 and genes with histone-related functions, including H3F3A and ATRX, in 39 LGGs and low-grade glioneuronal tumors (LGGNTs). Only a single non-silent somatic alteration was detected in 24 of 39 (62%) tumors. Intragenic duplications of the portion of FGFR1 encoding the tyrosine kinase domain (TKD) and rearrangements of MYB were recurrent and mutually exclusive in 53% of grade II diffuse LGGs. Transplantation of Trp53-null neonatal astrocytes expressing FGFR1 with the duplication involving the TKD into the brains of nude mice generated high-grade astrocytomas with short latency and 100% penetrance. FGFR1 with the duplication induced FGFR1 autophosphorylation and upregulation of the MAPK/ERK and PI3K pathways, which could be blocked by specific inhibitors. Focusing on the therapeutically challenging diffuse LGGs, our study of 151 tumors has discovered genetic alterations and potential therapeutic targets across the entire range of pediatric LGGs and LGGNTs. PMID:23583981
Zhang, Jinghui; Wu, Gang; Miller, Claudia P; Tatevossian, Ruth G; Dalton, James D; Tang, Bo; Orisme, Wilda; Punchihewa, Chandanamali; Parker, Matthew; Qaddoumi, Ibrahim; Boop, Fredrick A; Lu, Charles; Kandoth, Cyriac; Ding, Li; Lee, Ryan; Huether, Robert; Chen, Xiang; Hedlund, Erin; Nagahawatte, Panduka; Rusch, Michael; Boggs, Kristy; Cheng, Jinjun; Becksfort, Jared; Ma, Jing; Song, Guangchun; Li, Yongjin; Wei, Lei; Wang, Jianmin; Shurtleff, Sheila; Easton, John; Zhao, David; Fulton, Robert S; Fulton, Lucinda L; Dooling, David J; Vadodaria, Bhavin; Mulder, Heather L; Tang, Chunlao; Ochoa, Kerri; Mullighan, Charles G; Gajjar, Amar; Kriwacki, Richard; Sheer, Denise; Gilbertson, Richard J; Mardis, Elaine R; Wilson, Richard K; Downing, James R; Baker, Suzanne J; Ellison, David W
NASA Astrophysics Data System (ADS)
The past two decades have seen the reporting of microbial fossils within ancient oceanic basalts that could be identical to microbes within modern basalts. Here, we present new petrographic, mineralogical, and stable isotopic data for metabasalts containing filamentous structures in a Jurassic accretionary complex within the northern Chichibu Belt of the Yanadani area of central Shikoku, Japan. Mineralized filaments within these rocks are present in interstitial domains filled with calcite, pumpellyite, or quartz, and consist of iron oxide, phengite, and pumpellyite. ?13CPDB values for filament-bearing calcite within these metabasalts vary from -2.49‰ to 0.67‰. A biogenic origin for these filamentous structures is indicated by (1) the geological context of the Yanadani metabasalt, (2) the morphology of the filaments, (3) the carbon isotope composition of carbonates that host the filaments, and (4) the timing of formation of these filaments relative to the timing of low-grade metamorphism in a subduction zone. The putative microorganisms that formed these filaments thrived between eruption (Late Paleozoic) and accretion (Early Jurassic) of the basalt. The data presented here indicate that cryptoendolithic life was present within water-filled vesicles in pre-Jurassic intraplate basalts. The mineralogy of the filaments reflects the low-grade metamorphic recrystallization of authigenic microbial clays similar to those formed by the encrustation of prokaryotes in modern iron-rich environments. These findings suggest that a previously unusual niche for life is present within intraplate volcanic rocks in accretionary complexes.
Sakakibara, M.; Sugawara, H.; Tsuji, T.; Ikehara, M.
NASA Astrophysics Data System (ADS)
Research on the novel technology of fluidized roasting reduction of samples of low-grade pyrolusite using biogas residual as reductant has been conducted. According to the response surface design and the analysis of results, orthogonal experiments have been conducted on the major factors, and the effects on the manganese reduction efficiency have been studied. The maximum manganese reduction efficiency could be optimized to nearly 100%, when the mass ratio of biogas residual to pyrolusite was 0.16:1, the dosage of sulfuric acid was 1.6 times that of the stoichiometric amount, the roasting temperature was 680°C, and the roasting time was 70 min. The results in terms of manganese reduction efficiency of the actual experiments were close to those anticipated by modeling the experiments, indicating that the optimum conditions had a high reliability. Other low-grade pyrolusites such as Guangxi pyrolusite (China), Hunan pyrolusite (China), and Guizhou pyrolusite (China) were tested and all these materials responded well, giving nearly 100% manganese reduction efficiency.
Cai, Z. L.; Feng, Y. L.; Li, H. R.; Liu, X. W.; Yang, Z. C.
An electrochemical system for efficiently harvesting low-grade heat energy
NASA Astrophysics Data System (ADS)
Efficient and low-cost thermal energy-harvesting systems are needed to utilize the tremendous low-grade heat sources. Although thermoelectric devices are attractive, its efficiency is limited by the relatively low figure-of-merit and low-temperature differential. An alternative approach is to explore thermodynamic cycles. Thermogalvanic effect, the dependence of electrode potential on temperature, can construct such cycles. In one cycle, an electrochemical cell is charged at a temperature and then discharged at a different temperature with higher cell voltage, thereby converting heat to electricity. Here we report an electrochemical system using a copper hexacyanoferrate cathode and a Cu/Cu2+ anode to convert heat into electricity. The electrode materials have low polarization, high charge capacity, moderate temperature coefficients and low specific heat. These features lead to a high heat-to-electricity energy conversion efficiency of 5.7% when cycled between 10 and 60?°C, opening a promising way to utilize low-grade heat.
Lee, Seok Woo; Yang, Yuan; Lee, Hyun-Wook; Ghasemi, Hadi; Kraemer, Daniel; Chen, Gang; Cui, Yi
Pathology of low-grade gliomas: an update of emerging concepts.
Although the term low-grade glioma (LGG) is useful for its connotation of a slow-growing, better prognosis CNS primary neoplasm typically occurring in a young patient, it also serves as a potential diagnostic wastebasket, occasionally leading to conceptual errors, therapeutic uncertainty, or misinterpretation of clinical data. For example, the LGG designation is occasionally invoked as a justification for lumping together biologically unrelated entities such as pilocytic astrocytoma and diffuse astrocytoma. Whereas the former represents a benign and potentially surgically curable neoplasm that virtually never undergoes malignant transformation, the latter is a surgically incurable low-grade malignancy, prone to further malignant progression and eventual fatality. Therefore, although rare cases lacking a clear distinction may be encountered, the term LGG should be abandoned for a more specific diagnosis whenever possible. The primary goals of this paper are to review practical surgical pathology issues related to the diagnosis of diffuse LGGs and to update the reader on emerging clinicopathologic and molecular genetic concepts. Also discussed are current controversies of classification/grading and the role of ancillary testing via immunohistochemical and genetic techniques. PMID:12816723
Perry, Arie
Magnetic Separation and Magnetic Properties of Low-Grade Manganese Carbonate Ore
NASA Astrophysics Data System (ADS)
The relation between the magnetic separation behavior and magnetic properties of a low-grade manganese ore was analyzed before and after treatment by direct reduction with coal. It was found that raw ore with an initial average grade of 10.39% Mn and consisting of diamagnetic and paramagnetic minerals can be concentrated by high-intensity magnetic separation to produce a salable product with a grade of 22.75% Mn and a recovery of 89.88%. In contrast, direct reduction of the ore results in a new Mn-Fe oxide phase formed with a combination of ferromagnetic and paramagnetic properties, thereby increasing the magnetic susceptibilities of the ore by almost two orders of magnitude. The grade of Mn for the roasted ore could only be concentrated to 15.49% with a recovery of 66.67%. Therefore, it is concluded that the low-grade manganese ores with antiferromagnetic and paramagnetic (or diamagnetic, but not strongly ferromagnetic) properties could be efficiently beneficiated via high-intensity magnetic separation.
Wu, Y.; Shi, B.; Ge, W.; Yan, C. J.; Yang, X.
Charging-free electrochemical system for harvesting low-grade thermal energy.
Efficient and low-cost systems are needed to harvest the tremendous amount of energy stored in low-grade heat sources (<100 °C). Thermally regenerative electrochemical cycle (TREC) is an attractive approach which uses the temperature dependence of electrochemical cell voltage to construct a thermodynamic cycle for direct heat-to-electricity conversion. By varying temperature, an electrochemical cell is charged at a lower voltage than discharge, converting thermal energy to electricity. Most TREC systems still require external electricity for charging, which complicates system designs and limits their applications. Here, we demonstrate a charging-free TREC consisting of an inexpensive soluble Fe(CN)6 (3-/4-) redox pair and solid Prussian blue particles as active materials for the two electrodes. In this system, the spontaneous directions of the full-cell reaction are opposite at low and high temperatures. Therefore, the two electrochemical processes at both low and high temperatures in a cycle are discharge. Heat-to-electricity conversion efficiency of 2.0% can be reached for the TREC operating between 20 and 60 °C. This charging-free TREC system may have potential application for harvesting low-grade heat from the environment, especially in remote areas. PMID:25404325
Yang, Yuan; Lee, Seok Woo; Ghasemi, Hadi; Loomis, James; Li, Xiaobo; Kraemer, Daniel; Zheng, Guangyuan; Cui, Yi; Chen, Gang
Low Grade Glandular Lesions of the Sinonasal Tract: A Focused Review
The sinonasal tract is a complex anatomic site with an exhaustive list of possible diagnoses. While most biopsies or resections encountered routinely consist of common diagnoses such as inflammatory polyps and papillomas, occasional cases are more difficult, and separating reactive or benign from malignancy can be challenging. One of the most poorly understood and daunting categories is low grade glandular or tubular proliferations, particularly on small biopsies. Possible diagnoses such as reactive lesions, respiratory epithelial adenomatoid hamartoma (REAH), seromucinous (glandular) hamartoma (SH) and low grade sinonasal adenocarcinomas (LGSNAC) must be entertained. REAH is composed of respiratory epithelial lined submucosal glands with variable connection to the surface and periglandular hyalinization. SH is a tubular proliferation reminiscent of normal serous glands which may be associated with REAH. LGSNAC is a diverse group of bland tubular and/or papillary tumors, which have a recurrence potential but an as yet uncertain potential for metastasis or mortality. The management for these lesions can be vastly different and conservative management is preferable, making this distinction more than academic. However, complicating this category are controversies surrounding their nature as reactive lesions versus neoplasms, the histologic and immunohistochemical overlap, and possible precursor relationships between some of them. PMID:20237993
Outcomes of pediatric low-grade gliomas treated with radiation therapy: a single-institution study.
Radiation therapy is often considered the treatment of choice for low-grade gliomas. However, given the long-term effects of radiation on the developing brain, the appropriate use of radiation therapy in pediatric patients remains controversial. The purpose of this study was to evaluate progression-free survival (PFS) of pediatric low-grade glioma patients treated with radiation therapy. Data were obtained through a retrospective chart review of patients treated between 1991 and 2008 from a single tertiary care center in the midwest. The study population consisted of 17 patients, of whom 8 (47%) had tumor recurrence after radiation therapy. The median follow-up time was 8.2 years, with a range of 2.3 to 17.2 years. The median age at diagnosis was 5.4 years, and the median age at radiation therapy was 9.4 years. The 3- and the 10-year PFS were 69%± 11.7% and 46%± 13.3%, respectively. A significant difference in PFS was seen when comparing brainstem tumors with hypothalamic/optic pathway tumors (P=0.019). Differences in PFS based on the age at diagnosis, the extent of initial surgery, and indication for radiation therapy were not significant. A larger multicenter study is needed to better assess PFS in these patients. PMID:24714505
Raikar, Sunil S; Halloran, Donna R; Elliot, Michael; McHugh, Michele; Patel, Shaun; Gauvain, Karen M
This study was designed to quantitatively assess the microvascular permeability of oligodendroglioma using the volume transfer constant (K(trans)) and the volume of the extravascular extracellular space per unit volume of tissue (V(e)) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We aimed to evaluate the effectiveness of K(trans) and V(e) in distinguishing between low-grade and anaplastic oligodendroglioma. The maximal values of K(trans) and V(e) for 65 patients with oligodendroglioma (27 grade II, 38 grade III) were obtained. Differences in K(trans) and V(e) between the two groups were analysed using the Mann-Whitney rank-sum test. Receiver operating characteristic (ROC) curve analyses were performed to determine the cut-off values for the K(trans) and Ve that could differentiate between low-grade and anaplastic oligodendrogliomas. Values for K(trans) and Ve in low-grade oligodendrogliomas were significantly lower than those in anaplastic oligodendrogliomas (p < 0.001 and p < 0.001, respectively). ROC curve analysis showed that cut-off values of the K(trans) (0.037 min(-1)) and Ve (0.079) could be used to distinguish between low-grade and anaplastic oligodendrogliomas in a statistically significant manner. Our results suggest that DCE-MRI can distinguish the differences in microvascular permeability between low-grade and anaplastic oligodendrogliomas. PMID:23673143
Jia, Zhongzheng; Geng, Daoying; Liu, Ying; Chen, Xingrong; Zhang, Jun
Study of Supercritical Carbon Dioxide Power Cycle for Low Grade Heat Conversion
Research on supercritical carbon dioxide power cycles has been mainly focused on high temperature applications, such as Brayton cycle in a nuclear power plant. This paper conducts a comprehensive study on the feasibility of a CO2-based supercritical power cycle for low-grade heat conversion. Energy and exergy analyses of the cycle were conducted to discuss the obstacles as well as the potentials of using supercritical carbon dioxide as the working fluid for supercritical Rankine cycle, Carbon dioxide has desirable qualities such as low critical temperature, stability, little environmental impact and low cost. However, the low critical temperature might be a disadvantage for the condensation process. Comparison between a carbon dioxide-based supercritical Rankine cycle and an organic fluid-based supercritical Rankine cycle showed that the former needs higher pressure to achieve the same efficiency and a heat recovery system is necessary to desuperheat the turbine exhaust and pre-heat the pressure charged liquid.
Vidhi, Rachana [University of South Florida, Tampa; Goswami, Yogi D. [University of South Florida, Tampa; Chen, Huijuan [University of South Florida, Tampa; Stefanakos, Elias [University of South Florida, Tampa; Kuravi, Sarada [University of South Florida, Tampa; Sabau, Adrian S [ORNL
Roles of Chronic Low-Grade Inflammation in the Development of Ectopic Fat Deposition
Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders. PMID:25143667
Mei, Mei; Yang, Shumin; Li, Qifu
Nd:YAG laser photoresection of low-grade malignant tumors of the tracheobronchial tree.
Nineteen patients with low-grade malignant tumors of the tracheobronchial tree received Nd:YAG laser treatment. They were referred for palliation of symptomatic airway obstruction due to carcinoid (14 cases) or adenocystic carcinoma (five cases). In all patients, laser treatment was followed by symptomatic relief. Fifteen patients have done well and remain in good condition between six months and four years after laser photoresection. Two of the five patients with adenocystic carcinoma died because of hemoptysis at one and 49 months after laser therapy. In the group of 14 patients with carcinoids, two episodes of bleeding (more than 250 ml) occurred that were controlled by tamponade with the tube and coagulation by the laser beam itself. Two patients with carcinoid died of unrelated causes (stroke and gastric carcinoma). PMID:2157587
Díaz-Jiménez, J P; Canela-Cardona, M; Maestre-Alcacer, J
A preliminary report on the rapid fluorimetric determination of uranium in low-grade ores
A simple and very rapid fluorimetric procedure is described for the determination of uranium in low-grade shale and phosphate ores. The best working range is from 0.001 to about 0.04 percent U. The procedure employs batch extraction of uranium nitrate by ethyl acetate, using aluminum nitrate as the salting agent, prior to the visual fluorimetric estimation. The procedure is especially designed to save reagents; only 9.5 g of aluminum nitrate and 10 ml of ethyl acetate being used for one analysis. The solution of the sample by means of a fusion with NaOH-NaNO3 flux is rapid. After fusion the sample is immediately extracted without removing silica and other hydrolytic precipitates. Aluminum nitrate very effectively ties up fluoride and phosphate, thus eliminating steps required for their removal.
Grimaldi, F.S.; Levine, Harry
Intra-abdominal low-grade fibromyxoid sarcoma of the transverse mesocolon mimicking lymphoma.
Low-grade fibromyxoid sarcoma (LGFMS), first described by Evans in 1987, is a rare soft tissue tumor. LGFMS commonly involves the deep soft tissues of the lower extremities, inguinal area, shoulder, axilla, neck and buttock. Intra-abdominal LGFMS has been reported in ten cases in six English studies (small bowel, four cases; mesentery, two; falciform ligament, one; omentum, one; colon, one; diffuse, one), and radiologic imaging studies were done in four of the ten cases. In the present case, radiologic findings of LGFMS showed a well-demarcated multilobular hypoechoic mass on ultrasonography, a multilobular homogeneously enhancing solid mass in the transverse mesocolon on computed tomography and a mildly inhomogeneously enhancing solid mass with two different components on magnetic resonance imaging. We report the first case of LGFMS arising from the transverse mesocolon mimicking lymphoma in a young female patient. PMID:24652000
Kim, Kyung Joon; Seo, Jung Wook
Survival and low-grade glioma: the emergence of genetic information.
Significant gaps exist in our understanding of the causes and clinical management of glioma. One of the biggest gaps is how best to manage low-grade (World Health Organization [WHO] Grade II) glioma. Low-grade glioma (LGG) is a uniformly fatal disease of young adults (mean age 41 years), with survival averaging approximately 7 years. Although LGG patients have better survival than patients with high-grade (WHO Grade III or IV) glioma, all LGGs eventually progress to high-grade glioma and death. Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute suggest that for the majority of LGG patients, overall survival has not significantly improved over the past 3 decades, highlighting the need for intensified study of this tumor. Recently published research suggests that historically used clinical variables are not sufficient (and are likely inferior) prognostic and predictive indicators relative to information provided by recently discovered tumor markers (e.g., 1p/19q deletion and IDH1 or IDH2 mutation status), tumor expression profiles (e.g., the proneural profile) and/or constitutive genotype (e.g., rs55705857 on 8q24.21). Discovery of such tumor and constitutive variation may identify variables needed to improve randomization in clinical trials as well as identify patients more sensitive to current treatments and targets for improved treatment in the future. This article reports on survival trends for patients diagnosed with LGG within the United States from 1973 through 2011 and reviews the emerging role of tumor and constitutive genetics in refining risk stratification, defining targeted therapy, and improving survival for this group of relatively young patients. PMID:25552286
Claus, Elizabeth B; Walsh, Kyle M; Wiencke, John K; Molinaro, Annette M; Wiemels, Joseph L; Schildkraut, Joellen M; Bondy, Melissa L; Berger, Mitchel; Jenkins, Robert; Wrensch, Margaret
Low-grade coals: a review of some prospective upgrading technologies
There is a growing need of using low-grade coals because of higher quest for power generation. In the present carbon-constrained environment, there is a need of upgrading these coals in terms of moisture, ash, and/or other trace elements. The current paper reviews technologies used mainly categorized as drying for reducing moisture and cleaning the coal for reducing mineral content of coal and related harmful constituents, such as sulfur and mercury. The earliest upgrading of high-moisture lignite involved drying and manufacturing of briquettes. Drying technologies consist of both evaporative and non-evaporative (dewatering) types. The conventional coal cleaning used density separation in water medium. However, with water being a very important resource, conservation of water is pushing toward the development of dry cleaning of coal. There are also highly advanced coal-cleaning technologies that produce ultra-clean coals and produce coals with less than 0.1% of ash. The paper discusses some of the promising upgrading technologies aimed at improving these coals in terms of their moisture, ash, and other pollutant components. It also attempts to present the current status of the technologies in terms of development toward commercialization and highlights on problems encountered. It is obvious that still the upgrading goal has not been realized adequately. It can therefore be concluded that, because reserves for low-grade coals are quite plentiful, it is important to intensify efforts that will make these coals usable in an acceptable manner in terms of energy efficiency and environmental protection. 68 refs., 7 figs.
Hassan Katalambula; Rajender Gupta [University of Alberta, Edmonton, AB (Canada). Department of Chemical and Materials Engineering
Total lymphoid irradiation in alloimmunity and autoimmunity
Total lymphoid irradiation has been used as an immunosuppressive regimen in autoimmune disease and organ transplantation. The rationale for its use originated from studies of patients with Hodgkin disease, in whom this radiotherapy regimen was noted to induce profound and long-lasting immune suppression and yet was well tolerated, with few long-term side effects. Total lymphoid irradiation is a unique immunosuppressive regimen that produces a selective (and long-lasting) reduction in the number and function of helper T cells and certain subsets of B cells. Conventional immunosuppressive drugs show little selectivity, and their effects are short-lived. The most important aspect of total lymphoid irradiation is the potential for achieving transplantation tolerance and permanent remissions in autoimmune disease in laboratory animals. Attempts are being made to achieve similar goals in humans given total lymphoid irradiation, so that immunosuppressive drugs can be ultimately withdrawn from transplant recipients and patients with lupus nephritis. 28 references.
Strober, S.
Plasmablastic transformation of low-grade B-cell lymphoproliferative disorders is rarely reported, particularly in cases with clonal evolution. Moreover, the relationship of these 2 morphologically and immunophenotypically distinctive neoplasms remains elusive. Here, we report 2 exceptional cases of plasmablastic transformation with apparently direct transformation from their preceding low-grade B-cell lymphoproliferative disorder. In both cases, the plasmablastic transformation and low-grade lymphoproliferative disorder shared the same immunoglobulin heavy chain gene rearrangements and an identical chromosomal translocation. Notably, both plasmablastic transformation cases also carried MYC gene rearrangements on chromosome 8q24, which have been frequently identified in de novo plasmablastic lymphoma. Therefore, our data suggest that dysregulation of MYC gene may play a critical role in the pathogenesis of plasmablastic transformation. PMID:23791008
Pan, Zenggang; Xie, Qingmei; Repertinger, Susan; Richendollar, Bill G; Chan, Wing C; Huang, Qin
The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma. PMID:25120828
Chen, Ling; Pang, Shujie; Shen, Yan; Liu, Zaiping; Luan, Jing; Shi, Yiquan; Liu, Yixin
Ovarian low-grade serous carcinoma (LGSC) and high-grade serous carcinoma have distinct molecular profiles, clinical behaviors, and treatment responses. The survival advantage for patients with low-grade carcinoma compared with patients with high-grade histology remains controversial. We retrospectively reviewed the medical charts of 381 patients with ovarian serous carcinoma at Peking Union Medical College Hospital from 2007 to 2010. Patients were classified into two groups according to MD Anderson two-tier system: 35 (9.2%) cases with LGSC and 346 with high-grade serous carcinoma. Patients with low-grade serous ovarian cancer had a significantly younger age at diagnosis (46 versus 56 years, P=0.046), and their median progression-free survival (PFS) and overall survival values were 35.0 and 54.0 months, respectively. A multivariate analysis showed that, for serous ovarian cancer, the histological grade was a significant prognostic factor for PFS but not for overall survival (P=0.022 and P=0.0566, respectively). When stratified by the existence of a residual disease, patients with low-grade disease who underwent cytoreductive surgery without macroscopic residual disease (>1 cm) had a significantly improved median PFS time (36.0 months) compared with that of patients with high-grade carcinoma who received optimal cytoreductive surgery (16.0 months, P=0.017). Conversely, patients with low-grade and high-grade carcinoma who were left with macroscopic residue (>1 cm) experienced a similarly shorter median PFS (10.0 and 13.0 months, respectively, P=0.871). The International Federation of Gynecology and Obstetrics stage and residual disease were significant prognostic factors of low-grade carcinoma, while positive ascites was associated with a worse PFS value. Our data showed that LGSC is a different entity from high-grade carcinoma and that LGSC was associated with improved PFS after optimal cytoreductive surgery but not suboptimal operation. PMID:25342912
Chen, Ming; Jin, Ying; Bi, Yalan; Yin, Jie; Wang, Yongxue; Pan, Lingya
The morphometric differences between the urothelial cells (wet-fixed Papanicolaoustained) in the voided urine of 2 patients with low grade and high grade bladder tumours were measured. The morphometrical data of this learning set resulted in a cytomorphometrical classification rule, which was applied to a test set of 21 cases with low grade and high grade bladder tumours. The results of the cytomorphometrical classification rule correspond very well with the histomorphometrical classification and the histological grade of the parent tumours. The results indicate that it is feasible to classify bladder tumours using the cytomorphometrical data of the exfoliated urothelial cells alone. PMID:7130416
Ooms, E C; Kurver, P J; Boon, M E
Purpose. Since continuous relapse rates are characteristic for advanced low-grade non-Hodgkin's lymphomas (NHL), their treatment remains a problem. Previous phase II studies showed that bendamustine induced high remission rates in pre-treated low-grade NHL. To further examine its efficacy and side effects, bendamustine has been studied in a large number of patients with pre-treated low-grade NHL. Follow-up time was 3-8 years.
Karl Bremer
Melville wrote Bartleby the Scrivener as a literary portrayal of the Humoral theory of disease. Virchow disproved that theory five years after the novella was published, suggesting Melville was humanizing an unknown pathology. A clinical assessment of the text reveals low-grade lead poisoning, which best explains the strange behavior, abnormal appearance, and premature death of the character Bartleby as depicted
Gerard Bogin
A study of organic working fluids on system efficiency of an ORC using low-grade energy sources
Rankine cycles using organic fluids (as categorized into three groups: wet, dry, and isentropic fluids) as working fluids in converting low-grade energy are investigated in this study. The main purpose is to identify suitable working fluids which may yield high system efficiencies in an organic Rankine cycle (ORC) system. Efficiencies of ORC systems are calculated based on an assumption that
T. C. Hung; S. K. Wang; C. H. Kuo; B. S. Pei; K. F. Tsai
A low?grade metamorphic model for the Miocene volcanic sequences in the Andes of central Chile
Calc?alkaline basic volcanic rocks in a c. 600 m thick sequence of Miocene age, the Valle Nevado stratified sequence (VNSS), have been affected by very low grade metamorphism characterised by mineral assemblages of the zeolite facies. Metastable conditions prevailed, most of the igneous minerals being wholly or partially preserved. The main metamorphic phases are mafic phyllosilicates and zeolites of calco?sodic
L. Aguirre; D. Robinson; R. E. Bevins; D. Morata; M. Vergara; E. Fonseca; J. Carrasco
Introduction Medical treatment of low-grade (<50% luminal narrowing) symptomatic carotid stenosis has been the treatment of choice because trial data showed no evident benefit to carotid endarterectomy for these patients. Such patients may have recurrent neurological symptoms despite adequate medical therapy owing to recurrent plaque rupture. In such cases, carotid stenting may represent an option for treatment but has not been tested in trials because of previous failure of carotid endarterectomy to demonstrate any benefit for patients with low-grade carotid stenosis. The cases presented here illustrate the perioperative safety and potential benefit of carotid stenting for such patients with persistent neurological symptoms despite adequate medical therapy. Case material Two patients with low-grade stenosis and recurrent transient ischemic attack or stroke despite antiplatelet therapy were treated with carotid stenting. Both patients were treated after recent ipsilateral neurological events in the absence of an evident cardioembolic source. Carotid plaque ulceration thought to be related to the ischemic events was present in both cases. No perioperative complications were noted. On followup, the patients showed resolution of symptoms and had no new neurological events. Conclusion Carotid stenting of low-grade but symptomatic carotid plaque refractory to medical management represents a surgical option for treatment. Further studies may be warranted to evaluate stenting as a suitable treatment option. PMID:24920988
Shallwani, Hussain; Dumont, Travis M.; Wach, Michael M.; Levy, Elad I.; Siddiqui, Adnan H.
A method and apparatus for utilizing low grade thermal energy is shown to reduce the energy required to drive the compressor of a refrigeration or air conditioning system. The thermal energy is used to vaporize a fluid which is used as a motive fluid to drive a thermal compressor, such as a jet compressor or a vapor compression cycle compressor.
To better predict risk of progression of low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix in women with human papillomavirus (HPV) infections, 294 baseline cervical specimens from women with LSILs were evaluated. Specimens were tested for HPV DNA using hybrid capture 2 (HC2) and PCR-reverse line blotting. 65 LSILs with HPV DNA types 16, 18, 52, or 58 were examined for physical status, E2/E6 ratio and viral load at two time points, along with patient age. Women with LSILs whose viral loads increased between baseline and 6 month follow-up had a 45% risk of developing HSIL (OR=7.6, 95% CI=1.9–29.4, P<0.01), as evaluated by real-time PCR and a 44% risk (OR=6.1, 95% CI=1.6–22.7, P<0.01), as evaluated by HC2. The two viral load measures correlated well (Person's coefficient, r=0.687, P<0.001). Such evaluations of viral load changes (increased or not increased) through repeat HPV DNA testing could predict progression of disease in LSIL cases of HPV types 16, 18, 52, and 58, which correlates to clinical implications. PMID:17060938
Ho, C-M; Cheng, W-F; Chu, T-Y; Chen, C-A; Chuang, M-H; Chang, S-F; Hsieh, C-Y
Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity. PMID:25315424
Spyridaki, Eirini C; Simos, Panagiotis; Avgoustinaki, Pavlina D; Dermitzaki, Eirini; Venihaki, Maria; Bardos, Achilles N; Margioris, Andrew N
A dynamic model for the optimization of oscillatory low grade heat engines
NASA Astrophysics Data System (ADS)
The efficiency of a thermodynamic system is a key quantity on which its usefulness and wider application relies. This is especially true for a device that operates with marginal energy sources and close to ambient temperatures. Various definitions of efficiency are available, each of which reveals a certain performance characteristic of a device. Of these, some consider only the thermodynamic cycle undergone by the working fluid, whereas others contain additional information, including relevant internal components of the device that are not part of the thermodynamic cycle. Yet others attempt to factor out the conditions of the surroundings with which the device is interfacing thermally during operation. In this paper we present a simple approach for the modeling of complex oscillatory thermal-fluid systems capable of converting low grade heat into useful work. We apply the approach to the NIFTE, a novel low temperature difference heat utilization technology currently under development. We use the results from the model to calculate various efficiencies and comment on the usefulness of the different definitions in revealing performance characteristics. We show that the approach can be applied to make design optimization decisions, and suggest features for optimal efficiency of the NIFTE.
Markides, Christos N.; Smith, Thomas C. B.
Resetting of RbSr ages of volcanic rocks by low-grade burial metamorphism
We report a nine-point RbSr whole-rock isochron age of 70??3 Ma (MSWD 3.97) for Mid-Jurassic volcanic rocks. The same rocks have also been dated by the UThPb method on zircon, giving a crystallization age of 166 ?? 11 Ma, over twice as old as the RbSr age. The data demonstrate that whole-rock RbSr ages of volcanic rocks, even lava flows with SiO2 content as low as 57 wt.%, are susceptible to complete resetting. The rocks range in composition from rhyodacite tuffs to andesite lavas. The complete breakdown of all major minerals that contain Rb and Sr resulted in an alteration mineral assemblage consisting of phengite, albite, secondary quartz, and minor amounts of chlorite and epidote. Phengite is the K-bearing product of the breakdown of biotite and K-feldspar. Pressure during low-grade metamorphism of the volcanic rocks, estimated from phengite composition to have been in the range of 4 to 6 kbar, points to thrust-related burial as the main cause of resetting. Consequently, such reset isochrons may date large-scale events such as regional thrusting and metamorphism. The coherent resetting of the RbSr isochron suggests large-scale pervasive fluid movement during thrust-related burial metamorphism. ?? 1991.
Asmeroma, Y.; Damon, P.; Shafiqullah, M.; Dickinson, W.R.; Zartman, R.E.
Low-grade, M1 metamorphism of the western metamorphic belt near Juneau, Alaska
The western metamorphic belt is part of the Coast plutonic-metamorphic complex of western Canada and southeastern Alaska that developed as a result of tectonic overlap and/or compressional thickening of crustal rocks during collision of the Alexander terrane and Gravina assemblage on the west against the Yukon Prong and Stikine terranes to the east. Sub-greenschist to lower greenschist facies metabasalts exposed along the west end of the western metamorphic belt near Juneau, Alaska record the earliest metamorphic event (M1). These low-grade rocks are gradational with younger, higher-grade assemblages that define an inverted metamorphic gradient (metamorphic event M5). The most common metamorphic mineral assemblages are chlorite-epidote-actinolite with or without pumpellyite and stilpnomelane. There is no systematic distribution of metamorphic mineral assemblages in the study area, and all assemblages are in the pumpellyite-actinolite facies near the transition to the lower greenschist facies. Different low-variance assemblages can be attributed to minor differences in pressure, temperature, or X[sub CO[sub 2
Himmelberg, G.R. (Univ. of Missouri, Columbia, MO (United States). Dept. of Geology); Brew, D.A.; Ford, A.B. (Geological Survey, Menlo Park, CA (United States))
We report a surgical case of primary polymorphous low-grade adenocarcinoma (PLGA) of the minor salivary gland-type of the lung. A PLGA originating from the right upper lobar bronchial inlet was successfully treated by sleeve right upper lobectomy. PLGAs are thought to be indolent tumors that are preferentially localized to the palate, and they affect the minor salivary glands almost exclusively. Until now, two cases of distant metastases to the lung have been reported in the English literature. To the best of our knowledge, only one case of PLGA of minor salivary gland-type of the lung without evidence of a previous oropharyngeal primary tumor has been reported in the English literature. But the case was not a single lesion; it was bilateral tumors accompanied by tumors of the cervical lymph nodes. We report here the first case of a single primary PLGA of the minor salivary gland-type of the lung, which was successfully treated by sleeve bronchial resection of right upper lobe. PMID:17449954
Jung, Ji Han; Cho, Deog Gon; Jo, Min Seop; Yoo, Jinyoung; Song, So Hyang; Shim, Byoung Yong; Kim, Chi Hong; Kim, Hoon-Kyo
Tumor volumetric measurements in surgically inaccessible pediatric low-grade glioma.
Tumor measurement is important in unresectable pediatric low-grade gliomas (pLGGs) to determine either the need for treatment or assess response. Standard methods measure the product of the largest 2 lengths from transverse, anterior-posterior, and cranio-caudal dimensions (SM, cm). This single-institution study evaluated tumor volume measurements (VM, cm) in such pLGGs. Of 50 patients treated with chemotherapy for surgically inaccessible pLGG, 8 met the inclusion criteria of having 2 or more sequential MRI studies of T1-weighted Fast-Spoiled Gradient Recalled acquisition. SM and VM were performed by 2 independent neuroradiologists. Associations of measurement methods with defined therapeutic response criteria and patient clinical status were assessed. The mean tumor size at the first MRI scan was 20 cm and 398 cm according to SM and VM, respectively. VM results did not differ significantly from SM-derived spherical volume calculations (Pearson correlation, P<0.0001) with a high interrater reliability. Both methods were concordant in defining the tumor response according to the current criteria, although radiologic progressive disease was not associated with clinical status (SM: P=0.491, VM: P=0.208). In this limited experience, volumetric analysis of unresectable pLGGs did not seem superior to the standard linear measurements for defining tumor response. PMID:25517914
Kilday, John-Paul; Branson, Helen; Rockel, Conrad; Laughlin, Suzanne; Mabbott, Donald; Bouffet, Eric; Bartels, Ute
MYB upregulation and genetic aberrations in a subset of pediatric low-grade gliomas
Recent studies of genetic abnormalities in pediatric low-grade gliomas (LGGs) have focused on activation of the ERK/MAPK pathway by KIAA1549-BRAF gene fusions in the majority of pilocytic astrocytomas (PAs) and by rare mutations in elements of the pathway across histopathologically diverse LGGs. This study reports that MYB, an oncogene not previously implicated in gliomagenesis, is activated in a diverse subset of pediatric LGGs. The study cohort comprised 57 pediatric LGGs and a comparative cohort of 59 pediatric high-grade gliomas (HGGs). The LGG cohort included 34 PAs and 23 diffuse gliomas; fibrillary astrocytomas (n=14), oligodendroglial tumors (n=7), and angiocentric gliomas (n=2). MYB copy number abnormalities were disclosed using Affymetrix 6.0 SNP arrays and confirmed using interphase fluorescence in situ hybridization. Novel MYB amplifications that upregulate MYB RNA and protein expression were demonstrated in 2/14 diffuse astrocytomas. In addition, focal deletion of the terminal region of MYB was seen in 1 of 2 angiocentric gliomas (AGs). Increased expression of MYB was demonstrated by quantitative RT-PCR and immunohistochemistry. MYB upregulation at the protein level was demonstrated in a proportion of diffuse LGGs (60%), pilocytic astrocytomas (41%), and HGGs (19%), but abnormalities at the genomic level were only a feature of diffuse gliomas. Our data suggest that MYB may have a role in a subset of pediatric gliomas, through a variety of mechanisms in addition to MYB amplification and deletion. PMID:21046410
Tatevossian, Ruth G.; Tang, Bo; Dalton, James; Forshew, Tim; Lawson, Andrew R.; Ma, Jing; Neale, Geoff; Shurtleff, Sheila A.; Bailey, Simon; Gajjar, Amar; Baker, Suzanne J.; Sheer, Denise; Ellison, David W.
Low-grade fibromyxoid sarcoma with nuclear pleomorphism arising in the subcutis of a child.
Low-grade fibromyxoid sarcoma (LGFMS) represents a rare soft tissue tumor that was first characterized in 1987. LGFMS usually presents as a large, deeply situated mass in adults and is characterized by deceptively bland histopathologic features. LFGMS is less common in superficial soft tissue and in children. It is distinctly uncommon for LGFMS to exhibit nuclear pleomorphism. Herein, we present a case of a 10-year-old male who presented with a subcutaneous back mass that displayed features typical for LGFMS as well as scattered large, hyperchromatic and pleomorphic nuclei. The constellation of clinicopathologic features, including the young age of the patient, the small size and superficial location of the tumor and the presence of scattered nuclear pleomorphism are all unusual features for LGFMS. Fluorescent in situ hybridization (FISH) with a break-apart probe for FUS revealed the presence of a FUS gene rearrangement confirming the diagnosis of LGFMS. This case highlights the importance of maintaining a high index of suspicion for LGFMS even in the context of small, superficially-located tumors, pediatric patients or tumors with scattered nuclear pleomorphism. PMID:24188507
Sedrak, Michael P; Parker, Douglas C; Gardner, Jerad M
Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade endometrial stromal sarcoma.
Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare uterine neoplasms that are commonly driven by recurrent gene rearrangements. In conventional low-grade ESS, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1, and recently described ZC3H7-BCOR chimeric fusions have been reported in > 50% of cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE-FAM22A/B chimeric proteins that are associated with histologically high-grade and clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA sequencing with fluorescence in situ hybridization (FISH) and banding cytogenetics, we identified MBTD1 (malignant brain tumor domain-containing 1) and CXorf67 (chromosome X open reading frame 67) as the genes involved in the novel reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was validated in both cases using reverse-transcription polymerase chain reaction followed by Sanger sequencing. A specific FISH assay was developed to detect the novel t(X;17) translocation in formalin-fixed paraffin-embedded material, and resulted in identification of an additional low-grade ESS case positive for the MBTD1-CXorf67 fusion among 25 uterine stromal tumors [14 ESS and 11 undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and YWHAE rearrangements. Gene expression profiles of seven ESS (including three with YWHAE and two with JAZF1 rearrangements) and four UES without specific chromosomal aberrations indicated clustering of tumors with MBTD1-CXorf67 fusion together with low-grade JAZF1-associated ESS. The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade ESS and offers the opportunity to shed light on the functions of two poorly characterized genes. PMID:23959973
Dewaele, Barbara; Przybyl, Joanna; Quattrone, Anna; Finalet Ferreiro, Julio; Vanspauwen, Vanessa; Geerdens, Ellen; Gianfelici, Valentina; Kalender, Zeynep; Wozniak, Agnieszka; Moerman, Philippe; Sciot, Raf; Croce, Sabrina; Amant, Frederic; Vandenberghe, Peter; Cools, Jan; Debiec-Rychter, Maria
Waldeyer's ring is located at the juncture of the respiratory and alimentary tracts, where it is bombarded by inhaled and ingested antigens. However, knowledge of its exact function or consequences of its removal is incomplete. Recently, the murine nasal-associated lymphoid tissue (NALT) has been reported to have functional similarities to Waldeyer's ring and, thus, might be a suitable model to examine the function of oronasopharyngeal lymphoid tissues. To explore the capability of NALT to incite local mucosal and systemic immunity, we immunized mice intranasally (i.n.) with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS)-grafted microparticles (MP), an inoculant previously shown to induce robust systemic and mucosal humoral immunity following intragastric (i.g.) administration. We demonstrated that i.n. immunization with low doses of microentrapped, but not soluble, human serum albumin (HSA) evoked robust circulating IgG responses (P < 0.05). Additionally, NALT cells isolated from MP-treated mice proliferated in vitro when restimulated with HSA (P < 0.05), suggesting that i.n. immunization with HSA-containing MP incited specific immunity via NALT cell activation. Coinciding with these observations, after i.n. MP administration HSA-specific spot-forming cells (SFC) were observed in NALT, and later posterior cervical lymph nodes (pCLN) and spleen (SPL), suggesting that the observed MP-induced specific systemic antibody responses emanated from the NALT. We also showed that i.n. immunization with HSA-containing TS-PDMS-grafted MP stimulated interleukin-4 (IL-4)-secreting lymphocytes in the NALT. This cytokine microenvironment was probably responsible for driving the IgG1 sera response observed after i.n. MP administration, via the migration of NALT-derived IgG1-committed B cells. Interestingly, unlike i.g. MP administration, i.n. immunization with HSA-containing MP did not evoke detectable specific IgA in any lymphoid tissue examined, or in nasal secretions, probably reflecting differences between NALT and other mucosae-associated lymphoid tissues (MALT). PMID:9616375
Heritage, P L; Brook, M A; Underdown, B J; McDermott, M R
Lymphatic vessels and tertiary lymphoid organs
Tertiary lymphoid organs (TLOs) are accumulations of lymphoid cells in chronic inflammation that resemble LNs in their cellular content and organization, high endothelial venules, and lymphatic vessels (LVs). Although acute inflammation can result in defective LVs, TLO LVs appear to function normally in that they drain fluid and transport cells that respond to chemokines and sphingosine-1-phosphate (S1P) gradients. Molecular regulation of TLO LVs differs from lymphangiogenesis in ontogeny with a dependence on cytokines and hematopoietic cells. Ongoing work to elucidate the function and molecular regulation of LVs in TLOs is providing insight into therapies for conditions as diverse as lymphedema, autoimmunity, and cancer. PMID:24590281
Ruddle, Nancy H.
This invention relates to a procedure for converting low-grade thermal energy into mechanical energy in a turbine for further utilization and a plant for implementing the procedure. The procedure according to the invention is characterized in that a low-grade heating medium and a first cooling medium are evaporated in a heat exchanger. The steam is carried to a turbine for
Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia
The enhanced spatial and spectral resolution provided by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on the Mars Reconnaissance Orbiter (MRO) has led to the discovery of numerous hydrated silicate minerals on Mars, particularly in the ancient, cratered crust comprising the southern highlands. Phases recently identified using visible/near-infrared spectra include: smectite, chlorite, prehnite, high-charge phyllosilicates (illite or muscovite), the zeolite analcime, opaline silica, and serpentine. Some mineral assemblages represent the products of aqueous alteration at elevated temperatures. Geologic occurrences of these mineral assemblages are described using examples from west of the Isidis basin near the Nili Fossae and with reference to differences in implied temperature, fluid composition, and starting materials during alteration. The alteration minerals are not distributed homogeneously. Rather, certain craters host distinctive alteration assemblages: (1) prehnite-chlorite-silica, (2) analcime-silica-Fe,Mg-smectite-chlorite, (3) chlorite-illite (muscovite), and (4) serpentine, which furthermore has been found in bedrock units. These assemblages contrast with the prevalence of solely Fe,Mg-smectites in most phyllosilicate-bearing terrains on Mars, and they represent materials altered at depth then exposed by cratering. Of the minerals found to date, prehnite provides the clearest evidence for subsurface, hydrothermal/metamorphic alteration, as it forms only under highly restricted conditions (T = 200 400??C). Multiple mechanisms exist for forming the other individual minerals; however, the most likely formation mechanisms for the characteristic mineralogic assemblages observed are, for (1) and (2), low- grade metamorphism or hydrothermal (400??C has not been found.
Ehlmann, B.L.; Mustard, J.F.; Clark, R.N.; Swayze, G.A.; Murchie, S.L.
Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition.
Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane. Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning. It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates. Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age. Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones. Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition. Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age. Many fungal taxa were isolated and identified. It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition. Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces. Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same. In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition. PMID:15091479
Meng, F R; Bourque, C P; Belczewski, R F; Whitney, N J; Arp, P A
Purpose: The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning. Methods and Materials: Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years. Results: No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy. Conclusions: This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.
Di Pinto, Marcos [Department of Pediatric Psychology, Children's Hospital of Orange County, Orange, California (United States)] [Department of Pediatric Psychology, Children's Hospital of Orange County, Orange, California (United States); Conklin, Heather M. [Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)] [Department of Psychology, St. Jude Children's Research Hospital, Memphis, Tennessee (United States); Li, Chenghong [Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)] [Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E., E-mail: firstname.lastname@example.com [Division of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee (United States)
Proton Therapy in Pediatric Skull Base and Cervical Canal Low-Grade Bone Malignancies
Purpose: To evaluate outcomes and tolerance of high-dose photon and proton therapy in the management of skull base and cervical canal primary bony malignancies in children. Patients and Methods: Thirty children were treated postoperatively with high-dose photon-proton (29 patients) or protons-only (1 patient) radiotherapy. Twenty-six patients had chordomas (CH), 3 had low-grade chondrosarcomas (CS), and 1 had an aggressive chondroma (AC). The mean age was 12.8 years. At the time of radiation, all but 1 patient had a gross residue. The anatomic sites affected were skull base (n 16), cervical canal (n = 1), or both (n = 13). Mean total dose was 68.4 cobalt Gray equivalents, conventionally fractionated. Results: With a mean follow-up of 26.5 months, 5 of 30 children failed locally: 5 of 5 lesions were CH, 5 of 5 patients had experienced pain at presentation (p = 0.03), and 4 of 5 had cervical extension (p = 0.07). The 5-year overall survival/progression-free survival rates for CS and CH were 100%/100% and 81%/77%, respectively. Side effects were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Acute toxicity ranged between 0 and 2. Late toxicity of radiotherapy was severe in 1 patient (Grade 3 auditory) and minor or mild in the rest of the population (7 patients with Grade 2 pituitary dysfunction). Conclusions: High-dose combined fractionated photon-proton therapy is well tolerated in children and allows excellent local control with minimal long-term toxicity.
Habrand, Jean-Louis [Centre de Protontherapie de l'Institut Curie a Orsay, Campus Universitaire, Orsay (France)], E-mail: email@example.com; Schneider, Ralf M.D.; Alapetite, Claire; Feuvret, Loic [Centre de Protontherapie de l'Institut Curie a Orsay, Campus Universitaire, Orsay (France); Petras, Slavo [University Hospital, Caen Cyceron Laboratory, Caen (France); Datchary, Jean [Centre de Protontherapie de l'Institut Curie a Orsay, Campus Universitaire, Orsay (France); Grill, Jacques [Department of Pediatric Oncology, Institut Gustave-Roussy, Villejuif (France); Noel, Georges; Helfre, Sylvie; Ferrand, Regis; Bolle, Stephanie [Centre de Protontherapie de l'Institut Curie a Orsay, Campus Universitaire, Orsay (France); Sainte-Rose, Christian [Department of Pediatric Neurosurgery, University Hospital Necker-Enfants Malades, Paris (France)
Low-Grade Gliomas in Older Patients: Long-Term Follow-Up From Mayo Clinic
Background Low-grade gliomas (LGGs) are uncommon in older patients, and long-term clinical behavior and prognostic factors are not well defined in this group. Methods We retrospectively searched our patient database for the records of adult patients (?18 years) diagnosed as having nonpilocytic LGG between 1960 and 1992 at Mayo Clinic. The Kaplan-Meier method was used to estimate progression-free survival and overall survival (OS) in patients aged 55 years and older. Results Of 314 patients initially identified, 32 were aged at least 55 years, with a median (range) age at diagnosis of 61 (55-74) years. Median follow-up was 17.3 years for survivors. Operative pathologic diagnoses comprised astrocytoma (n=22, 69%), mixed oligoastrocytoma (n=7, 22%), and oligodendroglioma (n=3, 9%). Gross total resection was achieved in 1 patient, radical subtotal resection in 1, and subtotal resection in 14; 16 patients had biopsy only. Postoperative radiotherapy or chemotherapy was given to 23 patients (72%) and 1 patient (3%), respectively. Median OS was 2.7 years for all patients—3 years with resection and 2.2 years with biopsy only (P=.58). The 5- and 10-year OS rates were 31% and 18%, respectively. Factors adversely affecting OS on univariate analysis were enhancement on computed tomography (P<.001) and supratentorial location (P=.03). Conclusions This retrospective series of older patients suggests that intracranial LGG in this age group behaves aggressively. Pathologic sampling error failing to recognize higher-grade tumors does not seem to account for these poor outcomes. Aggressive management with maximally safe resection followed by adjuvant therapy should be strongly considered. PMID:19536875
Schomas, David A.; Laack, Nadia N.; Buckner, Jan C.; Brown, Paul D.
Long-term outcome of follicular low-grade lymphoma. A report of 91 patients.
We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression. PMID:8318560
Morel, P; Dupriez, B; Plantier-Colcher, I; Gosselin, B; Declercq, C; Pollet, J P; Bauters, F
Can we identify patients with low grade lymphoma for frontline ABMT?
Autologous Bone Marrow Transplant (ABMT), at this point, is an experimental procedure reserved for patients without cure potential with available conventional chemotherapy. Unfortunately, the Ann Arbor staging system has not been able to identify these cases since there are patients with Stage IV who do well and others who do not. We have reported on a risk model based on gender and tumor burden (TB) assessment that can stratify patients with uniform Ann Arbor stage IV follicular low-grade lymphoma (FLGL) into three prognostic groups: (a) a group of females with low TB who have achieved a plateau of failure free survival (FFS) and survival of 50% and 92%, respectively, and who should not receive frontline ABMT; (b) a group of males with high TB having a median FFS and survival of only 12 and 48 months, respectively, and who could potentially benefit from ABMT; (c) a large group of patients with other TB-sex combinations, who are continuously relapsing at ten year follow-up, and whose survival is dismal. Even some of these, who have at best a 50% ten year survival, have not reached a plateau in their survival curves. This large group of patients, like all stage IV patients, will have a median age of 60 years at the time of initial diagnosis and treatment, and will be probably over 60 years old by the time they relapse, at which time salvage therapy will have increased morbidity and mortality, more so if it includes ABMT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8481675
Romaguera, J E
Clinicodemographic factors influencing outcomes in patients with low-grade serous ovarian carcinoma
Background Low-grade serous carcinoma (LGSC) of the ovary is a rare tumor that is distinct from its high-grade counterpart. Our aim was to estimate if patient demographic factors and clinical treatment histories affected survival in a population of women with this disease. Methods A review of patients with pathologically-confirmed LGSC of the ovary diagnosed between 1977- 2009 was performed. Abstracted data included medical and social histories, anthropometric measurements, and details about diagnosis, treatment, and follow-up. Statistical analyses included Fisher's exact test, Cox proportional hazards models, and the Kaplan-Meier method. Results The study sample included 194 patients with a median follow-up of 60.9 months (range 1-383). By multivariable analyses, smoking was negatively associated with both overall survival (OS) (HR 1.73; 95% CI [1.03-2.92], p=0.04) and progression-free survival (PFS) (HR 1.72; 95% CI [1.00-2.96], p=0.05). Median OS was shorter in current smokers than former/never smokers (48.0 vs. 79.9 months; p=.002). PFS was also predicted by year of diagnosis >1994 (HR1.74, p=0.01). Although not statistically significant, hormone consolidation appeared to be associated with better OS (HR 0.15, p=.06) and better PFS (HR 0.44; p=.07). A smaller proportion of patients treated with hormone consolidation experienced recurrence compared to those who did not receive hormone consolidation (66.7% vs. 87.6%, p=0.07). Conclusion Smoking is negatively associated with survival outcomes in women with LGSC of the ovary, while consolidation treatment with hormone antagonists demonstrated a protective associative trend with survival. Both lifestyle modification and innovative treatment plans should be considered in this group of patients. PMID:21319148
Schlumbrecht, Matthew P.; Sun, Charlotte C.; Wong, Karen N.; Broaddus, Russell R.; Gershenson, David M.; Bodurka, Diane C.
Solidification/stabilisation of electric arc furnace waste using low grade MgO.
This study aims to evaluate the potential of low grade MgO (LGMgO) for the stabilisation/solidification (S/S) of heavy metals in steel electric arc furnace wastes. Relevant characteristics such as setting time, unconfined compressive strength (UCS) and leaching behaviour assessed by acid neutralisation capacity (ANC), monolithic and granular leaching tests were examined in light of the UK landfill Waste Acceptance Criteria (WAC) for disposal. The results demonstrated that all studied mix designs with Portland cement type 1 (CEM1) and LGMgO, CEM1-LGMgO 1:2 and 1:4 at 40% and 70% waste addition met the WAC requirements by means of UCS, initial and final setting times and consistence. Most of the ANC results met the WAC limits where the threshold pH values without acid additions were stable and between 11.9 and 12.2 at 28d. Granular leaching results indicate fixation of most of the metals at all mix ratios. An optimum ratio was obtained at CEM1-LGMgO 1:4 at 40% waste additions where none of the metals leaching exceeded the WAC limits and hence may be considered for landfill disposal. The monolithic leaching test results showed that LGMgO performed satisfactorily with respect to S/S of Zn, as the metal component present at the highest concentration level in the waste exhibited very little leaching and passed the leaching test requirement at all mix ratios studied. However, its performance with respect to Pb, Cd and Cr was less effective in reducing their leaching suggesting a higher cumulative rate under those leaching regimes. PMID:22172635
Cubukcuoglu, B; Ouki, S K
Surgical strategies in low-grade gliomas and implications for long-term quality of life.
Reports on long-term health related quality of life (HRQL) after surgery for World Health Organization grade II diffuse low-grade gliomas (LGG) are rare. We aimed to compare long-term HRQL in two hospital cohorts with different surgical strategies. Biopsy and watchful waiting was favored in one hospital, while early resections guided with three-dimensional (3D) ultrasound was favored in the other. With a population-based approach 153 patients with histologically verified LGG treated from 1998-2009 were included. Patients still alive were contacted for HRQL assessment (n=91) using generic (EQ-5D; EuroQol Group, Rotterdam, The Netherlands) and disease specific (EORTC QLQ-C30 and BN20; EORTC Quality of Life Department, Brussels, Belgium) questionnaires. Results on HRQL were available in 79 patients (87%), 25 from the hospital that favored biopsy and 54 from the hospital that favored early resection. Among living patients there was no difference in EQ-5D index scores (p=0.426). When imputing scores defined as death (zero) in patients dead at follow-up, a clinically relevant difference in EQ-5D score was observed in favor of early resections (p=0.022, mean difference 0.16, 95% confidence interval 0.02-0.29). In EORTC questionnaires pain, depression and concern about disruption in family life were more common with a strategy of initial biopsy only (p=0.043, p=0.032 and p=0.045 respectively). In long-term survivors an aggressive surgical approach using intraoperative 3D ultrasound image guidance in LGG does not lower HRQL compared to a more conservative surgical approach. This finding further weakens a possible role for watchful waiting in LGG. PMID:24798909
Jakola, Asgeir S; Unsgĺrd, Geirmund; Myrmel, Kristin S; Kloster, Roar; Torp, Sverre H; Sagberg, Lisa M; Lindal, Sigurd; Solheim, Ole
Gene expression trees in lymphoid development
Background The regulatory processes that govern cell proliferation and differentiation are central to developmental biology. Particularly well studied in this respect is the lymphoid system due to its importance for basic biology and for clinical applications. Gene expression measured in lymphoid cells in several distinguishable developmental stages helps in the elucidation of underlying molecular processes, which change gradually over time and lock cells in either the B cell, T cell or Natural Killer cell lineages. Large-scale analysis of these gene expression trees requires computational support for tasks ranging from visualization, querying, and finding clusters of similar genes, to answering detailed questions about the functional roles of individual genes. Results We present the first statistical framework designed to analyze gene expression data as it is collected in the course of lymphoid development through clusters of co-expressed genes and additional heterogeneous data. We introduce dependence trees for continuous variates, which model the inherent dependencies during the differentiation process naturally as gene expression trees. Several trees are combined in a mixture model to allow inference of potentially overlapping clusters of co-expressed genes. Additionally, we predict microRNA targets. Conclusion Computational results for several data sets from the lymphoid system demonstrate the relevance of our framework. We recover well-known biological facts and identify promising novel regulatory elements of genes and their functional assignments. The implementation of our method (licensed under the GPL) is available at . PMID:17925013
Costa, Ivan G; Roepcke, Stefan; Schliep, Alexander
Obesity is associated with metabolic alterations related to glucose homeostasis and cardiovascular risk factors. These metabolic alterations are associated with low-grade inflammation that contributes to the onset of these diseases. We and others have provided evidence that gut microbiota participates in whole-body metabolism by affecting energy balance, glucose metabolism, and low-grade inflammation associated with obesity and related metabolic disorders. Recently, we defined gut microbiota-derived lipopolysaccharide (LPS) (and metabolic endotoxemia) as a factor involved in the onset and progression of inflammation and metabolic diseases. In this review, we discuss mechanisms involved in the development of metabolic endotoxemia such as the gut permeability. We also discuss our latest discoveries demonstrating a link between the gut microbiota, endocannabinoid system tone, leptin resistance, gut peptides (glucagon-like peptide-1 and -2), and metabolic features. Finally, we will introduce the role of the gut microbiota in specific dietary treatments (prebiotics and probiotics) and surgical interventions (gastric bypass). PMID:22572877
Cani, Patrice D.; Osto, Melania; Geurts, Lucie; Everard, Amandine
Background Tumor recurrence following radical cystectomy for a low-grade superficial transitional cell carcinoma (TCC) is exceedingly uncommon and has not been reported previously. Case presentation We describe a case of a young male presenting with anorexia, weight loss and a large, painful locally destructive pelvic recurrence, ten years after radical cystoprostatectomy. The pathology was consistent with a low-grade urothelial carcinoma. After an unsuccessful treatment with cisplatin-based chemotherapy, the patient underwent a curative intent hemipelvectomy with complete excision of tumor and is disease free at one year follow-up. Conclusion A literature review related to this unusual presentation is reported and a surgical solutions over chemotherapy and radiotherapy is proposed. PMID:18826578
Dangle, Pankaj P; Wang, Wenle Paul; Mayerson, Joel; Mortazavi, Amir; Monk, Paul
This study explores the possibility of producing low grade crude palm oil (LGCPO)-based biodiesel using a two-stage process in which a phosphonium-based deep eutectic solvent (P-DES) and an alkali are used as catalysts. The pre-treatment of LGCPO was conducted using a P-DES composed of a hydrogen bond donor (i.e. p-toluenesulfonic acid monohydrate) and a salt (i.e. allyltriphenylphosphonium bromide) as a
Adeeb Hayyan; Mohd Ali Hashim; Farouq S. Mjalli; Maan Hayyan; Inas M. AlNashef
The objective was to carry out a pilot study exploring memory outcome in patients with temporal lobe epilepsy (TLE) and low-grade\\u000a tumour. A prospective study using a competence-related memory assessment was carried out in the Laboratory of Neuropsychology,\\u000a Epilepsy Center and Neurosurgical Department of the "C. Besta" National Neurological Institute in 24 TLE patients undergoing\\u000a surgical resection for left (n=12)
A. R. Giovagnoli; M. Casazza; E. Ciceri; G. Avanzini; G. Broggi
Human low-grade gliomas represent a population of brain tumors that remain a therapeutic challenge. Preclinical evaluation of agents, to test their preventive or therapeutic efficacy in these tumors, requires the use of animal nobreak models. Spontaneous gliomas develop in models of chemically induced carcinogenesis, such as in the transplacental N-ethyl-N-nitrosourea (ENU) rat model. However, without the ability to detect initial
Phillip E. Kish; Mila Blaivas; Myla Strawderman; Karin M. Muraszko; Donald A. Ross; Brian D. Ross; Gerald McMahon
The use of proton therapy in the treatment of benign or low-grade pediatric brain tumors.
Radiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade central nervous system tumors in children but is not without the risk of long-term treatment-related sequelae. Proton therapy (PRT) is an advanced RT modality with a unique dose-deposition pattern that allows for treatment of a target volume with reduced scatter dose delivered to normal tissues compared with conventional photon RT and is now increasingly utilized in children with the hope of mitigating radiation-induced late effects. This article reviews the current literature evaluating the use of PRT in benign and low-grade pediatric central nervous system tumors such as low-grade glioma, craniopharyngioma, and ependymoma. Multiple dosimetric studies support the use of PRT by demonstrating the ability of PRT to better spare critical structures important for cognitive development, endocrine function, and hearing preservation and to reduce the total body dose associated with second malignancy risk. Early clinical data demonstrate that PRT is well tolerated with rates of local tumor control comparable to conventional photon RT series, and long-term clinical data are awaited. PMID:25415686
Eaton, Bree R; Yock, Torunn
Low-grade proteinuria and systolic hypertension (SHT) are risk factors for allograft failure. Both are dynamic variables and their relationship is not independent. We have simultaneously analyzed the effects of proteinuria and SHT on graft outcomes in 805 adult Kidney Transplant Recipients and impact of their changes over time. Proteinuria and systolic blood pressure (SBP) were recorded for years 1 and 3 posttransplantation. Subjects with proteinuria >1?g/day were excluded. Patients were divided into groups based on proteinuria (Absent(A) <150?mg/day or low-grade(P)150?mg-1?g/day) and blood pressure (Normotensive-SBP <140?mmHg or hypertensive-SBP???140?mmHg). Graft survival was assessed in all four groups over 10 years by multivariate analysis. At the three annual time points (Year 1, 2 and 3) hypertensive patients with proteinuria had the worst graft survival. Patients with persistent proteinuria between years 1-2 and 2-3 had the poorest graft survival with an improvement if proteinuria regressed (P-A), especially in the Hypertensive group. The impact of proteinuria was highest in persistently hypertensive patients between years 1-3. Thus both proteinuria and SHT were associated with poor graft survival and the combination of the two led to the worst outcomes. Importantly, SHT was associated with significantly worse outcomes in patients with proteinuria. Patient cohort with SHT and low-grade proteinuria represent a selective group that might benefit from intervention. PMID:25648199
Cherukuri, A; Tattersall, J E; Lewington, A J P; Newstead, C G; Baker, R J
Many studies have been carried out with respect to packaging methods and temperature conditions of beef. However, the effects of packaging methods and temperature conditions on the quality characteristics have not been extensively studied in low-grade beef. Low-grade beef samples were divided into 3 groups (C: ziplock bag packaging, T1: vacuum packaging, and T2: modified atmosphere packaging (MAP), CO2/N2 = 3:7) and samples were stored at 4°C for 21 days. The water-holding capacity (WHC) was significantly lower in T1 than in the other samples up to 14 days of storage. The thiobarbituric acid reactive substances and volatile basic nitrogen values were significantly lower in T1 and T2 than in C after 7 to 14 days of storage. The total bacterial counts were significantly lower in T1 and T2 than in C after 14 days of storage. In a sensory evaluation, tenderness and overall acceptability were significantly higher in T1 and T2 than in C at the end of the storage period (21 days). We propose that the MAP method can improve beef quality characteristics of low-grade beef during cold storage. However, the beneficial effects did not outweigh the cost increase to implement MAP. PMID:25049769
Hur, S. J.; Jin, S. K.; Park, J. H.; Jung, S. W.; Lyu, H. J.
TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer.
Based on next-generation sequencing of early-onset prostate cancer (PCa), we earlier demonstrated that PCa in young patients is prone to rearrangements involving androgen-regulated genes-such as transmembrane protease, serine 2 (TMPRSS2)-v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-and provided data suggesting that this situation might be caused by increased androgen signaling in younger men. In the same study, an accumulation of chromosomal deletions was found in cancers of elderly patients. To determine how age-dependent molecular features relate to cancer phenotype, an existing data set of 11,152 PCas was expanded by additional fluorescence in situ hybridization analyses of phosphatase and tensin homolog (PTEN), 6q15 and 5q21. The results demonstrate that the decrease in TMPRSS2-ERG fusions with increasing patient age is limited to low-grade cancers (Gleason ?3+4) and that the significant increase in the deletion frequency with age was strictly limited to ERG-negative cancers for 6q15 and 5q21 but to ERG-positive cancers for PTEN. These data suggest that the accumulation of non-androgen-linked genomic alterations with advanced patient age may require an appropriate microenvironment, such as a positive or negative ERG status. The strong link of ERG activation to young patient age and low-grade cancers may help to explain a slight predominance of low-grade cancers in young patients. PMID:25015038
Steurer, Stefan; Mayer, Pascale Sophia; Adam, Meike; Krohn, Antje; Koop, Christina; Ospina-Klinck, Daniel; Tehrani, Ali Attarchi; Simon, Ronald; Tennstedt, Pierre; Graefen, Markus; Wittmer, Corinna; Brors, Benedikt; Plass, Christoph; Korbel, Jan; Weischenfeldt, Joachim; Sauter, Guido; Huland, Hartwig; Tsourlakis, Maria Christina; Minner, Sarah; Schlomm, Thorsten
The aim of this study was to investigate the effects of melatonin on low-grade inflammation and oxidative stress in young male Zucker diabetic fatty (ZDF) rats, an experimental model of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups, each composed of 10 rats: naive (N), vehicle treated (V), and melatonin treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Pro-inflammatory state was evaluated by plasma levels of interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?), and C-reactive protein (CRP). Also, oxidative stress was assessed by plasma lipid peroxidation (LPO), both basal and after Fe(2+)/H2O2 inducement. ZDF rats exhibited higher levels of IL-6 (112.4 ± 1.5 pg/mL), TNF-? (11.0 ± 0.1 pg/mL) and CRP (828 ± 16.0 µg/mL) compared with lean rats (IL-6, 89.9 ± 1.0, P < 0.01; TNF-?, 9.7 ± 0.4, P < 0.01; CRP, 508 ± 21.5, P < 0.001). Melatonin lowered IL-6 (10%, P < 0.05), TNF-? (10%, P < 0.05), and CRP (21%, P < 0.01). Basal and Fe(2+)/H2O2-induced LPO, expressed as malondialdehyde equivalents (µmol/L), were higher in ZDF rats (basal, 3.2 ± 0.1 versus 2.5 ± 0.1 in ZL, P < 0.01; Fe(2+)/H2O2-induced, 8.7 ± 0.2 versus 5.5 ± 0.3 in ZL; P < 0.001). Melatonin improved basal LPO (15%, P < 0.05) in ZDF rats, and Fe(2+)/H2O2- induced LPO in both ZL (15.2%, P < 0.01) and ZDF rats (39%, P < 0.001). These results demonstrated that oral melatonin administration ameliorates the pro-inflammatory state and oxidative stress, which underlie the development of insulin resistance and their consequences, metabolic syndrome, diabetes, and cardiovascular disease. PMID:23020082
Agil, Ahmad; Reiter, Russel J; Jiménez-Aranda, Aroa; Ibán-Arias, Ruth; Navarro-Alarcón, Miguel; Marchal, Juan Antonio; Adem, Abdu; Fernández-Vázquez, Gumersindo
Dehydration Behavior of Metapelites and Metabasites at Very low to low Grade Metamorphic Conditions
NASA Astrophysics Data System (ADS)
Thermodynamic calculations have been undertaken in the system Na-Ca-K-Fe-Mg-Al-Si-Ti-H-O with the PERPLE_X software package (Connolly, 1990 and updates) for a better understanding of the dehydration behavior of metapelites and metabasites during prograde metamorphism. To obtain reasonable results for the temperature range 150-450° C at pressures up to 25 kbar, the subsequent solid solution models were introduced being compatible with the applied thermodynamic data set of Holland & Powell (1998 and updates): a three component model for Mg-Fe2+-Fe3+-pumpellyite, a two component model for Fe2+-Mg- stilpnomelane, a four component amphibole model (tremolite - Fe2+-tremolite - glaucophane - Mg- riebeckite), and a four component Na-pyroxene model (acmite - jadeite - diopside - hedenbergite). The water contents released by prograde metamorphism up to 450° C from MORB and psammopelitic compositions on top of oceanic crust, were obtained by calculating P-T pseudosections. Metabasite contains 6-7 wt% H2O bound to minerals at 150° C depending on the oxidation state. Along geotherms lower than 7° C/km typical for young subduction zones, no water is released up to 400° C. However, reduction of the rock causes release of small amounts of water. Metapsammopelitic rocks also store about 6 wt% H2O in minerals at 150° C. Considerable amounts of water are liberated by mineral reactions already in the temperature range 150-250° C also at the above mentioned low geotherms. This behavior determines the rheological characteristics of the upper oceanic crust during early subduction. If water is exclusively released in the sedimentary portion of the downgoing crust only this material gets weakened to be scraped off to form accretionary wedges. At geotherms of 15-20° C/km both lithologies show significant dehydration at very low metamorphic grade. For instance, in cold frontal paleoaccretionary prisms of the Chilean Coastal Cordillera metapelites by far dominate whereas in hotter basal accretionary prisms both low grade basic oceanic crust and continental sediments occur. We also hypothesize that accretionary wedge complexes with a clear dominance of sediments should not have formed in hot subduction zones typical for Precambrian Earth.
Massonne, H.; Willner, A. P.
NASA Astrophysics Data System (ADS)
Titanite, TiO 2, and pseudorutile are associated with primary igneous Fe-oxide grains in basalt and rhyolite clasts from the Keweenaw Peninsula, Michigan, USA which were metamorphosed to the prehnite-pumpellyite facies. Pseudorutile occurs with titanite + TiO 2 in broad lamellae within titaniferous magnetites. It also occurs as intergrowths with titanite and Fe-oxide in embayments within primary oxide grains and in composite Fe-oxide-titanite grains that appear to represent nearly complete replacement of original Ti-bearing Fe-oxides. Thin {111} lamellae in titaniferous magnetite grains contain titanite, titanite + TiO 2 and titanite + TiO 2 + Fe-oxide. TiO 2 also occurs by itself in networks of closely spaced small elongated lenses in Fe-Ti oxides. Concentrations of CaAlSiO 4F + CaAlSiO 4(OH) in titanite range from 0 to 30%. The large variation in titanite compositions suggests that equilibrium was not achieved except on a very local scale: a conclusion also supported by local variations in the assemblages of Ti-bearing secondary minerals. Textures and mineral assemblages indicate that ulvospinel lamellae were altered to titanite and/or TiO 2 polymorphs while ilmenite was altered to pseudorutile and titanite ± TiO 2. The relative proportions of TiO 2 and titanite appear to reflect local variations in the composition of the metamorphic fluid phase that may be linked to the degree of interaction with a hydrothermal fluid. Titanite-rich regions may indicate a greater degree of fluid flushing than TiO 2-rich regions. Textures and mineral assemblages cannot distinguish between models in which pseudorutile and a TiO 2 polymorph formed during weathering or diagenesis followed by conversion of TiO 2 to titanite during metamorphism and models in which pseudorutile formed, together with titanite and TiO 2, during metamorphism. In either case, pseudorutile was able to persist through prehnite-pumpellyite metamorphism suggesting that it can be a significant Ti-rich accessory mineral in very low-grade metamorphic rocks.
Hansen, Edward; Reimink, Jesse; Harlov, Daniel
Multivariate analysis of prognostic factors in stage IV follicular low-grade lymphoma: a risk model.
We analyzed the records of 96 previously untreated patients with stage IV follicular low-grade lymphoma (FLGL) uniformly treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) chemotherapy from 1972 to 1982. The overall complete remission (CR) rate was 77%. At a median follow-up of 138 months, the 10-year cause-specific survival rate was 42% with a median survival of 100 months. Failure-free survival (FFS) was 15% at 10 years with a median FFS of 30 months. Multivariate analysis showed peripheral lymph node size (LN), degree of marrow involvement, and sex, in that order, to be important for FFS, while the number of extranodal sites (#ENS), LN, sex, and degree of marrow involvement were important for cause-specific survival. We devised a tumor burden (TB) model, incorporating #ENS, LN, and degree of marrow involvement. Three groups were identified with statistically significant differences in cause-specific survival and FFS. Those with low TB (one ENS exclusive of extensive marrow and nodal disease less than 5 cm) had a 10-year cause-specific survival of 73% compared with 24% for patients with high TB (greater than or equal to two ENS and nodal disease greater than or equal to 5 cm) (P less than .001) and 40% for those with intermediate TB (either greater than or equal to 2 ENS, or extensive marrow only, or nodal disease greater than 5 cm) (P = .050). Patients with low TB had a 10-year FFS rate of 32%, while the intermediate and high TB groups had 10% and 9% FFS, respectively (P = .003). Because sex was a very strong prognostic variable, we created a risk model for survival and FFS based on TB and sex. Females with low TB had the best prognosis (92% survival and 50% FFS at 10 years) and males with high TB had the worst outlook (median survival and FFS, 43 and 12 months, respectively). Other TB-sex combinations defined two groups with statistically significant differences in survival but comparable FFS. This model should aid in the design and analysis of future trials. PMID:1707956
Romaguera, J E; McLaughlin, P; North, L; Dixon, D; Silvermintz, K B; Garnsey, L A; Velasquez, W S; Hagemeister, F B; Cabanillas, F
Advanced Energy and Water Recovery Technology from Low Grade Waste Heat
The project has developed a nanoporous membrane based water vapor separation technology that can be used for recovering energy and water from low-temperature industrial waste gas streams with high moisture contents. This kind of exhaust stream is widely present in many industrial processes including the forest products and paper industry, food industry, chemical industry, cement industry, metal industry, and petroleum industry. The technology can recover not only the sensible heat but also high-purity water along with its considerable latent heat. Waste heats from such streams are considered very difficult to recover by conventional technology because of poor heat transfer performance of heat-exchanger type equipment at low temperature and moisture-related corrosion issues. During the one-year Concept Definition stage of the project, the goal was to prove the concept and technology in the laboratory and identify any issues that need to be addressed in future development of this technology. In this project, computational modeling and simulation have been conducted to investigate the performance of a nanoporous material based technology, transport membrane condenser (TMC), for waste heat and water recovery from low grade industrial flue gases. A series of theoretical and computational analyses have provided insight and support in advanced TMC design and experiments. Experimental study revealed condensation and convection through the porous membrane bundle was greatly improved over an impermeable tube bundle, because of the membrane capillary condensation mechanism and the continuous evacuation of the condensate film or droplets through the membrane pores. Convection Nusselt number in flue gas side for the porous membrane tube bundle is 50% to 80% higher than those for the impermeable stainless steel tube bundle. The condensation rates for the porous membrane tube bundle also increase 60% to 80%. Parametric study for the porous membrane tube bundle heat transfer performance was also done, which shows this heat transfer enhancement approach works well in a wide parameters range for typical flue gas conditions. Better understanding of condensing heat transfer mechanism for porous membrane heat transfer surfaces, shows higher condensation and heat transfer rates than non-permeable tubes, due to existence of the porous membrane walls. Laboratory testing has documented increased TMC performance with increased exhaust gas moisture content levels, which has exponentially increased potential markets for the product. The TMC technology can uniquely enhance waste heat recovery in tandem with water vapor recovery for many other industrial processes such as drying, wet and dry scrubber exhaust gases, dewatering, and water chilling. A new metallic substrate membrane tube development and molded TMC part fabrication method, provides an economical way to expand this technology for scaled up applications with less than 3 year payback expectation. A detailed market study shows a broad application area for this advanced waste heat and water recovery technology. A commercialization partner has been lined up to expand this technology to this big market. This research work led to new findings on the TMC working mechanism to improve its performance, better scale up design approaches, and economical part fabrication methods. Field evaluation work needs to be done to verify the TMC real world performance, and get acceptance from the industry, and pave the way for our commercial partner to put it into a much larger waste heat and waste water recovery market. This project is addressing the priority areas specified for DOE Industrial Technologies Program's (ITP's): Energy Intensive Processes (EIP) Portfolio - Waste Heat Minimization and Recovery platform.
Dexin Wang
NASA Astrophysics Data System (ADS)
The composition of fluid inclusions (FI) hosted in quartz veins from low-grade metamorphic rocks of the Bündnerschiefer (two locations near Thusis and Schiers that represent subgreenschist and lower greenschist facies conditions, respectively), Swiss Alps, was determined by combination of microthermometry and LA-ICPMS microanalysis. Elongate-blocky quartz and euhedral quartz crystals were sampled form two sets of veins, which are foliation-parallel and open fissure veins that crosscut the main foliation. The host rocks are organic-rich metapelites, that in places contain relatively high amounts of carbonate. Several metamorphic temperature indicators were used to determine the temperature and pressure during metamorphism of the host rocks. These included the Kübler index (Kübler & Jaboyedoff 2000), Raman spectroscopy on carbonaceous material (Beyssac et al., 2002), Na-Mg and Li-Mg fluid solute geothermometry (Giggenbach, 1988; Kharaka & Mariner, 1989) and mineral assemblages. The geothermometers point to equilibrium temperatures around 320±20 °C (Thusis) and 250±20 °C (Schiers). The results of pseudosection modeling show very close agreement with the pressure-temperature conditions that were derived from conventional geothermobarometry. The FI bulk salinity and homogenization temperatures are 4±0.2 wt% eqv. NaCl and 122-140 °C for Thusis, and 2±0.2 wt% and 82-86 °C at Schiers. Most of the important rock-forming elements have been successfully determined in individual FI, with consistent concentrations obtained for well-constrained fluid inclusion assemblages. The FI contain measurable concentrations of Na, K, Rb, Cs, Li, Ca, Mg, Al, Mn, Sr, Ba, B, As, B, Zn, Pb, Cu and S. Typical concentrations are 30-40 ppm Al, 5-7 ppm Mg, 300-400 ppm Ca, 3-5 ppm Mn, and 300-350 ppm S for FI from Thusis. Concentrations for most elements are roughly half an order of magnitude lower for FI from Schiers. The total element concentrations are lower compared with data from similar metamorphic vein settings (Yardley et al., 1993; Yardley, 2005). This likely reflects the lower salinity of fluids in the Bündnerschiefer veins, which exerts a major control on those elements that are complexed by chloride. Combining fluid inclusion isochores with independent geothermometers results in pressure estimates of 2.8-3.8 kbars for Thusis, and around 3.4 kbars for Schiers. The geothermal gradient decreases from the southern location (27-22 °C/km: Thusis) to the northern location (19 °C/km: Schiers), in agreement with their position during metamorphism. The fluid composition data, in conjunction with metamorphic indicators and petrological modeling, demonstrate that fluid-rock equilibrium was attained during metamorphism and vein formation. Fluid composition and pressure-temperature conditions remained essentially unchanged during the evolution of the vein systems. The veins evolved as rock-buffered closed systems, due to the low permeability of the organic-rich metapelites.
Miron, G. D.; Wagner, T.; Wälle, M.; Heinrich, C. A.
Characteristic of innate lymphoid cells (ILC).
Innate lymphoid cells (ILC) is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer) and lymphoid tissue inducer T cells (LTi), which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-?, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell - TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22) - which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22) cells or NK receptor-positive (LTi NKR+) LTi cells. Fourth population of ILC cells are ILC17 - producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2), nuocyte, innate type 2 helper cells (IH2) and multi-potent progenitor type 2 cells (MPPtype2). Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T. PMID:25531710
Adamiak, Mateusz; Tokarz-Deptu?a, Beata; Deptu?a, Wies?aw
The lymphoid follicle variant of dermatomyositis
Objective: To investigate the clinical and morphologic spectrum of early adult–onset dermatomyositis (DM), an inflammatory disease that affects small vessels of the muscle and the skin. Methods: Histologic evaluation of frozen muscle samples was employed to visualize the cellular organization of ectopic lymphoid structures in muscle biopsies obtained from 2 patients diagnosed with DM. Clinical presentation and morphologic features, as well as treatment and follow-up, were assessed and documented. Electron microscopy was used to confirm the light microscopic diagnosis of DM. Clonality analysis of B-cell populations using PCR was performed. Results: Muscle biopsy of both patients fulfilled the morphologic European Neuromuscular Centre criteria of DM. Analyses of muscle biopsy samples revealed ectopic lymphoid follicle-like structures that showed a remarkable similarity to secondary lymphoid organs (SLOs) with distinct T- and B-cell compartmentalization. Our 2 patients exhibited an atypical and mild clinical presentation and responded favorably to therapy. Conclusions: The clinical and histopathologic features of DM can be atypical, and the presence of SLOs is not inevitably linked to an unfavorable prognosis. PMID:25340071
Pehl, Debora; Aronica, Eleonora; Schonenberg-Meinema, Dieneke; Schneider, Udo; Heppner, Frank L.; de Visser, Marianne; Goebel, Hans H.; Stenzel, Werner
BACKGROUND: Arthroscopy is a highly sensitive method of evaluating high-grade cartilage lesions but the detection of low-grade lesions is often is unreliable. Objective measurements are required. A novel NIRS (near-infrared-spectroscopy) device for detection of low-grade cartilage defects was evaluated in a preliminary clinical study. METHODS: In 12 patients who had undergone arthroscopy, the cartilage lesions within the medial knee compartment
Gunter Spahn; Holger Plettenberg; Enrico Kahl; Hans M Klinger; Thomas Mückley; Gunther O Hofmann
A lower-dose, lower-toxicity cisplatin–etoposide regimen for childhood progressive low-grade glioma
After successfully using cisplatin (30 mg\\/m2\\/day) and etoposide (150 mg\\/m2\\/day) in ten three-day courses for progressive low-grade gliomas, a subsequent protocol reduced the daily doses of cisplatin\\u000a (to 25 mg) and etoposide (to 100 mg), with the objective of achieving the same response and three-year PFS rates with lower\\u000a neurotoxicity and myelotoxicity. We treated 37 patients (median age 6 years); 23 had optochiasmatic tumours
Maura MassiminoFilippo; Filippo Spreafico; Daria Riva; Veronica Biassoni; Geraldina Poggi; Carlo Solero; Lorenza Gandola; Lorenzo Genitori; Piergiorgio Modena; Fabio Simonetti; Paolo Potepan; Michela Casanova; Cristina Meazza; Carlo A. Clerici; Serena Catania; Iacopo Sardi; Felice Giangaspero
Rituximab is a novel anti-CD20 monoclonal antibody used in the treatment of relapsed low-grade non-Hodgkin lymphoma. To determine the impact of this therapy on the interpretation of posttherapy specimens, we reviewed the pretherapy and posttherapy bone marrow and peripheral blood morphologic and flow cytometric findings for 20 patients who received rituximab. Nine patients had a total of 13 posttherapy bone marrow specimens; all were positive for lymphoma before therapy. After therapy, 11 of 13 posttherapy bone marrow specimens were interpreted as positive or suggestive of lymphoma based on routine H&E-stained sections. However, immunohistochemical and/or flow cytometric immunophenotyping showed that 6 of the 11 cases were negative for lymphoma; the lymphoid infiltrates were composed entirely of T cells without B cells. We report that posttherapy bone marrow specimens from patients treated with rituximab may mimic residual lymphoma if examined by morphologic features alone. Familiarity with this finding and the use of ancillary immunophenotypic studies will aid in the accurate interpretation of posttherapy specimens. PMID:10587708
Douglas, V K; Gordon, L I; Goolsby, C L; White, C A; Peterson, L C
Purpose: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. Methods and Materials: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. Results: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. Conclusions: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.
Laack, Nadia N. [Division of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Brown, Paul D. [Division of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)]. E-mail: email@example.com; Ivnik, Robert J. [Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN (United States); Furth, Alfred F. M.S. [Cancer Center Statistics, Mayo Clinic, Rochester, MN (United States); Ballman, Karla V. [Division of Biostatistics, Mayo Clinic, Rochester, MN (United States); Hammack, Julie E. [Department of Neurology, Mayo Clinic, Rochester, MN (United States); Arusell, Robert M. [Roger Maris Cancer Center, Fargo, ND (United States); Shaw, Edward G. [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Buckner, Jan C. [Division of Medical Oncology, Mayo Clinic, Rochester, MN (United States)
AIM: To investigate the relationship between low-grade inflammation and several glycemic indices in a population-based sample of men and women. METHODS: The ATTICA study is a population-based cohort that randomly enrolled 1514 men and 1528 women (aged >18 years old), stratified by age and gender, from the Greater Athens area, during 2001-2002. Among several characteristics, inflammation markers (high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, homocysteine and amyloid A) and glycemic control indices (fasting blood glucose, insulin, HOMA) were measured in the participants. RESULTS: The prevalence of diabetes was 7.8% in men and 6.0% in women. The prevalence of impaired fasting glucose (IFG) was 21% in men and 12% in women. Diabetic subjects had 57% higher mean levels of C-reactive protein (p < 0.001), 22% higher mean levels of interleukin-6 (p < 0.001) and 60% higher levels of tumor necrosis factor-alpha (p < 0.001) compared to non-diabetic subjects. Homocysteine and serum amyloid A levels did not show significant differences among groups. CONCLUSION: Our study supports a positive association between low-grade inflammation and diabetes in a population-based sample of men and women without any evidence of cardiovascular disease, which is independent of demographic, clinical and lifestyle characteristics, including physical activity and dietary factors. PMID:17823694
Pitsavos, Christos; Tampourlou, Metaxia; Panagiotakos, Demosthenes B.; Skoumas, Yannis; Chrysohoou, Christina; Nomikos, Tzortzis; Stefanadis, Christodoulos
Gastric mucosal-associated lymphoid tissue lymphoma.
Gastric marginal zone B-cell lymphoma of mucosal-associated lymphoid tissue (MALT) is the predominant entity within the primary gastrointestinal lymphomas. Helicobacter pylori represents the decisive pathogenetic factor for gastric MALT lymphoma. The goal of treating gastric MALT lymphoma should be complete cure. The first choice of treatment is H pylori eradication. Patients with histologically persistent residual lymphoma after successful H pylori eradication and normalization of endoscopic findings should be managed by a watch-and-wait strategy. Patients who do not respond to H pylori eradication should be referred for radiation or chemotherapy. PMID:23639646
Fischbach, Wolfgang
An overview of ocular adnexal lymphoid tumors.
In comparison with our earlier colleagues quoted in the introduction, we have made substantial progress in understanding the biology of ocular adnexal lymphoid tumors. While we have refined various categories with prognostic clinical value regarding possible associated systemic disease, none is foolproof and all have varying degrees of unpredictability. Comparatively well-differentiated histologic subtypes predominate among ocular adnexal lymphoid tumors. Polyclonal lesions occur less than half as often as monoclonal B-cell lesions. Molecular genetic studies have revealed small clones of monoclonal populations among the B-cells comprising most of the immunophenotypically polyclonal lesions, but no clonal genetic rearrangements have been uncovered within the preponderant constituent T-cell populations. The overall prognosis for ocular adnexal lymphoid tumors is excellent; when lumped together, 67% are not found to be associated with systemic disease with mean follow-ups of over 4 years. This is similar to experience with extranodal and extralymphatic lesions in other sites of the body, which also frequently have a small lymphocyte composition. The incidence of nonocular disease in all categories of our studies, however, will probably increase with the acquisition of longer follow-ups. Careful histopathologic evaluation is as good as immunophenotypic analysis of these lesions in predicting clinical outcome in terms of associated nonocular disease. Polyclonal and well-differentiated B-cell monoclonal lesions displayed equivalent clinical behavior. Benign polyclonal lesions may be associated with systemic disease but in a minority of cases (27%), as has also been determined in earlier studies. Clinical staging is the single most important predictor of associated monocular disease. In this study, patients with stage I-E disease had an 87% chance of not developing any nonocular lymphomatous lesion. We believe that this figure may also somewhat decrease with the passage of time. Precise anatomic localization of the lesion within the adnexa had considerable predictive value. Lesions of the conjunctiva fared the best; those of the orbit had an intermediate prognosis; while lid lesions had the worst prognosis. The most favorable prognosis would be held by a conjunctival lymphoid lesion in stage I-E composed of small lymphocytes. The fact that there is a fairly close equivalence in outcome between polyclonal and monoclonal well-differentiated lesions indicates that these lesions are in the vast majority of cases primary hyperplasias or primary lymphomas. The discovery by genetic probes of small monoclonal populations in immunophenotypically polyclonal lesions suggests that there is an evolution that goes on in situ.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 PMID:2562543
Jakobiec, F A; Knowles, D M
Origin of chromosomal translocations in lymphoid cancer
Summary Aberrant fusions between heterologous chromosomes are among the most prevalent cytogenetic abnormalities found in cancer cells. Oncogenic chromosomal translocations provide cells with a proliferative or survival advantage. They may either initiate transformation or be acquired secondarily as a result of genomic instability. Here we highlight recent advances toward understanding the origin of chromosomal translocations in incipient lymphoid cancers and how tumor-suppressive pathways normally limit the frequency of these aberrant recombination events. Deciphering the mechanisms that mediate chromosomal fusions will open new avenues for developing therapeutic strategies aimed at eliminating lesions that lead to the initiation, maintenance, and progression of cancer. PMID:20371343
Nussenzweig, André; Nussenzweig, Michel C.
Innate Lymphoid Cells in the Skin.
Innate lymphoid cells (ILCs) are part of a heterogeneous family of innate immune cells with newly identified roles in mediating immunity, tissue homeostasis, and pathologic inflammation. Here, we review recent studies delineating the roles of ILCs in the pathogenesis of multiple inflammatory skin disorders and their unique effector functions. Finally, we address how these studies have informed our understanding of the regulation of ILCs and the therapeutic potential of targeting these cells in the context of skin inflammation.Journal of Investigative Dermatology advance online publication, 23 October 2014; doi:10.1038/jid.2014.401. PMID:25339380
Kim, Brian S
Helical tomotherapy for total lymphoid irradiation.
Total lymphoid irradiation is employed in the preparative regimens for allogeneic bone marrow and solid organ transplantation, solid organ transplant rejection, and chronic graft-versus-host disease. Linear accelerator-based radiotherapy, typically involving opposed anteroposterior and posteroanterior beams, has been commonly used; however, extended source-to-skin patient setup and/or field matching are required, and all organs within the beam coverage receive the entire prescribed dose. Megavoltage helical tomotherapy represents a technological advance in terms of both treatment delivery and patient positioning. The continuously rotating multileaf collimated fan beam allows highly conformal coverage of complex target geometries, in turn allowing avoidance of radiosensitive adjacent organs. In addition, the megavoltage computed tomographic scans allow potentially more accurate, targetbased setup verification. The present case report describes tomotherapy-based total lymphoid irradiation in an adult patient with late-onset cardiac transplant rejection. Treatment planning allowed dose minimization to the spinal cord, kidneys, intestinal compartment, and lungs. The patient tolerated treatment well without acute adverse effects, and he is now in early follow-up. PMID:19132495
McCutchen, Kathryn W; Watkins, John M; Eberts, Paul; Terwilliger, Lacy E; Ashenafi, Michael S; Jenrette, Joseph M
Retinoids Accelerate B Lineage Lymphoid Differentiation
Retinoids are known to have potent effects on hematopoietic stem cell integrity, and our objective was to learn if they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in marrow and spleens of ATRA treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of RAR/RXR agonist treatments suggested that RAR? mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow. PMID:18097013
Chen, Xinrong; Esplin, Brandt L.; Garrett, Karla P.; Welner, Robert S.; Webb, Carol F.
Aging impacts isolated lymphoid follicle development and function
BACKGROUND: Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures
Keely G McDonald; Matthew R Leach; Conway Huang; Caihong Wang; Rodney D Newberry
Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.
Gondi, Vinai [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Hermann, Bruce P. [Department of Neurology, University of Wisconsin, Madison, WI (United States); Mehta, Minesh P. [Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Tome, Wolfgang A., E-mail: email@example.com [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Biomedical Engineering, University of Wisconsin, Madison, WI (United States)
Polymorphous low-grade adenocarcinoma (PLGA) originating mostly in the minor salivary glands of the posterior hard and soft palate is characterised by its indolent growth and a slower rate of metastasis. Seldom does the PLGA present an aggressive behaviour and demonstrate distant metastasis, as in the present case where a 73-year-old female patient with a swelling in the maxillary alveolus was diagnosed as PLGA exhibiting high-grade transformation, subsequently metastasizing to the abdomen and lungs. The importance of immunomarkers, c-kit and ki-67 in deciphering the clinical behaviour of this PLGA is highlighted. Distant metastasis to the abdomen has not yet been reported; hence, this case of PLGA emphasises the importance of immunohistochemistry in assessing its aggressiveness and understanding a novel aspect of its pathogenesis. PMID:23661663
Thennavan, Aatish; Rao, Lakshmi; Radhakrishnan, Raghu
In a clinical pilot study with eleven metabolic syndrome patients, a simultaneous decrease in hs-CRP from 8.85 ± 4.09 to 4.92 ± 2.51 mg/L (-44.4%) (p < 0.0436) and HOMA-IR from 3.07 ± 0.63 to 2.60 ± 0.51mU/L × mg/dL (-15.3%) (p < 0.0120) as well as a beneficial change of arteriosclerotic, inflammatory and oxidative stress biomarkers were detected after 2-month treatment with Ginkgo biloba. Furthermore, both IL-6 (-12.9%, p < 0.0407) and nanoplaque formation (-14.3%, p < 0.0077) were additionally reduced. According to a large clinical trial elucidating the importance of insulin resistance and low-grade systemic inflammation for cardiovascular disease and overall mortality risk, these data might indicate a CVD/total mortality risk reduction. PMID:25463092
Siegel, G; Ermilov, E; Knes, O; Rodríguez, M
Purpose: To retrospectively review the results of temporary I-125 brachytherapy in 94 children and adolescents with low-grade glioma. Methods and Materials: Treatment was performed in progressive tumors roughly spherical in shape with a diameter of up to 5 cm, including 79 astrocytomas, 5 oligodendrogliomas, 4 oligoastrocytomas, 1 ependymoma, and 5 other tumors. Location was suprasellar/chiasmal in 44, thalamic/basal ganglia in 18, hemispheric in 15, midbrain/pineal region in 13, and lower brainstem in 3. Initially, 8% of patients were free of symptoms, 47% were symptomatic but not disabled, and 30% were slightly, 6% moderately, and 3% severely disabled. Results: 5- and 10-year survival was 97% and 92%. The response to I-125 brachytherapy over the long term was estimated after a median observation period of 38.4 (range, 6.4-171.0) months. At that time, 4 patients were in complete, 27 in partial, and 18 in objective remission; 15 showed stable and 30 progressive tumors. Treatment results did not correlate with age, sex, histology, tumor size, location, or demarcation of the tumor. Secondary treatment became necessary in 36 patients, including 19 who underwent repeated I-125 brachytherapy. At final follow-up, the number of symptom-free patients had risen to 21%. Thirty-eight percent showed symptoms without functional impairment, 19% were slightly and 11% moderately disabled, and only 4% were severely disabled. Conclusions: Response rates similar to those of conventional radiotherapy or chemotherapy can be anticipated with I-125 brachytherapy in tumors of the appropriate size and shape. We believe it to be a useful contribution to the treatment of low-grade gliomas in children.
Korinthenberg, Rudolf, E-mail: firstname.lastname@example.com [Division of Neuropaediatrics and Muscular Disorders, Department of Paediatrics and Adolescent Medicine, University Hospital, Albert-Ludwigs University, Freiburg im Breisgau (Germany); Neuburger, Daniela [Division of Neuropaediatrics and Muscular Disorders, Department of Paediatrics and Adolescent Medicine, University Hospital, Albert-Ludwigs University, Freiburg im Breisgau (Germany); Trippel, Michael; Ostertag, Christoph; Nikkhah, Guido [Department of Stereotactic Neurosurgery, Neurocentre, University Hospital, Albert-Ludwigs University, Freiburg im Breisgau (Germany)
Low grade cervical squamous abnormalities [low grade squamous intraepithelial lesions (LSIL, CIN1)] can be confused with or followed by high grade (HSIL, CIN2/3) lesions, expending considerable resources. Recently, a cell of origin for cervical neoplasia was proposed in the squamocolumnar junction (SCJ); HSILs are almost always SCJ marker-positive (+) but LSILs include SCJ+ and negative (?) subsets. Abnormal cervical biopsies from 214 patients were classified by two experienced pathologists ("panel") as LSIL or HSIL using published criteria. SILs were scored SCJ+ and SCJ- using SCJ-specific antibodies (Keratin7, AGR2, MMP7 and GDA). Assessments of interobserver agreement, p16ink4 staining pattern, proliferative index and outcome were compared. The original diagnostician agreed with the panel diagnosis of HSIL and SCJ- LSIL in all cases (100%). However for SCJ+ LSIL, panelists disagreed with each other on 15% and with the original diagnostician on 46.2%. Comparing SCJ- and SCJ+ LSILs, 60.2% and 94.9% scored p16ink4 positive, 23% and 74.4% showed strong (full-thickness) p16ink4 staining, and 0/54 (0%) and 8/33 (24.2%) with follow-up had an HSIL outcome respectively. Some SCJ+ LSILs are more likely to both generate diagnostic disagreement and be associated with HSIL. Conversely, SCJ- LSILs generate little observer disagreement and when followed, have a very low risk of HSIL outcome. Thus, SCJ biomarkers in conjunction with histology may segregate LSILs with very low risk of HSIL outcome and conceivably could be used as a management tool to reduce excess allocation of resources to the followup of these lesions. PMID:24076771
Herfs, Michael; Herran, Carlos Parra; Howitt, Brooke; Laury, Anna; Nucci, Marisa R; Feldman, Sarah; Jimenez, Cynthia A; McKeon, Frank D; Xian, Wa; Crum, Christopher P
The past decade has shed new light on the etiology of Alzheimer's disease (AD), which is the consequence of interactions between numerous lesions. There is a growing body of evidence that the most beneficial effects of treatment might only be achieved in the preclinical stage of dementia, prior to the immense hallmarks of neurodegeneration. In view of this, several studies have focused on mild cognitive impairment (MCI) as a state, which represents a less severe form of the neuropathological process. However, early treatment interventions initiated in MCI have failed to slow down progression of the disease. Thus, great effort has been made to indicate modifiable risk factors for MCI. Consistent with the role of vascular malfunction in AD, this approach has shown the predictive value of the metabolic syndrome (MetS), which is a multidimensional entity and includes visceral obesity, dyslipidemia, hyperglycemia and hypertension. Despite the positive results of several epidemiological studies, the exact mechanisms underlying the connection between MetS and AD remain uncertain and various theories are being assessed. MetS, similarly to AD, has been attributed to a low-grade chronic inflammation. There is a general consensus that the aberrant inflammatory response underlying MetS may arise from a deregulation of the endocrine homeostasis of adipose tissue. Hence, it might be assumed that the subclinical inflammation of adipose tissue may interact with the impaired central inflammatory response, leading to neurodegeneration. This article reviews the role of low-grade inflammation of adipose tissue in the pathophysiology of cognitive impairment and translates several considerable and unexplored findings from studies focused on subjects with MetS and animal models mimicking the phenotype of MetS into the etiology of AD. PMID:22921944
Misiak, Blazej; Leszek, Jerzy; Kiejna, Andrzej
Tolerance and Lymphoid Organ Structure and Function
This issue of Frontiers in Immunologic Tolerance explores barriers to tolerance from a variety of views of cells, molecules, and processes of the immune system. Our laboratory has spent over a decade focused on the migration of the cells of the immune system, and dissecting the signals that determine how and where effector and suppressive regulatory T cells traffic from one site to another in order to reject or protect allografts. These studies have led us to a greater appreciation of the anatomic structure of the immune system, and the realization that the path taken by lymphocytes during the course of the immune response to implanted organs determines the final outcome. In particular, the structures, microanatomic domains, and the cells and molecules that lymphocytes encounter during their transit through blood, tissues, lymphatics, and secondary lymphoid organs are powerful determinants for whether tolerance is achieved. Thus, the understanding of complex cellular and molecular processes of tolerance will not come from "96-well plate immunology," but from an integrated understanding of the temporal and spatial changes that occur during the response to the allograft. The study of the precise positioning and movement of cells in lymphoid organs has been difficult since it is hard to visualize cells within their three-dimensional setting; instead techniques have tended to be dominated by two-dimensional renderings, although advanced confocal and two-photon systems are changing this view. It is difficult to precisely modify key molecules and events in lymphoid organs, so that existing knockouts, transgenics, inhibitors, and activators have global and pleiotropic effects, rather than precise anatomically restricted influences. Lastly, there are no well-defined postal codes or tracking systems for leukocytes, so that while we can usually track cells from point A to point B, it is exponentially more difficult or even impossible to track them to point C and beyond. We believe this represents one of the fundamental barriers to understanding the immune system and devising therapeutic approaches that take into account anatomy and structure as major controlling principles of tolerance. PMID:22566853
Burrell, Bryna E.; Ding, Yaozhong; Nakayama, Yumi; Park, Kyung-Su; Xu, Jiangnan; Yin, Na; Bromberg, Jonathan S.
Skin as a peripheral lymphoid organ: revisiting the concept of skin-associated lymphoid tissues.
Antigen presentation to T cells is essential for the induction of adaptive immunity. This event takes place not solely in the lymph node (LN) but also in the skin. Recent in vivo trafficking studies using Kaede-transgenic mice reveal that skin-homing effector memory T cells alter their effector function and homing ability by transitioning to a central memory T cell-like phenotype through antigen recognition that occurs in the skin. In addition, these cells travel back and forth between the skin and draining LNs. These studies are evocative of the classic concept of skin-associated lymphoid tissues and underscore the critical role of skin as a peripheral lymphoid organ. PMID:21734715
Egawa, Gyohei; Kabashima, Kenji
Tertiary lymphoid tissues in the colon: friend and foe.
In mammals, a variety of different lymphoid tissues have evolved as an integral part of the immune system that allows the host to survive in a sometimes hostile environment. While the development of secondary lymphoid organs is programmed in the fetus, the induction of other lymphoid structures like isolated lymphoid follicles (ILFs) in the gut or tertiary lymphoid tissues (tLT) need additional external triggers after birth. It is well established that for the development of secondary lymphoid organs, as well as ILFs, RORgt expressing lymphoid tissue inducer (LTi) cells play an important role. Yet, the requirement of these cells for tLT induction, especially in the gut, was less clear. Here, I will discuss recent data demonstrating that RORgt expressing LTi cells are not required for the development of tLT in the colon. In contrast, such structures even develop spontaneously in the absence of RORgt. In RORgt (-/-) mice, this is part of the host's strategy to establish a viable homeostasis between the intestinal microbiota and the host, despite the loss of important components of the intestinal immune system in these mice. Although this highlights the amazing capacity of the immune system for adaptation, I will also discuss the adverse effects of such a compensatory immune mechanism for the host. PMID:21869608
Lochner, Matthias
NASA Astrophysics Data System (ADS)
Low grade heat sources have a large amount of thermal energy content. Due to low temperature, the conventional power generation technologies result in lower efficiency and hence cannot be used. In order to efficiently generate power, alternate methods need to be used. In this study, a supercritical organic Rankine cycle was used for heat source temperatures varying from 125°C to 200°C. Organic refrigerants with zero ozone depletion potential and their mixtures were selected as working fluid for this study while the cooling water temperature was changed from 10-25°C. Operating pressure of the cycle has been optimized for each fluid at every heat source temperature to obtain the highest thermal efficiency. Energy and exergy efficiencies of the thermodynamic cycle have been obtained as a function of heat source temperature. Efficiency of a thermodynamic cycle depends significantly on the sink temperature. At areas where water cooling is not available and ambient air temperature is high, efficient power generation from low grade heat sources may be a challenge. Use of passive cooling systems coupled with the condenser was studied, so that lower sink temperatures could be obtained. Underground tunnels, buried at a depth of few meters, were used as earth-air-heat-exchanger (EAHE) through which hot ambient air was passed. It was observed that the air temperature could be lowered by 5-10°C in the EAHE. Vertical pipes were used to lower the temperature of water by 5°C by passing it underground. Nocturnal cooling of stored water has been studied that can be used to cool the working fluid in the thermodynamic cycle. It was observed that the water temperature can be lowered by 10-20°C during the night when it is allowed to cool. The amount of water lost was calculated and was found to be approximately 0.1% over 10 days. The different passive cooling systems were studied separately and their effects on the efficiency of the thermodynamic cycle were investigated. They were then combined into a novel condenser design that uses passive cooling technology to cool the working fluid that was selected in the first part of the study. It was observed that the efficiency of the cycle improved by 2-2.5% when passive cooling system was used.
Vidhi, Rachana
9 CFR 113.31 - Detection of avian lymphoid leukosis.
Code of Federal Regulations, 2013 CFR
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...conducted on all biological products containing virus which has been propagated in substrates...the agent used to inactivate the vaccine virus would also inactivate lymphoid...
9 CFR 113.31 - Detection of avian lymphoid leukosis.
Code of Federal Regulations, 2011 CFR
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...conducted on all biological products containing virus which has been propagated in substrates...the agent used to inactivate the vaccine virus would also inactivate lymphoid...
9 CFR 113.31 - Detection of avian lymphoid leukosis.
Code of Federal Regulations, 2012 CFR
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...conducted on all biological products containing virus which has been propagated in substrates...the agent used to inactivate the vaccine virus would also inactivate lymphoid...
9 CFR 113.31 - Detection of avian lymphoid leukosis.
Code of Federal Regulations, 2010 CFR
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...conducted on all biological products containing virus which has been propagated in substrates...the agent used to inactivate the vaccine virus would also inactivate lymphoid...
9 CFR 113.31 - Detection of avian lymphoid leukosis.
Code of Federal Regulations, 2014 CFR
...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...conducted on all biological products containing virus which has been propagated in substrates...the agent used to inactivate the vaccine virus would also inactivate lymphoid...
In a prospective randomized fashion, this study evaluated embryo development in vitro after defragmentation versus assisted hatching alone of low grade day 3 embryos. Although a sustained decrease in day 5 fragmentation was observed in the defragmented group versus the assisted hatching only group, no difference in compaction rates or blastula formation rates were appreciated. PMID:20403590
Keltz, Martin; Fritz, Rani; Gonzales, Eric; Ozensoy, Serhan; Skorupski, Josh; Stein, Daniel
Background Low-grade inflammation has been hypothesized to underlie the coronary artery disease (CAD) risk associated with the metabolic syndrome, but the evidence is not conclusive. For peripheral arterial disease (PAD; as measured by the ankle-arm index), this association has not been studied before. The aim was to study whether the association between the metabolic syndrome and CAD or the severity
M. Jacobs; M. M. J. van Greevenbroek; C. J. H. van der Kallen; I. Ferreira; E. E. Blaak; E. J. M. Feskens; E. H. J. M. Jansen; C. G. Schalkwijk; C. D. A. Stehouwer
ERIC Educational Resources Information Center
The purpose of this study was to compare brain wave patterns produced by high and low grade point average students, while they were resting, solving problems, and subjected to stress situations. The study involved senior midshipmen at the United States Naval Academy. The high group was comprised of those whose cumulative grade point average was…
Montor, Karel
Results of the experimental studies carried out for developing a flowsheet for the recovery of cassiterite from the gravity tails of a low grade lode type tin ore (Tosham, Haryana) from India by froth flotation using three different collector reagents — alkyl phosphonic acid, sodium sulfosuccinamate and alkyl phosphoric acid ester are presented. The studies include micro-flotation of high purity
Vascular microarchitecture of murine colitis-associated lymphoid angiogenesis.
In permissive tissues, such as the gut and synovium, chronic inflammation can result in the ectopic development of anatomic structures that resemble lymph nodes. These inflammation-induced structures, termed lymphoid neogenesis or tertiary lymphoid organs, may reflect differential stromal responsiveness to the process of lymphoid neogenesis. To investigate the structural reorganization of the microcirculation involved in colonic lymphoid neogenesis, we studied a murine model of dextran sodium sulfate (DSS)-induced colitis. Standard 2-dimensional histology demonstrated both submucosal and intramucosal lymphoid structures in DSS-induced colitis. A spatial frequency analysis of serial histologic sections suggested that most intramucosal lymphoid aggregates developed de novo. Intravital microscopy of intravascular tracers confirmed that the developing intramucosal aggregates were supplied by capillaries arising from the quasi-polygonal mucosal plexus. Confocal optical sections and whole mount morphometry demonstrated capillary networks (185 +/- 46 microm diameter) involving six to ten capillaries with a luminal diameter of 6.8 +/- 1.1 microm. Microdissection and angiogenesis PCR array analysis demonstrated enhanced expression of multiple angiogenic genes including CCL2, CXCL2, CXCL5, Il-1b, MMP9, and TNF within the mucosal plexus. Intravital microscopy of tracer particle flow velocities demonstrated a marked decrease in flow velocity from 808 +/- 901 microm/sec within the feeding mucosal plexus to 491 +/- 155 microm/sec within the capillary structures. We conclude that the development of ectopic lymphoid tissue requires significant structural remodeling of the stromal microcirculation. A feature of permissive tissues may be the capacity for lymphoid angiogenesis. PMID:19382226
Turhan, Aslihan; Lin, Miao; Lee, Grace S; Miele, Lino F; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J
Superficially located enlarged lymphoid follicles characterise nodular gastritis.
Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis. PMID:25474513
Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro
Different lipidic wastes and low-grade oils and fats have been characterized and evaluated as feedstocks for the acid-catalyzed production of FAME. The characterization of these materials has revealed significant contents of free fatty acids, Na, K, Ca, Mg, P, unsaponifiable matter and humidity. Arenesulfonic acid-functionalized SBA-15 silica catalyst has provided yields to FAME close to 80% in the simultaneous esterification-transesterification of the different feedstocks, regardless of their nature and properties, using methanol under the following reaction conditions: 160 °C, 2 h, methanol to oil molar ratio of 30, 8 wt.% catalyst loading, and 2000 rpm stirring rate. Nevertheless, reutilization of the catalyst is compromised by high levels of impurities, especially because of deactivation by strong interaction of unsaponifiable matter with the catalytic sites. The conditioning of these materials by aqueous washing in the presence of cationic-exchange resin Amberlyst-15, followed by a drying step, resulted in a lower deactivation of the catalyst. PMID:21862322
Morales, Gabriel; Bautista, L Fernando; Melero, Juan A; Iglesias, Jose; Sánchez-Vázquez, Rebeca
Rituximab as first-line monotherapy in low-grade follicular lymphoma with a low tumor burden.
Patients with follicular lymphoma and a low tumor burden have a median overall survival of more than 10 years. Toxic conventional chemotherapy regimens are inappropriate in these patients, as they do not improve overall survival and the patients do not require palliation of symptoms. However, as most of these patients will ultimately die of their lymphoma, new therapies, with curative intent, are required. Rituximab is a human-mouse chimeric monoclonal antibody that has shown efficacy in patients with non-Hodgkin's lymphoma (NHL). The benign tolerability profile of rituximab makes it a suitable candidate for first-line treatment of follicular NHL patients with a low tumor burden. In a trial of 49 patients, 73% achieved a clinical response (26% complete response) with rituximab treatment. Molecular studies showed that 57% of patients achieved molecular remission (clearance of the bcl-2 molecular translocation from the blood, evaluated by polymerase chain reaction), 62% of these remaining bcl-2- for at least 1 year. There was a good correlation between molecular and clinical responses, with patients failing to achieve a molecular response at higher risk of disease progression. Rituximab monotherapy is therefore an effective and well-tolerated treatment for patients with low-grade lymphoma and a low tumor burden. PMID:11508931
Solal-Céligny, P
The pathophysiology of irritable bowel syndrome (IBS) is complex and not fully understood, so the aim of this study was to evaluate whether visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction, and low-grade inflammation of the gut wall are associated with diarrhea-predominant IBS (D-IBS). Sixty-two patients with D-IBS and 20 control subjects participated in the study. Using the ascending method of limits (AML) protocol, we demonstrated that D-IBS patients had significantly lower sensory thresholds compared with healthy controls (P<0.001). Using diverse methods, especially the ischemic sensitivity test, for the first time in China, we confirmed that D-IBS patients have somatic hypersensitivity. They had a significantly higher systolic blood pressure and heart rate after a cold stimulus, indicative of autonomic cardiovascular dysfunction. Compared with the control group, D-IBS patients had a significantly higher level of calprotectin (P<0.001). We also found significant correlations between visceral and somatic hypersensitivity, visceral hypersensitivity and autonomic cardiovascular dysfunction, and somatic hypersensitivity and autonomic cardiovascular dysfunction. Our findings may provide valuable suggestions for the treatment of D-IBS. PMID:25294380
Liu, Liang; Liu, Bei-ni; Chen, Shuo; Wang, Miao; Liu, Yang; Zhang, Yan-li; Yao, Shu-kun
It remains difficult to distinguish adenoid cystic carcinoma (ACC) from polymorphous low-grade adenocarcinoma (PLGA). Although these neoplasms exhibit nearly similar histologic patterns, their biologic behavior is significantly different. This study was carried out in an attempt to overcome the histological overlap between these tumors using immunohistochemical method for c-kit and galectin-3 proteins on twenty cases of salivary gland tumors including twelve ACC and eight PLGA. Results revealed positive cytoplasmic reactivity for c-kit in 100% of ACC cases and only in 25% of PLGA. On the other hand, galectin-3 expression was observed in 100% of both ACC and PLGA cases. Moreover, solid variant of ACC showed overexpression of both proteins than cribriform and tubular subtypes. Significant positive correlation between the two studied proteins in ACC and PLGA was also observed (p < 0.05). Upon these results, over expression of c-kit and galectin-3 in ACC cases supports the concept of solid variant as a high-grade tumor. Moreover, c-kit may be used as a helpful marker to distinguish ACC from PLGA in cases where the diagnosis can be challenging. PMID:24265903
El-Nagdy, Sherif; Mourad, Mohamed I.
Low-grade B-cell lymphomas of the skin, especially, primary cutaneous follicle center cell lymphoma has several distinctive features when compared with nodal/systemic follicular lymphomas, as they are frequently negative for bcl-2 and CD10, and only fewer than 25% of the cases show a bcl-2 rearrangement. The risk of transformation of a cutaneous low-grade B-cell lymphoma, such as primary cutaneous follicle center cell lymphoma, to primary cutaneous diffuse large B-cell lymphomas (PCDLBCL) has not been clearly delineated in the literature. Transformation of systemic/nodal follicular lymphoma into aggressive DLBCL is associated with rapid disease progression, refractoriness to treatment, and poor prognosis. The authors studied 82 cases of primary cutaneous DLBCL using antibodies for follicular dendritic cells (FDCs), CD21, and CD35 to detect networks of FDCs that could possibly indicate transformation of preexisting low-grade B-cell lymphoma to PCDLBCL. All cases were classified as PCDLBCL using strict histologic and immunophenotypic criteria. Fifty-three cases were classified as primary cutaneous DLBCL of "leg type," and 29 cases were classified as primary cutaneous DLBCL, "NOS" category. Immunohistochemical studies were performed in all 82 cases; in 15 cases, a CD21/CD35+ network of FDCs was noted within the tumor, indicating the presence of remnants of residual germinal centers, suggesting the possibility of a transformed low-grade B-cell lymphoma. In summary, the authors' findings seem to indicate that some cases of primary cutaneous DLBCL may result from transformation of a low-grade B-cell lymphoma. Further studies are necessary to evaluate the significance of their findings by using ancillary techniques including genetic analysis. PMID:24698933
Plaza, Jose A; Kacerovska, Denisa; Sangueza, Martin; Schieke, Stefan; Buonaccorsi, Noelle; Suster, Saul; Kazakov, Dmitry V
Innate lymphoid cells, possible interaction with microbiota.
Recent studies have identified novel lymphocyte subsets named innate lymphoid cells (ILCs) lacking antigen-specific receptors. ILCs are present in a wide variety of epithelial compartments and occupy an intermediate position between acquired immune cells and myeloid cells. ILCs are now classified into three groups: group 1 ILC, group 2 ILC, and group 3 ILC based on their cytokine production patterns that correspond to the helper T cell subsets Th1, Th2, and Th17, respectively. ILCs play important roles in protection against various invading microbes including multicellular parasites, and in the maintenance of homeostasis and repair of epithelial layers. Excessive activation of ILCs, however, leads to various inflammatory disease conditions. ILCs have thus attracted interests of many researchers in the fields of infectious immunity, inflammatory diseases, and allergic diseases. Because epithelial cells sense alterations in environmental cues, it is important to understand the functional interaction between epithelial cells, ILCs, and environmental factors such as commensal microbiota. We discuss in this review developmental pathways of ILCs, their functions, and contribution of commensal microbiota to the differentiation and function of ILCs. PMID:25502370
Moro, Kazuyo; Koyasu, Shigeo
Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985
Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.
Non-lymphoid and lymphoid cells in acute, chronic and relapsing experimental colitis.
In rodents, intracolonic administration of ethanol 30% induces an acute colitis, while administration of 2,4,6-trinitrobenzene sulphonic acid (TNBS) in ethanol induces a longer lasting colitis. In the acute and chronic stages of experimental colitis, lymphoid and non-lymphoid cells were studied in the colon by immunohistochemistry. During the acute inflammation a high damage score of the colon was observed, which was related to an increase in the number of macrophages and granulocytes. Also a change in distributional patterns of macrophage subpopulations was found. The chronic stage of TNBS-ethanol-induced colitis was characterized by an increase in the number of lymphocytes, especially T cells. These data suggest that macrophages and granulocytes are important in the acute phase of experimental colitis, while lymphocytes play a pivotal role in the chronic stage. As most inflammatory bowel disease (IBD) patients have relapses during the chronic disease, we attempted to induce a relapse during experimental colitis by giving a second i.p. or s.c. dose of TNBS. This resulted in increased damage scores of the colon, new areas of ulceration and a further increase in macrophage numbers. No effect on the number of granulocytes was seen. These results indicate that it is possible to mimic relapses in experimental colitis by a second administration of TNBS, and suggest that the rats had been sensitized by the first dose of TNBS, given into the colon. Images Fig. 4 PMID:7851016
Palmen, M J; Dieleman, L A; van der Ende, M B; Uyterlinde, A; Peńa, A S; Meuwissen, S G; van Rees, E P
Background: To define the spectrum of human papillomavirus (HPV) types and establish an age limit for triage HPV testing in atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). Materials and methods: 343 liquid-based cytological samples from the population-based screening programme with minor abnormalities were subjected to HPV genotyping (Linear Array, Roche, Basel, Switzerland). Results: High-risk human papillomavirus (HR-HPV) was found in 71% of LSIL and 49% of ASCUS cases (P<0.001). High-risk human papillomavirus prevalence was age-dependent in LSIL (P=0.01), with decreasing prevalence until the age of 50 years, followed by a slight increase. Human papillomavirus type 16 was the most common HR-HPV, found in 23% of HPV-positive women. Human papillomavirus type 18 was the sixth most common, found in 9.9% (P<0.001). An age-dependent quadratic trend was observed for multiple infections (P=0.01) with a trough at about 42 years. The most common HR-HPV types to show a coinfection with HPV16 (clade 9) were HPV39 (28%), 45 (38%), and 59 (46%), belonging to HPV18 clade 7. The frequency of low-risk (LR) vs probable HR and HR-HPV also followed an age-dependent quadratic trend. Conclusions: After the age of 25 years, HR-HPV prevalence is similar in LSIL and ASCUS cases, motivating a low age limit for triage HPV testing. Multiple infections and LR/HR-HPV dominance are age-dependent. Genotyping in longitudinal design is needed to elucidate the importance of multiple infections in cancer progression and in cross-protection from vaccination. PMID:19623178
Brismar-Wendel, S; Froberg, M; Hjerpe, A; Andersson, S; Johansson, B
Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing. PMID:25157573
Miotto, Eliane C.; Balardin, Joana B.; Vieira, Gilson; Sato, Joao R.; Martin, Maria da Graça M.; Scaff, Milberto; Teixeira, Manoel J.; Junior, Edson Amaro
Low grade adenosquamous carcinoma (LGASC) is rare but commonly reported to arise in association with benign proliferative and sclerosing breast lesions which themselves may show associated sclerosing or 'adenosquamous proliferation' (ASP) resembling LGASC, but are often derided as reactive mimics or attributed to earlier biopsy. Among other benign lesions, radial sclerosing lesion (RSL) may be associated with LGASC, yet attention is typically focused on its relationship to more common forms of mammary carcinoma. This study aimed to assess the presence and extent of ASP in the context of RSL in a small cohort of 20 cases and its similarity to LGASC.Twenty consecutive breast excisions that had a principal or incidental diagnosis of RSL were reviewed. RSLs that displayed foci of ASP were further examined with immunohistochemical markers for p63, calponin, cytokeratin 5/6, oestrogen and progesterone receptors.Sixty percent of excisions contained ASP either associated with a RSL or a concurrent papilloma, which morphologically and immunohistochemically were indistinguishable from the neoplastic ducts of LGASC. RSL with and without ASP broadly corresponded to accepted definitions for 'early' and 'late' lesions, respectively. ASP corresponded to the characteristic compact branching ducts of the core or nidus of a RSL.The morphological and immunophenotypic similarity of the ASP found in RSL and papillomata to LGASC warrants serious consideration that they are a potential precursor to LGASC, which may most commonly involute given the rarity of clinically apparent LGASC. Further study including micro-dissection of foci of ASP to compare its molecular genetic profile to that of LGASC is required. PMID:24842378
Wilsher, Mark James
We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitro and whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P < 0.05; hazard ratio (HR), 2.415) and the high p-p70S6K staining group (P < 0.05; HR, 2.249) were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = ?0.850, P < 0.001 in RT4 cells; r = ?0.835, P < 0.001 in 253J cells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P < 0.05). Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder. PMID:24625880
Kim, Soon-Ja; Kim, Jung Hoon; Jung, Hui Seok; Lee, Tae-Jin; Lee, Kyung Mee; Chang, In Ho
Follicular low-grade non-Hodgkin's lymphoma: long-term outcome with or without tumor progression.
Long-term outcome for 127 patients with follicular low-grade lymphoma was investigated. Therapy included radiotherapy (n = 23), low toxicity chemotherapy with or without radiotherapy (n = 76), or more intensive chemotherapy (n = 22). 6 patients had no initial therapy. Complete remission was obtained in 67% of patients. For patients under 60 years of age median survival was 8.7 yr compared with 3.8 yr for older patients, but survival from lymphoma was identical for the two age-groups: 75% at 5 yr, and 58% at 10 yr. The relatively low tumor mortality contrasted with a relapse-free survival of 30% at 10 yr, and relapse 8-9 yr after first remission. Examining the disease topography and the stability of histologic subtype in 78 patients with recurrent lymphoma, two types of relapse with different prognoses were identified: 1) with tumor progression (lymphoma dissemination to atypical extranodal sites and/or histologic conversion to an intermediate/high-grade lymphoma) seen in 56% of patients with a survival from lymphoma of 13% at 10 yr; and 2) without tumor progression (involvement of nodal sites, and unchanged histology) seen in 44% with a survival from lymphoma of 77% at 10 yr. Actuarial risk of tumor progression was 44% at 5 yr, and 67% at 10 yr. Except from the negative impact of a large tumor burden, it was not possible to identify patients with high risk for tumor progression. More important than all pretreatment factors was poor response to initial therapy (p = 0.0001). Due to lack of reliable risk factors, it is recommended that all younger patients be treated with the intention of achieving complete remission; a significant fraction might be curable. PMID:2917634
Ersbřll, J; Schultz, H B; Pedersen-Bjergaard, J; Nissen, N I
Background To identify changes in patient presentation, treatment, and outcomes of low-grade gliomas (LGGs) over the past 50 years. Methods Records of 852 adults who received a diagnosis at Mayo Clinic from 1960 through 2011 with World Health Organization grade II LGGs were reviewed and grouped by those who received a diagnosis before (group I: 1960–1989) and after (group II: 1990–2011) the routine use of postoperative MRI. Results Median follow-up was 23.3 and 8.7 years for groups I and II, respectively. Patients in group I more often presented with seizures, headaches, sensory/motor impairment, and astrocytoma histology. Over time, more gross total resections (GTRs) were achieved, fewer patients received postoperative radiotherapy (PORT), and more received chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 4.4 and 8.0 years, respectively. Although PFS was similar, 10-year OS was better in group II (47%) than in group I (33%; P < .0001). Improved PFS in multivariate analysis was associated with group I patients, nonastrocytoma histology, small tumor size, successful GTR, or radical subtotal resection (rSTR), PORT, and postoperative chemotherapy. Factors associated with improved OS in multivariate analysis were younger age, nonastrocytoma histology, small tumor size, and GTR/rSTR. Conclusions OS for LGG has improved over the past 50 years, despite similar rates of progression. In the modern cohort, more patients are receiving a diagnosis of oligodendroglioma and are undergoing extensive resections, both of which are associated with improvements in OS. Because of risk factor stratification by clinicians, the use of PORT has decreased and is primarily being used to treat high-risk tumors in modern patients. PMID:23814262
Youland, Ryan S.; Schomas, David A.; Brown, Paul D.; Nwachukwu, Chika; Buckner, Jan C.; Giannini, Caterina; Parney, Ian F.; Laack, Nadia N.
In this issue of Neurogastroenterology and Motility, Dr Ewa Wilcz-Villega and colleagues report low expression of E-cadherin, a tight junction protein involved in the regulation of paracellular permeability, in the colonic mucosa of patients with the irritable bowel syndrome (IBS) with predominance of diarrhea (IBS-D) or alternating symptoms (IBS-A). These findings constitute an improvement in our knowledge of epithelial barrier disruption associated with IBS. There is mounting evidence to indicate that a compromised epithelial barrier is associated with low-grade immune activation and intestinal dysfunction in at least a proportion of IBS patients. During the last 10 years of research, much interest has focused on the increase in the number of different types of immune cells in the gut mucosa of IBS patients including: mast cells, T lymphocytes, and other local cells such as enteroendocrine cells. The inflammatory mediators released by these cells or other luminal factors could be at the origin of altered epithelial barrier functions and enteric nervous system signaling, which lead to gut hypersensitivity. A current conceptual framework states that clinical symptoms of IBS could be associated with structural and functional abnormalities of the mucosal barrier, highlighting the crucial importance of elucidating the contributory role of epithelial barrier defects in the pathogenesis of IBS. More importantly, disruption of the epithelial barrier could also participate in the generation of persistent abdominal pain and discomfort mimicking IBS in patients with inflammatory bowel diseases considered in remission. This mini review gives a brief summary of clinical and experimental evidence concerning the mechanisms underlying epithelial barrier defects in IBS. PMID:24548256
Piche, T
BRAF and KRAS mutations in ovarian serous borderline tumors (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumor samples from 23 recurrent LGSC patients with known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for 5 patients, and either OSBT or LGSC were available for another 18 patients. Tumor cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumors that appeared to have wild-type KRAS by conventional PCR–Sanger sequencing were further analyzed by full COLD (coamplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR–Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in 10 patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in 7 OSBT samples and 6 LGSC samples. To our surprise, patients with the KRAS G12V mutation appeared to have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumor cells with or without detectable KRAS mutations. PMID:24549645
Tsang, Yvonne T.; Deavers, Michael T.; Sun, Charlotte C.; Kwan, Suet-Yan; Kuo, Eric; Malpica, Anais; Mok, Samuel C.; Gershenson, David M.; Wong, Kwong-Kwok
Purpose: Tracking the progression of low grade tumors (LGTs) is a challenging task, due to their slow growth rate and associated complex internal tumor components, such as heterogeneous enhancement, hemorrhage, and cysts. In this paper, the authors show a semiautomatic method to reliably track the volume of LGTs and the evolution of their internal components in longitudinal MRI scans. Methods: The authors' method utilizes a spatiotemporal evolution modeling of the tumor and its internal components. Tumor components gray level parameters are estimated from the follow-up scan itself, obviating temporal normalization of gray levels. The tumor delineation procedure effectively incorporates internal classification of the baseline scan in the time-series as prior data to segment and classify a series of follow-up scans. The authors applied their method to 40 MRI scans of ten patients, acquired at two different institutions. Two types of LGTs were included: Optic pathway gliomas and thalamic astrocytomas. For each scan, a "gold standard" was obtained manually by experienced radiologists. The method is evaluated versus the gold standard with three measures: gross total volume error, total surface distance, and reliability of tracking tumor components evolution. Results: Compared to the gold standard the authors' method exhibits a mean Dice similarity volumetric measure of 86.58% and a mean surface distance error of 0.25 mm. In terms of its reliability in tracking the evolution of the internal components, the method exhibits strong positive correlation with the gold standard. Conclusions: The authors' method provides accurate and repeatable delineation of the tumor and its internal components, which is essential for therapy assessment of LGTs. Reliable tracking of internal tumor components over time is novel and potentially will be useful to streamline and improve follow-up of brain tumors, with indolent growth and behavior.
Weizman, Lior, E-mail: firstname.lastname@example.com [School of Engineering and Computer Science, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel)] [School of Engineering and Computer Science, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Sira, Liat Ben [Department of Radiology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv 64239 (Israel)] [Department of Radiology, Tel Aviv Medical Center, Tel Aviv University, Tel Aviv 64239 (Israel); Joskowicz, Leo [School of Engineering and Computer Science and The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem 91904 (Israel)] [School of Engineering and Computer Science and The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Rubin, Daniel L.; Yeom, Kristen W. [Department of Radiology, Stanford University, Stanford, California 94305 (United States)] [Department of Radiology, Stanford University, Stanford, California 94305 (United States); Constantini, Shlomi; Shofty, Ben [Tel Aviv Medical Center, Dana Children's Hospital, Tel Aviv University, Tel Aviv 64239 (Israel)] [Tel Aviv Medical Center, Dana Children's Hospital, Tel Aviv University, Tel Aviv 64239 (Israel); Bashat, Dafna Ben [Tel Aviv Medical Center, Functional Brain Center, Tel Aviv University, Tel Aviv 64239 (Israel)] [Tel Aviv Medical Center, Functional Brain Center, Tel Aviv University, Tel Aviv 64239 (Israel)
Total lymphoid irradiation for multiple sclerosis
Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.
Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.
Background\\/Aim: Healthy individuals present variable responses of the hypothalamic-pituitary-adrenal (HPA) axis induced by different patterns of physical training. The aim of this study was to evaluate whether prolonged low-grade physical training influences the HPA axis and also glucocorticoid receptor-? (GR?) mRNA levels in mononuclear cells of obese adolescents. Methods: We studied 19 patients with BMI above the 95th percentile (male:female
Cláudia Dutra Costantin Faria; Roberta Borges Castro; Carlos Alberto Longui; Cristiane Kochi; Vera Lúcia Perino Barbosa; Tatiane Sousa e Silva; Mylene Neves Rocha; Murilo Rezende Melo; Osmar Monte
The study aimed to determine if age-associated low-grade inflammation aggravates the response to a stress, especially regarding to sarcopenia. Initial inflammatory status in 22-month-old rats was based on plasma ?2-macroglobulin and fibrinogen concentrations. The stress applied was a single intra-peritoneal injection of lipopolysaccharide followed by a 23-day period of malnutrition, i.e. a 4% casein diet distributed in quantity limited to
Gilles Mayot; Karine Vidal; Lydie Combaret; Denis Breuillé; Stephanie Blum; Christiane Obled; Isabelle Papet
The focus of this study is to characterize the bacterial community structure present during stirred-tank bioleaching of a low-grade nickel sulphide ore at different temperatures (5 to 45°C) and pH levels (3 and 5). This is a continuation of previous work, which was designed to assess the technical feasibility of applying elevated-pH bioleaching to this same ore from Manitoba, Canada.
Rory A. Cameron; C. William Yeung; Charles W. Greer; W. Douglas Gould; Saviz Mortazavi; Pierre L. Bédard; Lucie Morin; Lyne Lortie; Orlando Dinardo; Kevin J. Kennedy
We investigated the direct (additive) and interactive effects of the Job Demand-Control-Support (JDC-S) model's components on subsequent changes in three indicators of stress-induced low-grade inflammation in the body: C-reactive protein (CRP), fibrinogen and white blood cell count (WBC) plasma concentrations. These inflammation biomarkers have been shown to be implicated in the aetiology of cardiovascular disease. We studied separately healthy male
Arie Shirom; Sharon Toker; Shlomo Berliner; Itzhak Shapira
Background: While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem\\/progenitor cells as well as the prognostic value of stem\\/progenitor cell marker expression in glioma are poorly clarified. Methodology\\/Principal Findings: Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade
Johan Rebetz; Dongping Tian; Annette Persson; Bengt Widegren; Leif G. Salford; Elisabet Englund; David Gisselsson; Xiaolong Fan
BackgroundWhile neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem\\/progenitor cells as well as the prognostic value of stem\\/progenitor cell marker expression in glioma are poorly clarified.Methodology\\/Principal FindingsViable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were
Johan Rebetz; Dongping Tian; Annette Persson; Bengt Widegren; Leif G. Salford; Elisabet Englund; David Gisselsson; Xiaolong Fan; Karen S. Aboody
Elevated activation of the platelet-derived growth factor (PDGF) pathway, apoptosis evasion phenotype, and global DNA hypomethylation\\u000a are hallmarks frequently observed in cancers, such as in low-grade glioma (LGG). However, the orchestration of these malignant\\u000a functions is not fully elucidated in LGG. Our study reveals that the co-presence of these hallmarks in the same LGG is frequent\\u000a and confers poor prognosis
Emilie Debien; Eric Hervouet; Fabien Gautier; Philippe Juin; Francois M. Vallette; Pierre-Francois Cartron
Objective. The objective of our study was to compare immunocyte infiltrates in vulval epithelium from low-grade and high-grade vulval intraepithelial neoplasia (VIN) lesions to determine if difference in T-cell presence reflected the grade of VIN.Material and methods. Thirty-six vulval specimens were obtained from 24 patients who had previously undergone vulval biopsies for VIN, 14 high-grade diseases (VIN 3 with or
Nahid Gul; Raji Ganesan; David M Luesley
Quantitative Image Analysis of HIV-1 Infection in Lymphoid Tissue
NASA Astrophysics Data System (ADS)
Tracking human immunodeficiency virus-type 1 (HIV-1) infection at the cellular level in tissue reservoirs provides opportunities to better understand the pathogenesis of infection and to rationally design and monitor therapy A quantitative technique was developed to determine viral burden in two important cellular compartments in lymphoid tissues. Image analysis and in situ hybridization were combined to show that in the presymptomatic stages of infection there is a large, relatively stable pool of virions on the surfaces of follicular dendritic cells and a smaller pool of productively infected cells Despite evidence of constraints on HIV-1 replication in the infected cell population in lymphoid tissues, estimates of the numbers of these cells and the virus they could produce are consistent with the quantities of virus that have been detected in the bloodstream. The cellular sources of virus production and storage in lymphoid tissues can now be studied with this approach over the course of infection and treatment.
Haase, Ashley T.; Henry, Keith; Zupancic, Mary; Sedgewick, Gerald; Faust, Russell A.; Melroe, Holly; Cavert, Winston; Gebhard, Kristin; Staskus, Katherine; Zhang, Zhi-Qiang; Dailey, Peter J.; Balfour, Henry H., Jr.; Erice, Alejo; Perelson, Alan S.
Purpose: A prognostic index for survival was constructed and validated from patient data from two European Organisation for Research and Treatment of Cancer (EORTC) radiation trials for low-grade glioma (LGG). We sought to independently validate this prognostic index with a separate prospectively collected data set (Intergroup 86-72-51). Methods and Materials: Two hundred three patients were treated in a North Central Cancer Treatment Group-led trial that randomized patients with supratentorial LGG to 50.4 or 64.8 Gy. Risk factors from the EORTC prognostic index were analyzed for prognostic value: histology, tumor size, neurologic deficit, age, and tumor crossing the midline. The high-risk group was defined as patients with more than two risk factors. In addition, the Mini Mental Status Examination (MMSE) score, extent of surgical resection, and 1p19q status were also analyzed for prognostic value. Results: On univariate analysis, the following were statistically significant (p < 0.05) detrimental factors for both progression-free survival (PFS) and overall survival (OS): astrocytoma histology, tumor size, and less than total resection. A Mini Mental Status Examination score of more than 26 was a favorable prognostic factor. Multivariate analysis showed that tumor size and MMSE score were significant predictors of OS whereas tumor size, astrocytoma histology, and MMSE score were significant predictors of PFS. Analyzing by the EORTC risk groups, we found that the low-risk group had significantly better median OS (10.8 years vs. 3.9 years, p < 0.0001) and PFS (6.2 years vs. 1.9 years, p < 0.0001) than the high-risk group. The 1p19q status was available in 66 patients. Co-deletion of 1p19q was a favorable prognostic factor for OS vs. one or no deletion (median OS, 12.6 years vs. 7.2 years; p = 0.03). Conclusions: Although the low-risk group as defined by EORTC criteria had a superior PFS and OS to the high-risk group, this is primarily because of the influence of histology and tumor size. Co-deletion of 1p19q is a prognostic factor. Future studies are needed to develop a more refined prognostic system that combines clinical prognostic features with more robust molecular and genetic data.
Daniels, Thomas B. [Department of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN (United States); Brown, Paul D., E-mail: firstname.lastname@example.com [Department of Radiation Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN (United States); Felten, Sara J.; Wu, Wenting [Cancer Center Statistics, Mayo Clinic and Mayo Foundation, Rochester, MN (United States); Buckner, Jan C. [Division of Medical Oncology, Mayo Clinic and Mayo Foundation, Rochester, MN (United States); Arusell, Robert M. [Roger Maris Cancer Center, Meritcare Hospital CCOP, Fargo, ND (United States); Curran, Walter J. [Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Schiff, David [Department of Neurology, University of Virginia Health System, Charlottesville, VA (United States); Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)
Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive from LMP tumours. PMID:22163003
Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.
The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids
Soluble CD163 (sCD163) is a novel marker linked to states of low-grade inflammation such as diabetes, obesity, liver disease, and atherosclerosis, all prevalent in subjects with Turner syndrome (TS) and Klinefelter syndrome (KS). We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards to treatment with sex hormone therapy in males with and without KS and females with and without TS. Males with KS (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study. Females with TS (n=8) and healthy age-matched controls (n=8) participating in a randomized crossover trial. The intervention comprised of treatment with sex steroids. Males with KS had higher levels of sCD163 compared with controls (1.75 (0.47–6.90) and 1.36 (0.77–3.11) respectively, P<0.001) and the levels correlated to plasma testosterone (r=?0.31, P<0.01), BMI (r=0.42, P<0.001), and homeostasis model of assessment insulin resistance (r=0.46, P<0.001). Treatment with testosterone did not significantly lower sCD163. Females with TS not receiving hormone replacement therapy (HRT) had higher levels of sCD163 than those of their age-matched healthy controls (1.38±0.44 vs 0.91±0.40, P=0.04). HRT and oral contraceptive therapy decreased sCD163 in TS by 22% (1.07±0.30) and in controls by 39% (0.55±0.36), with significance in both groups (P=0.01 and P=0.04). We conclude that levels of sCD163 correlate with endogenous testosterone in KS and are higher in KS subjects compared with controls, but treatment did not significantly lower levels. Both endogenous and exogenous estradiol in TS was associated with lower levels of sCD163. PMID:24148221
Thomsen, Henrik H; Mřller, Holger J; Trolle, Christian; Groth, Kristian A; Skakkebćk, Anne; Bojesen, Anders; Hřst, Christian; Gravholt, Claus H
Interactions between the intestinal microbiota and innate lymphoid cells
The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741
Chen, Vincent L; Kasper, Dennis L
Childhood and adolescent lymphoid and myeloid leukemia.
Remarkable progress has been made in the past decade in the treatment and in the understanding of the biology of childhood lymphoid and myeloid leukemias. With contemporary improved risk assessment, chemotherapy, hematopoietic stem cell transplantation and supportive care, approximately 80% of children with newly diagnosed acute lymphoblastic leukemia and 50% of those with myeloid neoplasm can be cured to date. Current emphasis is placed not only on increased cure rate but also on improved quality of life. In Section I, Dr. Ching-Hon Pui describes certain clinical and biologic features that still have prognostic and therapeutic relevance in the context of contemporary treatment programs. He emphasizes that treatment failure in some patients is not due to intrinsic drug resistance of leukemic cells but is rather caused by suboptimal drug dosing due to host compliance, pharmacodynamics, and pharmacogenetics. Hence, measurement of minimal residual disease, which accounts for both the genetic (primary and secondary) features of leukemic lymphoblasts and pharmacogenomic variables of the host, is the most reliable prognostic indicator. Finally, he contends that with optimal risk-directed systemic and intrathecal therapy, cranial irradiation may be omitted in all patients, regardless of the presenting features. In Section II, Dr. Martin Schrappe performs detailed analyses of the prognostic impact of presenting age, leukocyte count, sex, immunophenotype, genetic abnormality, early treatment response, and in vitro drug sensitivity/resistance in childhood acute lymphoblastic leukemia, based on the large database of the Berlin-Frankfurt-Münster consortium. He also succinctly summarizes the important treatment components resulting in the improved outcome of children and young adolescents with this disease. He describes the treatment approach that led to the improved outcome of adolescent patients, a finding that may be applied to young adults in the second and third decade of life. Finally, he believes that treatment reduction under well-controlled clinical trials is feasible in a subgroup of patients with excellent early treatment response as evidenced by minimal residual disease measurement during induction and consolidation therapy. In Section III, Dr. Raul Ribeiro describes distinct morphologic and genetic subtypes of acute myeloid leukemia. The finding of essentially identical gene expression profiling by DNA microarray in certain specific genetic subtypes of childhood and adult acute myeloid leukemia suggests a shared leukemogenesis. He then describes the principles of treatment as well as the efficacy and toxicity of various forms of postremission therapy, emphasizing the need of tailoring therapy to both the disease and the age of the patient. Early results suggest that minimal residual disease measurement can also improve the risk assessment in acute myeloid leukemia, and that cranial irradiation can be omitted even in those with central-nervous-system leukemia at diagnosis. In Section IV, Dr. Charlotte Niemeyer describes a new classification of myelodysplastic and myeloproliferative diseases in childhood, which has greatly facilitated the diagnosis of myelodysplastic syndromes and juvenile myelomonocytic leukemia. The recent discovery of somatic mutations in PTPN11 has improved the understanding of the pathobiology and the diagnosis of juvenile myelomonocytic leukemia. Together with the findings of mutations in RAS and NF1 in the other patients, she suggests that pathological activation of RAS-dependent pathways plays a central role in the leukemogenesis of this disease. She then describes the various treatment approaches for both juvenile myelomonocytic leukemia and myelodysplastic syndromes in the US and Europe, emphasizing the differences between childhood and adult cases for the latter group of diseases. She also raises some controversial issues regarding treatment that will require well-controlled international clinical trials to address. PMID:15561680
Pui, Ching-Hon; Schrappe, Martin; Ribeiro, Raul C; Niemeyer, Charlotte M
'Managing' the immune system with total lymphoid irradiation
Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis.
Strober, S.
Lymphoid leukosis viruses and gs antigen in unincubated chicken eggs
Lymphoid leukosis viruses and viral group?specific antigen were found in albumen of unincubated chicken eggs stored at 8°C. Infectious virus was detected for up to 22 days and antigen was stable for 63 days. Tests for virus were conducted on albumen withdrawn from eggs prior to incubation and on extracts of embryos from the same eggs. When albumen was from
J. L. Spencer; L. B. Crittenden; B. R. Burmester; C. Romero; R. L. Witter
Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion.
The hematopoietic system sustains regeneration throughout life by balancing self-renewal and differentiation. To stay poised for mature blood production, hematopoietic stem cells (HSCs) maintain low-level expression of lineage-associated genes, a process termed lineage priming. Here, we modulated expression levels of Inhibitor of DNA binding (ID) proteins to ask whether lineage priming affects self-renewal of human HSCs. We found that lentiviral overexpression of ID proteins in cord blood HSCs biases myeloerythroid commitment at the expense of lymphoid differentiation. Conversely, reducing ID2 expression levels increases lymphoid potential. Mechanistically, ID2 inhibits the transcription factor E47 to attenuate B-lymphoid priming in HSCs and progenitors. Strikingly, ID2 overexpression also results in a 10-fold expansion of HSCs in serial limiting dilution assays, indicating that early lymphoid transcription factors antagonize human HSC self-renewal. The relationship between lineage priming and self-renewal can be exploited to increase expansion of transplantable human HSCs and points to broader implications for other stem cell populations. PMID:24388174
van Galen, Peter; Kreso, Antonija; Wienholds, Erno; Laurenti, Elisa; Eppert, Kolja; Lechman, Eric R; Mbong, Nathan; Hermans, Karin; Dobson, Stephanie; April, Craig; Fan, Jian-Bing; Dick, John E
OBJECT Surgery of suspected low-grade gliomas (LGGs) poses a special challenge for neurosurgeons due to their diffusely infiltrative growth and histopathological heterogeneity. Consequently, neuronavigation with multimodality imaging data, such as structural and metabolic data, fiber tracking, and 3D brain visualization, has been proposed to optimize surgery. However, currently no standardized protocol has been established for multimodality imaging data in modern glioma surgery. The aim of this study was therefore to define a specific protocol for multimodality imaging and navigation for suspected LGG. METHODS Fifty-one patients who underwent surgery for a diffusely infiltrating glioma with nonsignificant contrast enhancement on MRI and available multimodality imaging data were included. In the first 40 patients with glioma, the authors retrospectively reviewed the imaging data, including structural MRI (contrast-enhanced T1-weighted, T2-weighted, and FLAIR sequences), metabolic images derived from PET, or MR spectroscopy chemical shift imaging, fiber tracking, and 3D brain surface/vessel visualization, to define standardized image settings and specific indications for each imaging modality. The feasibility and surgical relevance of this new protocol was subsequently prospectively investigated during surgery with the assistance of an advanced electromagnetic navigation system in the remaining 11 patients. Furthermore, specific surgical outcome parameters, including the extent of resection, histological analysis of the metabolic hotspot, presence of a new postoperative neurological deficit, and intraoperative accuracy of 3D brain visualization models, were assessed in each of these patients. RESULTS After reviewing these first 40 cases of glioma, the authors defined a specific protocol with standardized image settings and specific indications that allows for optimal and simultaneous visualization of structural and metabolic data, fiber tracking, and 3D brain visualization. This new protocol was feasible and was estimated to be surgically relevant during navigation-guided surgery in all 11 patients. According to the authors' predefined surgical outcome parameters, they observed a complete resection in all resectable gliomas (n = 5) by using contour visualization with T2-weighted or FLAIR images. Additionally, tumor tissue derived from the metabolic hotspot showed the presence of malignant tissue in all WHO Grade III or IV gliomas (n = 5). Moreover, no permanent postoperative neurological deficits occurred in any of these patients, and fiber tracking and/or intraoperative monitoring were applied during surgery in the vast majority of cases (n = 10). Furthermore, the authors found a significant intraoperative topographical correlation of 3D brain surface and vessel models with gyral anatomy and superficial vessels. Finally, real-time navigation with multimodality imaging data using the advanced electromagnetic navigation system was found to be useful for precise guidance to surgical targets, such as the tumor margin or the metabolic hotspot. CONCLUSIONS In this study, the authors defined a specific protocol for multimodality imaging data in suspected LGGs, and they propose the application of this new protocol for advanced navigation-guided procedures optimally in conjunction with continuous electromagnetic instrument tracking to optimize glioma surgery. PMID:25552284
Mert, Aygül; Kiesel, Barbara; Wöhrer, Adelheid; Martínez-Moreno, Mauricio; Minchev, Georgi; Furtner, Julia; Knosp, Engelbert; Wolfsberger, Stefan; Widhalm, Georg
Diagnosis of intra-oral MALT lymphoma using seminested polymerase chain reaction.
Diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma based on histological examination alone is difficult. We report three patients with histologically suspected MALT lymphoma who developed lymphoproliferative lesions of the sublingual gland. Seminested polymerase chain reaction (PCR) analysis applied to formalin-fixed and paraffin-embedded specimens showed clonal rearrangement of immunoglobulin heavy chain genes in two patients and a polyclonal characteristic in one. The clinical findings and Southern blot analysis confirmed the accuracy of the diagnosis. The molecular method described can be applied routinely to processed specimens to obtain helpful information for the diagnosis of low-grade malignancies of lymphoproliferative disorders, such as MALT lymphoma. PMID:14706295
Honda, Kazufumi; Kusama, Hiroshi; Takagi, Satoshi; Sekine, Shigeki; Noguchi, Masayuki; Chiba, Hiroshige
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyo- mavirus. MCV DNA is integrated in ?80% of Merkel cell carcino- mas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody
Masahiro Shuda; Reety Arora; Hyun Jin Kwun; Huichen Feng; Ronit Sarid; María-Teresa Fernández-Figueras; Yanis Tolstov; Ole Gjoerup; Mahesh M. Mansukhani; Steven H. Swerdlow; Preet M. Chaudhary; John M. Kirkwood; Michael A. Nalesnik; Jeffrey A. Kant; Lawrence M. Weiss; Patrick S. Moore; Yuan Chang
Background Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS. Case presentation A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1? and IL-6 (pyretic cytokines), tumor necrosis factor-? and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview. Conclusions A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients. PMID:23497734
Background Glioma is the most common primary malignant central nervous system tumor in adult, and is usually not curable in spite of various therapeutic approaches. Clarification of the oncogenic process in its early stage is important for the diagnosis and effective therapy. Methods In the present study, we used the serological identification of antigens by recombinant cDNA expression cloning (SEREX) to explore the subtle changes of the protein expression in low-grade glioma. The levels of serum autoantibodies to the SEREX-identified glioma-related antigens were analyzed by ELISA, and the epitope site was identified using deletion mutants and overlap peptide array. Changes in the serum autoantibody levels were examined in the rat glioma model using C6 and 9?L glioma cell lines. Results We identified 31 glioma-related antigens by SEREX. Among them, the serum level of autoantibody to src-homology 3-domain GRB2-like 1 (SH3GL1) was significantly higher in patients with low-grade glioma than healthy volunteers or high-grade gliomas. The 10 amino-acids at the C-terminal were identified as the epitope site by the overlap peptide array and the ELISA using deletion mutants. The tissue expression of SH3GL1 protein increased in proportion to glioma progression. The rat glioma models confirmed the increase of anti-SH3GL1 autoantibody level in the early stage and the suppression in the late stage. Conclusion SH3GL1 may be involved in the oncogenic process of gliomas and effectively elicit an autologous antibody response in low-grade gliomas. The immunological reaction to SH3GL1 would contribute to the establishment of a novel diagnostic and therapeutic target for gliomas. PMID:23050879
Background Guangxi has become one of the provinces with the most severe HIV-1 epidemic in China, where heterosexual contact is the dominant transmission route. However, data of acute HIV infections and HIV incidence among female sex workers (FSWs) from low-grade venues are scant. Methods A cross-sectional survey was performed among FSWs from low-grade venues in Guangxi. HIV antibody screening was performed by rapid testing (RT). HIV antibody–negative specimens were screened by pooled nucleic acid amplification testing (NAAT) for acute HIV infections. HIV antibody-positive specimens were further analyzed by Western blot (WB), followed by an HIV-1 BED capture enzyme immunoassay (BED-CEIA) to identify the recent infections. HIV-1 incidence was estimated by the data of pooled NAAT and BED-CEIA, respectively. Results A total of 7936 FSWs were recruited and answered the questionnaires. We successfully collected the blood samples from 6469 (81.5%) participants, of which 139 (2.1%) were HIV antibody–positive and 6330 (97.9%) were HIV antibody-negative by RT. With pooled NAAT, 7 cases were found to be HIV RNA positive, representing an additional 5.0% of HIV-infected persons and an estimated HIV incidence of 1.45 (95% CI: 1.17–1.76) per 100 person years. There were 137 positive and 2 indeterminate by WB, of which 124 (90.5%) positive specimens were subjected to BED-CEIA testing identifying 28 recent infections. The HIV incidence determined by BED-CEIA testing was 1.04 (95% CI: 0.65–1.43) per 100 person years. The overall prevalence of HIV among FSWs from low-grade venues in Guangxi was 2.2% (95% CI: 1.9–2.6). Conclusions We found that the addition of HIV RNA screening to routine HIV antibody testing significantly improved the detection of HIV infection among FSWs from low-grade venues in Guangxi. Our findings also provided the useful baseline data of HIV incidence among this population for targeting local HIV prevention, intervention, monitoring and treatment. PMID:24918933
Shen, Zhiyong; Zhou, Yuejiao; Fang, Ningye; Wang, Lu; Wang, Bin; Wang, Jiangwei; Tang, Zhenzhu
This report describes a 6-year-old boy with disseminated low-grade astrocytoma and ventriculo-peritoneal shunt, who developed recurrent ascites while receiving sorafenib on a clinical trial. Laboratory analysis of the peritoneal fluid showed no elevation of protein content and no evidence of underlying infection or tumor dissemination. This report highlights ascites as a previously unrecognized adverse reaction to sorafenib in a patient with a ventriculo-peritoneal shunt. We conclude that such patients should be closely monitored for this complication when treated with sorafenib. PMID:24351969
Legault, Genevičve; Kieran, Mark W; Scott, Robert Michael; Chordas, Christine; Milla, Sarah S; Karajannis, Matthias A
Cervical cytological terminology varies from country to country. In the USA, the Pap smear is reported using the Bethesda system. The abnormal morphological changes described by this system include two very problematic categories: atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS). The management of ASCUS, which is similar to the British system 'borderline' smear, has been most problematic because the majority of women with this Pap result are normal, although approximately 5-11% have high-grade cervical intraepithelial neoplasia and 1 per 1000 has cervical cancer. Because AGUS is far less common and a significantly greater risk for high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ and cancer, its management is far less controversial, but it is problematic because of clinical confusion with the ASCUS terminology. Low-grade squamous intraepithelial neoplasia is almost entirely related to human papillomavirus. Documentation that certain high-risk types of human papillomavirus are necessary in the aetiology of cervical cancer has led to investigations into the management of these equivocal and low-grade Pap smear abnormalities by testing for these human papillomavirus types. PMID:11563869
Cox, J T
Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integrate an additional copy of the CCl2 gene in the Gt(ROSA)26Sor locus of the mouse genome via homologous recombination in embryonic stem cells. Short-term dietary manipulations were assessed and the findings include metabolic disturbances, premature death, and the manipulation of macrophage plasticity and autophagy. These results raise a number of mechanistic questions for future study. PMID:24453432
Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Mariné-Casadó, Roger; Rull, Anna; Beltrán-Debón, Raúl; Menendez, Javier A.; Vazquez-Martin, Alejandro; Sirvent, Juan J.; Martín-Paredero, Vicente; Corbí, Angel L.; Sierra-Filardi, Elena; Aragončs, Gerard; García-Heredia, Anabel; Camps, Jordi; Alonso-Villaverde, Carlos; Joven, Jorge
The aim of this study was to determine the correlation between expression of HPV16 E6, p53 and p21 proteins and the physical state of HPV16 in cervical cytologies without squamous intraepithelial lesions (Non-SIL) and with low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. 101 liquid-based cytological samples were analyzed. 50 samples were without squamous intraepithelial lesions (Non-IL) and 51 samples of low grade squamous intraepithelial lesions (LSIL), both with HPV16 infection. HPV16 infection was determined by PCR-RFLP, and the physical state of HPV16 by in situ hybridization with tyramide-amplification. The expression of E6, p53 and p21 proteins was evaluated by immunocytochemistry. The expression of HPV16 E6 protein was significantly higher in LSIL that in Non-SIL samples (p=0.006). We found a significant correlation between E6 expression and the physical state of HPV16 in Non-SIL (p=0.049). Our results suggest that high expression of E6 in LSIL is an early event of cervical carcinogenesis and perhaps can be used as an early marker. PMID:24482706
Tagle, Diana K Jiménez; Sotelo, Daniel Hernández; Illades-Aguiar, Berenice; Leyva-Vazquez, Marco A; Alfaro, Eugenia Flores; Coronel, Yaneth Castro; Hernández, Oscar del Moral; Romero, Luz del Carmen Alarcón
The attachment of Acidithiobacillus ferrooxidans and Leptospirillum ferriphilum spp. grown on ferrous medium or adapted to a pyrite mineral concentrate to four mineral substrata, namely, chalcopyrite and pyrite concentrates, a low-grade chalcopyrite ore (0.5 wt%) and quartzite, was investigated. The quartzite represented a typical gangue mineral and served as a control. The attachment studies were carried out in a novel particle-coated column reactor. The saturated reactor containing glass beads, which were coated with fine mineral concentrates, provided a quantifiable surface area of mineral concentrate and maintained good fluid flow. A. ferrooxidans and Leptospirillum spp. had similar attachment characteristics. Enhanced attachment efficiency occurred with bacteria grown on sulphide minerals relative to those grown on ferrous sulphate in an ore-free environment. Selective attachment to sulphide minerals relative to gangue materials occurred, with mineral adapted cultures attaching to the minerals more efficiently than ferrous grown cultures. Mineral-adapted cultures showed highest levels of attachment to pyrite (74% and 79% attachment for A. ferrooxidans and L. ferriphilum, respectively). This was followed by attachment of mineral-adapted cultures to chalcopyrite (63% and 58% for A. ferrooxidans and L. ferriphilum, respectively). A. ferrooxidans and L. ferriphilum exhibited lower levels of attachment to low-grade ore and quartz relative to the sulphide minerals. PMID:22410741
Africa, Cindy-Jade; van Hille, Robert P; Harrison, Susan T L
Background Arthroscopy is a highly sensitive method of evaluating high-grade cartilage lesions but the detection of low-grade lesions is often is unreliable. Objective measurements are required. A novel NIRS (near-infrared-spectroscopy) device for detection of low-grade cartilage defects was evaluated in a preliminary clinical study. Methods In 12 patients who had undergone arthroscopy, the cartilage lesions within the medial knee compartment were classified according to the ICRS protocol. With a NIR spectrometer system and an optical probe, similar in design to a hook used for routine arthroscopy, the optical properties of cartilage were measured during arthroscopy. Results The mean ratio of 2 NIR absorption bands of intact cartilage 3.8 (range 2.3 to 8.7).was significantly lower than that of cartilage with grade 1 lesions (12.8, range 4.8 to 19.6) and grade 2 lesions (13.4, range 10.4 to 15.4). No differences were observed between grade 1 and grade 2 lesions. Conclusion NIRS can be used to distinguish between ICRS grade 1 lesions and healthy cartilage during arthroscopic surgeries. The results of this clinical study demonstrate the potential of NIRS to objectify classical arthroscopic grading systems. PMID:17535439
Spahn, Gunter; Plettenberg, Holger; Kahl, Enrico; Klinger, Hans M; Mückley, Thomas; Hofmann, Gunther O
Background In muscular skeletal oncology aiming to achieve wide surgical margin is one of the main factors influencing patient prognosis. In cases where lesions are either meta or epiphyseal, surgery most often compromises joint integrity and stability because muscles, tendons and ligaments are involved in wide resection. When lesions are well circumscribed they can be completely resected by performing multi-planar osteotomies guided by computer-assisted navigation. We describe a case of low-grade chondrosarcoma of the distal femur where a simple but effective technique was useful to perform complex multiplanar osteotomies. No similar techniques are reported in the literature. Case presentation A 57 year-old Caucasian female was referred to our department for the presence of a distal femur chondrosarcoma. A resection with the presenting technique was scheduled. The first step consists of inserting several K-wires under CT-scan control to delimitate the tumor; the second step consists of tumor removal: in operative theatre, following surgical access, k-wires are used as guide positioning; scalpels are externally placed to k-wires to perform a safe osteotomy. Conclusions Computed assisted resections can be considered the most advantageous method to reach the best surgical outcome; unfortunately navigation systems are only available in specialized centres. The present technique allows for a multiplanar complex resection when navigation systems are not available. This technique can be applied in low-grade tumours where a minimal wide margin can be considered sufficient. PMID:25123066
Beyond NK Cells: The Expanding Universe of Innate Lymphoid Cells
For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development. PMID:24982658
Cella, Marina; Miller, Hannah; Song, Christina
Total lymphoid irradiation in refractory systemic lupus erythematosus
In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.
Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.
Treatment of intractable rheumatoid arthritis with lymphoid irradiation
Subdiaphragmatic lymphoid radiation was used as an alternative to cytotoxic drug therapy to treat six patients with progressive erosive rheumatoid arthritis. All were previously unresponsive to conventional therapy. Radiation (4,000 rad) was given to subdiaphragmatic lymphoid tissues in fractionated doses of 150 to 250 rad each. Three of the six patients demonstrated long-lasting clinical improvement with a decrease in synovitis and morning stiffness and an increase in joint function. All six patients showed a profound depression in the peripheral blood lymphocyte count which persisted for at least six months. The irradiation was well tolerated; there have been no serious complications due to radiotherapy with follow-up ranging from 13 to 36 months. The substantial efficacy in some patients and the lack of severe toxicity in all suggests that radiotherapy deserves further study as an alternative to cytotoxic drugs in the treatment of rheumatoid arthritis.
Strober, S.; Kotzin, B.L.; Hoppe, R.T.; Slavin, S.; Gottlieb, M.; Calin, A.; Fuks, Z.; Kaplan, H.S.
Type-2 innate lymphoid cells in asthma and allergy.
Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors ROR? and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets. PMID:25525730
McKenzie, Andrew N J
Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis
Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.
McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.
Analysis of RAS Oncogene Mutations in Human Lymphoid Malignancies
We investigated the frequency of mutations activating RAS oncogenes in human lymphoid malignancies, including B- and T-cell-derived acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. By the polymerase chain reaction\\/oligonucleotide hybridization method, DNA from 178 cases was analyzed for activating mutations involving codons 12 and 61 of the HRAS, KRAS and NRAS genes and codon 13 of the NRAS
Antonino Neri; Daniel M. Knowles; Angela Greco; Frank McCormick; Riccardo dalla-Favera
Treatment of intractable lupus nephritis with total lymphoid irradiation
Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis.
Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.
Transcription factors controlling innate lymphoid cell fate decisions.
The mucosal epithelium is in direct contact with symbiotic and pathogenic microorganisms. Therefore, the mucosal surface is the principal portal of entry for invading pathogens and immune cells accumulated in the intestine to prevent infections. In addition to these conventional immune system functions, it has become clear that immune cells during steady-state continuously integrate microbial and nutrient-derived signals from the environment to support organ homeostasis. A major role in both processes is played by a recently discovered group of lymphocytes referred to as innate lymphoid cells (ILCs) Innate lymphoid cells (ILCs) that are specifically enriched at mucosal surfaces but are rather rare in secondary lymphoid organs. In analogy to the dichotomy between CD8 and CD4 T cells, we propose to classify ILCs into interleukin-7 receptor ?-negative cytotoxic ILCs and IL-7R?(+) helper-like ILCs. Dysregulated immune responses triggered by the various ILC subsets have been linked to inflammatory diseases such as inflammatory bowel disease, atopic dermatitis and airway hyperresponsiveness. Here, we will review recent progress in determining the transcriptional and developmental programs that control ILC fate decisions. PMID:25038936
Klose, Christoph S N; Diefenbach, Andreas
Purpose: To present prospective neuropsychological data at baseline and follow-up in children and young adults with benign and low-grade gliomas treated with focal stereotactic conformal radiotherapy (SCRT). Methods and Materials: A total of 22 patients (age 4-25 years) with residual/progressive benign and low-grade brain tumors considered suitable for SCRT underwent detailed and in-depth neuropsychological and cognitive testing at baseline before SCRT. The test battery included measurement of age-adjusted intelligence quotients (IQs) and cognitive parameters of visual, spatial, visuomotor, and attention concentrations. Anxiety was measured using the State-Trait Anxiety Inventory for Children and Hamilton Anxiety Rating Scale for patients >16 years old. Patients were treated with high-precision conformal radiotherapy under stereotactic guidance to a dose of 54 Gy in 30 fractions. All neuropsychological assessments were repeated at 6 and 24 months after SCRT completion and compared with the baseline values. Results: The baseline mean full-scale IQ before starting RT for patients <16 years was 82 (range, 33-105). For those >16 years, the corresponding value was 72 (range, 64-129). Of 20 evaluable patients, 14 (70%) had less than average IQs at baseline, even before starting radiotherapy. The verbal IQ, performance IQ, and full-scale IQ, as well as other cognitive scores, did not change significantly at the 6- and 24-month follow-up assessments for all patients. The memory quotient in older children and young adults was maintained at 6 and 24 months after SCRT, with a mean value of 93 and 100, respectively, compared with a mean baseline value of 81 before RT. The mean anxiety score in children measured by the C1 and C2 components of the State-Trait Anxiety Inventory for Children (STAIC) was 48 and 40, respectively, which improved significantly to mean values of 30 and 26, respectively, at the 24-month follow-up assessment (p = 0.005). The mean depression score in patients >16 years old was 23 at baseline and had improved to 17 and 14 at the 6-month and 24-month follow-up assessments, respectively. Conclusion: Our data demonstrated neuropsychological impairment in a cohort of young patients with benign and low-grade tumors even before starting radiotherapy. SCRT, however, did not result in any additional worsening. These encouraging results need to be validated in a study with a larger number of patients and longer follow-up.
Jalali, Rakesh [Department of Radiation Oncology, Tata Memorial Hospital, Mumbai (India)]. E-mail: firstname.lastname@example.com; Goswami, Savita [Department of Clinical Psychology, Tata Memorial Hospital, Mumbai (India); Sarin, Rajiv [Department of Radiation Oncology, Tata Memorial Hospital, Mumbai (India); More, Niteen [Department of Radiation Oncology, Tata Memorial Hospital, Mumbai (India); Siddha, Manish [Department of Radiation Oncology, Tata Memorial Hospital, Mumbai (India); Kamble, Rashmi [Brain Tumor Foundation of India, Mumbai (India)
STUDY DESIGN.: Retrospective clinical data analysis. OBJECTIVE.: To investigate and verify our philosophy of spontaneous slip reduction following circumferential release via bilateral minimally invasive transforaminal lumbar interbody fusion (Mini-TLIF) for treatment of low-grade symptomatic isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA.: Symptomatic isthmic spondylolisthesis usually requires surgical intervention, and the most currently controversial focus is on method and degree of reduction; and Mini-TLIF is an attractive surgical procedure for isthmic spondylolisthesis. METHODS.: Between February 2004 and June 2008, 21 patients with low-grade isthmic spondylolisthesis underwent Mini-TLIF in our institute. Total resection of the scar around the pars interarticularis liberated the nerve roots, achieving posterior release as well. The disc was thoroughly resected, and the disc space was gradually distracted and thoroughly released with sequential disc shavers until rupture of anulus conjunct with anterior longitudinal ligament, accomplishing anterior release, so as to insert Cages. Because of circumferential release, the slipped vertebrae would tend to obtain spontaneous reduction, and with pedicle screw fixation, additional reduction would be achieved without any application of posterior translation force. Radiographs, Visual Analogue Scale, and Oswestry Disability Index were documented. All the cases were followed up for 10 to 26 months. RESULTS.: Slip percentage was reduced from 24.2% ± 6.9% to 10.5% ± 4.0%, and foraminal area percentage increased from 89.1% ± 3.0% to 93.6% ± 2.1%. Visual Analogue Scale and Oswestry Disability Index decreased from 7.8 ± 1.5 to 2.1 ± 1.1 and from 53.3 ± 16.2 to 17.0 ± 7.8, respectively. No neurologic complications were encountered. There were no signs of instrumentation failure. The fusion rate approached 100%. CONCLUSION.: Slip reduction is based on circumferential release. The procedure can be well performed via Mini-TLIF, the outcome of which is equally gratifying to that of instrumented slip reduction and traditional midline approach. There is no need to fully reduce the slipped vertebrae. Circumferential release contributes to achieving spontaneous slip reduction partially, which aids sufficiently in the surgical treatment of low-grade isthmic spondylolisthesis. PMID:20714277
Pan, Jie; Li, Lijun; Qian, Lie; Zhou, Wei; Tan, Jun; Zou, Le; Yang, Mingjie
A consortium of microorganisms from acid mine drainage samples was cultured in modified 9 K medium containing low-grade copper sulfide. The culture was maintained for sixty days and then transferred to fresh medium. This process was repeated three more times and a final consortium exhibiting a copper extraction rate of 89.3% was obtained. RFLP and microarrays analysis of 16S rRNA sequences retrieved from the consortia showed that Acidithiobacilluscaldus, Leptospirillumferriphilum, Sulfobacillus sp., Acidiphilium sp., and Sulfolobus spp. were represented in higher numbers in the consortia obtained in the copper-containing medium than in the original consortium. In contrast, a decrease in Acidithiobacillus ferrooxidans, Alicyclobacillus sp., Pseudomonas sp., and Sulfobacillus thermosulfidooxidans was observed. The abundance of genes related to sulfur metabolism from At. caldus and Sulfolobus spp., iron oxidation from Leptospirillum sp. and metal resistance from most of the detected microorganisms increased as the consortium was successively transferred into fresh medium. PMID:21862325
Liu, Yi; Yin, Huaqun; Liang, Yili; Shen, Li; Liu, Yao; Fu, Xian; Baba, Ngom; Zeng, Weimin; Qiu, Guanzhou; Liu, Xueduan
Low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland is a rare tumor. We report the cytologic features and histologic correlation of a patient with LGCCC. A 57-year-old man had a hardly palpable, nontender mass in the right cheek area followed over nine months. Radiologic analysis revealed a 1.2 cm multiseptated, cystic, solid nodule in an anterior superficial lobe of the right parotid gland. Fine-needle aspiration cytology revealed many irregular overlapping sheets or clusters of ductal epithelial cells forming solid, pseudopapillary, and cribriform architectures. Nuclei of the tumor cells revealed inconspicuous atypia with minimal size variation. On the basis of these findings, we confirmed a diagnosis of ductal epithelial proliferative lesion, favoring neoplasm, with uncertain malignant potential. Tumor excision was performed, revealing a tiny multicystic nodule (0.7 cm). Histopathologically, this tumor showed the characteristic morphology of LGCCC. This is the first report of cytomorphological findings of LGCCC in Korea. PMID:24421856
Ko, Young Sin
This report contains reduced 40Ar/39Ar data of white mica and K-feldspar mineral separates and matrix of a whole rock phyllite, all from low-grade metamorphic rocks of the Westminster terrane and adjacent strata in central Maryland. This report presents these data in a preliminary form, but in more detail than can be accommodated in todays professional journals. Also included in this report is information on the location of the samples and a brief description of the samples. The data contained herein are not interpreted in a geological context, and care should be taken by readers unfamiliar with argon isotopic data in the use of these results; many of the individual apparent ages are not geologically meaningful. This report is primarily a detailed source document for subsequent publications that will integrate these data into a geological context.
Kunk, Michael J.; McAleer, Ryan
In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to "nurture" than "nature," since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for "healthy aging," and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture. PMID:23657158
Ruiz-Núńez, Begońa; Pruimboom, Leo; Dijck-Brouwer, D A Janneke; Muskiet, Frits A J
We examined the relationship between grip strength declines and muscle-tendon responses induced by long-term performance of a high-repetition, low-force (HRLF) reaching task in rats. We hypothesized that grip strength declines would correlate with inflammation, fibrosis and degradation in flexor digitorum muscles and tendons. Grip strength declined after training, and further in weeks 18 and 24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed low-grade increases in inflammatory cytokines: IL-1? after training and in week 18, IL-1? in week 18, TNF-? and IL-6 after training and in week 24, and IL-10 in week 24, with greater increases in tendons than muscles. Similar cytokine increases were detected in serum with HRLF: IL-1? and IL-10 in week 18, and TNF-? and IL-6 in week 24. Grip strength correlated inversely with IL-6 in muscles, tendons and serum, and TNF-? in muscles and serum. Four fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles, tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2 in tendons and serum. Thus, motor declines correlated with low-grade systemic and musculotendinous inflammation throughout task performance, and increased fibrogenic and degradative proteins with prolonged task performance. Serum TNF-?, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related musculoskeletal disorders, although further studies in humans are needed. PMID:24015193
Gao, Helen G. L.; Fisher, Paul W.; Lambi, Alex G.; Wade, Christine K.; Barr-Gillespie, Ann E.; Popoff, Steven N.; Barbe, Mary F.
The long-term follow-up of the RTOG 9802 trial that compared 54 Gy of radiotherapy (RT) with the same RT followed by adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy in high-risk low-grade glioma shows a major increase in survival after adjuvant PCV chemotherapy. Median overall survival increased from 7.8 years to 13.3 years, with a hazard ratio of death of 0.59 (log rank: P = .002). This increase in survival was observed despite the fact that 77% of patients who progressed after RT alone received salvage chemotherapy. With this outcome, RT + PCV is now to be considered standard of care for low-grade glioma requiring postsurgical adjuvant treatment. Unfortunately, studies on molecular correlates associated with response are still lacking. This is now the third trial showing benefit from the addition of PCV to RT in grade II or III diffuse glioma. The optimal parameter for selecting patients for adjuvant PCV has not yet been fully elucidated, but several candidate markers have so far emerged. It is still unclear whether temozolomide can replace PCV and whether initial management with chemotherapy only is a safe initial treatment. Potentially, that may adversely affect overall survival, but concerns for delayed RT-induced neurotoxicity may limit acceptance of early RT in patients with expected long term survival. The current evidence supports that in future trials, grades II and III tumors with similar molecular backgrounds should be combined, and trials should focus on molecular glial subtype regardless of grade. PMID:25355680
van den Bent, Martin J
Background: The debate continues regarding the best management for women with low-grade abnormal cervical cytology attending colposcopy. We compared psychosocial outcomes of alternative management policies in these women. Methods: In all, 989 women, aged 20–59 years, with low-grade abnormal cytology, were randomised to immediate large loop excision (LLETZ) or two to four targeted punch biopsies taken immediately with recall for LLETZ if these showed cervical intra-epithelial neoplasia 2/3. At 6 weeks after the last procedure, women completed the hospital anxiety and depression scale (HADS) and the impact of event scale (IES). At 12, 18, 24 and 30 months post recruitment, women completed the HADS and process outcome specific measure (POSM). Prevalence of significant depression (?8), significant anxiety (?11) and distress (?9) and median POSM scores were compared between arms. Multivariate odds ratios (ORs) for immediate LLETZ vs biopsy and recall were computed. Results: Over the entire follow-up, there was no significant difference between arms in cumulative prevalence or risk of significant depression (OR=0.78, 95% CI 0.52–1.17) or significant anxiety (OR=0.83, 95% CI 0.57–1.19). At 6 weeks post procedure, distress did not differ significantly between arms. At later time points, 8–11% had significant depression and 14–16% had significant anxiety but with no differences between arms. The POSM scores did not differ between the arms. Conclusions: There is no difference in long- or short-term psychosocial outcomes of immediate LLETZ and punch biopsies with selective recall. PMID:21179033
Sharp, L; Cotton, S; Gray, N; Avis, M; Russell, I; Walker, L; Waugh, N; Whynes, D; Woolley, C; Thornton, A; Smart, L; Cruickshank, M; Little, J
Aging impacts isolated lymphoid follicle development and function
Background Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice. Results We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8??+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice. Conclusions Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence. PMID:21214915
Trafficking of. cap alpha. -L-fucosidase in lymphoid cells
The quantity of ..cap alpha..-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high ..cap alpha..-L-fucosidase in serum were established. Steady state levels of extracellular ..cap alpha..-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of ..cap alpha..-L-fucosidase are not adequately expressed in this system. ..cap alpha..-L-Fucosidase was also metabolically labelled with /sup 35/S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of ..cap alpha..-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between ..cap alpha..-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells.
DiCioccio, R.A.; Brown, K.S.
Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.
Growing evidence supports the involvement of human herpervirus 8, Kaposi's sarcoma associated herpesvirus (KSHV), in the pathology of primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma, but the exact mechanism of KSHV contribution to the oncogenic process remains elusive. We studied transgenic mice expressing the ORF K1 of KSHV, whose position in the KSHV genome corresponds to known lymphoproliferative genes of other herpesviruses. K1 protein was previously shown to contain a constitutively active ITAM domain, involved in activation of Akt and pro-survival signaling, and to inhibit Fas-mediated apoptosis by interfering with binding of FasL. All this pointed to a possible role of K1 in the pathogenesis of KSHV-associated cancers. K1 transgenic mice (80-90%) developed lymphoid hyperplasia and splenomegaly at 8 and 10 months of age, 25% had confirmed diagnosis of lymphoma, and 50% developed abdominal and/or hepatic tumors by 18 months of age. Histological examination showed loss of splenic architecture and increased cellularity. Lymph nodes showed disrupted architecture with effaced follicles and other pathological changes, including signs of angiofollicular lymphoid hyperplasia. One of the livers showed signs of angiosarcoma. In summary, our histology results revealed pathological changes in K1 transgenic mice similar to lymphoma, Castleman's disease, and angiosarcoma, suggesting that K1 may contribute to the development of KSHV-associated cancers. PMID:25301266
Berkova, Zuzana; Wang, Shu; Sehgal, Lalit; Patel, Keyur Pravinchandra; Prakash, Om; Samaniego, Felipe
Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation
Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.
Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.
Immunoglobulin Expression in Non-Lymphoid Lineage and Neoplastic Cells
It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon. PMID:19246641
Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang
Lymphoid Lesions of the Head and Neck: A Model of Lymphocyte Homing and Lymphomagenesis
Lymphoid lesions of the head and neck mainly affect the nasopharynx, nasal and paranasal sinuses, and salivary glands. These three compartments each are affected by a different spectrum of lymphoid malignancies and can serve as model for mechanisms of lymphomagenesis. The type of lymphoma seen reflects the underlying biology and function of the particular site involved. The nasopharynx and Waldeyer's
Elaine S. Jaffe
Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie.
The scrapie-associated form of the prion protein (PrPSc) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrPSc in lymphoid tissue could be used as a diagnostic test for scrapie, we studied the localization and distribution of PrPSc in various lymphoid tissues collected at necropsy from 55 sheep with clinical scrapie. Samples collected from the spleen, palatine tonsil, ileum, and five different lymph nodes were immunohistochemically stained for PrPSc. PrPSc was found to be deposited in a reticular pattern in the center of both primary and secondary lymphoid follicles. In addition, granules of PrPSc were seen in the cytoplasm in macrophages associated with the lymphoid follicles. In 54 (98%) of the 55 scrapie-affected sheep, PrPSc was detected in the spleen, retropharyngeal lymph node, mesenteric lymph node, and the palatine tonsil. However, only in the palatine tonsils was PrPSc present in a consistently high percentage of the lymphoid follicles. PrP was not detected in any of the lymphoid tissues of 12 sheep that had no neurohistopathological signs of a scrapie infection. We conclude that the tonsils are the best-suited lymphoid tissue to be biopsied for the detection of PrPSc in the diagnosis of clinical scrapie in living sheep. PMID:8727908
van Keulen, L J; Schreuder, B E; Meloen, R H; Mooij-Harkes, G; Vromans, M E; Langeveld, J P
Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie.
The scrapie-associated form of the prion protein (PrPSc) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrPSc in lymphoid tissue could be used as a diagnostic test for scrapie, we studied the localization and distribution of PrPSc in various lymphoid tissues collected at necropsy from 55 sheep with clinical scrapie. Samples collected from the spleen, palatine tonsil, ileum, and five different lymph nodes were immunohistochemically stained for PrPSc. PrPSc was found to be deposited in a reticular pattern in the center of both primary and secondary lymphoid follicles. In addition, granules of PrPSc were seen in the cytoplasm in macrophages associated with the lymphoid follicles. In 54 (98%) of the 55 scrapie-affected sheep, PrPSc was detected in the spleen, retropharyngeal lymph node, mesenteric lymph node, and the palatine tonsil. However, only in the palatine tonsils was PrPSc present in a consistently high percentage of the lymphoid follicles. PrP was not detected in any of the lymphoid tissues of 12 sheep that had no neurohistopathological signs of a scrapie infection. We conclude that the tonsils are the best-suited lymphoid tissue to be biopsied for the detection of PrPSc in the diagnosis of clinical scrapie in living sheep. PMID:8727908
van Keulen, L J; Schreuder, B E; Meloen, R H; Mooij-Harkes, G; Vromans, M E; Langeveld, J P
Occup Environ Med. Author manuscript Page /1 12 Occupational exposure to pesticides and lymphoid between occupational exposure to pesticides and the risk of lymphoid neoplasms (LN) in men. Methods in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific
Paris-Sud XI, Université de
The development and function of mucosal lymphoid tissues: a balancing act with micro-organisms.
Mucosal surfaces are constantly exposed to environmental antigens, colonized by commensal organisms and used by pathogens as points of entry. As a result, the immune system has devoted the bulk of its resources to mucosal sites to maintain symbiosis with commensal organisms, prevent pathogen entry, and avoid unnecessary inflammatory responses to innocuous antigens. These functions are facilitated by a variety of mucosal lymphoid organs that develop during embryogenesis in the absence of microbial stimulation as well as ectopic lymphoid tissues that develop in adults following microbial exposure or inflammation. Each of these lymphoid organs samples antigens from different mucosal sites and contributes to immune homeostasis, commensal containment, and immunity to pathogens. Here we discuss the mechanisms, mostly based on mouse studies, that control the development of mucosal lymphoid organs and how the various lymphoid tissues cooperate to maintain the integrity of the mucosal barrier. PMID:24569801
Randall, T D; Mebius, R E
Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid
Abstract We conducted a phase I-II clinical trial to assess the safety and efficacy of combining lutetium-177 ((177)Lu)-octreotate with capecitabine and temozolomide in treating advanced low-grade neuroendocrine tumors (NETs). All 35 patients received fixed activities of 7.8 GBq (177)Lu-octreotate each 8 weeks, with 14 days of capecitabine 1500 mg/m(2) for 4 cycles. In phase I, successive cohorts of patients received escalating doses of temozolomide in groupings of 100, 150, and 200 mg/m(2) in the last 5 days of each capecitabine cycle. In phase II, patients were treated with 200 mg/m(2) temozolomide. Treatment was well tolerated in all dosage groups. No dose-limiting grade 2, 3, or 4 toxicities were seen in cohorts 1 (100 mg/m(2)) or 2 (150 mg/m(2)). Twenty-eight patients completed treatment at the 200 mg/m(2) temozolomide level. Adverse events were mild to moderate. The commonest toxicities were transient nausea grade 2 (18%), grade 3 (3%), thrombocytopenia grade 2 (24%), and neutropenia grade 3 (6%). There were no grade 4 events. Thirty-four patients were evaluable for tumor response. Overall, complete response (CR) was achieved in 15% (95% CI 3-27); partial response (PR), in 38% (95% CI 22-55); stable disease (SD), in 38% (95% CI 22-55); and 3 patients failed to respond to treatment. Median progression free survival (PFS) was 31 months (95% CI 21-33), and median overall survival (OS) has not been reached with 90% surviving at 24 months follow-up (range 21-30). Overall objective response rate (ORR) in patients with gastroenteropancreatic NETs showed CR 16% (95% CI 3-28), PR 41% (95% CI 24-58), SD 37% (95% CI 21-54), and PD 6% (95% CI 0-15). Response rates were higher in patients with gastropancreatic NETs than in those with bowel primaries (enteric-NETs); CR 18% versus 13%, PR 64% versus 13%, SD 12% versus 67%. (177)Lu-octreotate, in combination with capecitabine and temozolomide, is well tolerated in patients with advanced low-grade NETs, and shows substantial tumor control rates. PMID:23078020
Claringbold, Phillip G; Price, Richard A; Turner, J Harvey
NASA Astrophysics Data System (ADS)
Metamorphic rocks of the Slavonian Mts. (NE Croatia) cropping out on the SW edge of the Pannonian Basin belong to the Bihor nappe system of Tisia Mega-Unit i.e. of the lithospheric fragment broken off from the southern margin of the European plate. The present-day position of this Unit resulted from complex regional-scale Mesozoic and Cenozoic movements during the Alpine-Carpathian-Dinaridic orogenic system geodynamic evolution. Usually, the metamorphic rocks of the Slavonian Mts. are interpreted as a part of igneous-metamorphic complex belonging to metamorphic belt formed during or even prior to the Variscan orogeny. Until recently, the Alpine metamorphic evolution was considered insignificant and often neglected or described just in general terms due to considerable lack of geothermobarometric, phase equilibrium, fossil and/or geochronological age constraints. The chlorite schists are widely distributed lithology in the area, comprising simple peak metamorphic mineral assemblage chlorite + plagioclase (albite) + muscovite + quartz ± garnet and are associated to the local complex called Psunj complex (PsC). Metamorphic conditions for non-garnetiferous chlorite schists are obtained with chlorite (Al(IV)) thermometry and white mica barometry are 300 °C and 2.4±0.6 kbar. The chlorite schists are thrusted over (~ to the NE) microtectonically similar chloritoid-bearing schists that reached peak P-T values of 3.5-4 kbar and 340-380 °C. At least two distinct penetrative low-grade metamorphic foliations recorded in the chlorite schists are accompanied by existence of different populations of small (~3.5 µm) low-Th monazites, giving an average age 99±15 Ma. Histogram of obtained ages shows two peaks at 120 and 80 Ma while age modelling recognized two peaks at 113±20 and 82±23 Ma. First Alpine (113±20 Ma) event represents a rare record of late Early Cretaceous thermal event that affected Bihor nappe system. The age contradicts common opinion that Bihor nappe escaped thermal changes during east-facing thrusting i.e. "Austrian orogeny". The second (82±23 Ma) monazite age population is tentatively associated with Late Cretaceous regional orogenic event characterized by low-grade low-pressure metamorphism. The post-tectonic growth of chloritoid (in chloritoid schist) with respect to S2 foliation indicates that the major phase of Alpine deformation predates the peak metamorphic conditions (thermal climax) leaving opened the possibility for detection of three distinct events during the Cretaceous. Hence, the prograde Alpine metamorphic event(s) had a more significant influence on the evolution of the southern part of Tisia Mega-Unit than previously considered.
Balen, Dražen
Purpose: There is no consensus on the treatment strategy for adult patients with cerebral low-grade glioma. The diagnosis and primary treatment are usually undertaken by surgery. Some investigators doubt the efficacy of postoperative radiotherapy (RT), whereas others advise routine postoperative RT. We report the primary results of a multicenter randomized trial on this controversy.Methods and Materials: From 24 European centers,
Abul B. M. F Karim; Denes Afra; Philippe Cornu; Norman Bleehan; Simon Schraub; Olivier De Witte; François Darcel; Sally Stenning; Marianne Pierart; Martine Van Glabbeke
Background and purpose: It is crucial to accurately differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) preoperatively, as treatment strategies vary. So we performed a meta-analysis to assess the sensitivity and specificity of fractional anisotropy (FA) value derived from diffusion tensor imaging (DTI) in differentiating HGGs from LGGs. Materials and methods: Between January 2005 and June 2014, relevant articles were searched from the Embase and Medline databases for analysis. Statistical analyses were performed using Meta-Disc 1.4. Results: A total of 221 patients included in the FA analysis: 127 with HGGs and 94 LGGs. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) for differentiating HGGs from LGGs were 93% (95% CI 0.87-0.97), 85% (95% CI 0.76-0.92), and 55.41 (95% CI 16.77-183.07), respectively. And computation of heterogeneity metrics revealed an acceptable level of the between-study heterogeneity of DOR (I2=30.9%). Conclusions: The results of our meta-analysis present that the FA derived from DTI act as a useful diagnostic marker could be used in distinguishing the HGGs from LGGs in the preoperative and the clinical application values are to be confirmed by further larger case-control studies. PMID:25419413
Liang, Ruofei; Wang, Xiang; Li, Mao; Yang, Yuan; Luo, Jiewen; Mao, Qing; Liu, Yanhui
Diffuse gliomas consist of both low- and high-grade varieties, each with distinct morphological and biological features. The often extended periods of relative indolence exhibited by low-grade gliomas (LGG; WHO grade II) differ sharply from the aggressive, rapidly fatal clinical course of primary glioblastoma (GBM; WHO grade IV). Nevertheless, until recently, the molecular foundations underlying this stark biological contrast between glioma variants remained largely unknown. The discoveries of distinctive and highly recurrent genomic and epigenomic abnormalities in LGG have both informed a more accurate classification scheme and pointed to viable avenues for therapeutic development. As such, the field of neuro-oncology now seems poised to capitalize on these gains to achieve significant benefit for LGG patients. This report will briefly recount the proceedings of a workshop held in January 2013 and hosted by Accelerate Brain Cancer Cure (ABC2) on the subject of LGG. While much of the meeting covered recent insights into LGG biology, its focus remained on how best to advance the clinical management, whether by improved preclinical modeling, more effective targeted therapeutics and clinical trial design, or innovative imaging technology. PMID:24305708
Huse, Jason T.; Wallace, Max; Aldape, Kenneth D.; Berger, Mitchel S.; Bettegowda, Chetan; Brat, Daniel J.; Cahill, Daniel P.; Cloughesy, Timothy; Haas-Kogan, Daphne A.; Marra, Marco; Miller, C. Ryan; Nelson, Sarah J.; Salama, Sofie R.; Soffietti, Riccardo; Wen, Patrick Y.; Yip, Stephen; Yen, Katharine; Costello, Joseph F.; Chang, Susan
The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in 6 adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh frozen whole pancreatic tissue using PCR and sequencing. Non-diabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetes patients (2 of 9 controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (1 of 9 controls). Enterovirus specific RNA sequences were detected in 4 of 6 cases (0 of 6 controls). The results were confirmed in different laboratories. Only 1.7 % of the islets contained VP1 positive cells and the amount of enterovirus RNA was low. The results provides evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, being consistent with the possibility that a low grade enteroviral infection in the pancreatic islets contribute to disease progression in humans. PMID:25422108
Krogvold, Lars; Edwin, Bjřrn; Buanes, Trond; Frisk, Gun; Skog, Oskar; Anagandula, Mahesh; Korsgren, Olle; Undlien, Dag; Eike, MortenC; Richardson, Sarah J; Leete, Pia; Morgan, Noel G; Oikarinen, Sami; Oikarinen, Maarit; Laiho, Jutta E; Hyöty, Heikki; Ludvigsson, Johnny; Hanssen, Kristian F; Dahl-Jřrgensen, Knut
A simple and novel method to quantify adulterations of extra virgin olive oil (EVOO) with refined olive oil (ROO) and refined olive-pomace oil (ROPO) is described here. This method consists of calculating chaotic parameters (Lyapunov exponent, autocorrelation coefficients, and two fractal dimensions, CPs) from UV-vis scans of adulterated EVOO samples. These parameters have been successfully linearly correlated with the ROO or ROPO concentrations in 396 EVOO adulterated samples. By an external validation process, when the adulterating agent concentration is less than 10%, the integrated CPs/UV-vis model estimates the adulterant agent concentration with a mean correlation coefficient (estimated versus real concentration of low grade olive oil) greater than 0.97 and a mean square error of less than 1%. In light of these results, this detector is suitable not only to detect adulterations but also to measure impurities when, for instance, a higher grade olive oil is transferred to another storage tank in which lower grade olive oil was stored that had not been adequately cleaned. PMID:20070088
Torrecilla, José S; Rojo, Ester; Domínguez, Juan C; Rodríguez, Francisco
The paper deals with experimental design and optimization of leaching process of uranium and associated metals from low-grade, Polish ores. The chemical elements of interest for extraction from the ore were U, La, V, Mo, Yb and Th. Sulphuric acid has been used as leaching reagent. Based on the design of experiments the second-order regression models have been constructed to approximate the leaching efficiency of elements. The graphical illustrations using 3-D surface plots have been employed in order to identify the main, quadratic and interaction effects of the factors. The multi-objective optimization method based on desirability approach has been applied in this study. The optimum condition have been determined as P=5 bar, T=120 °C and t=90 min. Under these optimal conditions, the overall extraction performance is 81.43% (for U), 64.24% (for La), 98.38% (for V), 43.69% (for Yb) and 76.89% (for Mo) and 97.00% (for Th). PMID:24857897
Zakrzewska-Koltuniewicz, Gra?yna; Herdzik-Koniecko, Irena; Cojocaru, Corneliu; Chajduk, Ewelina
The adsorption phenomena and specific reaction processes of phosphate onto wasted low grade iron ore with high phosphorus (WLGIOWHP) were studied in this work. Zeta potential and Fourier transform infrared spectroscopy (FTIR) analyses were used to elucidate the interaction mechanism between WLGIOWHP and aqueous solution. The results implied that the main adsorption mechanism was the replacement of surface hydroxyl groups by phosphate via the formation of inner-sphere complex. The adsorption process was characterized by chemical adsorption onto WLGIOWHP. The non-electrostatic model (NEM) was used to simulate the surface adsorption of phosphate onto WLGIOWHP. The total surface site density and protonation constants for NEM (N(T)=1.6×10(-4) mol/g, K(a1)=2.2×10(-4), K(a2)=6.82×10(-9)) were obtained by non-linear data fitting of acid-base titrations. In addition, the NEM was used to establish the surface adsorption complexation modeling of phosphate onto WLGIOWHP. The model successfully predicted the adsorption of phosphate onto WLGIOWHP from municipal wastewater. PMID:24910055
Yuan, Xiaoli; Bai, Chenguang; Xia, Wentang; An, Juan
Early magnetite in sedimentary rocks must be preserved to retain a paleomagnetic signature; however, reactions such as Fe{sub 3}O{sub 4} + 3 FeS{sub 2} + CH{sub 4}' = (organic matter) = 6 FeS' (pyrr.) + CO{sub 2} + 2 H{sub 2}O tend to the right for temperatures less than {approximately}200C. Such low temperatures strongly imply that magnetite can be destroyed merely by deep burial. Such pyrrhotite formation is illustrated by very low-grade metamorphism in a contact aureole surrounding the Jurassic Notch Peak stock in the central House Range of western Utah. The stock invades a Cambrian sedimentary sequence containing miogeoclinal limestones with intercalated siltstones. Limestones in the aureole yield a scattered, two-polarity remagnetization, residing in pyrrhotite, which extends into rocks that appear unmetamorphosed (temperatures {approximately}250C). The pyrrhotite could not have been precipitated from externally derived fluids because oxygen isotopic data from the limestones show no influence of magmatic or phreatic water; hence, it must have formed in situ, as in the above equation. Outside the aureole, a characteristic magnetization is preserved that apparently reflects late Paleozoic remagnetization and that probably resides in authigenic magnetite. Hence, it appears that this relatively late magnetite was in turn destroyed by modest reheating from the pluton. In general, thermal remagnetization of sedimentary rocks is probably rare: chemical changes probably have a much more profound effect on the paleomagnetic signatures.
Gillett, S.L. (Univ. of Nevada, Reno (United States))
Objective To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging. Methods All patients from 9/2005-12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells. Results Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion. Conclusions Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases. PMID:24099838
Kim, Christine H.; Khoury-Collado, Fady; Barber, Emma L.; Soslow, Robert A.; Makker, Vicky; Leitao, Mario M.; Sonoda, Yukio; Alektiar, Kaled M.; Barakat, Richard R.; Abu-Rustum, Nadeem R.
Elevated activation of the platelet-derived growth factor (PDGF) pathway, apoptosis evasion phenotype, and global DNA hypomethylation are hallmarks frequently observed in cancers, such as in low-grade glioma (LGG). However, the orchestration of these malignant functions is not fully elucidated in LGG. Our study reveals that the co-presence of these hallmarks in the same LGG is frequent and confers poor prognosis in patients with LGG. Our data also indicate that the apoptosis evasion phenotype of these cells harboring a hypomethylation-induced activation of the PDGF pathway is associated with a hypomethylation of the bcl-xl and bcl-w genes and the phosphorylation and/or downregulation of three major pro-apoptotic BH3-only proteins: PUMA, Bad, and Bim. Consistent with this, we demonstrate that the use of folate, a DNA-methylating agent, promotes the reprogramming of the sensitivity of glioma cells to ABT-737/etoposide-induced apoptosis and reduces the dose of ABT-737 required to promote etoposide-induced apoptosis. This work supports the idea that the inclusion of folate and/or ABT-737 could be a promising adjuvant in the design of anti-glioma therapeutic protocols in clinical studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13148-011-0035-5) contains supplementary material, which is available to authorized users. PMID:21949549
Debien, Emilie; Hervouet, Eric; Gautier, Fabien; Juin, Philippe; Vallette, Francois M; Cartron, Pierre-Francois
NASA Astrophysics Data System (ADS)
The catalytic-oxidative leaching of a mixed ore, which consists of low-grade oxide copper ore and oxide zinc ore containing ZnS, was investigated in ammonia-ammonium sulfate solution. The effect of the main parameters, such as mass ratio of copper ore to zinc ore, liquid-to-solid ratio, concentration of lixivant, leaching time, and temperature, was studied. The optimal leaching conditions with a maximum extraction of Cu 92.6 pct and Zn 85.5 pct were determined as follows: the mass ratio of copper ore to zinc ore 4/10 g/g, temperature 323.15 K (50 °C), leaching time 6 hours, stirring speed 500 r/min, liquid-to-solid ratio 3.6/1 cm3/g, concentration of lixivant including ammonia 2.0 mol/dm3, ammonium sulfate 1.0 mol/dm3, and ammonium persulfate 0.3 mol/dm3. It was found that ZnS in the oxide zinc ore could be extracted with Cu(II) ion, which was produced from copper ore and was used as the catalyst in the presence of ammonium persulfate.
Liu, Zhi Xiong; Yin, Zhou Lan; Hu, Hui Ping; Chen, Qi Yuan
The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azumolene for the treatment of low-grade non-Hodgkin's lymphoma is warranted. PMID:9635834
Shamash, J.; Salam, A. H.; Davies, D. C.; Williams, A.; Joel, S.; Lister, T. A.
Pyrite oxidation and release of the oxidation products from a low-grade coal waste dump to stream, groundwater and soil was investigated by geochemical and hydrogeochemical techniques at Alborz Sharghi coal washing plant, Shahrood, northeast Iran. Hydrogeochemical analysis of water samples indicates that the metal concentrations in the stream waters were low. Moreover, the pH of the water showed no considerable change. The analysis of the stream water samples shows that except the physical changes, pyrite oxidation process within the coal washing waste dump has not affected the quality of the stream water. Water type was determined to be calcium sulphate. The results of the analysis of groundwater samples indicate that the pH varies from 7.41 to 7.51. The concentrations of the toxic metals were low. The concentration of SO4 is slightly above than its standard concentration in potable water. It seems that the groundwater less affected by the coal washing operation in the study area. Geochemical analysis of the sediment samples shows that Fe concentration decreases gradually downstream the waste dump with pH rising. SO(4) decreases rapidly downstream direction. Copper, Zn and Co concentrations decrease with distance from the waste dump due to a dilution effect by the mixing of uncontaminated sediments. These elements, in particular, Zn are considerably elevated in sediment sample collected at the nearest distance to the waste dump. There is no doubt that such investigations can help to develop an appropriate water remediation plan. PMID:21350923
Doulati Ardejani, Faramarz; Jodieri Shokri, Behshad; Moradzadeh, Ali; Shafaei, Seyed Ziadin; Kakaei, Reza
Endometrial stromal tumors (ESTs) are composed of cells resembling endometrial stroma, and are divided into benign and malignant types based on morphology. Endometrial stromal nodule (ESN) is a benign localized tumor, and endometrial stromal sarcoma (ESS) is an infiltrative and potentially metastatic neoplasm. A series of genetic aberrations contribute to pathological diagnosis of ESTs. At present, subsets of ESN and ESS-low grade (ESS-LG) are characterized as JAZF1-SUZ12/JJAZ1 gene fusion. The ESTs that show higher grade atypia but lack nuclear pleomorphism include YWHAE-FAM22?ESS. Here we report an unusual case of ESTs. Sudden colonic perforation occurred to the patient, and emergency surgery was performed. Pathological findings suggested metastatic ESS. Thorough medical examination of the genital organs detected a 1?cm-sized well-demarcated uterine tumor. Microscopically, the tumor lacked infiltrative features, conforming to the definition of ESN. Both lesions demonstrated identical cytology and shared JAZF1-SUZ12 gene fusion. Endometriosis was not found in any areas of the resected organs, strongly suggesting that the uterine orthotopic tumor metastasized. The current case uncovered the problems of differential diagnosis between ESN and ESS-LG. We demonstrate detailed pathological features of the two lesions, and discuss the possibility of orthotopic EST with limited infiltration to develop into ESS-LG. PMID:24750188
Tokinaga, Aya; Furuya, Mitsuko; Niino, Hitoshi; Udaka, Naoko; Asai-Sato, Mikiko; Sekido, Hitoshi; Miyagi, Etsuko
Developmental programming of natural killer and innate lymphoid cells.
In recent years we have witnessed a blooming interest in innate lymphoid cell (ILC) biology thanks to the discovery of novel lineages of ILC that are phenotypically and functionally distinct from NK cells. While the importance of these novel ILC subsets as essential functional components of the early immune responses are now clearly established, many questions remain as to how early ILC developmental fates are determined and how specific effector functions associated with individual ILC subsets are achieved. As the founding member of the ILC family, properties of NK cells have defining attributes that characterize this group of innate effectors. Analysing their developmental rules may provide clues to principles that guide ILC development in general. PMID:23490162
Vosshenrich, Christian A J; Di Santo, James P
Role of the gut as a primary lymphoid organ.
The TCR-??/?? CD8?? intraepithelial T lymphocytes (T-IEL) located in the gut mucosa of the small intestine are an abundant population believed to have a major role in ensuring the integrity of the gut wall. Here, we describe their unique characteristics and the controversies regarding the origin and differentiation of these T-IELs. We show how accumulated experimental evidence has finally arrived at a unifying concept, which demonstrates that these cells originate from early thymus precursors that have not yet undergone TCR rearrangement and TCR-??/?? commitment. These precursors colonize the gut lamina propria during the perinatal period and complete rearrangements and TCR-??/?? commitment while migrating to the epithelium. Therefore, the gut epithelium, which shares the same embryonic origin as the thymus epithelium, behaves as a primary lymphoid organ responsible for the differentiation of a major local T cell set. PMID:21704078
Peaudecerf, Laetitia; Rocha, Benedita
Group 2 innate lymphoid cells in lung inflammation
Although allergic asthma is a heterogeneous disease, allergen-specific T helper 2 (Th2) cells producing the key cytokines involved in type 2 inflammation, interleukin-4 (IL-4), IL-5 and IL-13, are thought to play a major role in asthma pathogenesis. This model is challenged by the recent discovery of group 2 innate lymphoid cells (ILC2) that represent a critical innate source of type 2 cytokines. These ILC2 are activated by epithelial cell-derived cytokines, including IL-25 and IL-33, which have been implicated in the initiation of asthma. In this review, we will discuss recent studies supporting a significant role for ILC2 in lung inflammation, with special attention to allergen-induced asthma. PMID:23866009
Li, Bobby W S; Hendriks, Rudi W
Immunophenotypic characterization of lymphoid cell infiltrates in vitiligo
The pathogenesis of vitiligo is still controversial. The purpose of this study was to gain insight into the nature of lymphoid cells infiltrating depigmented areas of skin in vitiligo. Immunochemical procedures were carried out in biopsies from 20 patients with active lesions to search for cells expressing CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD25, CD30, CD56, CD68 and CD79a. Results indicate that early lesions are infiltrated mainly by dendritic cells, whereas older lesions display significantly lower proportions of these cells and increased percentages of mature T cells. This finding might suggest that the autoimmune reactivity towards melanocyte antigens might be T cell-dependent and antigen-driven. It is possible that a non-immune offence of melanocytes is responsible for the exposure of intracellular antigens, while autoreactivity might be a secondary, self-perpetuating mechanism. PMID:23607858
Sanchez-Sosa, S; Aguirre-Lombardo, M; Jimenez-Brito, G; Ruiz-Argüelles, A
BACKGROUND: Various histological classifications developed for nodal lymphomas failed to be of value in extranodal lymphomas. More recently, gastric lymphoma is considered to represent a distinctive group derived from mucosa associated lymphoid tissue (MALT). AIM: To study the prognostic value of malignancy grading based on the concept that most gastric lymphomas are of MALT origin, the endoscopic as well as clinical characteristics in 114 patients with primary gastric non-Hodgkin's lymphoma were evaluated. RESULTS: In univariate analysis, patients with low grade lymphoma (n = 51) were younger, had less advanced stage, and less frequently bulky disease than those with high grade lymphoma (n = 63). In multivariate analysis weight loss and increased erythrocyte sedimentation rate were significantly less frequent in low grade (45% and 22%) compared with high grade lymphoma (75% and 53%). In low grade lymphoma endoscopic findings were often interpreted as a benign condition (27 of 51), in contrast with high grade lymphoma, where carcinoma was most frequently (37 of 63) suspected. In low grade lymphoma complete remission rate was 92%, and five year survival 75%, In high grade lymphoma results were significantly less favourable (p = 0.0001): complete remission in 68%, and a five year survival of 46%. CONCLUSION: Malignancy grading was strongly correlated with treatment outcome; endoscopically low grade lymphoma was often hard to distinguish from benign conditions, whereas high grade lymphoma often revealed carcinoma-like features. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8944565
Taal, B G; Boot, H; van Heerde, P; de Jong, D; Hart, A A; Burgers, J M
The natural cytotoxicity receptor NKp46 is an activating receptor expressed by several distinct innate lymphoid cell (ILC) subsets, including NK cells, some ?? T cells and intestinal ROR?t(+) IL-22(+) cells (NCR22 cells, IL-22-producing NKp46(+) cell). NCR22 cells may play a role in mucosal barrier function through IL-22-mediated production of anti-bacterial peptides from intestinal epithelial cells. Previous studies identified a predominant proportion of NCR22 cells in gut cryptopatches (CP), lymphoid structures that are strategically positioned to collect and integrate signals from luminal microbes; however, whether CP or other lymphoid structures condition NCR22 cell differentiation is not known. Programmed and inducible lymphoid tissue development requires cell-surface-expressed lymphotoxin (LT)?(1) ?(2) heterotrimers (provided by lymphoid tissue inducer (LTi) cells) to signal lymphotoxin-? receptor (LTR)(+) stromal cells. Here, we analyzed NCR22 cells in LT?R-deficient Ncr1(GFP/+) mice that lack organized secondary lymphoid tissues. We found that NCR22 cells develop in the absence of LT?R, become functionally competent and localize to the lamina propria under steady-state conditions. Following infection of LT?R(-/-) mice with the Gram-negative pathogen Citrobacter rodentium, IL-22 production from NCR22 cells was not affected. These results indicate that organized lymphoid tissue structures are not critical for the generation of an intact and fully functional intestinal NCR22 cell compartment. PMID:21341264
Satoh-Takayama, Naoko; Lesjean-Pottier, Sarah; Sawa, Shinichiro; Vosshenrich, Christian A J; Eberl, Gérard; Di Santo, James P
Tertiary lymphoid organs emerge in tissues in response to nonresolving inflammation. Recent research characterized artery tertiary lymphoid organs in the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis-associated lymphocyte aggregates are organized into distinct compartments, including separate T-cell areas harboring conventional, monocyte-derived, lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors and memory cells; B-cell follicles containing follicular dendritic cells in activated germinal centers; and peripheral niches of plasma cells. Artery tertiary lymphoid organs show marked neoangiogenesis, aberrant lymphangiogenesis, and extensive induction of high endothelial venules. Moreover, newly formed lymph node-like conduits connect the external lamina with high endothelial venules in T-cell areas and also extend into germinal centers. Mouse artery tertiary lymphoid organs recruit large numbers of naďve T cells and harbor lymphocyte subsets with opposing activities, including CD4(+) and CD8(+) effector and memory T cells, natural and induced CD4(+) regulatory T cells, and memory B cells at different stages of differentiation. These data suggest that artery tertiary lymphoid organs participate in primary immune responses and organize T- and B-cell autoimmune responses in advanced atherosclerosis. In this review, we discuss the novel concept that pro- and antiatherogenic immune responses toward unknown arterial wall-derived autoantigens may be organized by artery tertiary lymphoid organs and that disruption of the balance between pro- and antiatherogenic immune cell subsets may trigger clinically overt atherosclerosis. PMID:24855201
Mohanta, Sarajo Kumar; Yin, Changjun; Peng, Li; Srikakulapu, Prasad; Bontha, Vineela; Hu, Desheng; Weih, Falk; Weber, Christian; Gerdes, Norbert; Habenicht, Andreas J R
Intestinal nodular lymphoid hyperplasia and extraintestinal lymphoma--a rare association.
Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of innumerable small discrete nodules involving a variable segment of the gastrointestinal tract. The association between nodular lymphoid hyperplasia and other benign and malignant diseases has been clearly described, with an increased risk of gastrointestinal tumours, namely gastrointestinal lymphoma. However, the association with extraintestinal lymphoma seems extremely rare. The authors present a clinical case of a patient with nodular lymphoid hyperplasia of the small and large intestine that subsequently developed an extraintestinal lymphoma (diffuse large B-cell lymphoma). PMID:22870792
Monsanto, P; Lérias, C; Almeida, N; Lopes, S; Cabral, J E; Figueiredo, P; Silva, M; Juliăo, M; Gouveia, H; Sofia, C
Pathologic features of the gastric mucosa adjacent to primary MALT-lymphomas.
The frequency of reported cases of primary gastric mucosa-associated lymphoid tissue (MALT)-lymphoma is increasing worldwide. Helicobacter pylori plays a preponderant role in its pathogenesis. Gastric MALT-lymphoma arises from nonrecirculating centrocytelike cells located at the periphery of reactive lymphoid follicles, which are common in patients infected with this microorganism. Histopathologic features other than lymphoid follicles have not been well described. In this study the authors describe the morphologic changes in the gastric mucosa adjacent to MALT-lymphomas. From the files of the departments of pathology at the Instituto Nacional de Cancerologia and the Instituto Nacional de la Nutricion in Mexico City, primary gastric MALT-lymphomas were retrieved. Patients with hematoxylin-eosin-stained histologic sections, including the overt neoplasia and the neighboring gastric mucosa, were selected. Lymphoid follicles as well as intestinal metaplasia, atrophy, and eosinophils were evaluated as present or absent and graded as proposed by the Updated Sydney System for gastritis. Fifty-one patients were eligible for analysis. There were 35 low-grade and 16 high-grade primary MALT-lymphomas. Forty-seven patients (92.6%) showed reactive lymphoid follicles in the neighboring mucosa, 32 patients (69.5%) had intestinal metaplasia, and 26 patients (54.1%) demonstrated atrophy. In 41 patients (73.8%) there was an increased number of eosinophils. Our findings suggest that lymphoid follicles, intestinal metaplasia, atrophy, and eosinophils in an endoscopic biopsy are markers of both gastric lymphoma and carcinoma. PMID:10509954
Herrera-Goepfert, R; Arista-Nasr, J; Alba-Campomanes, A
Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue tumor exhibiting considerable morphologic overlap with low grade fibromyxoid sarcoma (LGFMS). Moreover, both SEF and LGFMS show MUC4 expression by immunohistochemistry. While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors. In contrast, recent studies pointed out that SEF harbor frequent EWSR1 rearrangements, with only a minority of cases showing FUS-CREB3L2 fusions. In an effort to further characterize the molecular characteristics of pure SEF and hybrid SEF/LGFMS lesions, we undertook a clinicopathologic, immunohistochemical and genetic analysis of a series of 10 SEF and 8 hybrid SEF/LGFMS tumors. The mortality rate was similar between the two groups, 44% within the pure SEF group and 37% in the hybrid SEF/LGFMS with a mean overall follow-up of 66 months. All but one pure SEF and all hybrid SEF/LGFMS tested cases showed MUC4 immunoreactivity. The majority (90%) of pure SEF cases showed EWSR1 gene rearrangements by FISH with only one case exhibiting FUS rearrangement. Of the 9 EWSR1 positive cases, 6 cases harbored CREB3L1 break-apart, two had CREB3L2 rearrangement (a previously unreported finding) and one lacked evidence of CREB3L1/2 abnormalities. In contrast, all hybrid SEF/LGFMS tumors exhibited FUS and CREB3L2 rearrangements. These results further demarcate a relative cytogenetic dichotomy between pure SEF, often characterized by EWSR1 rearrangements, and hybrid SEF/LGFMS, harboring FUS-CREB3L2 fusion; the latter group recapitulating the genotype of LGFMS. PMID:25231134
Prieto-Granada, Carlos; Zhang, Lei; Chen, Hsiao-Wei; Sung, Yun-Shao; Agaram, Narasimhan P; Jungbluth, Achim; Antonescu, Cristina R
Although reduced natural killer (NK) cell levels have been reported consistently in patients with coronary artery disease (CAD), the clinical significance and persistence of this immune perturbation is not clarified. In this study we characterized the NK cell deficit further by determining (i) differentiation surface markers and cytokine profile of NK cell subsets and (ii) ability to reconstitute NK cell levels over time. Flow cytometry was used to analyse NK cell subsets and the intracellular cytokine profile in 31 patients with non-ST elevation myocardial infarction (non-STEMI), 34 patients with stable angina (SA) and 37 healthy controls. In blood collected prior to coronary angiography, the proportions of NK cells were reduced significantly in non-STEMI and SA patients compared with controls, whereas NK cell subset analyses or cytokine profile measurements did not reveal any differences across groups. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of metabolic syndrome. Moreover, interleukin (IL)-6 levels remained high in patients with sustained NK cell deficit, whereas a decline in IL-6 (P?0·001) was seen in patients with a pronounced increase in NK cells. In conclusion, we found no evidence that reduction of NK cells in CAD patients was associated with aberrations in NK cell phenotype at any clinical stage of the disease. Conversely, failure to reconstitute NK cell levels was associated with a persistent low-grade inflammation, suggesting a protective role of NK cells in CAD. PMID:24298947
Backteman, K; Ernerudh, J; Jonasson, L
In the experimental arm of a randomised trial, women were tested both for liquid-based cytology and human papillomavirus (HPV) DNA and referred for colposcopy if cytology was ASCUS (atypical cells of undetermined significance) or more severe. We considered those with ASCUS (757) or LSIL (low-grade squamous intraepithelial lesions) (485) and a valid HPV test who received colposcopy. We computed sensitivity, specificity and ROC curves with different values of relative light units (RLU, that are related to viral load) as cut off, using cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) at blind histology review as the endpoint. The area under the receiver operating characteristic (ROC) curve was significantly less among women aged 25-34 years than in those older, both considering ASCUS/AGUS (atypical glandular cells of undetermined significance) (p=0.0355) and LSIL (p=0.0009). At age 35-60 the curves for ASCUS and LSIL were similar, while at age 25-34 the area under the curve for LSIL was significantly less than for ASCUS (p=0.0084). With LSIL cytology, specificity of Hybrid Capture 2 with 2 RLU cut-off was 35.0% (95%CI 28.4-42.1) at age 25-34 and 64.5% (95%CI 58.3-70.3) at age 35-60. In conclusion, triaging by HPV testing performed better in women aged over 35 years than those younger. For older women, HPV triaging should also be considered for managing those with LSIL cytology. PMID:17223540
Ronco, Guglielmo; Cuzick, Jack; Segnan, Nereo; Brezzi, Silvia; Carozzi, Francesca; Folicaldi, Stefania; Dalla Palma, Paolo; Del Mistro, Annarosa; Gillio-Tos, Anna; Giubilato, Pamela; Naldoni, Carlo; Polla, Enzo; Iossa, Anna; Zorzi, Manuel; Confortini, Massimo; Giorgi-Rossi, Paolo
Background: Cyclin-A and cyclin-E are regulators of G1–S phase of normal cell cycle. Integration of human papilloma virus high-risk (HR-HPV) could alter this mechanism, and its overexpression has been associated with poor prognosis in cervical cancer. Aim: To determine the expression of cyclin-A and cyclin-E, types of HR-HPV and physical state of DNA in cytologies with the diagnosis of low-grade squamous intraepithelial lesion (LSIL). Materials and Methods: 115 cytological specimens in liquid base (liquid-PREP™) were analyzed. 25 specimens were with no signs of SIL (NSIL) and without HPV; 30 with NSIL with low-risk HPV (LR-HPV); 30 with NSIL with HR-HPV; and 30 with both LSIL and HR-HPV. The expression of cyclins was evaluated by immunocytochemistry; and the detection of viral DNA was done by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) for genotyping or sequencing of HPV. The physical state of HPV was evaluated by in situ hybridization with amplification with tyramide. Results: In the cytologies NSIL with LR-HPV, the expression of cyclin-A and cyclin-E was found respectively in 23.3% and 33.3% of the specimens. Among the specimens of NSIL with HR-HPV, 33.3% expressed cyclin-A and 40% cyclin-E, while 100% of the LSILs expressed the 2 cyclins. On the other hand, 100% of the samples NSIL with LR-HPV presented an episomal pattern. Of the specimens of NSIL with HR-HPV, 56.6% exhibited an episomal pattern, 23.3% integrated and 20%, mixed. Among the LSILs, 90% were mixed and 10% integrated. Conclusions: The cyclins A and E are present in the LSILs that occur predominantly in mixed state in the presence of HR-HPV. PMID:23661932
Zubillaga-Guerrero, MI; Illades-Aguiar, B; Leyva-Vazquez, MA; Flores-Alfaro, E; Castańeda-Saucedo, E; Muńoz-Valle, JF; Alarcón-Romero, LC
Purpose A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). Patients and Methods Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ? 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. Results In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02). Conclusion PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy. PMID:22851558
Shaw, Edward G.; Wang, Meihua; Coons, Stephen W.; Brachman, David G.; Buckner, Jan C.; Stelzer, Keith J.; Barger, Geoffrey R.; Brown, Paul D.; Gilbert, Mark R.; Mehta, Minesh P.
Aim To report the long-term follow-up of a cohort of adult patients with LGG post-operatively irradiated in one institution, and to identify prognostic factors for progression free survival. Background There is little consensus about the optimal treatment for low-grade glioma (LGG), and the clinical management of LGG is one of the most controversial areas in neurooncology. Radiation therapy is one option for treatment of patients with LGG, whereas other options include postoperative observation. Materials and methods Between 1975 and 2005, 180 patients with LGG (WHO II) received postoperative irradiation after non radical (subtotal or partial) excision. Patients had to be 18 years of age or older, and have histologic proof of supratentorial fibrillary (FA), protoplasmic (PA) or gemistocytic astrocytoma (GA). Radiotherapy was given within 3–10 weeks after surgery. Treatment fields were localized and included the preoperative tumor volume, with a 1–2 cm margin, treated to a total dose of 50–60 Gy in 25–30 fractions over 5–6 weeks. Results Actuarial ten-year progression free survival (APFS) in the whole group was 19%. The worse prognosis was observed in patients with GA. Ten-year APFS rates for GA, PA and FA were 10%, 18% and 22%, respectively. Conclusion The findings from our long-term cohort of 180 patients with LGG confirmed by uni- and multivariate analysis demonstrated that only astrocytoma histology significantly determined the prognosis. The best survival was observed in patients with the fibrillary variant, and the worst for the gemistocytic one. PMID:24377015
Mucha-Ma?ecka, Anna; Gli?ski, Bogdan; Hetna?, Marcin; Jarosz, Magdalena; Urba?ski, Jacek; Fr?czek-B?achut, Beata; Dymek, Pawe?; Ma?ecki, Krzysztof; Chrostowska, Agnieszka
Background C-reactive protein (CRP) is a well-established marker of inflammation. The level of CRP is affected by several lifestyle factors. A slightly increased CRP level, also known as low-grade inflammation (LGI), is associated with increased risk of several diseases, especially cardiovascular disease. The aim of this study was to identify predictors of increased CRP levels in healthy individuals. We therefore assessed CRP in a large cohort of blood donors. Methods We measured plasma CRP levels in 15,684 participants from the Danish Blood Donor Study. CRP was measured by a commercial assay. Furthermore, all participants completed a standard questionnaire on smoking status, alcohol consumption, physical activity, diet, and various body measurements. Female participants also reported the use of contraception, childbirth, and menopausal status. The relationship between LGI (defined here as a plasma CRP level between 3 mg/L and 10 mg/L) and predictors was explored by multivariable logistic regression analysis. Results were presented as odds ratios (OR) with 95% confidence intervals (CI). Results We found LGI in a total of 1,561 (10.0%) participants. LGI was more frequent in women using combined oral contraception (OC) (29.9%) than in men (6.1%) and women not using OC (7.9%). Among premenopausal women, OC was the strongest predictor of LGI (odds ratio?=?8.98, p<0.001). Additionally, body mass index (BMI) and waist circumference were positively associated with LGI. Conclusion High BMI and abdominal obesity strongly predicted LGI among healthy individuals. However, the most striking finding was the high prevalence of LGI among premenopausal women who used combined oral contraception. Although the significance of CRP as a marker of inflammation is well known, the role of CRP in pathogenesis is still uncertain. The impact of oral contraception on CRP levels should nevertheless be considered when CRP is used in risk assessment. PMID:24516611
Sřrensen, Cecilie J.; Pedersen, Ole B.; Petersen, Mikkel S.; Sřrensen, Erik; Kotzé, Sebastian; Thřrner, Lise W.; Hjalgrim, Henrik; Rigas, Andreas S.; Mřller, Bjarne; Rostgaard, Klaus; Riiskjćr, Mads; Ullum, Henrik; Erikstrup, Christian
Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.
Strober, S.; Farinas, M.C.; Field, E.H.; Solovera, J.J.; Kiberd, B.A.; Myers, B.D.; Hoppe, R.T.
Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie
were seen in the cytoplasm in macrophages associated with the lymphoid follicles. In 54 (98%) of the 55 scrapie-affected sheep, PrP Sc was detected in the spleen, retropharyngeal lymph node, mesenteric lymph node, and the palatine tonsil. However, only in the palatine tonsils was PrP Sc present in a consistently high percentage of the lymphoid follicles. PrP was not detected
Keulen van L. J. M; B. E. C. Schreuder; R. H. Meloen; G. Mooij-Harkes; M. E. W. Vromans; J. P. M. Langeveld
Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity
NASA Astrophysics Data System (ADS)
The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor ROR?t. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.
van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inęs; Goverse, Gera; Labăo-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique
Clinical drawbacks of total lymphoid irradiation: the cons
Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.
Myers, L.W.; Ellison, G.W.; Fahey, J.L.; Tesler, A.; Gottlieb, M.S.
Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.
Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma. Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma. To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis. Results showed that incidence of clonal heterogeneity varied from 25% to 69% among different types of lymphoma. Survival analysis revealed that mantle cell lymphoma and diffuse large B-cell lymphoma with clonal heterogeneity showed significantly poorer prognosis, and that clonal heterogeneity was confirmed as an independent predictor of poor prognosis for both types of lymphoma. Interestingly, 8q24.1 (MYC) gain, 9p21.3 (CDKN2A/2B) loss and 17p13 (TP53, ATP1B2, SAT2, SHBG) loss were recurrent genomic lesions among various types of lymphoma with clonal heterogeneity, suggesting at least in part that alterations of these genes may play a role in clonal heterogeneity. PMID:24815991
Suguro, Miyuki; Yoshida, Noriaki; Umino, Akira; Kato, Harumi; Tagawa, Hiroyuki; Nakagawa, Masao; Fukuhara, Noriko; Karnan, Sivasundaram; Takeuchi, Ichiro; Hocking, Toby D; Arita, Kotaro; Karube, Kennosuke; Tsuzuki, Shinobu; Nakamura, Shigeo; Kinoshita, Tomohiro; Seto, Masao
Immune regulation by non-lymphoid cells in transplantation
Regulatory cells play a crucial role in the induction and maintenance of tolerance by controlling T cell as well as B and natural killer (NK) cell-mediated immunity. In transplantation, CD4+CD25+forkhead box P3+ T regulatory cells are instrumental in the maintenance of immunological tolerance, as are several other T cell subsets such as NK T cells, double negative CD3+ T cells, ?? T cells, interleukin-10-producing regulatory type 1 cells, transforming growth factor-?-producing T helper type 3 cells and CD8+CD28? cells. However, not only T cells have immunosuppressive properties, as it is becoming increasingly clear that both T and non-T regulatory cells co-operate and form a network of cellular interactions controlling immune responses. Non-T regulatory cells include tolerogenic dendritic cells, plasmacytoid dendritic cells, mesenchymal stem cells, different types of stem cells, various types of alternatively activated macrophages and myeloid-derived suppressor cells. Here, we review the mechanism of action of these non-lymphoid regulatory cells as they relate to the induction or maintenance of tolerance in organ transplantation. PMID:19196251
Dugast, A-S; Vanhove, B
Treatment of experimental myasthenia gravis with total lymphoid irradiation
Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.
de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.
Novel agents and biomarkers for acute lymphoid leukemia
New genetic markers for adult acute lymphoblastic leukemia (ALL) have been found to have prognostic impact, such as the lymphoid transcription factor gene IKZF1 alterations, which are associated with a high rate of leukemic relapse in B-ALL. Although complete remission rates by induction chemotherapy in ALL are now high, the long-term survival is still disappointing. Improvements in the survival outcome of ALL have been observed in young adults as a result of the use of pediatric inspired regimens and the broadening of the number of patients who are eligible for allogeneic SCT. Development of new and less toxic agents also provide promise to improve the outcome in adult ALL, such as tyrosine kinase inhibitors in Ph-positive ALL, rituximab in CD20-positive disease, blinatumomab in precursor B-ALL and nelarabine in T-lineage ALL. Challenges for the future are to implement genomic profiling into the clinical setting to guide risk stratification and providing novel targets for tailored therapies. PMID:23773228
Tissue-specific effector functions of innate lymphoid cells
Innate lymphoid cells (ILCs) is the collective term for a group of related innate lymphocytes, including natural killer (NK) cells and the more recently discovered non-NK ILCs, which all lack rearranged antigen receptors such as those expressed by T and B cells. Similar to NK cells, the newly discovered ILCs depend on the transcription factor Id2 and the common ?-chain of the interleukin-2 receptor for development. However, in contrast to NK cells, non-NK ILCs also require interleukin-7. In addition to the cytotoxic functions of NK cells, assuring protection against tumour development and viruses, new data indicate that ILCs contribute to a wide range of homeostatic and pathophysiological conditions in various organs via specialized cytokine production capabilities. Here we summarize current knowledge on ILCs with a particular emphasis on their tissue-specific effector functions, in the gut, liver, lungs and uterus. When possible, we try to highlight the role that these cells play in humans. PMID:23489335
Björkström, Niklas K; Kekäläinen, Eliisa; Mjösberg, Jenny
Type-2 innate lymphoid cells in human allergic disease
Purpose of review Recent decades have seen allergic diseases become endemic in a number of developed countries. Understanding the inflammatory processes that dictate these allergic responses is therefore important. Recent findings Critical to many allergic responses is the inappropriate release of the type-2 immune-regulatory cytokines: interleukin-4, interleukin-5, interleukin-9, and interleukin-13. The study of these inflammatory mediators has led directly to the development of two new asthma treatments: anti-interleukin-5 and anti-interleukin-13. Until recently, T helper 2 cells were considered to be the major cellular source of type-2 cytokines; however, a paradigm shift occurred with the discovery of a novel population, type-2 innate lymphoid cells (ILC2s), that can produce huge levels of type-2 cytokines and are sufficient to induce allergy in mice. This discovery raises interesting questions about how innate and adaptive type-2 immunity might interact to induce relapsing and remitting episodes of allergy in patients. Summary It is essential that alongside the mechanistic investigation using model organisms, the roles of ILC2s in human disease be explored. Here, we discuss how ILC2 traits, discovered in mouse models, have informed research in humans and how newly identified human ILC2 pathways might provide potential therapeutic benefits in the future. PMID:25115682
Barlow, Jillian L.; McKenzie, Andrew N.J.
Activated type 2 innate lymphoid cells regulate beige fat biogenesis.
Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2- and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4R? in PDGFR?(+) APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PAPERCLIP: PMID:25543153
Lee, Min-Woo; Odegaard, Justin I; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B; Nussbaum, Jesse C; Yun, Karen; Locksley, Richard M; Chawla, Ajay
Mucosa-Associated Bacterial Diversity in Necrotizing Enterocolitis
Background Previous studies of infant fecal samples have failed to clarify the role of gut bacteria in the pathogenesis of NEC. We sought to characterize bacterial communities within intestinal tissue resected from infants with and without NEC. Methods 26 intestinal samples were resected from 19 infants, including 16 NEC samples and 10 non-NEC samples. Bacterial 16S rRNA gene sequences were amplified and sequenced. Analysis allowed for taxonomic identification, and quantitative PCR was used to quantify the bacterial load within samples. Results NEC samples generally contained an increased total burden of bacteria. NEC and non-NEC sample sets were both marked by high inter-individual variability and an abundance of opportunistic pathogens. There was no statistically significant distinction between the composition of NEC and non-NEC microbial communities. K-means clustering enabled us to identify several stable clusters, including clusters of NEC and midgut volvulus samples enriched with Clostridium and Bacteroides. Another cluster containing both NEC and non-NEC samples was marked by an abundance of Enterobacteriaceae and decreased diversity among NEC samples. Conclusions The results indicate that NEC is a disease without a uniform pattern of microbial colonization, but that NEC is associated with an abundance of strict anaerobes and a decrease in community diversity. PMID:25203729
Brower-Sinning, Rachel; Zhong, Diana; Good, Misty; Firek, Brian; Baker, Robyn; Sodhi, Chhinder P.; Hackam, David J.; Morowitz, Michael J.
Biofilm formation of mucosa-associated methanoarchaeal strains
Although in nature most microorganisms are known to occur predominantly in consortia or biofilms, data on archaeal biofilm formation are in general scarce. Here, the ability of three methanoarchaeal strains, Methanobrevibacter smithii and Methanosphaera stadtmanae, which form part of the human gut microbiota, and the Methanosarcina mazei strain Gö1 to grow on different surfaces and form biofilms was investigated. All three strains adhered to the substrate mica and grew predominantly as bilayers on its surface as demonstrated by confocal laser scanning microscopy analyses, though the formation of multi-layered biofilms of Methanosphaera stadtmanae and Methanobrevibacter smithii was observed as well. Stable biofilm formation was further confirmed by scanning electron microscopy analysis. Methanosarcina mazei and Methanobrevibacter smithii also formed multi-layered biofilms in uncoated plastic ?-dishesTM, which were very similar in morphology and reached a height of up to 40 ?m. In contrast, biofilms formed by Methanosphaera stadtmanae reached only a height of 2 ?m. Staining with the two lectins ConA and IB4 indicated that all three strains produced relatively low amounts of extracellular polysaccharides most likely containing glucose, mannose, and galactose. Taken together, this study provides the first evidence that methanoarchaea can develop and form biofilms on different substrates and thus, will contribute to our knowledge on the appearance and physiological role of Methanobrevibacter smithii and Methanosphaera stadtmanae in the human intestine. PMID:25071757
Bang, Corinna; Ehlers, Claudia; Orell, Alvaro; Prasse, Daniela; Spinner, Marlene; Gorb, Stanislav N.; Albers, Sonja-Verena; Schmitz, Ruth A.
Purpose: High-dose therapy (HDT) is currently under investigation for patients with advanced low-grade non-Hodgkin lymphoma (NHL). We report on the toxicity of a modified HDT that combines total-body irradiation (TBI) with involved-field irradiation (IF-RT) for patients with bulky disease or residual lymphomas > 2 cm after induction chemotherapy. Patients and Methods: 41 patients received HDT which consisted of high-dose cyclophosphamide
Marcel Ott; Heinz Schmidberger; Bernhard Wörmann; Clemens F. Albrecht; Olivier Pradier; Clemens F. Hess
Background Low level connective tissue inflammation has been proposed to play a role in thyroid associated ophthalmopathy (TAO). The aim of this study was to investigate this postulate by a musculoskeletal approach together with biochemical parameters. Methods 13 patients with TAO and 16 controls were examined. Erythrocyte levels of Zn, Cu, Ca2+, Mg, and Fe were determined. The musculoskeletal evaluation included observational data on body posture with emphasis on the orbit-head region. The angular foot position in the frontal plane was quantified following gait observation. The axial orientation of the legs and feet was evaluated in an unloaded supine position. Functional propioceptive tests based on stretch stimuli were done by using foot inversion and foot rotation. Results Alterations in the control group included neck tilt in 3 cases, asymmetrical foot angle during gait in 2, and a reaction to foot inversion in 5 cases. TAO patients presented facial asymmetry with displaced eye fissure inclination (mean 9.1°) as well as tilted head-on-neck position (mean 5.7°). A further asymmetry feature was external rotation of the legs and feet (mean 27°). Both foot inversion as well as foot rotation induced a condition of neuromuscular deficit. This condition could be regulated by gentle acupressure either on the lateral abdomen or the lateral ankle at the acupuncture points gall bladder 26 or bladder 62, respectively. In 5 patients, foot rotation produced a phenomenon of moving toes in the contra lateral foot. In addition foot rotation was accompanied by an audible tendon snapping. Lower erythrocyte Zn levels and altered correlations between Ca2+, Mg, and Fe were found in TAO. Conclusion This whole body observational study has revealed axial deviations and body asymmetry as well as the phenomenon of moving toes in TAO. The most common finding was an arch-like displacement of the body, i.e. eccentric position, with foot inversion and head tilt to the contra lateral side and tendon snapping. We propose that eccentric muscle action over time can be the basis for a low grade inflammatory condition. The general implications of this model and its relations to Zn and Se will be discussed. PMID:17319961
Moncayo, Roy; Moncayo, Helga
Objective: LGGs (low-grade gliomas) are sometimes encountered by chance during radiological examinations. These incidentally discovered LGGs (IDLGGs) were relatively under-studied in the literature. The purpose of current study is to review a cohort of patients with IDLGGs surgically treated in our institution for their clinical and histological aspects and determine their IDH1 and 1p19q status. Methods: All patients with hemispheric LGGs receiving operation in our institution between 2001 and 2004 were reviewed. Clinical, radiological and treatment data of the patients were collected and IDLGGs were retrieved and compared with symptomatic LGGs. Histological review was carried out and formalin-fixed paraffin embedded (FFPE) tissues of IDLGGs were examined for IDH1/IDH2 mutation and 1p/19q codeletion. Results: Twenty three IDLGGs (10.4%) were identified while 196 patients had symptomatic LGGs. The reasons for patients with IDLGGs having radiological examination included trauma (47.8%), dizziness (26.1%), unrelated headache (21.7%), and health checkup (4.4%). Clinically, patients with IDLGGs had higher preoperative KPS (P < 0.001), smaller tumor volume (P = 0.014), lower frequency of eloquent areas involvement (P < 0.001) and higher rate of complete resection (P = 0.037) comparing to those with symptomatic LGGs. Histologically, there is a preponderance of oligodendroglial differentiation with 6 oligodendrogliomas and 11 oligoastrocytomas but there were also 6 astrocytomas. IDH1 mutation and 1p/19q co-deletion were detected in 95.7% (22/23) and 69.6% (16/23) of IDLGGs, respectively. The latter encompassed all but one of the cases of oligodendroglial tumors. Patients with IDLGGs had longer overall survival than those with symptomatic LGGs (P = 0.027). Conclusions: We conclude that the majority of IDLGGs are IDH1 mutated and are predominantly oligodendroglial tumors. With a median follow-up of 9.3 years to our series, we conclude that patients with IDLGGs had better prognosis than those with symptomatic LGGs. The favorable prognosis of IDLGGs may be accounted by the higher practicability of extensive resection, non-eloquent tumor location and smaller tumor volume. Frequent IDH1 mutation and 1p/19q co-deletion in IDLGGs may also contribute to the favorable prognosis of this subgroup of patients.
Zhang, Zhen-Yu; Chan, Aden Ka-Yin; Ng, Ho-Keung; Ding, Xiao-Jie; Li, Yan-Xi; Shi, Zhi-Feng; Zhu, Wei; Zhong, Ping; Wang, Yin; Mao, Ying; Yao, Yu; Zhou, Liang-Fu
Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised ? for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction. PMID:25313576
Wood, Adrian D; Strachan, Anna A; Thies, Frank; Aucott, Lorna S; Reid, David M; Hardcastle, Antonia C; Mavroeidi, Alexandra; Simpson, William G; Duthie, Garry G; Macdonald, Helen M
Background Previous studies support a role for mitogen-activated protein kinase pathway signaling, and more recently Akt/mammalian target of rapamycin (mTOR), in pediatric low-grade glioma (PLGG), including pilocytic astrocytoma (PA). Here we further evaluate the role of the mTORC1/mTORC2 pathway in order to better direct pharmacologic blockade in these common childhood tumors. Methods We studied 177 PLGGs and PAs using immunohistochemistry and tested the effect of mTOR blockade on 2 PLGG cell lines (Res186 and Res259) in vitro. Results Moderate (2+) to strong (3+) immunostaining was observed for pS6 in 107/177 (59%) PAs and other PLGGs, while p4EBP1 was observed in 35/115 (30%), pElF4G in 66/112 (59%), mTOR (total) in 53/113 (47%), RAPTOR (mTORC1 component) in 64/102 (63%), RICTOR (mTORC2 component) in 48/101 (48%), and pAkt (S473) in 63/103 (61%). Complete phosphatase and tensin homolog protein loss was identified in only 7/101 (7%) of cases. In PA of the optic pathways, compared with other anatomic sites, there was increased immunoreactivity for pS6, pElF4G, mTOR (total), RICTOR, and pAkt (P < .05). We also observed increased pS6 (P = .01), p4EBP1 (P = .029), and RICTOR (P = .05) in neurofibromatosis type 1 compared with sporadic tumors. Treatment of the PLGG cell lines Res186 (PA derived) and Res259 (diffuse astrocytoma derived) with the rapalog MK8669 (ridaforolimus) led to decreased mTOR pathway activation and growth. Conclusions These findings suggest that the mTOR pathway is active in PLGG but varies by clinicopathologic subtype. Additionally, our data suggest that mTORC2 is differentially active in optic pathway and neurofibromatosis type 1–associated gliomas. MTOR represents a potential therapeutic target in PLGG that merits further investigation. PMID:24203892
Hütt-Cabezas, Marianne; Karajannis, Matthias A.; Zagzag, David; Shah, Smit; Horkayne-Szakaly, Iren; Rushing, Elisabeth J.; Cameron, J. Douglas; Jain, Deepali; Eberhart, Charles G.; Raabe, Eric H.; Rodriguez, Fausto J.
Lymphoid lesions of the head and neck: a model of lymphocyte homing and lymphomagenesis.
Lymphoid lesions of the head and neck mainly affect the nasopharynx, nasal and paranasal sinuses, and salivary glands. These three compartments each are affected by a different spectrum of lymphoid malignancies and can serve as model for mechanisms of lymphomagenesis. The type of lymphoma seen reflects the underlying biology and function of the particular site involved. The nasopharynx and Waldeyer's ring are functionally similar to the mucosal associated lymphoid tissue (MALT) of the gastrointestinal tract and are most commonly affected by B-cell lymphomas, with mantle cell lymphoma being a relatively frequent subtype. The most prevalent lymphoid lesion of the salivary gland is lymphoepithelial sialadenitis, associated with Sjögren's syndrome. Lymphoepithelial sialadenitis is a condition in which MALT is acquired in a site not normally containing lymphoid tissue. Patients with Sjögren's syndrome are at increased risk to develop B-cell lymphomas, most commonly MALT lymphomas. The nasal and paranasal sinuses are the prototypical site for the development of extranodal natural killer (NK) /T-cell lymphoma, nasal type. This condition must be distinguished from other conditions causing the clinical picture of lethal midline granuloma, including Wegener's granulomatosis and infectious disorders. Lymphomatoid granulomatosis is common in the lung but is rarely seen in the midline facial structures. PMID:11904341
Jaffe, Elaine S
Nasal Associated Lymphoid Tissue of the Syrian Golden Hamster Expresses High Levels of PrPC
The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection. PMID:25642714
Clouse, Melissa D.; Shikiya, Ronald A.; Bartz, Jason C.; Kincaid, Anthony E.
Cutaneous pseudolymphomas: inflammatory reactive proliferations.
Skin is an organ of the immune and lymphoid systems. Lymphoid tissue analogous to gut mucosa-associated lymphoid tissue proliferates in the skin in response to antigenic stimulation. This putative skin-associated tissue is called skin-associated lymphoid tissues (SALT). In the opinion of this author, cutaneous pseudolymphomas represent inflammatory, reactive proliferations of SALT following antigenic stimulation of the cutaneous immune cells. Cutaneous pseudolymphomas commonly involve the exposed areas such as head and neck region and upper extremities. They appear as localized nodules, plaques or noduloplaques. They include B- and T-cell pseudolymphomas. Their histologic patterns include nodular, diffuse, band-like and folliculitis-like morphology. Most pseudolymphomas are idiopathic, but some are secondary to known etiologies (drug intake, arthropod assaults, infectious agents and traumas). Cutaneous pseudolymphomas are usually polyclonal proliferations that regress spontaneously or after treating the underlying etiology. Rare cases harbor clonal lymphoid populations and can progress to low-grade lymphomas. Herein, the author reviews the etiology, clinicopathologic features and diagnosis of the cutaneous pseudolymphomas. PMID:24191857
Hussein, Mahmoud Rezk Abdelwahed
Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia
Background In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. Methods In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. Results At a median follow-up of 9.4 months, ibrutinib significantly improved progression-free survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. Conclusions Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL. (Funded by Pharmacyclics and Janssen; RESONATE ClinicalTrials.gov number, NCT01578707.) PMID:24881631
Byrd, J.C.; Brown, J.R.; O'Brien, S.; Barrientos, J.C.; Kay, N.E.; Reddy, N.M.; Coutre, S.; Tam, C.S.; Mulligan, S.P.; Jaeger, U.; Devereux, S.; Barr, P.M.; Furman, R.R.; Kipps, T.J.; Cymbalista, F.; Pocock, C.; Thornton, P.; Caligaris-Cappio, F.; Robak, T.; Delgado, J.; Schuster, S.J.; Montillo, M.; Schuh, A.; de Vos, S.; Gill, D.; Bloor, A.; Dearden, C.; Moreno, C.; Jones, J.J.; Chu, A.D.; Fardis, M.; McGreivy, J.; Clow, F.; James, D.F.; Hillmen, P.
Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors
Interleukin-7 (IL-7) promotes survival and expansion of lymphoid precursors. We show here that, in addition, IL-7 has a fundamental role, as early as the stage of the multipotent (B/T/NK) common lymphoid progenitor (CLP), in maintaining the B cell differentiation program open. CLPs generated in the absence of IL-7 have normal T/NK differentiation potential, but severely impaired B potential. Accordingly, CLPs from IL-7–deficient mice express lower amounts of early B cell factor (EBF) and Pax5 than wild-type CLPs, but similar amounts of GATA-3. Importantly, induced overexpression of EBF is sufficient to restore the B potential in these cells. These results indicate that IL-7 directs commitment of CLPs by modulating EBF expression. This is the first example of a cytokine influencing lymphoid lineage commitment in multipotent progenitors and highlights the relevance of the expression of a functional IL-7 receptor at the CLP stage. PMID:15767371
Dias, Sheila; Silva, Hamilton; Cumano, Ana; Vieira, Paulo
Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.
Trentham, D.E. (Harvard Medical School, Boston, MA); Belli, J.A.Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.
Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.
Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.
Shared dependence on TOX for development of lymphoid tissue inducer cell and NK cell lineages
Thymocyte selection-associated HMG box factor (TOX) is a DNA-binding factor required for development of CD4 T cells, natural killer T cells, and T regulatory cells. Here we document that both NK cell development and lymphoid tissue organogenesis are inhibited in the absence of TOX. We find that development of lymphoid tissue inducer cells, a rare subset of specialized cells that plays an integral role in lymphoid tissue organogenesis, requires TOX. Tox is highly upregulated in immature NK cells in the bone marrow, consistent with the loss of mature NK cells in the absence of this nuclear protein. Thus, multiple cell lineages in the immune system share a TOX-dependent step for development. PMID:20818394
Aliahmad, Parinaz; Torre, Brian de la; Kaye, Jonathan
Lymphoid hyperplasia detected as a single mass in the gallbladder: report of a case.
We herein report a case of lymphoid hyperplasia of the gallbladder that showed unique images on computed tomography and ultrasonography. A 42-year-old female was referred to our hospital for evaluation and treatment of a gallbladder tumor. Ultrasonography and computed tomography showed a mass in the wall of the gallbladder neck, without typical findings of benign or malignant tumors. The serum levels of tumor markers, such as carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, and cytokeratin 19 fragment, were all within normal limits. Laparoscopic cholecystectomy was therefore performed. There were no stones in the gallbladder. Macroscopically, the submural tumor had a clear border without a capsule and a cystic portion. Its cut surface was grayish white. Microscopically, many lymph follicles with germinal centers were recognized in the subserosal layer. The lymphocytes were morphologically normal. We diagnosed lymphoid hyperplasia with chronic cholecystitis. Lymphoid hyperplasia of the gallbladder is extremely rare. PMID:22699402
Yamamoto, Satoshi; Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Mikamori, Manabu; Fujiwara, Yushi; Nagahara, Hisashi; Xiang, Zhang; Sakurai, Katsunobu; Inoue, Ken
Human lymphoid development in the absence of common ?-chain receptor signaling.
Despite the power of model systems to reveal basic immunologic mechanisms, critical differences exist between species that necessitate the direct study of human cells. Illustrating this point is the difference in phenotype between patients with SCID caused by mutations affecting the common ?-chain (?c) cytokine signaling pathway and mice with similar mutations. Although in both species, null mutations in either IL-2RG (which encodes ?c), or its direct downstream signaling partner JAK3, result in T and NK cell deficiency, an associated B cell deficiency is seen in mice but not in humans with these genetic defects. In this study, we applied recent data that have revised our understanding of the earliest stages of lymphoid commitment in human bone marrow (BM) to determine the requirement for signaling through IL-2RG and JAK3 in normal development of human lymphoid progenitors. BM samples from SCID patients with IL-2RG (n = 3) or JAK3 deficiency (n = 2), which produce similar "T-NK-B+" clinical phenotypes, were compared with normal BM and umbilical cord blood as well as BM from children on enzyme treatment for adenosine deaminase-deficient SCID (n = 2). In both IL-2RG- and JAK3-SCID patients, the early stages of lymphoid commitment from hematopoietic stem cells were present with development of lymphoid-primed multipotent progenitors, common lymphoid progenitors and B cell progenitors, normal expression patterns of IL-7RA and TLSPR, and the DNA recombination genes DNTT and RAG1. Thus, in humans, signaling through the ?c pathway is not required for prethymic lymphoid commitment or for DNA rearrangement. PMID:24771849
Kohn, Lisa A; Seet, Christopher S; Scholes, Jessica; Codrea, Felicia; Chan, Rebecca; Zaidi-Merchant, Sania; Zhu, Yuhua; De Oliveira, Satiro; Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Kohn, Donald B; Crooks, Gay M
Genetic methylation and lymphoid malignancies: biomarkers of tumor progression and targeted therapy
Lymphoid malignancies, mainly including lymphocytic leukemia and lymphoma, are a group of heterogeneous diseases. Although the clinical outcome of patients has been significantly improved with current immuno-chemotherapy, definitive biomarkers remain to be investigated, particularly those reflecting the malignant behavior of tumor cells and those helpful for developing optimal targeted therapy. Recently, genome-wide analysis reveals that altered genetic methylations play an important role in tumor progression through regulation of multiple cellular transduction pathways. This review describes the pathogenetic effect of the aberrant genetic methylation in lymphoid malignancies, with special emphasis on potential therapeutic strategies targeting key signaling networks. PMID:24252620
Flow cytometry and its use in the diagnosis and management of mature lymphoid malignancies.
The last decade has seen major advances in flow cytometric immunophenotyping and this has expanded the utility of flow cytometry to investigate the antigens present on normal and neoplastic haematopoietic cells. This review summarizes how flow cytometry is used currently in the diagnosis and management of mature lymphoid malignancies. The establishment of disease-specific phenotypes allows the creation of assays which can detect neoplastic cells with high specificity and sensitivity. Certain lymphoid neoplasms are well defined immunophenotypically, while others are more heterogeneous. The availability of more sophisticated cytometers and a wider selection of antibodies in routine diagnostic laboratories will lead to the resolution of these more complex disease entities. PMID:21261686
de Tute, Ruth M
Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation
Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.
Tanay, A.; Field, E.H.; Hoppe, R.T.; Strober, S.
Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.
Gaston, J.S.; Strober, S.; Solovera, J.J.; Gandour, D.; Lane, N.; Schurman, D.; Hoppe, R.T.; Chin, R.C.; Eugui, E.M.; Vaughan, J.H.
An appendix removed 15 days before onset of symptoms of subacute sclerosing panencephalitis was examined retrospectively for measles virus ribonucleic acid (RNA). Tissue sections hybridised in situ to a cloned measles virus probe of deoxyribonucleic acid specific for nucleocapsid protein showed that many cells of the lymphoid tissue contained measles virus RNA. In contrast, only a few infected lymphoid cells were detected in three out of six seropositive controls and none in three seronegative infants. A widespread chronic viral infection of the immune system, established after measles, may promote or even initiate nerve cell infection in subacute sclerosing panencephalitis. Images p524-a PMID:3092900
Fournier, J G; Lebon, P; Bouteille, M; Goutieres, F; Rozenblatt, S
Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case: firstname.lastname@example.com Running title: Occupational pesticides exposure and lymphoma Keywords: occupation: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms
Paris-Sud XI, Université de
EBI2 was recently shown to direct the delayed movement of activated B cells to inter and outer follicular regions of secondary lymphoid organs and to be required for mounting a normal T-dependent antibody response. Here we show that EBI2 promotes an early wave of antigen-activated B cell migration to the outer follicle in mice. Later, when B cells have moved to the T zone in a CCR7-dependent manner, EBI2 helps distribute the cells along the B-T boundary. Subsequent EBI2-dependent movement to the outer follicle coincides with CCR7 downregulation and is promoted by CD40 engagement. Using a bioassay, we identify a proteinase K resistant, hydrophobic EBI2 ligand activity in lymphoid and non-lymphoid tissues. Production of EBI2 ligand activity by a cell line is sensitive to statins, suggesting production in an HMG-CoA reductase-dependent manner. CD40 activated B cells show sustained EBI2-dependent responsiveness to the bioactivity. These findings establish a role for EBI2 in helping control B cell position at multiple stages during the antibody response and they suggest EBI2 responds to a broadly distributed lipid ligand. PMID:21844396
Kelly, Lisa M.; Pereira, Joăo P.; Yi, Tangsheng; Xu, Ying; Cyster, Jason G.
NASA Astrophysics Data System (ADS)
Lymphoid tissues from asymptomatic HIV-infected individuals, as compared with symptomatic HIV-infected subjects, show limited histopathological changes and lower levels of HIV expression. In this report we correlate the control of HIV replication in lymph nodes to the non-cytolytic anti-HIV activity of lymphoid tissue CD8+ cells. Five subjects at different stages of HIV-related disease were studied and the ability of their CD8+ cells, isolated from both lymphoid tissue and peripheral blood, to inhibit HIV replication was compared. CD8+ cells from lymphoid tissue and peripheral blood of two HIV-infected long-term survivors suppressed HIV replication at a low CD8+:CD4+ cell ratio of 0.1. The CD8+ cells from the lymphoid tissue of a third asymptomatic subject suppressed HIV replication at a CD8+:CD4+ cell ratio of 0.25; the subject's peripheral blood CD8+ cells showed this antiviral response at a lower ratio of 0.05. The lymphoid tissue CD8+ cells from two AIDS patients were not able to suppress HIV replication, and the peripheral blood CD8+ cells of only one of them suppressed HIV replication. The plasma viremia, cellular HIV load as well as the extent of pathology and virus expression in the lymphoid tissue of the two long-term survivors, were reduced compared with these parameters in the three other subjects. The data suggest that the extent of anti-HIV activity by CD8+ cells from lymphoid tissue relative to peripheral blood correlates best with the clinical state measured by lymphoid tissue pathology and HIV burden in lymphoid tissues and blood. The results and further emphasis to the importance of this cellular immune response in controlling HIV pathogenesis.
Blackbourn, David J.; Mackewicz, Carl E.; Barker, Edward; Hunt, Thomas K.; Herndier, Brian; Haase, Ashley T.; Levy, Jay A.
Determination of the expression and spatial distribution of molecular epitopes, or antigens, in patient tissue specimens has substantially improved the pathologist's ability to classify disease processes. Certain disease pathophysiologies are marked by characteristic increased or decreased expression of developmentally controlled antigens, defined as Cluster of Differentiation markers, that currently form the foundation for understanding lymphoid malignancies. While chromogens and organic
Thomas J Fountaine; Stephen M Wincovitch; David H Geho; Susan H Garfield; Stefania Pittaluga
Total lymphoid irradiation in heart transplantation: Adjunctive treatment for recurrent rejection
In the face of recurrent heart transplant graft rejection refractory to all conventional immunotherapy, retransplantation is customary treatment. The case of a heart transplant recipient unsuitable for retransplantation whose recurrent rejection was successfully treated with postoperative total lymphoid irradiation is described.
Frist, W.H.; Winterland, A.W.; Gerhardt, E.B.; Merrill, W.H.; Atkinson, J.B.; Eastburn, T.E.; Stewart, J.R.; Eisert, D.R. (Vanderbilt Univ. Medical Center, Nashville, TN (USA))
Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells
BACKGROUND: Glucocorticoids are frequently used as a primary chemotherapeutic agent in many types of human lymphoid malignancies because they induce apoptosis through activation of the glucocorticoid receptor, with subsequent alteration of a complex network of cellular mechanisms. Despite clinical usage for over fifty years, the complete mechanism responsible for glucocorticoid-related apoptosis or resistance remains elusive. The mitogen-activated protein kinase pathway
Aaron L Miller; Anna S Garza; Betty H Johnson; E Brad Thompson
L-Selectin Ligands in Lymphoid Tissues and Models of Inflammation
Both lymphocyte recirculation through the lymphoid tissues and leukocyte recruitment to sites of inflammation are essential components of immune surveillance, and are necessary for sustained protection against pathogens. This process is mediated by the leukocyte-endothelial adhesion cascade of which the interaction of leukocyte L-Selectin with its endothelial ligand initiates the first critical tethering and rolling step. As well as discussing
Adil I. Khan; R. Clive Landis; Rajneesh Malhotra
Interleukin2 receptor ? chain regulates the size and content of the peripheral lymphoid compartment
Interleukin-2 receptor ? chain (IL-2R?) expression occurs at specific stages of early T and B lymphocyte development and is induced upon activation of mature lymphocytes. Young mice that lack IL-2R? have phenotypically normal development of T and B cells. However, as adults, these mice develop massive enlargement of peripheral lymphoid organs associated with polyclonal T and B cell expansion, which,
Dennis M. Willerford; Jianzhu Chen; Judith A. Ferry; Laurie Davidson; Averil Ma; Frederick W. Alt
Social stress affects migration of blood T cells into lymphoid organs
The effect of social confrontation stress on the normal distribution of blood T cells into lymphoid organs and some other body tissues was studied. Social stress was induced by placing a male Fischer 344 (F334) rat into the home cage of a resident opponent. 51Cr-labeled blood T cells isolated from syngeneic donor, were intravenously injected into recipients immediately before confrontation.
Volker Stefanski; André Peschel; Stefan Reber
The human lymphoid-specific transcription factor OTF-2 contains a homoeodomain that is required for DNA binding and binds specifically to DNA elements that are recognized by Drosophila homoeodomain proteins, suggesting coevolutionary relationships between mammalian and invertebrate homoeodomain proteins and their DNA recognition elements.
Claus Scheidereit; James A. Cromlish; Thomas Gerster; Kiyoshi Kawakami; Carmen-Gloria Balmaceda; R. Alexander Currie; Robert G. Roeder
We examined the frequencies of loss of heterozygosity at 13 different loci distributed on 9 chromosomes in 30 human ovarian carcinomas. The same tumors were also examined for the presence of amplification of the HER-2/neu and H-ras protooncogenes. The results confirmed earlier findings that losses of heterozygosity occurred at nonrandom frequencies on chromosomes 3, 6, and 11 in these tumors. None of the tumors examined showed amplification at the H-ras locus. The HER-2/neu gene, however, was amplified in approximately one-third of the tumors, in agreement with earlier studies from other laboratories. We subdivided our tumor specimens according to their histological grades, which can be regarded as representing different stages of tumor progression. Losses of heterozygosity on chromosomes 3 or 11 were not seen in low grade lesions, although they were present in most of the high grade tumors examined. Losses of heterozygosity on chromosome 6 as well as HER-2/neu amplification, in contrast, were present in several low grade tumors and were not more frequent in high grade lesions. We conclude that the latter two abnormalities are associated with cellular functions involved at earlier stages of ovarian tumor development, whereas inactivation of genes on chromosome 3 or 11 is associated with later steps that may be incompatible with the well differentiated phenotype. PMID:1677312
Zheng, J P; Robinson, W R; Ehlen, T; Yu, M C; Dubeau, L
"An Unusual Urological Tumour": Above the Collar and below the Belt.
Bladder lymphomas are rarely primary tumours and more commonly associated with systemic lymphoma, either as nonlocalised bladder lymphoma or as secondary bladder lymphoma. Primary bladder lymphomas (PBL) tend to be low-grade mucosa-associated lymphoid tissue (MALT) type, contrasting with diffuse large cell or follicular centre cell types more commonly seen in secondary bladder lymphoma. Bladder involvement by systemic lymphoma infers poor prognosis and patients often have no localising symptoms (typically a postmortem diagnosis). Other treatments are preferred over surgery for all bladder lymphomas, except where diagnosis is uncertain or for relief of irritative bladder symptoms. We describe a unique case of systemic high-grade B-cell lymphoma with simultaneous cutaneous renal and bladder lesions at presentation. PMID:23056972
Mayer, Erik K; Undre, Shabnam; Cohen, Daniel C; Walker, Marjorie M; Vale, Justin A; Patel, Anup
A unique case of kidney's collecting system MALT lymphoma
Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) are mostly seen in the gastrointestinal tract. MALT lymphomas involving kidney are extremely rare. We report on a case of MALT lymphomas of the kidney. A 74-year-old woman presented with an episode of gross hematuria and right flank pain. In renal sonography, we found a hypoecho lesion measuring 61 × 58 × 44 mm in the lower pole of right kidney. A computed tomography scan revealed an enlarged hypodense soft tissue measuring 62 × 42 × 37 mm within the pelvic brim of the right kidney, with extension to the proximal portion of the ipsilateral ureter and engulfed it. The patient underwent a right radical nephrectomy. The pathology specimen indicated a lymphoprolifrative disorder involving the kidney and ureter. To obtain a definitive diagnosis, we used an immunohistochemistry, which confirmed the diagnosis of a MALT lymphoma. PMID:24678358
Asgari, Seyed Alaeddin; Aval, Hamidreza Baghani; Asgari, Seyed Ali; Kheradmand, Keyvan