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pubmed_765_7241
BACKGROUND AND OBJECTIVE Although nodal and distant metastasis is rare in T1 lung adenocarcinoma, it is related to poor clinical prognosis. Association between galectin-3 (Gal-3) expression level, and clinical outcome of T1 lung adenocarcinoma has not been clarified. METHODS From January 2009 to December 2014, 74 patients with surgically resected T1 lung adenocarcinoma were enrolled in this retrospective cohort study. Patient outcomes were followed up until December 2019. Gal-3 expression level in primary tumors was assessed immunohistochemically and evaluated based on the staining intensity and percentage. Patient characteristics and correlation between Gal-3 expression level and clinical outcomes were reviewed. RESULTS Low Gal-3 expression was associated with increased metastatic events (p = 0.03), especially distant metastasis (p = 0.007), and mortality rate (p = 0.04). Kaplan-Meier analysis revealed that high Gal-3 expression level was associated with favorable recurrence-free survival in T1 lung adenocarcinoma (log-rank p = 0.048) and T1a (≤ 2 cm, American Joint Committee on Cancer (AJCC) 7th edition) lung adenocarcinoma (log-rank p = 0.043). Gal-3 expression along with tumor size showed a larger area under curve (AUC) than tumor size alone for predicting metastatic events (AUC = 0.747 vs. 0.681) and recurrence (AUC = 0.813 vs. 0.766) in T1a lung adenocarcinoma in the receiver-operating characteristic curve. CONCLUSION Low Gal-3 expression level in primary tumors was remarkably associated with increased metastatic events and reduced recurrence-free survival in T1 lung adenocarcinoma. We suggest that Gal-3 expression level in addition to tumor size may potentially be stronger than tumor size alone in predicting metastasis in T1a lung adenocarcinoma patients.
10.3390/jcm9061990
pubmed_18_13181
The nuclear transcription factor E2-related factor 2 (Nrf2) has been shown to play pivotal roles in preventing xenobiotic-related toxicity and carcinogen-induced carcinogenesis. These protective roles of Nrf2 have been attributed in part to its involvement in the induction of Phase II drug conjugation/detoxification enzymes as well as antioxidant enzymes through the Nrf2-antioxidant response element (ARE) signaling pathways. This review summarizes the current research status of the identification of Nrf2-regulated drug metabolism enzymes (DMEs), especially Phase II DMEs, and Phase III drug transporters. In addition, the molecular mechanisms underlying the coordinated regulation of Phase II DMEs and Phase III transporters will also be discussed based on findings published in the literature.
10.1002/bdd.680
pubmed_812_2861
PURPOSE The present study was designed to elucidate the molecular genetic basis of a congenital stationary cone dysfunction characterized by congenital nystagmus, moderate visual impairment, and markedly disparate color vision deficiencies between two affected cousins. METHODS Ophthalmic examinations with emphasis on color vision and electrophysiology. Molecular genetic analysis of the X-linked cone opsin genes, mutation screening of the CNGA3, CNGB3, and GNAT2 genes, and heterologous splicing experiments. RESULTS Whereas the proband was found to carry a homozygous frameshift mutation (Tyr95fs) in GNAT2, her cousin was compound heterozygous for the Tyr95fs and a new intronic mutation c.461 + 24G-->A. Heterologous expression in COS7 cells showed that the latter causes a splicing defect that results in early translation termination. Yet, this mutation is leaky, giving rise to small amounts of correctly spliced transcripts and offer an explanation for the diverging clinical findings in the cousins, one best described as incomplete achromatopsia and the other with oligocone trichromacy. CONCLUSIONS The cases presented broaden the phenotypic spectrum of GNAT2 mutations and underline the increasing importance of molecular genetics in the clinical diagnosis of atypical ophthalmic phenotypes.
10.1167/iovs.04-0317
pubmed_553_6600
The Token Test for Children (TT) was administered to 97 children aged 3-6 yrs enrolled in pre-school programs, together with the Memphis Comprehensive Developmental Scale (MCDS). The 2 tests covaried closely, particularly in the MCDS "Language" and "Cognitive" subtests. Of the 97 Ss, teachers identified 31 as having "special needs". The TT identified such children better than the best of the MCDS subtests ("Language"), but the teachers did poorly in identifying children shown to have language difficulties. In addition to its economical use as a language screening device, the TT might well become part of a standard pre-school admission test battery.
pubmed_553_6600
pubmed_164_17554
Secretions from the gular and the paracloacal glands of adult male and female American alligators (Alligator mississippiensis) were extracted with chloroform, weighed, and analyzed by thin-layer chromatography. In both sexes, more lipoidal secretions were recovered from the paracloacal glands than from the gular glands. Females produce more lipoidal secretions in both sets of glands than do males. The thin-layer chromatograms of extracts from both glands exhibit bands consistent with aliphatic alcohols, sterols, free fatty acids, and steryl esters. Triglycerides, hydrocarbons, phosphatidylethanolamine, and lysophosphatidylcholine also are indicated in some chromatograms. Gland, sex, and individual differences are suggested in the thinlayer profiles.
10.1007/BF01021263
pubmed_173_3260
PURPOSE To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥ 65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. METHODS A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥ 65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. RESULTS ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥ 65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1-3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes (p = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. CONCLUSIONS One out of every 30 urgent admissions of patients aged ≥ 65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.
10.1007/s00228-015-1974-0
pubmed_197_2518
OBJECTIVES State Children's Health Insurance Program (SCHIP) in the USA plays a critical role in healthcare service utilization. This study assesses children's needs for healthcare services among the variations of SCHIP. METHODS This study applies the PRECEDE-PROCEED behavioral model to analyze the behavior of children with healthcare needs and unmet healthcare needs by using the National Survey of Children with Special Healthcare Needs of the USA. RESULTS Children who were previously under a Medicaid program are apt to enroll in SCHIP programs. SCHIP children with healthcare needs are more likely than comparable non-SCHIP children to use hospital outpatient departments instead of using doctors' offices and health centers. Children under the SCHIP single and SCHIP combination programs are more likely to use doctors' offices and health centers than those in the Medicaid expansion program. SCHIP combination or SCHIP Medicaid expansion states are significantly less likely to have unmet healthcare needs than children in SCHIP single states. CONCLUSIONS Medicaid has a significant impact on the SCHIP program. There is a substitution of healthcare service facilities between hospital outpatient departments and either the doctors' offices or health centers.
10.1016/j.healthpol.2010.07.012
pubmed_836_16008
BACKGROUND There is a lack of knowledge on child health as well as family well-being in IVF/ICSI twins. METHODS These data originated from questionnaires completed by mothers taking part in a national cohort study of twin and singleton births occurring in Denmark in 1997. The overall response rate was 83%. The three cohorts consisted of all IVF/ICSI twin children (n = 472), all IVF/ICSI singletons (n = 634) and all non-IVF/ICSI twin children (n = 1132) born in Denmark in 1997. RESULTS No major differences in physical health were observed between IVF/ICSI twins and non-IVF/ICSI twins. Compared with IVF/ICSI singletons, more IVF/ICSI twins were admitted to a neonatal intensive care unit (NICU) (P < 0.01) and more had surgical interventions (P = 0.03) and special needs (P = 0.02), moreover they had poorer speech development (P < 0.01). Correspondingly, IVF/ICSI twin mothers rated their infant's general health poorer than IVF/ICSI singleton mothers did. All discrepancies between IVF/ICSI twins and singletons disappeared after stratification for birthweight except for NICU admissions and speech development. Multiple logistic regression analyses showed that both IVF/ICSI and non-IVF/ICSI twin parents experienced more marital stress [odds ratio (OR) 2.9, 95% CI 2.2-3.8] and that twins had more impact on the mother's life (OR 1.7, 95% CI 1.2-2.4) compared with singletons. Nevertheless, the only predictor of low divorce/separation risk was IVF/ICSI treatment. CONCLUSION Our study indicates that physical health of IVF/ICSI twins is comparable with that of non-IVF/ICSI twins. However, physical health of IVF/ICSI twins is poorer and the implications for the families stronger compared with IVF/ICSI singletons.
10.1093/humrep/deg257
pubmed_746_6035
Surimi was prepared from the thornback ray (Raja clavata L. 1758) and divided into two groups. The first group was prepared with 4% sorbitol, 4% sucrose and 0.3% sodium tripolyphosphate as a cryoprotectant, while surimi in second group was prepared with 8% sorbitol and 0.3% sodium tripolyphosphate. The frozen surimi samples were stored at 23.8 +/- 2 degrees C for 6 months. The total volatile basic nitrogen (8.40 mg/100 g for group A, 6.30 mg/100 g for group B), trimethylamine nitrogen (2.55 mg/100 g for group A, 2.38 mg/100 g for group B), thiobarbituric acid (1.29 mg malondialdehyde/100 g for group A, 1.17 mg malondialdehyde/ 100 g for group B), and pH values (7.34 for group A, 6.98 for group B) of surimi increased during frozen storage but remained within the acceptable limits. Total psychrophilic aerobic bacteria counts and sensory evaluation points in both groups decreased during frozen storage. The results of this study showed that thornback ray was found to be suitable for surimi production and the surimis were still acceptable at the end of the 6-month storage period.
10.1080/09637480701343762
pubmed_133_11806
Collectins are a family of calcium-dependent collagenous lectins that appear to be important in innate host defense. We investigated the ability of three human collectins, namely, lung surfactant proteins A (SP-A) and D (SP-D) and the serum mannose-binding protein (MBP), to bind to the surface glycoproteins of respiratory syncytial virus (RSV). SP-A was shown to bind to the F (fusion) glycoprotein but not to the viral G (attachment) glycoprotein, and binding was completely abrogated in the presence of EDTA. Neither SP-D nor MBP bound to either glycoprotein. SP-A also neutralized RSV in a calcium dependent fashion. These results support a role for SP-A in the defense of infants against infection with RSV and indicate a possible mechanism for its protective activity.
10.1086/315134
pubmed_422_3149
To test the efficacy of thrombolytic therapy in massive pulmonary embolism, we conducted a prospective randomized controlled trial. Eight patients were randomized to receive either 1,500,000 IU of streptokinase in 1 hour through a peripheral vein followed by heparin or heparin alone. All patients had major risk factors for deep vein thrombosis (DVT) and were considered to have high clinical suspicion for pulmonary embolism (PE). At baseline all patients had a similar degree of systemic arterial hypotension, pulmonary arterial hypertension, and right ventricular dysfunction. The time of onset of cardiogenic shock in both groups was comparable (2.25 +/- 0.5 hours in the streptokinase group and 1.75 +/- 0.96 hours in the heparin group). The four patients who were randomized to streptokinase improved in the first hour after treatment, survived, and in 2 years of follow-up are without pulmonary arterial hypertension. All four patients treated with heparin alone died from 1 to 3 hours after arrival at the emergency room (p = 0.02). Post-thrombolytic therapy the diagnosis of PE was sustained in the streptokinase group by high probability V/Q lung scans and proven DVT. A necropsy study performed in three patients in the heparin group showed massive pulmonary embolism and right ventricular myocardial infarction, without significant coronary arterial obstruction. The results indicate that thrombolytic therapy reduces the mortality rate of massive acute pulmonary embolism.
10.1007/BF01062714
pubmed_396_3246
The Lower Palaeozoic sequences west of the Leinster Granite and in the Slievenamon Inlier of southeast Ireland have been palynologically re-investigated. Most of the productive samples yielded sufficient identifiable acritarchs for positive stratigraphical age determinations for several of the formations. The samples also include rare cryptospores, scolecodonts and tubular structures. Previous work in the area west of the Leinster Granite proposed an unbroken succession from Early Ordovician Ribband Group turbidites and volcanics passing up conformably to Early Ordovician to Late Silurian Kilcullen Group. The new palynological data clearly show that the Kilcullen Group in this area is entirely Silurian (Llandovery-early Wenlock) in age, also results obtained from the same group at Slievenamon confirm the previously reported Silurian age. Ordovician acritarchs found in the Kilcullen Group of both study areas are reworked and range in age from late Tremadoc to Llanvirn. The new data reveal a major stratigraphic break between the Ribband Group dated as Early and Middle Ordovician and the Silurian Kilcullen Group. This major break extends some hundreds of kms southwest to the Dingle Peninsula and possibly equates with a similar discontinuity in the Isle of Man to the northeast. This break would thus appear to be a major feature within the northwestern Avalonian margin sequence.
10.1016/s0034-6667(00)00052-x
pubmed_245_9087
Emerging evidence suggests that the multiligand receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 protein (HMGB1) contribute to the pathophysiology of ischaemic stroke (IS). The present study aimed to investigate the association of RAGE and HMGB1 variants with the risk of IS. A total of 1,034 patients and 1,015 age- and sex-matched healthy controls were genotyped to detect five genetic variants of the RAGE gene and four genetic variants of the HMGB1 gene using the Multiplex SNaPshot assay. We found that the rs2070600 variant of RAGE was associated with an increased risk of IS (OR = 1.19, 95% CI: 1.02-1.38, P = 0.043), whereas the rs2249825 variant of HMGB1 was associated with a decreased risk of IS (OR = 0.83, 95% CI: 0.71-0.98, P = 0.041). Further stratification by IS subtypes revealed that the presence of the TT genotype of the RAGE rs2070600 variant confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.036). Moreover, patients with the variant T allele of the RAGE rs2070600 variant presented with reduced serum soluble RAGE production. Patients carrying the variant G allele of the HMGB1 rs2249825 variant exhibited significantly lower infarct volumes than those with the major CC genotype. These clues may help in the development of optimal personalized therapeutic approaches for IS patients.
10.18632/oncotarget.22112
pubmed_355_13745
We have adapted the enzyme-linked immunospot assay (ELISPOT) to enumerate the cells from Plasmodium falciparum-primed donors that produce IgG in vitro in response to malaria antigens. In vitro activation of cell cultures with two synthetic peptides (EENVEHDA)4, and (LGRSGGDIIKMQTL) corresponding to immunodominant T cell epitopes of the ring-infected erythrocyte surface antigen (Pf155/RESA) gave specific antibody-secreting cells (ASC) in five and six of the 15 P. falciparum-primed donors from Cameroon. Antibodies produced after a stimulation by synthetic peptides reacted also with total parasite proteins. However, crude P. falciparum antigen did not trigger a higher number of cells than did synthetic peptides. The absence of significant relation between the presence of sera antibodies and in vitro ASC against the same peptide suggests that the kinetics of circulating primed lymphocytes and antibodies are different. We evaluated 0.04-0.29% of peripheral blood B cells to be the frequency of memory cells specific to a single Pf155/RESA epitope in these donors. This study suggests that the ELISPOT assay should permit the analysis of B cell responses to malarial antigens at the single-cell level and its applicability to epidemiological field studies. This assay should be well suited to the identification of T helper epitopes capable of inducing the production of antibodies by human B cells, and will constitute an important tool for the selection of immunogens to be included in a subunit vaccine.
10.1111/j.1365-2249.1993.tb03355.x
pubmed_943_7937
DNA vaccination induces antigen-specific immune responses with characteristics distinct from other vaccination modes. In the present study, the contribution of the plasmid backbone adjuvant effect to the quality of the DNA-raised antibody response was investigated. For this purpose, three intradermal primings were compared in mice using: (1) the recombinant Schistosoma haematobium glutathione S-transferase antigen (rSh28GST): (2) rSh28GST supplemented with a non-coding plasmid; and (3) a Sh28GST-encoding plasmid. In contrast to immunization with the protein, DNA immunization elicited a very stable antibody (Ab) response over a prolonged period of time. This feature was attributed to the plasmid backbone, because co-administration of the non-coding plasmid with rSh28GST allowed the maintenance of the specific Ab response. A strong anamnestic Ab response was induced after intradermal boost with rSh28GST only in the mice primed with pMSh. This indicated that the selective ability of DNA vaccination to induce memory humoral response was independent of the plasmid backbone. In contrast the plasmid backbone was found to strongly participate in the preferential IgG2a Ab production observed. These results suggest that, following DNA immunization, the Th1-biased profile and the maintenance of the long-lived Ab response could be attributed to an adjuvant effect of the plasmid backbone during priming, whereas the strength of B-cell memory was independent of this effect.
10.1016/s0264-410x(01)00174-8
pubmed_341_10868
Despite much progress globally, TB is still one of the top 10 causes of death worldwide. Several studies have shown the importance of implementing different preventive strategies alongside treatment of TB disease, including BCG vaccination and treatment of latent tuberculosis infection (LTBI). Large-scale population level LTBI treatment is not currently part of WHO guidelines which recommend LTBI treatment only to high risk populations. Moreover, BCG has been widely used in the past decades to both prevent infection with M. tuberculosis and reduce rates of reactivation. In this viewpoint we discuss the hypothesis of BCG vaccination following latent TB treatment and its potential impact across different settings.
10.1016/j.ijid.2019.02.026
pubmed_41_19947
This paper aims to analyze the curative effect of Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease. 97 patients with chronic pelvic inflammatory disease admitted to our hospital from June 2015 to June 2016 were selected and randomly divided into observation group and control group. Patients in control group were treated with Kangfuxiaoyan suppository and patients in the observation group were treated with Jin'gangteng capsule combined with kangfuxiaoyan suppository treatment. The curative effect between the two groups was compared. The scores of symptoms and signs in the observation group after treatment were lower than those in the control group. The total effective rate of the observation group was higher than that of the control group, and there was significant difference between the two groups, P<0.05. Jin'gangteng capsule combined with Kangfuxiaoyan suppository in the treatment of chronic pelvic inflammatory disease can improve the treatment efficiency and promote the rapid and effective relief of clinical symptoms and signs.
pubmed_41_19947
pubmed_567_2158
The efficacy of the controversial treatment of submucosal diathermy to the inferior turbinates (SMDIT) was evaluated objectively. Twenty-seven patients with chronic rhinitis were investigated by hourly posterior rhinomanometry to assess changes in total and minimum (Fmin) and maximum (Fmax) unilateral nasal airflow over 5 h, before and 2-3 months after standardized SMDIT treatment. Nasal airflow was recorded at a sample pressure of 75 Pa and the results are reported as medians with interquartile range. Whilst SMDIT caused a significant 51% increase (p < 0.0001) in total nasal airflow from 246 cm3/s (131) to 371 cm3/s (133) the changes in unilateral airflow provided further evidence which strongly supported the benefits of this operation. Unilateral Fmin significantly increased by 136% (p < 0.0001) from 69 cm3/s (82) to 163 cm3/s (74) and Fmax significantly increased by 23% (p < 0.0001) from 171 cm3/s (74) to 211 cm3/s (59). The effect of surgery was to "splint" to the turbinate in a state of relative vasoconstriction. Our findings therefore provide functional evidence of submucosal fibrosis following SMDIT. The greater percentage change in unilateral Fmin suggests that this parameter is a more sensitive index of the effect of nasal surgery than total nasal airflow measurements. The importance of considering the nose as two separate airways in the evaluation of nasal treatments is emphasized.
10.1080/00016489950180270
pubmed_304_17581
The printed wire boards (PWBs) in electronic waste (E-waste) have been found to contain large amounts of toxic substances. Studies have concluded that the waste PWBs are hazardous wastes because they fails the toxicity characteristic leaching procedure (TCLP) test with high level of lead (Pb) leaching out. In this study, two treatment methods - high-pressure compaction and cement solidification - were explored for rendering the PWBs into non-hazardous forms so that they may be safely disposed or used. The high-pressure compaction method could turn the PWBs into high-density compacts with significant volume reduction, but the impact resistance of the compacts was too low to keep them intact in the environment for a long run. In contrast, the cement solidification could turn the PWBs into strong monoliths with high impact resistance and relatively high compressive strength. The leaching of the toxic heavy metal Pb from the solidified samples was evaluated by both a dynamic leaching test and the TCLP test. The dynamic leaching results revealed that Pb could be effectively confined in the solidified products under very harsh environmental conditions. The TCLP test results showed that the leaching level of Pb was far below the regulatory level of 5mg/L, suggesting that the solidified PWBs are no longer hazardous. It was concluded that the cement solidification is an effective way to render the waste PWBs into environmentally benign forms so that they can be disposed of as ordinary solid wastes or beneficially used in the place of concrete in some applications.
10.1016/j.jhazmat.2006.11.039
pubmed_705_4606
We describe the phenotypic and functional properties of B lineage cells developing in fetal liver organ cultures (FLOC) of mouse embryos at day 14 or 15 of gestation which contain pro/pre-B-I cells. FLOC B cell development proceeds to mature IgM+, IgD+ and CD23+ lipopolysaccharide-reactive B cells within a culture period of 5-6 days. The phenotypes and relative proportions of pro/pre-B-I, pre-B-II, immature and mature B cells from FLOC were similar to that seen in livers freshly isolated from age-matched, i.e. newborn, mice. More importantly, the numbers of cells recovered in the different B lineage subpopulations from FLOC were close to those developed in vivo. Hence, in contrast to single-cell suspension cultures of fetal liver, FLOC allow the proliferative expansion of pre-B cell receptor-expressing pre-B-II cells. FLOC from embryos of mice with targeted mutations in the RAG-2 and lambda5 genes, which cannot expand by proliferative expansion of their pre-B-II compartment in vivo because they cannot express a pre-B cell receptor on their surface, show this same defect in vitro. FLOC are accessible to the action of mAb and cytokines. Thus, addition of anti-IL-7 receptor mAb to FLOC of normal mice inhibits B cell development at the transition of pro/pre-B-I to pre-B-II cells. This inhibition is reversed by addition of excess rIL-7. Addition of IL-7 alone stimulates the proliferation of pro/pre-B-I cells and inhibits their differentiation to pre-B-II and immature B cells, as it does in single-cell suspension cultures. FLOC should be useful to study the effects of other mAb, cytokines, ligands and other molecules on early B cell development.
10.1093/intimm/10.1.49
pubmed_993_2044
Action potentials (AP) of neurons A and B could be only elicited in the presence of Na-+ ions. An increase in [Ca-++]0 led to depolarization of neurons, enhancement of their excitability, AP, overshoot, of positive afterpotential, AP duration, AP maximal rate of fall (Vf) and to decrease in AP maximal rate of rise (Vr). After addition of CaCl2 up to 50 mmoles into the Ringer solution, the membrane resistance (R) increased. If the [Na-+]0 was equimolarly diminished, R increased up to the [Ca-++]0 30 mmoles, but at greater [Ca-++]0 R fall below the initial value. The regularities were independent of the initial value of resting potential (RP). At high [Ca-++]0 Ca-++ contributed to the generation of the inward current during AP while Na-+ caused an increase in ionic (calcium) membrane permeability at rest. At high [Ca-++]0, Na-+ was also necessary for support of membrane channels which maintained the inward and outward currents during the AP.
pubmed_993_2044
pubmed_134_13696
Genetic studies in Caenorhabditis elegans identified an evolutionarily conserved CED-2 (CrkII), CED-5 (DOCK180), CED-12 (ELMO), CED-10 (Rac1) module important for cell migration and phagocytosis of apoptotic cells. Previous studies have shown that DOCK180 and ELMO comprise an unconventional bipartite Dbl homology domain-independent Rac guanine nucleotide exchange factor (Rac-GEF); but it is still unclear how CrkII functions in Rac-GEF activity. In this study, we have characterized a unique function of CrkII in phagocytosis and Rac activation mediated by the C-terminal SH3 domain, a region of CrkII that has no clear cellular or biochemical function. We found that mutations that disrupt the C-terminal SH3 domain of CrkII (CrkII-SH3-C) abrogate engulfment of apoptotic cells and impair cell spreading on extracellular matrix. Surprisingly, despite the effects on engulfment, W276K CrkII strongly potentiated Rac-GTP loading when ectopically expressed in HEK 293T cells. Contrary to the effects of the true dominant negative SH2 domain mutants (R38K CrkII) and SH3-N domain mutants (W170K CrkII) that prevent macromolecular assembly of signaling proteins, W276K CrkII increases association between DOCK180 and CrkII as well as constitutive tethering of the Crk/DOCK180/ELMO protein complex that interacted with RhoG. Our results indicate that while N-terminal SH3 of CrkII promotes assembly between CrkII and DOCK180, the C-terminal SH3 of CrkII regulates the stability and turnover of the DOCK180/ELMO complex. Studies with W276K CrkII may offer a unique opportunity to study the structure and function of the DOCK180/ELMO Rac-GEF.
10.1002/jcp.20288
pubmed_505_13497
The recent identification of the CARD15/NOD2 gene as a susceptibility locus for Crohn's disease represents an important step towards the delineation of the immunopathogenesis of inflammatory bowel disease. CARD15 functions as an intracellular receptor for bacterial components and thus represents an important link between inflammatory bowel disease and innate immunity. Three major CARD15/NOD2 gene mutations have been associated with Crohn's disease in Caucasians in several independent studies. Together, they explain about 20% of the genetic susceptibility for Crohn's disease. Genotype-phenotype analyses demonstrated an association of these mutations with ileum-specific disease, an increased incidence of the fibrostenotic phenotype and an earlier age of disease onset. Beside these associations, no other relationship between the CARD15/NOD2 genotype and disease behavior or response to treatment has been detailed so far. Thus, the clinical impact of knowing the patient's genotype is limited at this time. Screening for CARD15 mutations in order to identify high-risk individuals or to introduce an individualized disease management is therefore currently not recommended.
10.1159/000075357
pubmed_108_19448
Brassinosteroids are known to promote cell elongation in a wide range of plant species but their effect on cell division has not been as extensively studied. We examined the effect of brassinolide on the kinetics and final division frequencies of regenerating leaf mesophyll protoplasts of Petunia hybrida Vilm v. Comanche. Under optimal auxin and cytokinin conditions, 10-100 nM brassinolide accelerated the time of first cell division by 12 h but had little effect on the final division frequencies after 72-120 h of culture. One micromolar brassinolide showed the same acceleration of first cell division but inhibited the final division frequency by approximately 20%. Under sub-optimal auxin conditions, 10-100 nM brassinolide both accelerated the time of first cell division and dramatically increased the 72- to 120-h final division frequencies. Isolated protoplasts may provide a useful model system to investigate the molecular mechanisms of brassinosteroid action on cell proliferation.
10.1007/s002990050510
pubmed_532_12307
A robust and regioselective palladium-catalyzed intermolecular aerobic oxidative cyclization of 2-ethynylanilines with isocyanides to the synthesis of 4-halo-2-aminoquinolines is reported herein. The procedure constructs various 4-halo-2-aminoquinolines with moderate to excellent yields (47-94%) and broad substrates scope. Furthermore, this process can be easily extended to synthesis of various 6H-indolo[2,3-b]quinolines via an intramolecular Buchwald-Hartwig cross-coupling reaction in two-step one-pot manner.
10.1021/jo401707j
pubmed_74_4353
BACKGROUND L-asparaginase is a key component of treatment for patients with acute lymphoblastic leukaemia (ALL) in the UK. Commonly used forms of asparaginase are native E. coli-derived asparaginase (native asparaginase) and pegaspargase in first-line combination therapy, and native Erwinia chrysanthemi-derived asparaginase (Erwinia asparaginase) as second-line treatment. The objective of this study was to evaluate the cost-effectiveness of pegaspargase versus native asparaginase in first-line combination therapy for patients with newly diagnosed ALL. A combined decision tree and health-state transition Markov cost-effectiveness model was developed to assess the relative costs and health outcomes of pegaspargase versus native asparaginase in the UK setting. RESULTS In base case analyses, first-line pegaspargase (followed by Erwinia asparaginase in cases of hypersensitivity) dominated first-line native asparaginase followed by Erwinia asparaginase; i.e. resulted in lower costs and more quality-adjusted life year gain. The favourable hypersensitivity rates and administration profile of pegaspargase led to lifetime cost savings of £4741 versus native asparaginase. Pegaspargase remained cost-effective versus all treatment strategies in all scenario analyses, including use of the 2500 IU/m2 dose, recommended for patients ≤21 years of age. CONCLUSIONS Pegaspargase, as part of multi-drug chemotherapy, is a cost-effective option for the treatment of newly diagnosed ALL. Based on this study, The National Institute for Health and Care Excellence Technology Appraisal Committee concluded that it could recommend pegaspargase as a cost-effective use of National Health Service resources in England & Wales for treating ALL in children, young people and adults with untreated, newly diagnosed disease. TRIAL REGISTRATION UKALL 2011, EudraCT number 2010-020924-22; UKALL 2003, EudraCT number 2007-004013-34; UKALL14, EudraCT number 2009-012717-22.
10.1186/s13561-019-0257-3
pubmed_56_19332
The synthesis of two novel (+)-isocampholenic acid-derived amines has been realized starting from commercially available (1S)-(+)-10-camphorsulfonic acid. The novel amines as well as (+)-isocampholenic acid have been used as building blocks in the construction of a library of amides using various aliphatic, aromatic, and amino acid-derived coupling partners using BPC and CDI as activating agents. Amide derivatives have been assayed against several enzymes that hold potential for the development of new drugs to battle bacterial infections and Alzheimer's disease. Compounds 20c and 20e showed promising selective sub-micromolar inhibition of human butyrylcholinesterase [Formula: see text] ([Formula: see text] values [Formula: see text] and [Formula: see text], respectively).
10.1007/s11030-016-9668-9
pubmed_26_776
We investigated the anti-allergic effects of one strain (T120) of a lactic acid bacteria (LAB) isolated from Mongolian fermented milk using atopic dermatitis (AD) model mice (NC/Nga mice). Strain T120 has already been identified as Enterococcus faecium and shown to induce strong production of IL-12 (Kimura et al. 2006). In in vitro studies, strain T120 suppressed total IgE production and induced IL-12 and IFN-gamma production by splenocytes of NC/Nga mice. The additional examination of various neutralization antibodies was performed to elucidate in detail the mechanism of depressed IgE production by strain T120. As a result, it became clear that IL-12 induced by strain T120 increased production of IFN-gamma and total IgE production was mainly controlled by the IFN-gamma. In order to define the cells which produce IL-12 powerfully by this strain, antigen-presenting cells (APCs) such as macrophages and dendritic cells (DCs) were removed from the splenocytes, and the reactivity of these cells to the strain was examined. Induction of IL-12 and IFN-gamma by strain T120 became significantly very low by removal of APCs from splenocytes. Therefore, it was clear that strain T120 acted on APCs and induced production of IL-12. Further, this strain enhanced the production of IL-10 by splenocytes. In in vivo studies, intraperitoneal injection of strain T120 inhibited serum IgE elevation and atopic dermatitis symptoms in NC/Nga mice. These results suggest that an anti-allergic effect of strain T120 depends on the increased production of IL-12 by APCs activated by the strain and following the increased production of IFN-gamma. Further, activation of regulatory T cells by strain T120 may inhibit atopic disease.
10.1017/S0022029908003725
pubmed_124_5708
As one phase of a comprehensive population study of women, bone density was determined in the third lumbar vertebra by dual photon absorptiometric technique. The method involves the use of two radionuclides, which both emit gamma radiation but with different energies (241Am with 59.6 keV and 137Cs with 662 keV). Women in three age strata were studied: 46, 54 and 62 yr. All women aged 46 were still menstruating, while the age strata 54 and 62 were subdivided into two groups: those who still menstruated or had been postmenopausal for a short time and those who had been postmenopausal for many years. The bone mineral content was higher in premenopausal or recently postmenopausal 54-yr-old women than in women of the same age who had been postmenopausal for a long time (P less than 0.01). A similar trend was found for women aged 62 (P less than 0.10). The differences could not be explained by differences in other factors studied, such as body weight, body height, smoking habits or physical activity. No significant differences were found when women with similar menopausal status in different age groups were compared.
10.1016/0378-5122(79)90006-9
pubmed_70_276
Endothelial dysfunction is a marker of atherosclerosis and contributes to the atherogenic process and the development of atherothrombotic complications. Oxidative stress has been implicated in the development of endothelial dysfunction through alterations of the nitric oxide metabolism. A number of evidence suggests a role for phagocytic-cell-mediated oxidative stress in diminished nitric oxide availability that is present in patients with atherosclerotic risk factors such as arterial hypertension. Thus, the combination of an excessive production of reactive oxygen species, namely superoxide anion, with an impaired antioxidant defense capacity leading to oxidative stress may facilitate the development and progression of atherosclerosis. Findings from recent clinical studies suggest that this mechanism can be operative in patients with cerebrovascular disease. This view may increase our capabilities to understand the pathophysiology of cerebrovascular disease, as well as to stimulate the design of new therapeutic strategies aimed to prevent and control the atherosclerotic process in patients presenting this condition.
10.1159/000107376
pubmed_565_1202
OBJECTIVE To investigate the role of trefoil peptides in modulation of gastric adaptation to water restraint stress (WRS) in rats. METHODS Wistar rats were exposed to single or repeated WRS for 4 hours every other day for up to 6 days, gastric mucosal blood flow (GMBF) was measured by LDF-3 flowmeter, the extent of gastric mucosal lesions was evaluated grossly and histologically, and expression of PS2 intestinal trefoil peptide (ITF), cyclooxygenase (COX-2), inducible nitric oxide synthase (iNOS) and transferase growth factor-alpha (TGF-alpha) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS One application of WRS produced extensive gastric mucosal erosion. With repeated WRS, the gastric mucosa became adapted to the stress of WRS, and the ulcerative index (UI) was reduced by 22.0% that of one WRS challenge after four consecutive WRS. Expression of PS2 was markedly decreased and expression of ITF, COX-2, iNOS and TGF-alpha were markedly increased after single stress. But this adaptation to WRS was accompanied by increased GMBF and active cell proliferation in the neck region of gastric glands, and by increased expression of PS2, ITF, TGF-alpha, but reduced expression of COX-2 and iNOS. CONCLUSION Gastric adaptation to WRS injury involves enhanced cell proliferation, increased expression of PS2, ITF, TGF-alpha and reduced expression of COX-2 and iNOS, suggesting trefoil peptides might play an important modulating role in this phenomenon.
pubmed_565_1202
pubmed_647_13728
In order to identify indirect molecular biomarkers of anabolic treatments in veal calves, an animal experiment was performed using two combinations of growth promoters (consisting of boldenone undecylenate and estradiol benzoate, and of testosterone enantate and estradiol benzoate). We selected a set of 12 genes that are known to be androgen responsive in other mammalian species. The expression profile of this set of genes was analysed on prostate samples of veal calves using a real-time RT-PCR approach. For each selected gene the corresponding bovine sequence was obtained and a gene specific real-time assay was optimised and validated. The amplification was shown to be highly specific, linear and efficient. High reproducibility (<1%) and low-test variability (<2.5%) were also been achieved. Messenger RNA levels were quantified in prostate samples, non-parametric analysis of variance showed significant up-regulation of three genes (MAF, ESR1 and AR) and significant down-regulation of four genes (HMGCS1, HPGD, DBI, and LIM) in treated samples when compared with untreated controls. To assess the possibility of identifying hormone-treated animals by molecular means we performed a discriminant analysis that was effective in classifying treated and non-treated samples with an accuracy of 93%. Our results indicate that identification of treatment with steroid hormones in veal calves by means of gene expression analysis is a feasible approach and could be improved increasing both the number of genes and the number of controls analysed.
10.1016/j.domaniend.2005.05.008
pubmed_187_22631
The binding of IgG in antiserum to Escherichia coli J5 to the surface of Enterobacteriaceae and to cell wall fragments released from serum-exposed bacteria was studied in a search for potentially protective epitopes other than lipopolysaccharide (LPS). IgG titers to multiple heterologous gram-negative smooth bacteria increased following incubation of the bacteria in serum and decreased following absorption with serum-exposed heterologous bacteria. IgG eluted from absorbing bacteria bound to at least three conserved bacterial outer membrane proteins (OMPs), but not LPS, as assessed by immunoblotting. The same OMPs were present in LPS-containing macromolecular cell wall fragments released by incubation of heterologous gram-negative bacteria in human serum. Part of the protection offered by J5 antiserum could be from binding of IgG to conserved OMPs at the bacterial surface or to OMPs in cell-wall fragments released from dying bacteria.
10.1086/514121
pubmed_257_21300
The thyroid nodules represent the most frequent endocrinopathy, because clinically palpable nodules are detectable in 4-5% of the general population. Such pathological condition includes adenomas, carcinoma, intraglandular haematomas or cysts, focal thyroiditis, etc. Fine-needle aspiration cytology allows a correct diagnosis in about 90% of the cases, distinguishing focal thyroiditis from nodular goiter or thyroid malignancies. The new instrumental and cytological studies make the choice for surgical interventions more selective. At the Institution of General and Cardiovascular Surgery, University of Milan, 597 patients underwent surgery from 1966 to January 1988. The observed nodular (toxic or non toxic) thyropathies were 498 (83.4%). Cold nodules represented about a third (34%) of the nodular thyropathies. Thyroid carcinomas were 33 (5.6%). This study is aimed to analyze our surgical attitude with respect to nodular thyropathies, the surgical procedures adopted and the observed complications.
pubmed_257_21300
pubmed_1089_17186
Australian women constitute a majority of the aged population in Australia, and are more likely than men to be single in old age as well as dependent upon the means-tested Age Pension with no, or only limited, income supplementation from other sources such as occupational superannuation. Based upon research on a national sample of 1016 Australian women, aged across the adult life span, this paper reports age cohort patterns of work, family, and economic expectations for old age. While work and family patterns of Australian women are changing, the clear trend remains towards labour force withdrawal and part-time work for long periods while children are present in the home. The implications of these patterns for income security in old age are discussed.
10.1007/BF00117003
pubmed_906_24272
To evaluate clinoptilolite, a natural zeolite, as a candidate material for a permeable reactive barrier for removal of strontium from groundwater, we investigated particle release and permeability reduction in clinoptilolite and sand porous media. In flow-through column experiments, we tested the effects of solution chemistry, grain size, and clinoptilolite pretreatment on particle release and hydraulic conductivity. Permeability reduction occurred not in the clinoptilolite itself but only in finer-grained sand down-gradient of the clinoptilolite. Solutions of high ionic strength inhibited particle release and prevented clogging. Clinoptilolite of larger grain size produced slightly less particle release and clogging. Two pretreatments of the clinoptilolite, rinsing to remove fine particles and calcining to improve strength, reduced particle release and clogging. Calcining, however, significantly reduced the strontium binding strength of the clinoptilolite.
10.1021/es001868s
pubmed_446_13667
CONTEXT Children consume more than one-third of their daily food intake in schools, suggesting that these environments are ideal places for intervening on poor dietary behaviors. OBJECTIVE To assess the impact of strategy-focused menu planning on the sodium content of student meals served in the Los Angeles Unified School District (LAUSD). DESIGN Pre- and post-LAUSD menu change analyses for school years (SY) 2010-2011 and 2011-2012 were performed using nutritional analysis data and food production records. The analyses assessed changes in sodium content by meal categories. SETTING 900+ schools, grades K-12, operated by the LAUSD. PARTICIPANTS The LAUSD Food Services Branch, which serves about 650 000 meals per day. INTERVENTION A multistage menu planning approach that focused on implementing evidence-based strategies to improve the nutritional content of school breakfast and lunch menus. Engagement and formation of multisectoral partnerships, including public health and parent/student groups, were vital elements of the intervention process. MAIN OUTCOME MEASURE(S) Sodium content changes in the LAUSD menu, SY 2010-2011 versus SY 2011-2012; other measures include documentation of program reach. RESULTS From SY 2010-2011 to SY 2011-2012, the mean unweighted sodium levels for elementary (K-5) breakfast and for secondary (6-12) breakfast and lunch decreased. These changes met or exceeded the 2014-2015 US Department of Agriculture sodium targets for school meals and for secondary breakfast, the 2022-2023 target(s). These results, however, were not as notable once student food selection patterns (weighted data) and condiments were considered in the analysis. CONCLUSIONS Use of strategy-focused menu planning as a mechanism to reduce sodium in school meals appeared to be promising, demonstrating favorable declines in mean sodium levels for at least 3 of 4 meal categories in the LAUSD. Student food selection patterns and condiments use, however, can affect the strength of the intervention.
10.1097/PHH.0b013e31829f2e50
pubmed_834_8528
The problem in the study of the mechanisms of school-children's health formation during their study at school can be solved by applying a systems approach with the use of a multifactorial analysis which combines a host of some environmental components into a number of risk factors identified from the degree of their impact on the health status of pupils. In accordance with the contribution to the dispersion of signs, the role of intraschool environmental factors increases from 12.5% in primary school children to 20.6% in those leaving the eighth form. As pupils grow up, the contribution of sociohygienic factors decreases from 27.5% at the beginning of school study to 13.8% at its end. The pathological affliction factor is 23.3% on admission to school and little changed (20.8%) in old schoolchildren. In cities, the highest contribution to the impact on schoolchildren's health is made by the natural and climatic factor; climatic conditions and environmental pollution account for 10 and 20%, respectively.
pubmed_834_8528
pubmed_345_10158
PET studies play an important role in the early detection of Alzheimer's and Parkinson's diseases (AD and PD). Fluorine-18 fluorodeoxyglucose (F-FDG) PET imaging of regional cerebral glucose metabolism and PET amyloid imaging are the two major PET studies for AD. F-FDG PET is highly sensitive for the early diagnosis of AD, in predicting conversion from mild cognitive impairment to AD, and in differentiating AD from other dementias. PET amyloid imaging is positive in the majority of patients with AD. Negative amyloid PET reduces the likelihood of AD. The main limitations of PET amyloid imaging is its high positivity in the normal elderly population and in other medical conditions with amyloid pathologies. Various PET tracers are available to assess motor and cognitive dysfunctions in PD. PET tracers targeting presynaptic dopaminergic function (F-DOPA, radiolabeled PET tracers assessing the availability of dopamine transporters and vesicular monoamine transporters) and postsynaptic dopamine receptors are used to assess motor dysfunction in PD. PET tracers, particularly dopamine transporters, are highly sensitive in the early diagnosis of PD. Uptake of PET tracers in the striatum is inversely correlated with disease severity. PET is valuable in differentiating PD from other movement disorders. PET studies, particularly F-FDG PET, help to evaluate cortical metabolism in PD patients with cognitive dysfunction and dementia.
10.1097/MNM.0000000000000320
pubmed_882_1276
BACKGROUND AND PURPOSE Our aim was to address the correlation between small fiber loss and amyotrophic lateral sclerosis (ALS) for disease onset, phenotype, genotype, duration, severity and sensory findings. METHODS Consecutive patients referred for suspected ALS were screened. Exclusion criteria were possible ALS and previous diagnosis or known risk factors for small fiber neuropathies. A sural nerve conduction study (NCS) was bilaterally recorded. The ALS functional rating scale revised was administered and loss of functions were calculated using the Milano-Torino staging (MITOS) system. Sensory symptoms and signs were recorded. Genetic analysis was performed by the next-generation sequencing approach. Skin biopsy was performed at the distal leg and intraepidermal nerve fiber (IENF) density was quantified in three non-consecutive sections following published guidelines. Findings were referred to age- and sex-adjusted normative values. RESULTS Fifty-seven patients including six with facial onset sensory and motor neuronopathy (FOSMN) were enrolled. Eight (15.7%) pure ALS patients and five (83%) FOSMN patients complained of sensory disturbances with different distributions. Sural NCS was normal in all except two patients. IENF density was reduced in 75.4% of pure ALS and 50% of FOSMN patients, without correlation with any disease features. IENF density was similarly reduced in bulbar (78.5%), flail limb (87.5%), pyramidal (100%), and spinal (68.2%) onset, as well as in genetic (83.3%) and sporadic (82%) ALS. There was no correlation with genotype, disease duration and severity. CONCLUSIONS Intraepidermal nerve fiber loss is a feature of most ALS patients. It does not correlate with onset, phenotype, course and severity of the disease, and cannot be considered a clinical or prognostic biomarker.
10.1111/ene.12936
pubmed_663_2336
As hepatitis B and C share modes of transmission, their combined occurrence is not uncommon, particularly in areas where both viruses are endemic and in individuals at high-risk of parenteral infection. Both viral hepatitis infections form an important global public health problem, responsible for over half a billion chronic infections worldwide. Their distinctive characteristics impact upon their epidemiology, transmission, and the success of the different prevention strategies. Since several decades a safe and effective vaccine has been available to prevent hepatitis B virus (HBV) infection. Universal vaccination is the cornerstone of global HBV control. Despite major success, vaccine uptake is hampered, and increasing efforts are required to eliminate acute and chronic hepatitis B. Unlike hepatitis C and HIV, HBV has not captured sufficient attention from policymakers, advocacy groups, or the general public: a major challenge for the future. Although progress has been made in the development of an hepatitis C vaccine, short-term successes are not expected. Even without a vaccine, successes can be reported in the field of hepatitis C due to e.g. implementation of universal precautionary measures in health-care settings, screening of blood and blood products, and identification and counselling of infected people. Despite important efforts, transmission in injecting drug users is increasing.
10.1016/j.bpg.2008.11.008
pubmed_38_10346
Although overweight and obese individuals are turning to Internet communities for social support for weight loss, there is no validated online instrument for measuring the subjective social support experiences of participants in these communities. The authors' objective was to determine whether an online version of a validated paper questionnaire, the Weight Management Support Inventory, is appropriate for measuring social support among members of Internet weight loss communities. The authors administered the paper and online versions of the questionnaire in random, counterbalanced fashion to 199 members of a large Internet weight loss community. Scores for the paper and online versions were comparable in between-subjects and within-subjects comparisons. Convergent validity is suggested by the finding that participants who posted messages on Internet forums several times per day reported more social support than those who posted less frequently. However, the instrumental (tangible) support items did not load significantly on the instrumental support factor, suggesting that instrumental support is not relevant to the social support exchanged among participants in these communities. The authors conclude that the online, modified Weight Management Support Inventory, without items for instrumental support, is an appropriate instrument for measuring social support for weight loss among members of Internet weight loss communities.
10.1080/10810730.2010.535106
pubmed_792_7771
Females, especially older women, historically have been excluded from coronary heart disease (CHD) studies. The PrimeTime program was a randomized clinical trial designed to study the effects of a comprehensive lifestyle management program (very low-fat vegetarian diet, smoking cessation, stress-management training, moderate exercise, and group support) on changes in behavioral risk factors among postmenopausal women with CHD. The study also explored program effects on four psychosocial clusters: coping with stress, distress, social support, and self-efficacy. The program produced significant behavioral improvements in 4- and 12-months adherence to diet, physical activity, and stress-management in the PrimeTime women compared to the Usual Care (UC) group. In addition, the PrimeTime participants demonstrated improvements relative to UC on psychosocial measures of self-efficacy, perceived social support, and ability to cope with stress. Strengths and weaknesses of the study, and implications for future research are discussed.
10.1016/s0738-3991(98)00074-3
pubmed_215_5935
Foamy viruses are nonpathogenic retroviruses that offer unique opportunities for gene transfer into various cell types including hematopoietic stem cells. We used a simian foamy virus type 1 vector (SFV-1) containing a LacZ reporter gene with a titer of 1-5 x 10(6) viral particles/ml that was free of replication-competent retrovirus to transduce human umbilical cord blood CD34+ cells. Transduced CD34+ cord blood cells were transplanted into NOD/SCID mice and plated in serum-free methylcellulose culture to determine the transduction efficiency of human hematopoietic progenitor cells. A transduction efficiency of about 20% was obtained. At 6-10 weeks posttransplantation, human hematopoietic cell engraftment and marking were determined. Marrow from transplanted mice demonstrated human cell engraftment by the presence of human (CD45+) cells containing both CD19+ lymphoid and CD33+ myeloid cells. Serial sampling of NOD/SCID bone marrow revealed the presence of 6.7-14.0% CD45+ cells at 6 weeks posttransplant as compared to 3.6-27.2% CD45+ cells at 9-10 weeks posttransplant. Human progenitors examined from NOD/SCID bone marrow cells 9 weeks posttransplant revealed from 7.4 to 25.9% of the colonies exhibiting X-gal staining. Our study demonstrates the ability of a simian foamy virus vector to transduce the SCID-repopulating cell and offers a promising new gene delivery system for use in hematopoietic stem cell gene therapy.
10.1006/viro.2002.1604
pubmed_99_6027
A 33-year-old woman had developed cortical deafness with profound initial deafness lasting for eleven months after pneumococcal meningitis ten years previously. CT scan demonstrated bilateral temporal lobe lesions, predominantly on the left side where it extended into the adjacent parietal and frontal lobes. Audiometry suggested integrity of the internal ear and brain stem. Early auditory evoked potentials were present, while potentials of moderate latency and delayed potentials were abolished. Neuropsychological investigations demonstrated total absence of spoken language, contrasting with conservation of written language, though with agrammatism and an impossibility of identifying non-verbal noises, spoken language, and music. The patient could not identify rhythms, pitch, melodies or the different types of music. The musical quality of sound stimuli and musical pleasure were, however spared as shown by recognition of tape recorded sound stimuli with written denomination and designation of images in multiple choice tests. The relations between auditory agnosia, "pure" verbal deafness and cortical deafness are discussed. Reported cases are reviewed and an attempt is made to demonstrate the existence of several levels in the integration of musical stimuli, the most elementary of which could be the perception of the musical quality of sounds, as was the case in the present patient.
pubmed_99_6027
pubmed_662_1088
A controlled trial of fetal heart rate (FHR) monitoring in a low-risk obstetric population was carried out in 989 patients at the Mercy Maternity Hospital and Queen Victoria Medical Centre. The use of monitoring failed to demonstrate any improvement in perinatal outcome. Monitoring was associated with an increased intervention rate and a small increase in the number of babies who remained in the isolette beyond 3 days. This study does not support the view that FHR monitoring should be used in all labors. Further study in a larger sample is recommended.
10.1016/s0002-9378(15)33273-7
pubmed_424_16109
The CSH1 gene product is the first protein implicated to affect the phenotype of cell surface hydrophobicity in Candida albicans. Ablation of expression of CSH1 resulted in a 75% loss of the cell surface hydrophobicity (CSH) phenotype. When the C. albicans csh1 knockout derivative was cultured from frozen stocks, it had reacquired CSH levels similar to the parent strain and isogenic reintegrant in the absence of Csh1p re-expression through an unknown mechanism. Prior to reacquisition of CSH, the knockout was less adherent to fibronectin than the parent. Comparison of the csh1 knockout and CSH1 reintegrant in a hematogenous dissemination model allows analysis of Csh1p contribution to virulence using matched strains with similar levels of CSH. No statistical significance between the knockout and reintegrant was found in virulence based on median day of survival, although a reproducible delay in onset of lethal infection for the knockout was observed. A modest difference in mucosal colonization in a vaginal infection model was also observed between the knockout and reintegrant. The present study demonstrates that Csh1p contributes to virulence of C. albicans in mice, but other gene products also contribute to the CSH phenotype and virulence.
10.1016/j.femsle.2005.02.010
pubmed_462_6000
Whether karyotyping is indicated in a fetus with choroid plexus cysts who is otherwise structurally normal is still controversial. Many authors have suggested basing the decision on cyst size, bilaterality, persistence with advancing gestational age, and association with other anomalies. We report a case of large bilateral choroid plexus cysts in a fetus with trisomy 21 who had no evidence of congenital anomalies or ultrasonographic signs of Down syndrome. Cyst sizes diminished by half over a 3-week period of follow-up. It appears that diminishing size alone should not be considered sufficient reassurance about the normality of the fetal karyotype. A similar case has been previously reported, and it is conceivable that choroid plexus cysts are associated not only with trisomy 18 but also with trisomy 21.
10.1016/0002-9378(92)91680-9
pubmed_852_4297
OBJECTIVE To investigate the cause of an outbreak of bovine cysticercosis (Taenia saginata) infection on a cattle property in north-western New South Wales (NSW). METHODS Cystic lesions were detected in the muscles of cattle during routine meat inspection at slaughter. These lesions were confirmed to be cysticerci of T. saginata through histology and polymerase chain reaction (PCR). Data on cattle maintenance were obtained through interviews with feedlot owners and staff. A suspect feed supplement was investigated. RESULTS Between 5 July to 13 December 2010, 390 feedlot cattle from north-western NSW were slaughtered in abattoirs in NSW and Queensland. Of these, 138 animals had been maintained exclusively in feedlot enclosures from 80 to 300 days. Bovine cysticercosis was discovered in 80 cattle (58%, 26 carcasses were condemned). Another 18 cattle spent 24 h in the feedlot before being moved onto pasture and 1 of them was found to be infected. During the 5 months following the initial outbreak, a further 275 cattle were slaughtered; 2 of 51 heifers retained in the feedlot for a further 100 days were infected. None of the 234 animals grazed exclusively on pasture on the property were infected. Bovine cysticercosis was confirmed through examination of histological sections of muscle lesions and PCR using DNA extracted from cysticerci. No eggs of T. saginata were recovered from the feed supplement using a standard flotation method. CONCLUSIONS The source of infection arose from rations contaminated with human faeces. All possibilities for local contamination were eliminated during the investigation. The suspected source of infection was imported copra meal, which was used as a feed supplement.
10.1111/avj.12023
pubmed_439_26766
OBJECTIVE To investigate the potential of whole-body positron emission tomography/computed tomography (PET/CT) with a macrophage tracer to image arthritis in patients with early rheumatoid arthritis (RA). METHODS Thirty-five previously untreated, clinically active patients with early RA underwent whole-body PET/CT scanning with the macrophage tracer (R)-[11C]PK11195 in addition to clinical assessment (Disease Activity Score in 44 joints [DAS44]). Tracer uptake was assessed quantitatively as standardized uptake values (SUVs). In addition, 2 readers blinded to clinical assessment visually scored tracer uptake in joints. Clinical and PET variables were compared using Cohen , linear regression/correlation, and t tests, where appropriate. RESULTS All but 1 patient showed enhanced tracer uptake in at least 1 joint. Twelve percent of all joints (171/1470) were visually positive on the PET scan, most frequently the small joints in feet (40%) and hands (37%), followed by wrists (15%). Correlations of visual scores with clinical findings both at patient and joint levels were absent or weak. In contrast, average SUVs in the hands, feet, and whole body showed significant correlations with DAS44 scores, with the best correlation seen in the feet (R = 0.29, P < 0.01). CONCLUSION Clinically active patients with early RA had increased joint uptake of a macrophage PET tracer, especially in the feet. Quantitative, but not visual PET measures of whole body and joint groups, particularly the feet, showed moderate and statistically significant correlations with clinical outcome.
10.3899/jrheum.210928
pubmed_271_15427
Granulocytic anaplasmosis caused by Anaplasma phagocytophilum is an emerging tick-borne zoonosis worldwide. The obligate intracellular pathogen is transmitted by Ixodes ticks and infects neutrophils in humans and animals, resulting in clinical symptoms ranging from asymptomatic seroconversion to mild, severe, or fatal disease. Since the initial description of human granulocytic anaplasmosis (HGA) in the United States in 1990, HGA has been increasingly recognized in America, Europe, and Asia. This review describes the epidemiology, diagnosis, and treatment of HGA and provides background information on the potential vectors and reservoirs of A. phagocytophilum.
10.1089/vbz.2011.0753
pubmed_1092_22239
BACKGROUND The study of specific genes expressed in the testis is important to understanding testis development and function. Spermatogenesis is an attractive model for the study of gene expression during germ cell differentiation. Spermatogenesis associated-19 (Spata-19) is a recently-identified important spermatogenesis-related gene specifically expressed in testis. Its protein product is involved in sperm cell development and reproduction. In this report we examined the expression of Spata-19 mRNA in mouse testis, fetus, and cell lines. METHODS Reverse transcription-polymerase chain reaction (RT-PCR), nested PCR, and PCR-restriction fragment length polymorphism (PCR-RFLP) were used to analyze Spata-19 mRNA expression in different stages of mouse testis development, mouse fetus, mouse embryonic fibroblasts (MEF), mouse embryonic stem cells (mESC), Sertoli cells, and NIH/3T3 cells. RESULTS We identified a novel splice variant of Spata-19 in the mouse genome that it is expressed in the fetus and after the meiotic phase of spermatogenesis, and over-expressed in the post-meiotic stage of mouse spermatogenesis. This novel splice variant was absent in five days old mice testis, mESC, MEF, Sertoli, and NIH/3T3 cell lines. CONCLUSION The Spata-19 has a large novel splice variant in mouse testis that is expressed beyond meiotic phase of testis development. We suggest that this new Spata-19 mRNA variant might be involved in mitochondrial maintenance in sperm cells, and might be correlated with androgen secretion ‎and male fertility.
pubmed_1092_22239
pubmed_893_3795
Proteins often exist as their multimeric forms when they function as so-called biological assemblies consisting of the specific number and arrangement of protein subunits. Consequently, elucidating biological assemblies is necessary to improve understanding of protein function. Template-Based Modeling (TBM), based on known protein structures, has been used widely for protein structure prediction. Actually, TBM has become an increasingly useful approach in recent years because of the increased amounts of information related to protein amino acid sequences and three-dimensional structures. An apparently similar situation exists for biological assembly structure prediction as protein complex structures in the PDB increase, although the inference of biological assemblies is not a trivial task. Many methods using TBM, including ours, have been developed for protein structure prediction. Using enhanced profile-profile alignments, we participated in the 12th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP12), as the FONT team (Group # 480). Herein, we present experimental procedures and results of retrospective analyses using our approach for the Quaternary Structure Prediction category of CASP12. We performed profile-profile alignments of several types, based on FORTE, our profile-profile alignment algorithm, to identify suitable templates. Results show that these alignment results enable us to find templates in almost all possible cases. Moreover, we have come to understand the necessity of developing a model selection method that provides improved accuracy. Results also demonstrate that, to some extent, finding templates of protein complexes is useful even for MEDIUM and HARD assembly prediction.
10.1002/prot.25432
pubmed_748_17609
Electromagnetically induced transparency is an effect observed in atomic systems, originating from quantum interference, in which electromagnetic transitions to and from a certain quantum state become suppressed. This dark state is also characterized by a quantum phase, relative to other states, which theoretically should stop evolving, but remain phase coherent, during transparency. We test this theoretical prediction using techniques developed for liquid-state nuclear magnetic resonance quantum computation, applied to a spin-7/2 nuclear spin system. A sequence of quantum operations is applied to create the dark state, and during transparency its phase evolution is measured relative to a reference state using Ramsey interferometry. Experimental measurements of the fringe visibility are in excellent agreement with theoretical expectations, taking into account measured decoherence rates.
10.1103/PhysRevLett.93.033601
pubmed_181_1726
BACKGROUND Balloon pulmonary angioplasty (BPA) is an alternative therapy for patients with chronic thromboembolic pulmonary hypertension who are ineligible for standard therapy, pulmonary endarterectomy. Although there are several classifications of vascular lesions, these classifications are based on the features of the specimen removed during pulmonary endarterectomy. Because organized thrombi are not removed during balloon pulmonary angioplasty, we attempted to establish a new classification of vascular lesions based on pulmonary angiographic images. We evaluated the success and complication rate of BPA in accordance with the location and morphology of thromboembolic lesions. METHODS AND RESULTS We reviewed 500 consecutive procedures (1936 lesions) of BPA in 97 patients with chronic thromboembolic pulmonary hypertension and investigated the outcomes of BPA based on the lesion distribution and the angiographic characteristics of the thromboembolic lesions, as follows: type A, ring-like stenosis lesion; type B, web lesion; type C, subtotal lesion; type D, total occlusion lesion, and type E, tortuous lesion. The success rate was higher, and the complication rate was lower in ring-like stenosis and web lesions. The total occlusion lesions had the lowest success rate. Tortuous lesions were associated with a high complication rate and should be treated only by operators with extensive experience with BPA. CONCLUSIONS We modified the previous angiographic classification and established a new classification for each vascular lesion. We clarified that the outcome and complication rate of the BPA are highly dependent on the lesion characteristics.
pubmed_181_1726
pubmed_656_9736
BACKGROUND The COVID-19 pandemic is an international public health crisis. The risk of getting an infection with COVID-19 might impact the emotional well-being in patients with cancer. The aim of this study was to investigate quality of life (QoL) for patients with cancer during the COVID-19 pandemic. PATIENTS AND METHODS A cross-sectional survey, including questions about demographics, concerns of COVID-19 impact on cancer treatment and outpatient clinic visits, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was sent to patients with cancer at the Department of Oncology, Odense University Hospital, Denmark. The survey was open from 15th May to 29th May 2020, and 4.571 responded. Results were compared to the Danish 'Barometer Study' conducted by the Danish Cancer Society to elucidate experiences with the Danish healthcare system prior to COVID-19 pandemic. RESULTS In total, 9% of patients with cancer had refrained from consulting a doctor or the hospital due to fear of COVID-19 infection, and 80% were concerned about contracting COVID-19 to some extent. Seventeen patients were tested positive for COVID-19. The mean global QoL and emotional functioning (EF) scores were 71.3 and 82.8, respectively. In comparison to the 'Barometer Study', no clinical significant differences in QoL and EF scores were observed. Multivariate analysis demonstrated that being 'Concerned about contracting corona-virus' was correlated with lower QoL and EF scores. Factors associated with being concerned of contracting COVID-19 were comorbid conditions, incurable cancer, receiving medical cancer treatment and female gender. CONCLUSION Danish patients with cancer during the COVID-19 pandemic did not have lower scores of QoL and emotional functioning compared to the Danish 'Barometer Study'. However, the study suggests that concerns of contracting COVID-19 was correlated with lower scores of QoL.
10.1080/0284186X.2020.1830169
pubmed_82_20211
To study a step of the very complex processes of the formation of the neuromuscular junction (NMJ), we have analysed the clustering of acetylcholine receptors (AChR) and acetylcholinesterase (AChE) in myotubes cultured in various conditions. On the surface of rat myotubes cultured in the presence of spinal cord cells from embryonic rat, numerous AChE clusters appeared. Such clusters are always co-localized with AChR clusters, but the reverse is not true: the number of AChR clusters largely exceeds that of AChE clusters. Very few AChE clusters formed when such co-cultures were treated with monoclonal antibodies (mAbs) against the main immunogenic region (MIR) of the AChR, which provoke internalization and degradation of the AChRs of the muscular membrane. The total levels of AChE and proportions of molecular forms were unaffected. We also used non-innervated myotubes in which addition of agrin, a protein normally synthesized by motoneurons, transported to nerve terminals and inserted into the synaptic basal lamina, induces the formation of small clusters of AChE. When added to rat myotubes devoid of membrane AChR, agrin-induced AChE clusters did not form. Finally, we analysed the capacity of the variant of the C2 mouse muscle cell line deficient in AChR (1R-) to form clusters of AChE in co-cultures with spinal cord cells from rat: no formation of AChE clusters could be observed. In all these different systems of cultures, the conditions which prevented clustering of AChR (anti-AChR antibodies, deficiency of the variant C2 cell line) also suppressed AChE clustering. We concluded that clustering of AChR is a prerequisite for clustering of AChE, so that NMJ formation implies the sequential accumulation of these two components.
10.1046/j.1460-9568.1998.00165.x
pubmed_41_22742
BACKGROUND To minimize surgical morbidity, surgeons may opt to perform segmental limited surgery instead of fusion extension for adjacent segment disease (ASD) after lumbar fusion surgery. This study evaluated clinical outcomes from segmental limited surgery without fusion extension for ASD and assessed which clinical factors were associated with reoperation after segmental limited surgery. METHODS Medical data of 50 patients who underwent segmental limited surgery for ASD after lumbar fusion surgery between 2005 and 2015 were reviewed. Demographic data, ASD type, preoperative disc and facet degeneration, ASD location, and surgical summary were collected. The primary outcome was reoperation rate at 24 months after surgery. RESULTS Of patients, 28 (56%) experienced recurrent radiculopathy (visual analog scale score ≥4). Revision surgery was performed in 22 patients (44%). Reoperation was performed more frequently in multilevel fusion first-surgery cases (15/23; 65.2%) than single-level fusion first-surgery cases (7/27; 25.9%; P = 0.005). The lowermost mobile segment group had a lower reoperation-free survival rate than the other group (hazard ratio = 9.85, 95% confidence interval 1.32-73.54, P = 0.01 [log-rank]). The 2-year reoperation-free survival rate for the lowermost mobile segment group was 31.5%, whereas the rate for the other group was 83.3%. CONCLUSIONS Segmental limited surgery as a treatment for ASD after lumbar fusion surgery is likely to fail frequently and result in a high rate of recurrent radiculopathy and revision surgery. Fusion extension surgery is especially recommended for ASD at the lowermost mobile segment owing to the high failure rate.
10.1016/j.wneu.2017.10.150
pubmed_1124_19797
OBJECTIVES Hormone replacement therapy protects from cardiovascular disease at the menopause in part by reduction of menopausal pro-atherogenic serum lipid changes. Tibolone has beneficial effects on lipids, although serum high density lipoprotein levels decrease. This study aimed primarily to establish the effects of long-term administration of tibolone on a new surrogate marker for cardiovascular disease risk, the measurement of carotid artery intima-media thickness (CIMT) using high-resolution ultrasound. METHODS Measurement of CIMT and assessment of carotid atherosclerotic plaques were undertaken in 31 women on tibolone and 30 voluntary controls from an ongoing open-label study of tibolone. RESULTS The two groups were comparable, except for mean age and prevalence of current smokers. Repeatability of CIMT measurements was acceptable (CV, 10.0%). CIMT was significantly thicker in those with atherosclerotic plaques and increased systolic blood pressure. Prevalence of plaques was raised in those who had ever smoked, and those with elevated systolic blood pressure. There was no influence of tibolone on CIMT, whether plaques were present or not. CONCLUSIONS This reliable technique demonstrates associations between CIMT and established risk factors. CIMT was significantly thicker in those with existing plaques. We did not demonstrate an effect of long-term tibolone use on either CIMT or prevalence of plaques.
10.3109/13697139909025558
pubmed_133_8416
BACKGROUND Methods widely used to detect apoptosis do not allow us to easily distinguish between nuclei from viable or necrotic cells. Even if apoptosis and necrosis seem to occur as alternatives at the single cell level, they could be present simultaneously in a cell population much more frequently than expected. For this reason, attention was focused on attempting to recognize, by multiparameter flow cytometry, the characteristics of viable cells and of apoptotic or necrotic dead cells. METHODS Apoptosis and necrosis were induced in vitro in murine thymocytes and lymphocytes from adult peripheral blood by using dexamethasone or prostaglandin E2 treatment and heat shock at 60 degrees C or hydrogen peroxide, respectively. Traditional methods, such as DNA gel electrophoresis and propidium iodide staining followed by single-fluorescence analysis or annexin-V-fluorescein isothiocyanate plus propidium iodide staining by using flow cytometry, were compared with a new method. This method consisted of combined light-scatter and red fluorescence analysis by flow cytometry after isolation of nuclei by hypotonic solution as well as high-dose detergent treatment and DNA staining with propidium iodide. RESULTS Results showed that, although traditional methods such as DNA-gel electrophoresis and single-parameter fluorescence flow cytometry analysis were unable, as expected, to discriminate among viability, apoptosis, and necrosis, our new method has enabled us to easily identify nuclei from viable, apoptotic, and necrotic cells. Results obtained by using our method were comparable to those obtained by using two-color analysis of cells after propidium iodide/annexin V staining. CONCLUSIONS A highly reproducible, inexpensive, rapid, and easily accessible method of analysis has been developed for simultaneously detecting apoptosis and necro sis.
10.1002/(sici)1097-0320(19990201)35:2<145::aid-cyto6>3.0.co;2-2
pubmed_288_24241
PURPOSE We retrospectively evaluated the feasibility and safety of a modified prophylactic donor lymphocytes infusion (DLI) approach in advanced leukemia. MATERIALS AND METHODS Thirty-three patients with advanced leukemia received modified prophylactic DLI; that is, granulocyte colony-stimulating factor-primed peripheral blood progenitor cells instead of steady-donor lymphocyte harvests were used, and a short-term immunosuppressive agent (cyclosporine A or methotrexate 10 mg once per week for 2 to 4 weeks) was used for prevention of DLI-associated graft versus host disease (GVHD) after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation. RESULTS Thirty-nine infusions were performed in 33 patients. The mononuclear cells and median CD3+ cells infused for DLI were 1-2 x 10(8) and 0.93 x 10(6) per kilogram, respectively. Six patients experienced II-IV-grade acute GVHD. Twenty patients developed chronic GVHD. No GVHD-related death or transfusion-related pancytopenia was observed. With an 18-month median follow-up, 16 patients were in disease-free survival, and overall survival at 1 and 1.5 years was 69.0% and 50.2%, respectively. CONCLUSION The modified prophylactic DLI strategy might represent a step forward in the treatment of advanced leukemia.
10.1007/s10875-008-9193-4
pubmed_806_23138
Three new Direct Oral Anticoagulants (DOACs), rivaroxaban, apixaban and dabigatran etexilate are available on the French market. Management of DOAC-induced bleeding risk remains challenging. For elective procedures with high hemorrhagic risk, a last DOAC intake five days before procedure ensures complete elimination in all patients. Heparin bridging therapy should be proposed only to patients at high thrombotic risk. For elective procedures with low hemorrhagic risk, the DOAC intake of the night before procedure should be omitted. For urgent procedures with high bleeding risk, DOAC plasmatic concentration can be helpful: concentration lower than 30 ng/mL should enable performing the procedure; a high concentration is associated with a higher bleeding risk, especially if higher than 400 ng/mL. In case of massive bleeding, no antidote is approved yet; activated prothrombin concentrates or non-activated 4-factors prothrombin concentrates could be considered.
pubmed_806_23138
pubmed_492_14089
While U.S. courts consider a lawsuit alleging that the military's "don't ask, don't tell" policy violates the rights of gay and lesbian service members, the policy continues to jeopardize the health of those service members, the military, and the country at large.
10.1056/NEJMp1012496
pubmed_439_23620
The brittle fracture of polyurethane elastomer (PUE) under high-speed impact limits its application in high-speed impact protection. Here, based on the principle of free radical polymerization and π-π conjugation, composite nanoparticles (C-MWCNTs) are prepared by copolymerization of epoxy group ionic liquid (GVIMBr) and divinylbenzene (DVB) on MWCNTs using DVB as a linker. C-MWCNTs participate in the curing process of PUE through epoxy groups to form in situ crosslinked C-MWCNTs/PUE, which improves the energy absorption and high-speed impact properties of PUE. Compared with neat PUE, the maximum compressive strength and energy absorbed by C-MWCNTs/PUE are increased by 46.3% and 23.6%, respectively. By observing the microsurface and fracture morphology of C-MWCNTs/PUE, the relationship between macroscopic mechanical properties and microstructure is constructed. The improvement of the mechanical properties of the C-MWCNTs/PUE is attributed to the interfacial interaction and homogeneous dispersion of the C-MWCNTs in the PUE matrix. These microscopic effects are caused by the good compatibility between GVIMBr and PUE matrix and the synergistic enhancement between GVIMBr and MWCNTs.
10.1039/d1ra07174b
pubmed_779_4150
A 70-year-old woman with metastatic small-cell lung cancer was referred for isolated left optic disc edema that was incidentally discovered. She had normal visual function, and dilated fundus examination revealed a small, cupless optic nerve in the right eye and moderate optic disc edema in the left eye. Magnetic resonance imaging (MRI) of the orbits with contrast was normal, and MRI brain and magnetic resonance venography were normal without signs of raised intracranial pressure. Lumbar puncture showed a normal opening pressure and normal cerebrospinal fluid contents. A diagnosis of incipient non-arteritic anterior ischemic optic neuropathy (NAION) was made, and the optic disc edema resolved after 4 months. Incipient NAION is an uncommon cause of unilateral optic disc edema with preserved visual function and is a diagnosis of exclusion. In diagnosing incipient NAION, other causes of optic disc edema must first be ruled out. These alternative causes include papilledema, optic nerve sheath meningioma or other orbital masses, and vitreopapillary traction. Incipient NAION is thought to be caused by subclinical ischemia. This case indicates that incipient NAION may also occur in patients with metastatic cancer and is possibly related to their hypercoagulable state. Although there is no treatment once vision loss develops, the optimization of risk factors may prevent the progression of incipient NAION to classic NAION.
10.1159/000516573
pubmed_187_18803
Variation in colorectal cancer rates between countries and within ethnic groups upon migration and/or Westernization suggests a role for some aspects of Western lifestyle in the etiology of this disease. We conducted a population-based case-control study in the multiethnic population of Hawaii to evaluate associations between colorectal cancer and a number of characteristics of the Western lifestyle (high caloric intake, physical inactivity, obesity, smoking, and drinking) and some of their associated diseases. We interviewed in person 698 male and 494 female United States-born or immigrant Japanese, Caucasian, Filipino, Hawaiian, and Chinese patients diagnosed in 1987-1991 with colorectal cancer and 1192 population controls matched on age, sex, and ethnicity. Conditional logistic regression was used to estimate odds ratios adjusting for dietary and nondietary risk factors. Place of birth and duration of residence in the United States were unrelated to colorectal cancer risk. Energy intake (independent of the calorie source) and body mass index were directly associated with risk, and lifetime recreational physical activity was inversely associated with risk. The associations with these factors were independent of each other, additive (on the logistic scale) and stronger in men. When individuals were cross-categorized in relation to the medians of these variables, those with the higher energy intake and body mass index and lower physical activity were at the highest risk (for males, OR, 3.0; 95% confidence interval, 1.8-5.0, and for females, OR, 1.7; 95% confidence interval, 1.0-3.2). Smoking in the distant, as well as recent, past and alcohol use were directly associated with colorectal cancer in both sexes. Individuals with a history of diabetes or frequent constipation were at increased risk for this cancer, whereas past diagnosis of hypercholesterolemia was inversely associated with risk. The findings were consistent between sexes, among ethnic groups, and across stages at diagnosis, making bias an unlikely explanation. These results confirm the data from immigrant studies that suggest that the increase in colorectal cancer risk experienced by Asian immigrants to the United States occurred in the first generation because we found no difference in risk between the immigrants themselves and subsequent generations. They also agree with recent findings that suggest that high energy intake, large body mass, and physical inactivity independently increase risk of this disease and that a nutritional imbalance, similar to the one involved in diabetes, may lead to colorectal cancer.
pubmed_187_18803
pubmed_1052_8089
Tomatoes are one of the most consumed crops in the whole world because of their versatile importance in dietary food as well as many industrial applications. They are also a rich source of secondary metabolites, such as phenolics and flavonoids. In the present study, we described a method to produce these compounds from hairy roots of tomato (THRs). Agrobacterium rhizogenes strain A4 was used to induce hairy roots in the tomato explants. The Ri T-DNA was confirmed by polymerase chain reaction amplification of the rolC gene. Biomass accumulation of hairy root lines was 1.7-3.7-fold higher compared to in vitro grown roots. Moreover, THRs efficiently produced several phenolic compounds, such as rutin, quercetin, kaempferol, gallic acid, protocatechuic acid, ferulic acid, colorogenic acid, and caffeic acid. Gallic acid [34.02 μg/g of dry weight (DW)] and rutin (20.26 μg/g of DW) were the major phenolic acid and flavonoid produced by THRs, respectively. The activities of reactive oxygen species enzymes (catalase, ascorbate peroxidase, and superoxide dismutase) were quantified. The activity of catalase in THRs was 0.97 ± 0.03 mM H2O2 min(-1) g(-1), which was 1.22-fold (0.79 ± 0.09 mM H2O2 min(-1) g(-1)) and 1.59-fold (0.61 ± 0.06 mM H2O2 min(-1) g(-1)) higher than field grown and in vitro grown roots, respectively. At 100 μL/g concentration, the phenolic compound extract caused 53.34 and 40.00% mortality against Helicoverpa armigera and Spodoptera litura, respectively, after 6 days. Surviving larvae of H. armigera and S. litura on the phenolic compound extract after 6 days showed 85.43 and 86.90% growth retardation, respectively.
10.1021/jf405695y
pubmed_38_9616
This study quantified alterations in root dentin permeability after exposure to different acid beverages. Twenty-five third molars were sectioned below the cementoenamel junction, the root segment was collected, and the pulp tissue was removed. The root segments were connected to a hydraulic pressure apparatus to measure the permeability of root dentin after the following sequential steps, with 5 specimens in each: 1) phosphoric acid etching for 30 s (maximum permeability), 2) root planning to create new smear layer, 3) exposure to different acid substances for 5 min (orange, cola drink, vinegar, white wine, lemon juice), 4) toothbrushing with sonic toothbrush for 3 min, 5) toothbrushing with sonic toothbrush plus dentifrice for 3 min. Considering step I as 100%, the data were converted into percentage and each specimen was its own control. Data were analyzed statistically by Kruskal-Wallis and Dunn's post test at 5% significance level. All acidic substances increased dentin permeability significantly after scraping (p< 0.05). Toothbrushing after exposure to acid substances decreased dentin permeability and the association with dentifrice accentuated the decrease (p< 0.05), except for the specimens treated with cola drink. Thus, it may be concluded that all tested acid fruit juices increased dentin permeability, and toothbrushing with or without dentifrice can decrease root dentin permeability after dentin exposure to acid diet.
pubmed_38_9616
pubmed_335_19944
The rapid development of metastatic lesions remains the leading cause of mortality for patients with osteosarcoma. CD155 serves a key role in cancer cell migration, invasion and metastasis. However, the function and mechanism of CD155 has not been explored in osteosarcoma metastasis. In the present study, we found that CD155 was significantly upregulated in lung metastatic tissue and the highly metastatic cell line K7M2-WT (K7M2) of osteosarcoma. Overexpression of CD155 in K7M2 cells enhanced lung metastasis, while inhibition of CD155 by an anti-CD155 monoclonal antibody reduced metastasis. Blocking of CD155 also decreased migration and invasion of K7M2 cells in vitro. A western blot analysis revealed that blocking of CD155 inhibits metastasis by downregulating focal adhesion kinase (FAK) and phosphorylated FAK (pFAK) in osteosarcoma. The results revealed that CD155 serves a crucial role in the metastasis of osteosarcoma by regulating FAK and may provide a novel molecular target for therapeutic intervention in metastatic osteosarcoma.
10.3892/ol.2018.8228
pubmed_583_16445
Family caregivers of older adults experience high levels of chronic stress and psychological distress, which are known to impair cognition. Very little research, however, has assessed the impact of caregiving on key cognitive outcomes such as learning and memory. This study compared 16 spouse caregivers with 16 matched controls using standardized neuropsychological measures of learning, episodic memory, and working memory. Analyses compared groups on these cognitive outcomes and examined whether psychological distress mediated group differences in cognition. Results indicated that caregivers were significantly more distressed than non-caregivers and exhibited deficits in learning, recall of episodic information after short and long delays, and working memory. Furthermore, the majority of group differences in cognitive outcomes were mediated by psychological distress. This study adds to a small body of literature demonstrating impaired cognitive functioning among family caregivers. It also suggests that distress is one of a number of possible underlying mechanisms leading to disruptions in learning and memory in this population.
10.1093/geronb/gbp076
pubmed_241_3707
The synthesis of two new tritopic double-scorpiand receptors in which two equivalent 5-(2-aminoethyl)-2,5,8-triaza[9]-(2,6)-pyridinophane moieties have been linked with 2,6-dimethylpyridine (L1) or 2,9-dimethylphenanthroline (L2) units is reported for the first time. Their acid-base behaviour and Zn(2+) coordination chemistry have been studied by pH-metric titrations, molecular dynamic calculations, NMR, UV-Vis and steady-state fluorescence techniques. L1 and L2 behave, respectively, as hexaprotic and heptaprotic bases in the experimental conditions used (298.1 +/- 0.1 K, 0.15 mol dm(-3) NaCl, pH range under study 2.0-11.0). These ligands are able to form mono-, bi- and trinuclear Zn(2+) complexes depending on the Zn(2+)-receptor molar ratio. Interaction of L1 and L2 with pyrophosphate (PPi), tripolyphosphate (TPP) and adenosine 5'-triphosphate (ATP) has been followed by pH-metric titrations, (1)H and (31)P NMR techniques and molecular dynamic analysis. Finally, formation of mixed complexes Zn(2+)-L-PPi, Zn(2+)-L-TPP and Zn(2+)-L-ATP has been studied for both receptors by potentiometric titrations.
10.1039/b927418a
pubmed_181_10325
Diffusion tensor imaging (DTI) has recently started to be adopted into clinical investigations of spinal cord (SC) diseases. However, DTI applications to the lower SC are limited due to a number of technical challenges, related mainly to the even smaller size of the SC structure at this level, its position relative to the receiver coil elements and the effects of motion during data acquisition. Developing methods to overcome these problems would offer new means to gain further insights into microstructural changes of neurological conditions involving the lower SC, and in turn could help explain symptoms such as bladder and sexual dysfunction. In this work, the feasibility of obtaining grey and white matter (GM/WM) DTI indices such as axial/radial/mean diffusivity (AD/RD/MD) and fractional anisotropy (FA) within the lumbosacral enlargement (LSE) was investigated using a reduced field-of-view (rFOV) single-shot echo-planar imaging (ss-EPI) acquisition in 14 healthy participants using a clinical 3T MR system. The scan-rescan reproducibility of the measurements was assessed by calculating the percentage coefficient of variation (%COV). Mean FA was higher in WM compared to GM (0.58 and 0.4 in WM and GM respectively), AD and MD were higher in WM compared to GM (1.66 μm2ms-1 and 0.94 μm2ms-1 in WM and 1.2 μm2ms-1 and 0.82 μm2ms-1 in GM for AD and MD respectively) and RD was lower in WM compared to GM (0.58 μm2ms-1 and 0.63 μm2ms-1 respectively). The scan-rescan %COV was lower than 10% in all cases with the highest values observed for FA and the lowest for MD. This pilot study demonstrates that it is possible to obtain reliable tissue-specific estimation of DTI indices within the LSE using a rFOV ss-EPI acquisition. The DTI acquisition and analysis protocol presented here is clinically feasible and may be used in future investigations of neurological conditions implicating the lower SC.
10.1371/journal.pone.0164890
pubmed_52_7410
Glycosylations are well-established steps in numerous biosynthetic pathways, and the attached sugar moieties often influence the specificity or pharmacology of the modified compounds. The sorangicins belong to the polyketide family of natural products, and exhibit antibiotic activity through inhibition of bacterial RNA polymerase. We have identified the sorangicin biosynthetic gene cluster in the producing myxobacterium Sorangium cellulosum So ce12. Within the cluster, sorF encodes a putative glycosyltransferase. To determine its function in sorangicin biosynthesis, SorF was heterologously expressed as a fusion protein in Escherichia coli. After purification by affinity chromatography, SorF was found to glucosylate sorangicin A in vitro, utilizing UDP-alpha-D-glucose as the natural donor substrate. Additionally, SorF showed high flexibility towards further UDP- and dTDP-sugars and was able to transfer several other sugar moieties-alpha-D-galactose, alpha-D-xylose, beta-L-rhamnose, and 6-deoxy-4-keto-alpha-D-glucose-onto the aglycon. SorF is therefore one of the rare glycosyltransferases able to transfer both D- and L-sugars, and could thus be used to generate novel sorangiosides.
10.1002/cbic.200700024
pubmed_915_6970
Alteration of macrophage polarization from inflammatory (M1) to anti-inflammatory (M2) phenotype can have striking implications for the regeneration of injured tissues, treatment of inflammatory diseases, and relief of autoimmune disorders. Although certain cytokines like interleukin (IL)-4 and IL-13 are capable of inducing M2 macrophage polarization, their therapeutic potential in vivo is suffering from low efficacy due to their instability and poor access to target cells. Here, we report the synthesis of IL-4-loaded hyaluronic acid (HA) particle for the targeted delivery of cytokines through the high affinity of HA to CD44 receptors of macrophages. HA carriers composed of low, middle, and high molecular weight (MW) polymers were synthesized using divinyl sulfone (DVS) cross-linking. The MW of HA had a negligible effect on the physicochemical properties and biocompatibility of the macrophages, but as an indicative of M2 polarization, a significant change in the arginase-1 (Arg-1) activity, TNF-α release, and IL-10 secretion was observed for the HA particles prepared with high MW polymers. Therefore, these particles were loaded with IL-4 for simultaneous macrophage targeting and M1 to M2 reprogramming, evidenced by a remarkable increase in the Arg-1 to iNOS ratio, as well as CD163 and CD206 upregulation in the M1 macrophages, which were initially triggered by lipopolysaccharide and interferon-γ.
10.1021/acsomega.8b03182
pubmed_222_14108
OBJECTIVE Percutaneous transluminal angioplasty (PTA) is accepted as a safe and effective procedure for the treatment of stenotic arterial lesions of various sites. However, distal embolism may cause serious complications in the PTA of cephalic arteries. By monitoring embolic signals using transcranial Doppler (TCD) ultrasonography, we speculated regarding the safety and/or risk of PTA for vertebral and subclavian artery stenosis. METHODS Twelve consecutive patients undergoing PTA for subclavian and vertebral artery stenosis of atherosclerotic origin were studied. All patients were refractory to initial medical treatment and were considered for PTA. During the PTA procedure, all patients were heparinized. Before, during, and after PTA, TCD monitoring was performed to detect embolic signals for 30 minutes at each time. After PTA, anticoagulant and antiplatelet therapies were continued in all patients. RESULTS Before, during, and after PTA, a steady flow signal could be obtained from each vertebral artery monitored using TCD ultrasonography. No embolic signals were detected in any patient before angioplasty. During angioplasty, one embolic signal was detected immediately after balloon deflation in 1 of 12 patients. Several embolic signals were detected after the procedure in 6 of 12 patients, but thereafter embolic signals became less frequent in number. Three days after angioplasty, embolic signals were not detected in any patient. There were no serious complications caused by the PTA procedure. CONCLUSION TCD monitoring may be a useful modality for detection of microemboli during and after PTA in the posterior circulation. We suspected that subclinical microemboli are released from the dilated vessels for 3 days after vertebral and subclavian PTA and that anticoagulant or antiplatelet therapies may prevent embolic complications after the procedure.
pubmed_222_14108
pubmed_244_11565
Skin microbial flora was believed to can implicate skin health, and many recent reports point out a close linkage between the dysbiosis of the microbiome with the disease. Changes of microbiota, including diversity, species, and abundance, have been demonstrated in disease states, and it was believed the changes may cause infection and chronicity of the debilitating wounds. And it was been found a reverse of the dysbiosis after the effective treatment, but it failed to find a positive effect of antibiotic therapy on skin disease without significant clinical infection. The microbiomes were compared to the 'second gene reservoir', and indicated that their co-existing with the human being is a result of co-evolution. The current studies have shown that the microbial community on the skin surface should have an ideal optimal state, which can effectively regulate the immune tolerance and help to avoid the invasion of external pathogenic bacteria, then the body can be in a relatively healthy state. In this paper, we hypothesized that failing to maintain the harmonious relationship between microbes and human beings is the reason we suffering from most skin diseases, including chronic non-healing wounds. Thus, the dysbiosis of skin microbiota theory can help us better understand the mechanism of wound formation and problems encountered in wound treatment.
10.1016/j.mehy.2020.109720
pubmed_454_13928
Paniceae demonstrate unique variability of photosynthetic physiology and anatomy, including both non-Kranz and Kranz species and all subtypes of the latter. This variability suggests hypotheses of independent origin or reversals (e.g., from C(4) to C(3)). These hypotheses can be tested by phylogenetic analysis of independent molecular characters. The molecular phylogeny of 57 species of Paniceae was explored using sequences from the grass-specific insert found in the plastid locus rpoC2. Phylogenetic analyses confirmed some long-recognized alliances in Paniceae, some recent molecular phylogenetic results, and suggested new relationships. Broadly, Paniceae were found to be paraphyletic with Andropogoneae, Panicum was found to be polyphyletic, and Oplismenus hirtellus was resolved as the sister group to the remaining ingroup species. A particularly well-supported clade in the rpoC2 tree included four genera with non-Kranz species and three with distinctively keeled paleas. As previously suggested, the PCK (phosphoenol pyruvate carboxykinase) C(4) subtype arose once within Paniceae. All clades with non-Kranz species had Kranz ancestors or sister taxa suggesting repeated loss of the Kranz syndrome.
pubmed_454_13928
pubmed_157_8886
Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN.
10.1007/s00787-016-0819-4
pubmed_19_3636
Although endometriosis is a common disease in women of reproductive age, rectal endometriosis is rare and lymph node involvement by endometriosis is considered uncommon. We report a 37-year-old woman who had irregular lower abdominal pain and changes in bowel habits. She was operated on with suspected rectal cancer, but the histological diagnosis was rectal endometriosis with lymph node involvement. In women who suffer from digestive complaints, endometriosis should be considered in differential diagnosis. Rectal endometriosis has the ability to invade adjacent tissue as true malignant tumors. Therefore, lymph node involvement should be considered in rectal endometriosis.
10.1111/j.1447-0756.2010.01467.x
pubmed_558_16946
OBJECT The authors conducted a study to evaluate the advantages of a 3D volume-rendering technique (VRT) in follow-up digital subtraction (DS) angiography of coil-embolized intracranial aneurysms. METHODS One hundred nine patients with 121 intracranial aneurysms underwent endovascular coil embolization and at least 1 follow-up DS angiography session at the authors' institution. Two neuroradiologists independently evaluated the conventional 2D DS angiograms, rotational angiograms, and 3D VRT images obtained at the interventional procedures and DS angiography follow-up. If multiple follow-up sessions were performed, the final follow-up was mainly considered. The authors compared the 3 techniques for their ability to detect aneurysm remnants (including aneurysm neck and sac remnants) and parent artery stenosis based on the angiographic follow-up. The Kruskal-Wallis test was used for group comparisons, and the kappa test was used to measure interobserver agreement. Statistical analyses were performed using commercially available software. RESULTS There was a high statistical significance among 2D DS angiography, rotational angiography, and 3D VRT results (X(2) = 9.9613, p = 0.0069) when detecting an aneurysm remnant. Further comparisons disclosed a statistical significance between 3D VRT and rotational angiography (X(2) = 4.9754, p = 0.0257); a high statistical significance between 3D VRT and 2D DS angiography (X(2) = 8.9169, p = 0.0028); and no significant difference between rotational angiography and 2D DS angiography (X(2) = 0.5648, p = 0.4523). There was no statistical significance among the 3 techniques when detecting parent artery stenosis (X(2) = 2.5164, p = 0.2842). One case, in which parent artery stenosis was diagnosed by 2D DS angiography and rotational angiography, was excluded by 3D VRT following observations of multiple views. The kappa test showed good agreement between the 2 observers. CONCLUSIONS The 3D VRT is more sensitive in detecting aneurysm remnants than 2D DS angiography and rotational angiography and is helpful for identifying parent artery stenosis. The authors recommend this technique for the angiographic follow-up of patients with coil-embolized aneurysms.
10.3171/2009.7.JNS081718
pubmed_81_14320
The field lines of the Poynting vector for light emitted by a dipole with a rotating dipole moment show a vortex pattern near the location of the dipole. In the far field, each field line approaches a straight line, but this line does not appear to come exactly from the location of the dipole. As a result, the image of the dipole in its plane of rotation seems displaced. Secondly, the image in the far field is displaced as compared with the image of a source for which the field lines run radially outward. It turns out that both image displacements are the same. The displacements are of subwavelength scale, and they depend on the angles of observation. The maximum displacement occurs for observation in the plane of rotation and equals lambda/pi, where lambda is the wavelength of the light.
10.1364/ol.33.001446
pubmed_112_9542
The uptake of 125I-tyramine cellobiose (TC) by isolated rat hepatocytes and by total rat liver is markedly higher than that of 14C-sucrose and 125I-PVP, suggesting that TC does not enter the cells by fluid phase endocytosis. The distribution of radioactivity after differential centrifugation shows that the compound is shared out amongst sedimentable structures and unsedimentable fraction. Analysis by isopycnic centrifugation indicates that quickly after its penetration into the cells, most of sedimentable 125I-TC is associated with lysosomes. Such an intracellular localization is confirmed by the distributions observed after free flow electrophoresis and by the fact that radioactivity and cathepsin C, a lysosomal hydrolase, are simultaneously released from a mitochondrial fraction treated with glycyl-L-phenylalanine-2-naphthylamide. Pretreatment of the rats with chloroquine, an acidotropic drug that accumulates in lysosomes, prevents to some extent the entry of 125I-TC into these organelles. Experiments performed with purified lysosomes show that 14C-sucrose does not cross the lysosomal membrane when 125I-TC accumulates linearly with time in the fractions. These results are explained by supposing that the linkage of tyramine to cellobiose allow the disaccharide to diffuse through the plasma and the lysosome membranes, and that the accumulation of the molecule in these organelles results from its weak basic properties. 125I-TC could be an interesting molecule with which to study acidotropism in the whole animal and in isolated and cultured cells.
10.1016/0005-2736(92)90011-a
pubmed_946_15088
Twenty-seven consecutive patients with suspected lone atrial fibrillation were studied by M-mode echocardiography. Echocardiography disclosed structural or functional cardiac abnormalities in only two (12%) of 17 patients without any sign of underlying heart disease by history or physical examination, whereas an accompanying or underlying cardiac disorder was found in 6 (60%) of 10 patients with ambiguous clinical findings. It is concluded that echocardiography is of minor value in patients with lone atrial fibrillation if symptoms and signs of other cardiac disorders are totally absent, but the presence of even minor or ambiguous clinical abnormalities seems to be a clear indication for echocardiography in these patients. It is, however, emphasized that echocardiography appears to guide the clinical management in less than 20% of patients with clinically suspected lone atrial fibrillation.
10.1111/j.0954-6820.1983.tb03700.x
pubmed_541_17538
OBJECTIVE Somatostatin is an endogenous inhibitor of hormone secretion and cell proliferation. Treatment with somatostatin analogues in humans causes a reduction in size and secretory activity of endocrine tumours, including GH-secreting pituitary adenomas. This study was aimed to characterize the intracellular mechanisms mediating the in vitro antiproliferative and antisecretory effects of somatostatin and its analogue lanreotide, on primary cultures of GH-secreting pituitary adenoma cells. DESIGN Thirteen GH-secreting pituitary adenoma postsurgical specimens were analysed for somatostatin receptor (SSTR) mRNA expression and a subset of them was analysed in vitro for the effect of somatostatin on cell proliferation, assessed by means of [3H]-thymidine uptake, and GH release, using an immunoradiometric assay. Moreover, the intracellular signalling involved in such effects has been studied. RESULTS All the adenomas analysed expressed at least one somatostatin receptor subtype mRNA. SSTR2 mRNA was identified in 77% of the adenomas, SSTR1 and SSTR3 in 69% and SSTR5 in 60%. Somatostatin and lanreotide inhibited cell proliferation in phorbol ester (PMA)-stimulated conditions (10/13 adenomas), as well as after fetal calf serum (3/3 adenomas) or IGF-I stimulation (2/2 adenomas). Conversely, GHRH or forskolin treatments did not significantly affect DNA synthesis in adenoma cells in the presence or absence of somatostatin (2/2 and 4/4 adenomas, respectively). Vanadate pretreatment reversed somatostatin inhibition of PMA-induced DNA synthesis suggesting an involvement of tyrosine phosphatase in this effect (2/2 adenomas); this was confirmed by the direct induction of tyrosine phosphatase activity in two adenomas after somatostatin treatment. Somatostatin and also lanreotide caused significant inhibition of phorbol ester, forskolin, GHRH and KCl-dependent increase of GH secretion in the culture medium. Moreover, voltage-sensitive calcium channel activity induced by 40 mm KCl depolarization in microfluorimetric analysis, was significantly reduced (5/5 adenomas). CONCLUSIONS These data show that somatostatin and lanreotide inhibit human GH-secreting pituitary adenoma cell proliferation and hormone release in vitro, and suggest that the activation of tyrosine phosphatases may represent intracellular signals mediating the antiproliferative effects and that the inhibition of the voltage-dependent calcium channels and adenylyl cyclase activities may control GH secretion.
10.1046/j.1365-2265.2003.01811.x
pubmed_397_17931
A series of pyrrolobenzodiazepine-azepane conjugates linked through different alkane spacers have been prepared and their DNA thermal denaturation studies have been carried out. One of the compound (4b), elevates the DNA helix melting temperature of the CT-DNA by 2.0 degrees C after incubation for 36 h at 37 degrees C.
10.1016/j.bmcl.2005.11.090
pubmed_126_20326
Laser energy is widely used in medical sciences nowadays. Recently it has gained importance in urology as an alternative treatment, less invasive than conventional surgical approaches, to benign prostatic hypertrophy (BPH). The Authors present a review of the literature describing the different approaches to the laser treatment of BPH: visual laser ablation of the prostate (VLAP), TULIP, contact vaporization and interstitial laser therapy. They try to show vantages and limitations of this technique respect to conventional surgery. They also present their personal experience with VLAP. They conclude that prostate laser therapy is an alternative to TURP for patients suffering for uncomplicated BPH of small to medium volumes (< 40 ml). According to literature's data and personal experience, it seems that VLAP, the easiest technique, is able to achieve the best results.
pubmed_126_20326
pubmed_749_15988
OBJECTIVE Changes in immune system have been reported in schizophrenia. This study aimed to evaluate the involvement of IL-33, a member of the IL-1 cytokine family, in schizophrenia and its association with cognitive performance in these patients. METHODS Forty patients with chronic schizophrenia and 40 healthy subjects participated in the study. Serum levels of IL-33 and sST2 (soluble form of the IL-33 receptor) were measured using enzyme-linked immunosorbent assay (ELISA). Patients were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). RESULTS Patients with schizophrenia and controls presented similar serum levels of IL-33 and sST2. Levels of both markers were positively correlated with cognitive performance in patients with schizophrenia. CONCLUSION We found a significant correlation between IL-33 and sST2 levels and cognition in schizophrenia. Our results might help in the understanding of how immune markers are associated with cognitive impairment in schizophrenia. It remains to be determined whether the association between IL-33/sST2 and cognition is restricted to patients with schizophrenia.
10.1016/j.comppsych.2017.01.008
pubmed_1010_6810
To investigate the clinical characteristics of dermatomyositis, to investigate the types and clinical features of dermatomyositis complicated with malignant tumor, and to provide evidence for clinical diagnosis, treatment and prognostic evaluation.
 Methods: The clinical manifestations and laboratory test results for 108 cases of dermatomyositis with complications in the Second Xiangya Hospital of Central South University were analyzed.
 Results: Patients aged from 14 to 60 years accounted for 62.96%. The first symptom was single skin rash (54.63%), and the most characteristic cutaneous features were asymmetrical proximal myositis with various degrees (97.22%). The visceral involvement was as follows: the digestive tract (31.48%), the heart (19.44%), the lung (26.85%), and the thyroid damage (12.96%). Twelve (11.11%) patients were combined with malignant tumor. The positive rates for albumin (ALB), glutamic oxalacetic transaminase (AST), glutamic-pyruvic transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), erythrocyte sedimentation rate (ESR), anti Jo-1 antibody, anti ribonucleoprotein (RNP) antibody, and anti-topoisomerasel (Scl) antibody were 25.93%, 46.30%, 28.70%, 87.04%%, 51.85%, 26.85%, 55.56%, 2.27%, 8.99%, and 2.27%, respectively. The patients were divided into a tumor group and a non-tumor group. The chi-square test results from clinical symptoms and laboratory tests suggested that increase of ESR was a risk factor for dermatomyositis combining tumor. The main strategy of therapy was corticosteroids.
 Conclusion: Dermatomyositis possesses typical skin lesions and dermatitis is the most common initial symptom of dermatomyositis. In clinic, diagnosis of dermatomyositis should be timely combined with muscle enzymes test, electromyography and muscle biopsy. Dermatomyositis can easily involve many organs. Thus relevant examinations (such as chest X-ray and CT) should be done preventively. Rapid ESR is a risk factor for dermatomyositis complicated with malignant tumor and it can be used as an index to guide clinical diagnosis.
10.11817/j.issn.1672-7347.2019.180726
pubmed_1042_14952
Actinobacillus pleuropneumoniae is the etiologic agent of porcine pleuropneumonia. Currently, there are 18 different serotypes; the serotype 8 is the most widely distributed in the United States, Canada, United Kingdom, and southeastern Brazil. In this study, genomes of seven A. pleuropneumoniae serotype 8 clinical isolates were compared to the other genomes of twelve serotypes. The analyses of serotype 8 genomes resulted in a set of 2352 protein-coding sequences. Of these sequences, 76.6% are present in all serotypes, 18.5% are shared with some serotypes, and 4.9% were differential. This differential portion was characterized as a series of hypothetical and regulatory protein sequences: mobile element sequence. Synteny analysis demonstrated possible events of gene recombination and acquisition by horizontal gene transfer (HGT) in this species. A total of 30 sequences related to prophages were identified in the genomes. These sequences represented 0.3 to 3.5% of the genome of the strains analyzed, and 16 of them contained complete prophages. Similarity analysis between complete prophage sequences evidenced a possible HGT with species belonging to the family Pasteurellaceae. Thus, mobile genetic elements, such as prophages, are important components of the differential portion of the A. pleuropneumoniae genome and demonstrate a central role in the evolution of the species. This study represents the first study done to understand the genome of A. pleuropneumoniae serotype 8.
10.1155/2020/9354204
pubmed_892_7659
Alcoholics who died because they were run over by trains, by precipitation, or were smoking in bed, were compared with a group of controls. A higher number of alcoholics were run over by trains, the manner of death most often being suicide. There was a significantly higher number of controls who fell from a height. The manner of death in the group "smoking in bed' was more often accidental and occurred more frequently in alcoholics. Preventive measures are suggested.
10.1016/0379-0738(96)01911-1
pubmed_644_12351
Settling one's end-of-life affairs in the face of coronary artery bypass graft surgery (CABG) can be both distressing and beneficial for individuals who are facing imminent threat of death. Religious thoughts, common in this context, may offer some comfort and support for facing this process. However, few empirical studies have addressed the role of religious or spiritual involvement in the settling of one's end-of-life affairs in cardiac patients. This prospective study investigated the effect of religious and spiritual factors on whether decisions regarding end-of-life had been made in a sample of middle-aged and older patients undergoing CABG. In particular, we expected faith factors of an intrinsic nature would promote this decision. Two weeks pre-operatively, patients (mean age = 65 years) were recruited for interviews. One hundred seventy-seven CABG patients completed the pre-operative and post-operative follow-up one month after surgery, while 96 offered information regarding their engagement in settling end-of-life affairs. Cardiac indicators were obtained from the computerized Society of Thoracic Surgeons' Adult Cardiac Database (STS). Multiple regression analyses revealed that private religiousness increased the likelihood of having engaged in end-of-life decision planning by nearly half again (OR = .1.47, 95% CI = 1.10, 1.96, p < .05) and that experiencing reverence in secular contexts nearly doubled the likelihood (OR = .1.99, 95% CI = 1.16, 3.44, p < .05). The reduced likelihood of having made plans was observed among those who scored higher on experiencing reverence in religious contexts (OR = .44, 95% CI = .23, .87, p < .05) and among patients using petitionary prayer (OR = .21, 95% CI = .04, .98,p < .05). These effects manifested after controlling for age, impacted functioning, and number of diseased arteries. Therefore, faith factors appear to have independent but complex effects on end-of-life decision making in middle-aged and older cardiac patients.
10.2190/PM.38.1.k
pubmed_877_19248
Protein homeostasis, or proteostasis, is essential for cellular fitness and viability. Many environmental factors compromise proteostasis, induce global proteome stress, and cause diseases. The proteome stress sensor is a powerful tool for dissecting the mechanism of cellular stress and finding therapeutics that ameliorate these diseases. In this work, we present a multicolor HaloTag-based sensor (named AgHalo) to visualize and quantify proteome stresses in live cells. The current AgHalo sensor is equipped with three fluorogenic probes that turn on fluorescence when the sensor forms either soluble oligomers or insoluble aggregates upon exposure to stress conditions, both in vitro and in cellulo. In addition, AgHalo probes can be combined with commercially available always-fluorescent HaloTag ligands to enable two-color imaging, allowing for direct visualization of the AgHalo sensor both before and after cells are subjected to stress conditions. Finally, pulse-chase experiments can be performed to discern changes in the cellular proteome in live cells by first forming the AgHalo conjugate and then either applying or removing stress at any desired time point. In summary, the AgHalo sensor can be used to visualize and quantify proteome stress in live cells, a task that is difficult to accomplish using previous always-fluorescent methods. This sensor should be suited to evaluating cellular proteostasis under various exogenous stresses, including chemical toxins, drugs, and environmental factors.
10.1021/acs.biochem.8b00135
pubmed_575_12291
To assess the bioequivalence of 2 formulations of aripiprazole orally disintegrating tablets and to monitor their safety and tolerability in Chinese subjects, a single-site, open-label, randomized, 2-preparation, single-dose, 2-period crossover design was conducted. All 60 subjects were randomly divided into the fasting group and the fed group. Blood samples were collected at scheduled times after a single oral dose of orodispersible tablets containing 10 mg of aripiprazole. In the fasting state, the geometric mean ratios (90% confidence intervals [CIs]) of the test/reference formulation were 92.22%-100.20% for the area under the concentration-time curve (AUC) from time zero to the last measured concentration (AUC0-t ), 91.73%-100.14% for the AUC from administration to infinite time (AUC0-∞ ), and 98.52%-112.52% for the maximum plasma concentration (Cmax ). In the fed state, AUC0-t , AUC0-∞ , and Cmax were 92.23%-100.20%, 91.73%-100.14%, and 95.91%-105.13%, respectively. The 90%CIs of the test/reference AUC ratio and Cmax ratio were within the acceptance range of 80.00%-125.00% for bioequivalence. Neither the maximum peak plasma concentration (tmax ) nor the terminal elimination half-life (t1/2 ) showed any significant difference. No serious adverse events) were encountered during the study. The test and reference formulations were bioequivalent under both fasting and fed conditions and were found to be safe and tolerated.
10.1002/cpdd.954
pubmed_659_17065
Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacterium Synechocystis as a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated ata residue in the regulatory latch domain (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival of Synechocystis in the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans.
10.1111/febs.16471
pubmed_651_7734
Turnover of N-methyl groups in non-histone chromosomal (NHC) and high mobility group (HMG) proteins from chinese hamster ovary cell nuclei was compared with that of the peptide backbone. Cells grown with tritiated amino-acids and methionine (Me-14C) were resuspended in unlabeled medium, and aliquots removed at 4 time points. Halflives were calculated from the decay of the respective specific activities by the method of least squares. Ratios of halflives for 14C and 3H calculated from the first order rate decay curves of the specific activities were shown to be close to unity.
10.1016/0309-1651(83)90112-1
pubmed_391_2903
The authors report a patient with mucinous adenocarcinoma of the pancreas with multiple cystic spaces, lined with malignant columnar cells and papillary formation; adjacent pancreatic tissue shows chronic pancreatitis. This is an unusual case report.
pubmed_391_2903
pubmed_910_12543
Approximately 0.5% of all births occur before the third trimester of pregnancy, and these very early deliveries result in the majority of neonatal deaths and more than 40% of infant deaths. A recent executive summary of proceedings from a joint workshop defined periviable birth as delivery occurring from 20 0/7 weeks to 25 6/7 weeks of gestation. When delivery is anticipated near the limit of viability, families and health care teams are faced with complex and ethically challenging decisions. Multiple factors have been found to be associated with short-term and long-term outcomes of periviable births in addition to gestational age at birth. These include, but are not limited to, nonmodifiable factors (eg, fetal sex, weight, plurality), potentially modifiable antepartum and intrapartum factors (eg, location of delivery, intent to intervene by cesarean delivery or induction for delivery, administration of antenatal corticosteroids and magnesium sulfate), and postnatal management (eg, starting or withholding and continuing or withdrawing intensive care after birth). Antepartum and intrapartum management options vary depending upon the specific circumstances but may include short-term tocolytic therapy for preterm labor to allow time for administration of antenatal steroids, antibiotics to prolong latency after preterm premature rupture of membranes or for intrapartum group B streptococci prophylaxis, and delivery, including cesarean delivery, for concern regarding fetal well-being or fetal malpresentation. Whenever possible, periviable births for which maternal or neonatal intervention is planned should occur in centers that offer expertise in maternal and neonatal care and the needed infrastructure, including intensive care units, to support such services. This document describes newborn outcomes after periviable birth, provides current evidence and recommendations regarding interventions in this setting, and provides an outline for family counseling with the goal of incorporating informed patient preferences. Its intent is to provide support and guidance regarding decisions, including declining and accepting interventions and therapies, based on individual circumstances and patient values.
pubmed_910_12543
pubmed_355_18933
Ventricular tachycardia is the diagnosis in approximately 80% of cases of WCT and in approximately 95% of cases with structural heart disease. The presence of atrioventricular dissociation, fusion beats, capture beats, and concordance are important findings strongly suggesting VT; whereas, QRS frontal axis and ventricular rate provide less definitive diagnostic information. A QRS width greater than 160 msec. for LBBB configuration WCT or greater than 140 msec. for RBBB configuration argues strongly for VT. The QRS morphology may be very helpful in selected cases. The duration of the arrhythmia does not discriminate between the etiologies of WCT, as all rhythms may be hemodynamically stable for prolonged periods. Finally, response to treatment may give diagnostic information in addition to therapeutic benefit.
pubmed_355_18933
pubmed_520_11082
For baled silages, production of clostridial fermentation products can be exacerbated by exceeding normal moisture targets (45% to 55%), and/or by the application of dairy slurry before harvest. Our objectives were to test a microbial inoculant as a mitigant of clostridial products in high-moisture, grass-legume (52% ± 13.8% cool-season grasses, 44.0% ± 14.0% legumes [predominately alfalfa]) baled silages in swards that were fertilized with dairy slurry. A secondary objective was to examine the effects of bale moisture and inoculation on the aerobic stability of these fermented silages following exposure to air. After the first-cutting was removed, three manure treatments were applied as a whole-plot factor: 1) control (no manure); 2) slurry applied immediately to stubble (63,250 L/ha); or 3) slurry applied after a 1-wk delay (57,484 L/ha). An interactive arrangement of bale moisture (64.1% or 48.4%) and inoculation (yes or no) served as a subplot term in the experiment. The inoculant contained both homolactic (Lactococcus lactis 0224) and heterolactic (Lactobacillus buchneri LB1819) bacteria. The experimental design was analyzed as a randomized complete block with four replications, and the study included 48 experimental units (1.2 × 1.2-m round bales). Total fermentation acids were affected (P ≤ 0.021) by slurry application strategies, but this was likely related to inconsistent bale moisture across slurry-application treatments. Concentrations of butyric acid were low, and there were no detectable contrasts comparing manure treatments (mean = 0.05%; P ≥ 0.645). Bale moisture affected all measures of fermentation, with bales made at 64.1% moisture exhibiting a more acidic final pH (4.39 vs. 4.63; P < 0.001), less residual water-soluble carbohydrates (2.1% vs. 5.1%; P < 0.001), as well as greater lactic acid (4.64% vs. 2.46%; P < 0.001), acetic acid (2.26% vs. 1.32%; P < 0.001), and total fermentation acids (7.37% vs. 3.97%; P < 0.001). Inoculation also reduced pH (4.47 vs. 4.56; P = 0.029), and increased acetic acid (1.97% vs. 1.61%; P < 0.001) and 1,2-propanediol (1.09% vs. 0.72%; P < 0.001) compared to controls. During a 34-d aerobic exposure period, maximum surface bale temperatures were not affected (P ≥ 0.186) by any aspect of treatment, likely due to the prevailing cool ambient temperatures; however, yeast counts were numerically lower in response to greater (P < 0.001) production of acetic acid that was stimulated by both high bale moisture and inoculation.
10.1093/jas/skac325
pubmed_201_12524
BACKGROUND The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture. DESIGN A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period. DISCUSSION Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period. TRIAL REGISTRATION ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017.
10.1186/s13063-017-2188-9