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Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP. Glycoproteins encoded by the major histocompatibility complex class I region (MHC class I) present peptide antigens to cytotoxic T cells (CTLs). Peptides are delivered to the site of MHC class I assembly by the transporter associated with antigen processing (TAP), and cell lines that lack this transporter are unable to present endogenous antigens to CTLs. Although it has been shown that a fraction of newly synthesized class I molecules are in physical association with TAP, it is not known whether this interaction is functionally relevant, or where on the class I molecule the TAP binding site might be. C1R cells transfected with a mutant HLA-A2.1 heavy chain (HC), where threonine at position 134 in the alpha 2 domain is changed to lysine (T134K), are unable to present endogenous antigens to CTLs. We have studied the biochemistry of this mutant in C1R cells, and found that a large pool of unstable empty class I HC-beta 2m (beta-2 microglobulin) heterodimers exist that are rapidly transported to the cell surface. The T134K mutant seemed to bind peptide antigens and assemble with beta 2m as efficiently as wild-type HLA-A2.1. However, we show here that the inefficiency with which T134K presents intracellular antigen is associated with its inability to interact with the TAP heterodimer. These experiments establish that the class I-TAP interaction is obligatory for the presentation of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP. Wild-type HLA-A2.1 molecules in TAP-deficient cells are retained in the ER, whereas T134K is rapidly released to the cell surface, but is unstable, suggesting a role for the TAP complex as an intracellular checkpoint that only affects the release of class I molecules with stably bound peptide ligands.
{ "pile_set_name": "PubMed Abstracts" }
Supersensitivity in a chain of closely spaced electric dipoles with variable moments. A chain of closely spaced oscillators is studied theoretically. The oscillators are interrelated electric dipoles whose moments may vary within a wide range. An expression for the oscillator interaction potential is suggested. On the basis of this potential, a one-dimensional nonlinear equation of motion is derived with allowance made for dissipation and external driving. A numerical investigation is carried out, and various nonlinear phenomena are revealed in the chain. Among them are the size effect and ultrasensitivity, i.e., a giant response of the chain to extremely weak periodic perturbations. The findings are compared with previously obtained experimental results on naturally occurring objects with similar structure. It is inferred that the model is realistic.
{ "pile_set_name": "PubMed Abstracts" }
Dynamic characteristic analysis and startup optimization design of an intermediate drive belt conveyor with non-uniform load. As an important transportation equipment, belt conveyor plays an important role in underground coal mine production and is an indispensable component. In this article, taking the intermediate drive belt conveyor of Shanxi Tongmei Group Tongxin Mine as an example, the continuous dynamic method is adopted to comprehensively consider the non-uniform load distribution of the belt conveyor, and mathematical modeling of the intermediate drive belt conveyor is performed. The dynamic characteristics of the conveyor belt are analyzed. The MATLAB software is used to analyze the change of the conveyor belt tension under different starting accelerations. Based on the analysis results, the starting acceleration is optimized, and the new combined parabolic acceleration curve presented here is more suitable for the actual working condition of the belt conveyor. In this article, the startup timing of the head and middle motors of the belt conveyor is also discussed in depth. The start timing design of the belt conveyor is described, which provides a reference for the design of the belt conveyor with an intermediate drive.
{ "pile_set_name": "PubMed Abstracts" }
Effects of phenanthrene on hepatic enzymatic activities in tilapia (Oreochromis niloticus female x O. aureus male). The effects of phenanthrene (Phe) on hepatosomatic index (HSI) and hepatic enzymatic activities in hybrid tilapia (Oreochromis niloticus female x O. aureus male) were investigated via the static freshwater exposure at dosage of 50, 100, and 400 microg/L for 4-14 d. Compared with the control group, HSI was significantly decreased (P < 0.05) at 400 microg/L at day 14. Increased enzymatic activities (P < 0.05) were observed for catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) at either 100 or 400 microg/L at day 8 and 14, as well as for CAT at 50 microg/L at day 14, except for GPx at 400 microg/L at day 8. Ethoxyresorufin O-deethylase (EROD) activity was significantly increased (P < 0.05) at all dosage at day 4 as well as at 50 microg/L at day 8, but significantly decreased at either 100 or 400 microg/L at day 14 (P < 0.05). Glutathione-S-transferase (GST) activity was not affected. The results suggest that CAT, GPx, SOD and EROD, as well as HSI in tilapia may be used as the biomarkers or indexes for evaluating or monitoring the pollution of polycyclic aromatic hydrocarbons (PAHs) such as Phe.
{ "pile_set_name": "PubMed Abstracts" }
Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? The zeta chain is a 16-kDa molecule associated with the T-cell receptor (TCR)-CD3 complex in T lymphocytes and FcgammaRIII in CD3(-)CD56(+)CD16(+) natural killer (NK cells). The zeta chain functions as a transmembrane signaling molecule in lymphocytes. Expression of zeta was found to be decreased in CD4(+) and CD8(+) T lymphocytes isolated from the tumor site or from the peripheral circulation of patients with cancer. A quantitative flow cytometry-based assay for zeta-chain expression allows for reproducible serial evaluations of disease- or therapy-associated changes in expression of this signaling molecule in phenotypically defined subsets of immune cells. Semiquantitative evaluation of zeta expression in paraffin-embedded tissue specimens can link it to the conventional markers of prognosis or survival. Several distinct mechanisms may be responsible for decreased/absent zeta in T cells of patients with cancer. Monitoring for zeta expression is useful for assessing immune competence in these patients and for following changes in immune competence during anticancer therapies. Correlations made between clinical findings, pathologic results, and zeta expression in immune cells suggest that low/absent zeta is predictive of poor prognosis and survival in patients with cancer. Thus, zeta is emerging as a clinically relevant signaling molecule, which also seems to predict a favorable response to biologic therapies and could be helpful in a selection of patients for immunotherapy trials. Validation studies have yet to be performed for this putative immunologic biomarker. Its consistent use for monitoring under standardized conditions of cancer patients treated with biotherapies may help in confirming a role for zeta as a correlate of prognosis or survival.
{ "pile_set_name": "PubMed Abstracts" }
[The importance of the home for healthy and disabled elderly persons]. The majority of old people live in private households and they want to remain there. Starting from this insight, the study is focused on the interaction between older people and their home environment. Some theoretical assumptions on the role of housing are presented, namely the competence theory perspective, the continuity theory perspective, the perspective of research on leisure time and everyday life activities, the environmental adaptation perspective, and the environmental gerontology perspective. Previous research has shown that there is a strong correlation between environmental-relevant competence loss (e.g., mobility impairment) and objective living arrangements. Little attention has been paid, however, to the subjective meaning of home in old age (e.g., processes like familiarity or stimulation), either with or without competence loss. This paper presents preliminary results of an investigation into that "Aging in Place" issue, based on semi-structured interviews with 84 participants between the age of 62-92 (M = 77 years). Forty-two subjects were in good health status, 42 suffered from severe mobility impairments. The participants were visited at home and all interviews were tape-recorded. On one hand, the general meaning of home, on the other, specific sections of the home environment were analyzed (most favorite place within the home, favorite meaningful things). The results revealed that the two groups of participants are similar as far as the general meaning of home is concerned. In the experience of the most favorite place at home, subjects suffering from mobility impairments are tending more to an environmental "centralization" than healthy subjects do. With respect to personal objects, the most often mentioned meaning was "reminiscence". By and large, the results of this work support the view that knowledge about the meaning of home can be of help to better understand how old people create their meaningful everyday life at home and why they want to "stay put"; in addition, the results can be used in planning living arrangements for people of all ages.
{ "pile_set_name": "PubMed Abstracts" }
Factors affecting health-related quality of life assessed with the SF-36v2 health survey in outpatients with chronic-stage ischemic stroke in Japan--cross-sectional analysis of the OASIS study. The number of chronic-stage ischemic stroke patients in Japan continues to increase, because of decreasing mortality. This study was designed to ascertain health-related quality of life (HRQOL) in ischemic stroke patients and to analyze in detail factors affecting HRQOL. 2,069 outpatients (1,226 males, 843 females; mean age: 71 years; median duration after onset: 20.5 months) with chronic-stage ischemic stroke visiting 150 institutions in Japan were enrolled. HRQOL was evaluated using the second version of the patient self-administered Medical Outcome Study 36-Item Short-Form Health Survey (SF-36v2) questionnaire. All 8 domain scores and the physical component summary (PCS) score of SF-36v2 in stroke patients were significantly lower than those of Japanese national norms (JNN). The PCS score (36.6 +/- 16.1) and mental component summary (MCS) score (50.0 +/- 10.2) were lower than those of age-matched JNN (p < 0.001). Age, modified Rankin Scale (mRS), duration after onset and Japan Stroke Scale Depression score (JSS-D) were significantly correlated with PCS, as were role limitation because of physical problem, bodily pain, vitality and role limitation because of emotional problem scores; duration after onset and JSS-D were significantly correlated with MCS. Negative factors for PCS were older age, higher mRS, presence of subjective symptoms, neurological signs, rehabilitation and concomitant antidepressants. Negative factors for MCS were presence of subjective symptoms, psychiatric signs and concomitant antidepressants. HRQOL scores in ischemic stroke patients (chronic stage) are significantly correlated with not only age, mRS, duration after onset and JSS-D, but also presence of subjective symptoms and neurological/psychiatric signs, which could be targets for treatment.
{ "pile_set_name": "PubMed Abstracts" }
Contact dermatitis with a highlight on silver: a review. Contact dermatitis is an inflammatory reaction in the skin that arises from exposure to an irritant or allergen. Irritant contact dermatitis is the most common form of dermatitis and occurs when any substance disrupts the epidermal skin barrier. All individuals are susceptible to this type of reaction. Allergic contact dermatitis is a delayed Type IV hypersensitivity reaction that occurs in individuals that have previously been sensitized to a particular antigen. Patients with wounds are at particular risk of developing either an allergic or irritant contact dermatitis. Various contributing factors, including an impaired skin barrier that allows for easier absorption of potential allergens and exposure to a number of wound care products and dressings, can be allergenic or irritating. Silver compounds are widely used in wound care for their antimicrobial properties. These products are generally well tolerated, but infrequently are causative agents in contact dermatitis. The following review will summarize contact dermatitis cases due to silver that have been described in the literature. Despite their widespread use in wound care, there has only been one confirmed case of contact dermatitis secondary to silver-containing wound products. It is possible that more cases have been missed simply because silver is not commonly considered to be an allergen. Routine use of patch testing for silver allergy in these patients may lead to an increased number of recognized cases. .
{ "pile_set_name": "PubMed Abstracts" }
Differentially expressed genes implicated in unexplained recurrent spontaneous abortion. Recurrent spontaneous abortion occurs in approximately 3% of women with diagnosed pregnancies. The etiology in approximately 40% of recurrent spontaneous abortion is unexplained. To elucidate unexplained recurrent spontaneous abortion at the molecular level, we systemically identified differentially expressed genes during implantation window period in unexplained recurrent spontaneous abortion and characterized their functions in a human endometrial cell line. Expression levels of implantation-related genes selected from previously reported, various microarray data were determined to identify differentially expressed genes between normal fertile and unexplained recurrent spontaneous abortion subjects by real-time quantitative RT-PCR. Of 29 implantation-related genes, the transcript levels of cellular retinoic acid binding protein 2 and olfactomedin 1 were higher, whereas that of complement component 4 binding protein alpha was lower in subjects with unexplained recurrent spontaneous abortion, compared to normal fertile subjects. A correlation was evident between the transcript and protein levels of complement component 4 binding protein alpha and cellular retinoic acid binding protein 2. Expression of cellular retinoic acid binding protein 2 was positively correlated with retinoic acid-related genes in normal fertile subjects, but no significant association was observed in unexplained recurrent spontaneous abortion subjects. In relation to complement component 4 binding protein alpha, C5a receptor protein level was significantly higher in subjects with unexplained recurrent spontaneous abortion. Stable expression of cellular retinoic acid binding protein 2 and olfactomedin 1 in a human endometrial cell line inhibited cell growth and induced cell accumulation in the S and G(2)-M phase fractions, but did not trigger apoptosis. This study represents the first systematic identification of differentially expressed genes in unexplained recurrent spontaneous abortion. Defective cell growth by the differentially expressed genes suggests their implication in implantation failure in women with unexplained recurrent spontaneous abortion.
{ "pile_set_name": "PubMed Abstracts" }
Influence of the physicochemical properties of inorganic supports on the activity of immobilized bacteria for water denitrification. The denitrification of polluted water was studied by using supported E-coli bacteria. The physicochemical characteristics of supports and the influence of these properties on the bacteria performance were analyzed. Inorganic supports oxides and zeolites were selected in order to cover a wide range of porosity and surface chemical properties and the denitrification process systematically studied. Consecutive denitrification cycles in batch experiments and the toxicity of supports were also analyzed. The acidity of supports provokes a slower reduction processes, favoring also a high concentration of intermediate nitrites in solution for longer periods. The NO3(-) reduction is faster than the NO2(-) one, being also less influenced by the support characteristics. Anyway, the total denitrification is reached in all cases. The best performance was obtained with bacteria supported on mesoporous and non-acid silica support.
{ "pile_set_name": "PubMed Abstracts" }
New assays to measure equine influenza virus-specific Type 1 immunity in horses. Equine influenza virus (EIV) is a leading cause of respiratory disease in horses. Equine influenza infection induces a long-term immunity to re-infection. Recent strategies of vaccination aim to mimic this immunity by stimulating both antibody and cellular immune responses. Cell-mediated immunity (CMI) to influenza is well defined in man, but little has been done to characterise the responses in the horse. Additionally, the development of reliable assays for the measurement of equine CMI has lagged behind serological methods and vaccine development. In this study, two methods of measuring EIV-specific T lymphocyte responses have been developed. An EIV 'bulk' cytotoxic T lymphocytes (CTL) assay using equine dermal fibroblasts as target cells has been adapted from a method used in the 1980s. This method was also complemented with a new EIV-specific IFNgamma synthesis assay. When compared with the measurement of EIV-specific IFNgamma synthesis previously described, this method required the amplification of EIV-specific lymphocytes by culture and was sensitive enough to detect stimulation of EIV-specific T lymphocytes induced by experimental infection with EIV or vaccination with recombinant canarypox viruses coding for EIV-HA molecules. This study provides the tools to characterise the stimulation of CMI by the new generation of vaccines against equine influenza.
{ "pile_set_name": "PubMed Abstracts" }
[Determination of quantitative proteinuria from a single urine sample based on the protein:creatinine ratio]. Assessment of quantitative proteinuria is associated with collection of urine over several hours. This is, however, not always possible, in particular in ambulatory patients. Therefore efforts are made to assess the urinary protein per 24 hours on the basis of the proteinuria index, i.e. the ratio protein:creatinine in a single urine specimen. In a group of forty patients the authors demonstrated the closest correlation (correlation coefficient = 0.910374) between quantitative proteinuria and the index of proteinuria in urine specimens which were collected during daily activity. The closeness of this correlation depends on renal function. Assessment of quantitative proteinuria from a single urine sample on the basis of the protein:creatinine ratio is therefore useful in subjects with a preserved or not very restricted renal function.
{ "pile_set_name": "PubMed Abstracts" }
Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study. Integrated F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is widely used for mediastinal lymph node (MLN) staging in patients with non-small cell lung cancer (NSCLC). However, FDG-PET/CT has certain limitations. Prediction of occult MLN metastasis could allow selection of candidates for preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. This study defined risk factors for occult MLN metastasis in patients with NSCLC patients who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. Consecutive patients with NSCLC who underwent staging using integrated FDG-PET/CT as an adjunct to CT prior to lung resection from October 2006 to September 2009 were evaluated retrospectively. The prevalence of MLN metastasis in patients diagnosed as clinical N0-1 was analyzed according to clinicopathological factors such as tumor location, tumor size, histology, and FDG uptake by the primary tumor. Risk factors for occult MLN metastasis were defined by multivariate analysis. Patterns of occult MLN metastasis were also analyzed and the involved MLNs were further examined histopathologically. The incidence of MLN metastasis was 11% (24 patients of 224). Multivariate analysis identified adenocarcinoma (P=0.04), tumors located in upper or middle lobe (P=0.02), tumor size >3 cm (P=0.01), and SUV(max) of primary tumor >4.0 g/ml (P=0.04) as significant risk factors for MLN metastasis. The pattern of occult MLN metastasis was typical for NSCLC cases. The size of metastatic foci were small, with 68% of foci smaller than 4.0mm. The present study demonstrated that adenocarcinoma, tumors located in the upper or middle lobe, tumor size >3 cm, and SUV(max) of primary tumor >4.0 g/ml are risk factors for occult MLN metastasis in patients with NSCLC who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. Patients with tumors located in the right upper or middle lobe are considered candidates for cervical mediastinoscopy because the involved metastatic mediastinal lymph nodes are easily accessible by these modalities.
{ "pile_set_name": "PubMed Abstracts" }
In-plane mechanical response of TiO2 nanotube arrays - intrinsic properties and impact of adsorbates for sensor applications. In-plane mechanical response of TiO2 nano-tube arrays is intrinsically characterized by very low elastic moduli and significant damping, while both are strongly affected by presence of adsorbates. These findings suggest use of TiO2 nanotube arrays as novel types of sensors, actuators as well as highly stretchable coatings in biomedical applications.
{ "pile_set_name": "PubMed Abstracts" }
In vivo spectroscopic properties of the fluorescent pH indicator biscarboxyethyl carboxyfluorescein. Transcutaneous detection of fluorescence from an injection of the pH-sensitive probe biscarboxyethyl carboxyfluorescein (BCECF) has been used to monitor plasma pH in conscious animals. The fluorescence signal must be calibrated with reference to a standard curve. This standard, calibration curve has been achieved using in vitro methods. Here it is shown that temperature influences the calibration curve determination in vitro and hence influences the pH determined from transcutaneous measurements. Two calibration curves have been obtained, one at room temperature (approximately 25 degrees C) and the other at 37 degrees C. At pH 7.01 the calibration curves intersect, so that, at more alkaline pH values, use of room temperature calibration data will lead to an overestimate of plasma pH. Below pH 7.01, plasma pH will be underestimated. Transcutaneous fluorescence spectra recorded from a mouse injected with BCECF are shown, indicating that baseline plasma pH was estimated about 0.3 pH units too high using room temperature calibration, and that the extent of acidification when the animal was allowed to breathe an atmosphere containing 15% CO2 was overestimated by 0.7 pH units. Additionally, it is shown that in vitro bovine serum albumin at concentrations comparable with albumin concentrations in vivo shifts the absorption, fluorescence excitation and emission spectra of BCECF. However, fluorescence spectra recorded in vivo show no such shift. The results indicate that in vitro calibration for transcutaneous fluorescence measurements in vivo can be misleading, and that in the case of pH measurement inattention to temperature can lead to spurious results.
{ "pile_set_name": "PubMed Abstracts" }
Quantifying the clinical significance of drug-drug interactions: scaling pharmacists' perceptions of a common interaction classification scheme. To develop a precise, interval level scale of the clinical significance of drug-drug interactions that reflects the professional judgments of practicing pharmacists. A convenience sample of 63 practicing pharmacists representing hospital (clinical and staff) and retail (chain and independent) practice settings. Pharmacists judged the similarity among 15 interaction categories that have been commonly used to classify drug-drug interactions. A multidimensional scaling technique produced a spatial representation (i.e., a psychological map) of the structure inherent in those similarity judgments. Pharmacists' ratings of clinical significance were projected onto that same spatial representation using a multiple regression procedure, and the resulting information was used to develop a scale of clinical significance. The clinical significance scale developed from pharmacists' judgments was substantially different from a comparison scale published in a popular reference. The new scale was more precise than the comparison scale, and it also approximated an interval level of measurement. The judgments used to produce the new clinical significance scale were not reliably influenced by pertinent demographic characteristics of the sample. Inconsistencies between published clinical significance scales and the professional judgments of practitioners could affect patient care to the degree that a summary measure of clinical significance affects a practitioner's response to a potential drug-drug interaction. The clinical significance scale developed in this study has good measurement characteristics and reflects the professional judgments of practicing pharmacists. Use of the new scale is recommended on these grounds, although further assessment of its generality is warranted.
{ "pile_set_name": "PubMed Abstracts" }
Desalinated versus recycled water: public perceptions and profiles of the accepters. Many countries' water resources are limited in both quantity and quality. While engineering solutions can now safely produce recycled and desalinated water from non-potable sources at a relatively low cost, the general public is sceptical about adopting these alternative water sources. Social scientists, policy makers and technical experts need to better understand what is causing this lack of acceptance by the general population and how acceptance levels for recycled and desalinated water can be increased. This study is the first to conduct a comparative analysis of knowledge, perceptions, and acceptability, and determine segments of residents who are more open-minded than the general population toward the use of recycled and desalinated water. The Australian population once perceived desalinated water as environmentally unfriendly, and recycled water as a public health hazard. The general level of knowledge about these two concepts as potential water sources has historically been low. After nearly five years of serious drought, accompanied by severe water restrictions across most of the country, and subsequent media attention on solutions to water scarcity, Australians now show more acceptance of desalinated water for close-to-body uses, and less resistance to recycled water for garden watering and cleaning uses. The types of people likely to be strong accepters of the two alternative water sources are distinctly different groups, and can be reached through different media mixes. This finding has significant implications for policy makers and water practitioners.
{ "pile_set_name": "PubMed Abstracts" }
Subunit movement in individual H+-ATP synthases during ATP synthesis and hydrolysis revealed by fluorescence resonance energy transfer. F-type H+-ATP synthases synthesize ATP from ADP and phosphate using the energy supplied by a transmembrane electrochemical potential difference of protons. Rotary subunit movements within the enzyme drive catalysis in either an ATP hydrolysis or an ATP synthesis direction respectively. To monitor these subunit movements and associated conformational changes in real time and with subnanometre resolution, a single-molecule FRET (fluorescence resonance energy transfer) approach has been developed using the double-labelled H+-ATP synthase from Escherichia coli. After reconstitution into a liposome, this enzyme was able to catalyse ATP synthesis when the membrane was energized.
{ "pile_set_name": "PubMed Abstracts" }
A gastric-brooding asteroid, Smilasterias multipara. The gastric-brooding asterinid sea star, Smilasterias multipara, broods from late August to early November in the shallow sublittoral zone of southeastern Australia. We observed males and females spawning in the laboratory. They shed gametes through gonopores on the sides of the arms. The eggs were orange, about 1.0 mm in diameter, and heavier than seawater. They were externally fertilized by sperm, and placed into the stomach of the female by the tube feet. Twenty-four hours after fertilization, the first cleavage occurred. Cleavage was equal, total, and radial. Development via a non-feeding lecithotrophic brachiolaria was direct, there being no planktrotrophic bipinnaria or brachiolaria larva. Embryos developed, through wrinkled blastula and gastrula stages, into brachiolariae with arms. All of the surfaces of the brachiolaria were covered by cilia. At metamorphosis, a starfish rudiment appeared on the posterior portion of the larval body, while the anterior portion of the larval body was absorbed. Two months after fertilization, metamorphosis was complete. After metamorphosis, juveniles in the stomach grew six pairs of tube feet in each arm. Juveniles, 3 mm in diameter, emerged from the mouth of the mother in early November. Developmental evidence suggests that this asteroid has evolved mechanisms for the protection of larvae and juveniles from gastric digestion.
{ "pile_set_name": "PubMed Abstracts" }
Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations. Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial-type colorectal tumors, that is, laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF and PIK3CA genes and abnormal expression of the p53, beta-catenin and MYC proteins were analyzed using direct DNA sequencing and immunohistochemistry for 50 protruded-type tumors (Protruded), 35 granular-type LSTs (LST-G) and 19 nongranular-type LSTs (LST-NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors. In univariate analyses, significant differences were noted in the percentages with KRAS mutations (Protruded, LST-G, LST-NG = 30.0%, 54.3%, 21.1%, respectively, p = 0.0156), nuclear accumulation of beta-catenin (Protruded, LST-G, LST-NG = 50.0%, 37.1%, 68.4%, respectively, p = 0.0267), expression of MYC (Protruded, LST-G, LST-NG = 26.0%, 17.1%, 42.1%, respectively, p = 0.0456) and LOH at the APC gene locus (Protruded, LST-G, LST-NG = 22.0%, 20.0%, 47.4%, respectively, p = 0.0302). Multivariate analysis demonstrated that the macroscopic subtype of LST was significantly associated with KRAS mutation (for LST-NG: odds ratio [OR] 0.23, 95% CI 0.06-0.90) and nuclear accumulation of beta-catenin (for LST-NG: OR 4.05, 95% CI 1.11-14.8). Our data revealed that the 2 subtypes of LST have different molecular characteristics, suggesting that 2 or more different molecular mechanisms result in colorectal tumors with a similar growth pattern.
{ "pile_set_name": "PubMed Abstracts" }
Complete monosaccharide analysis by high-performance anion-exchange chromatography with pulsed amperometric detection. Monosaccharide analysis is a critical way to profile the composition of complex carbohydrates. Methods to analyze neutral and amino sugars have been established for a long time, but methods for acidic sugars are rare. The acidic sugars, including uronic acids and sialic acids, are also important components in some complex carbohydrates. In this report, a high-performance anion-exchange chromatography method with pulsed amperometric detection was initially developed to analyze acidic sugars including different uronic acids and sialic acids. Subsequently, a method to profile complete monosaccharides, including most neutral, amino, and acidic sugars, was developed. This method has a limit of quantitation of ~12.5 × 10(-3) nmol for each sugar as well as good linearity over a wide range. This is a convenient procedure because it avoids additional derivatization of monosaccharides and has a broad application to a wide range of complex carbohydrates. The monosaccharide compositions of a variety of complex carbohydrates such as different glycosaminoglycans, alginate, fucoidan, and glycans were profiled by this comprehensive method. In addition, the hydrolysis patterns of these complex carbohydrates are discussed.
{ "pile_set_name": "PubMed Abstracts" }
[Essential thrombocythaemia and other myeloproliferative disorders with thrombocythaemia treated with Thromboreductin. A report from the database of register for the 1st quarter of 2010]. In the Czech Republic, anagrelid is used according to the recommendations of the Czech Working Group on Myeloproliferative Disorders for treatment ofthrombocythaemias associated with chronic myeloproliferative disorders--mainly essential thrombocythaemia and, regularly, reports are being presented from the Register of Patients Treated with Thromboreductin, most recently last year (Vnitr Lék 2009; 55: I-XII). The Register commenced in 2005 and from then it aims to determine detailed clinical and laboratory profiles of the patients. The structure of the Register has changed significantly in the course of its existence, reflecting the reports from each of the analyses conducted so far. Also, the data entry in the database improves every year and it reaches 97% on some of the items. The longest evaluation period in some of the patients is 108 months. By April 2010, the Register database contained data on 717 patients. Of these, 672 patients with the diagnosis of a Ph-negative chronic myeloproliferative disorder were evaluated. This year's analysis included the patients with essential thrombocythaemia, polycythaemia vera and primary myelofibrosis only. The analysis included 418 women and 254 men with median age of50 years. Unlike the first years, 2/3 of the current sample are non pretreated patients, meaning that the patients reach the specialized centres early in their treatment. Also, patients, and the older patients in particular, are more frequently treated with combined regimens including Thromboreductin. We increasingly observe hypertension as one of the monitored risk factors preceding the disease and laboratory parameters showJAK2 mutation in more than a half of patients while some form ofthrombotic diathesis is found in the anamnesis of 7-10% of patients. Some bleeding is observed in 1-5% of the registered patients. In comparison to the previous years, this is a decrease in the prevalence of clinical symptoms prior to the disease onset; this is very likely associated with an earlier patient diagnosis within the asymptomatic phase of the disease. Therapeutically, we achieve a fast treatment response but there still are 16.3% of sufficient afterone year of treatment. Thromboreductin dose is increasing but even in this group it does not exceeds the mean of 2.38 mg per 24 hours. Complications are observed in 6.2% of patients in the first year of therapy, and ofthese, thrombotic events in about 2.5% and (small) bleeding complications in 4% of patients. The data suggest that we still do not reach treatment response in a certain proportion of patients after a year of their therapy. Even though the care results from the analysed data improve every year, the Register helps to uncover some issues that still remain, such as treatment intensification and other treatment modifications.
{ "pile_set_name": "PubMed Abstracts" }
Non-obese patients with type 2 diabetes and prediabetic subjects: distinct phenotypes requiring special diabetes treatment and (or) prevention? A major reason for the increased incidence of type 2 diabetes mellitus (T2DM) across the world is the so-called obesity epidemic, which occurs both in developed and developing countries. However, a large proportion of patients with T2DM in European and, in particular, Asian countries are non-obese. The non-obese T2DM phenotype is characterized by disproportionally reduced insulin secretion and less insulin resistance, as compared with obese patients with T2DM. Importantly, non-obese patients with T2DM have a similar increased risk of cardiovascular disease as obese T2DM patients. The risk of T2DM in non-obese patients is influenced by genetics as well as factors operating in utero indicated by low birth weight. Furthermore, this phenotype is slightly more prevalent among patients with latent autoimmune diabetes in adults, characterized by positive anti-GAD antibodies. The recently identified TCF7L2 gene polymorphism resulting in low insulin secretion influences the risk of T2DM in both obese and non-obese subjects, but is relatively more prevalent among non-obese patients with T2DM. Furthermore, the Pro12Ala polymorphism of the PPAR gamma gene influencing insulin action increases the risk of T2DM in non-obese subjects. Despite a "normal" body mass index, non-obese patients with T2DM are generally characterized by a higher degree of both abdominal and total fat masses (adiposity). Prevention of T2DM with lifestyle intervention is at least as effective in non-obese as in obese prediabetic subjects, and recent data suggest that metformin treatment targeting insulin resistance and non-glycemic cardiovascular disease risk factors is as beneficial in non-obese as in obese patients with T2DM. Nevertheless, non-obese patients with T2DM may progress to insulin treatment more rapidly as compared with obese patients with T2DM.
{ "pile_set_name": "PubMed Abstracts" }
Applying personal reflective critical incident reviews in critical care. Critical care nurses can use the personal reflective critical incident review to subjectively relate common experiences relating to crisis and then devise nursing strategies to help alleviate it. This review article, related to a current situation on an intensive care unit, helps the nurse cope with the stress of the unit. Critical care nurses must react to situations that affect everyone, including themselves. Analyzing their own reactions during a crisis situation helps nurses to accomplish this goal.
{ "pile_set_name": "PubMed Abstracts" }
Ankylosing spondylitis and heart abnormalities: do cardiac conduction disorders, valve regurgitation and diastolic dysfunction occur more often in male patients with diagnosed ankylosing spondylitis for over 15 years than in the normal population? The objective of this study was to determine the rate of selected cardiac pathologies (conduction disorders, valve regurgitation and diastolic dysfunction) in patients with long-standing ankylosing spondylitis (AS) and compare the results with the prevalence in the normal population. A rheumatologic (structured questionnaire interview) and cardiac evaluation (resting electrocardiography and echocardiography) was performed in 100 male subjects with AS and a disease duration of more than 15 years. The rates for conduction disorders, aortic and mitral valve regurgitation and diastolic dysfunction were compared with the corresponding results in the literature among the normal population. In patients with long-standing AS there was no increased rate for valve regurgitation (mitral and aortic valve) and for arrhythmia. Diastolic dysfunction occurred more often in patients with long-standing AS. However, this might be caused by the presence of other cardiovascular risk factors such as age and hypertension. According to these results, a cardiologic evaluation with echocardiography should not be recommended routinely in patients with long-standing AS. To confirm these results, a large prospective study with patients with long-standing AS and with a matched control group should be performed in the future.
{ "pile_set_name": "PubMed Abstracts" }
[Ulceromutilating acroosteopathy of the feet (author's transl)]. The cutaneo-osseous syndrome of ulceromutilating acroosteopathy, occurring in a rare hereditary and a "symptomatic" form, represents a nosologically clearly defined disease of the forefoot. Main symptoms are painless, deeply penetrating plantar ulcers with hyperkeratotic edges, non-segmental peripheral sensory neuropathy with a more or less dissociated disturbance of sensitivity and pyrexia of the forefoot (or single toes) without typical clinical signs of inflammation. Secondary symptoms, obligatory in therapy-resistant cases, include (almost) non-reactive acroosteolyses of the "neuropathic" type. The disease, increasing potentially in frequency and not recognised sufficiently, can only be treated successfully when pathogenic risk and precipitation factors are abolished selectively. Twenty-five cases could be observed over a period of 11 years with an increasing incidence.
{ "pile_set_name": "PubMed Abstracts" }
Alkylfurans: effects of alkyl side-chain length on insecticidal activity. The insecticidal activity of five alkylfurans against the generalist insect herbivore beet armyworm, Spodoptera exigua, was examined. Two naturally occurring compounds, the avocadofurans 2-(pentadecyl)furan (1) and 2-(heptadecyl)furan (2), previously isolated from specialized avocado idioblast oil cells, and three homologues, 2-(tetradecyl)furan (3), 2-(hexadecyl)furan (4), and 2-(octadecyl)furan (5), were synthesized. Bioassays of alkylfurans 1-5 using a 9-day diet-incorporation initiated with neonates showed that all alkylfurans tested significantly increased S. exigua larval mortality and reduced larval weights, with maximal biological activity detected among the naturally occurring alkylfurans 1 and 2.
{ "pile_set_name": "PubMed Abstracts" }
[Physician involvement in the prevention of trauma. Reflection on 10 years of practice of the REAGIR program]. Physician's implication in road traffic traumatology prevention has been realized for ten years, in "REAGIR" program. This program consists in analysis of the most serious road traffic accidents and proposals of preventive measures, directly to authorities. Results show the efficacy of this program (diminution of mortality and morbidity). Physicians' contribution in prevention is necessary, specific and effective.
{ "pile_set_name": "PubMed Abstracts" }
Antibody responsiveness during immunization and challenge of genetically modified antibody responder mice with murine hepatitis virus 3. The aim of this study was to evaluate some immunological patterns involved in natural and acquired resistance against MHV3 using the original model of genetically modified lines of mice selected for high (HIII) and low (LIII) antibody responsiveness. As previously shown, a lower pre-existing anti-MHV antibody level was found in susceptible HIII mice as compared to resistant LIII mice. Mortality rates of the F1 (H x L) hybrids and F2 and backcross segregants reflected co-dominance of both characters and the survivors had higher preexisting anti-MHV antibody titers. The present data show that both lines had the potential to synthesize antibodies and that the resistance acquired by the susceptible HIII mice paralleled the antibody synthesis. Nevertheless, higher antibody titers were necessary to confer resistance in HIII mice than in LIII ones. When compared to uvMHV3, a single immunization with a related infectious MHV strain induced a higher antibody synthesis and led the HIII mice to resist the MHV3 challenge. A direct correlation between the antibody level and resistance to infection was always observed in HIII mice. Although mounting a Th2 response as indicated by IgG1 responses, they were also able to readily synthesize large amounts of IgG2a antibodies after immunization or during infection, reflecting a Th1 response. The transfer of anti-MHV antibodies to susceptible HIII mice was capable of conferring resistance to MHV3, providing the antibodies were present before virus infection and in large amounts. The resistance and the survival time of these animals increased with the level of antibody administered. If these direct and clear data suggest that HIII mice can acquire resistance through antibodies, the basis of the resistance of the resistant LIII mice may rely on mechanisms less dependent on antibodies.
{ "pile_set_name": "PubMed Abstracts" }
Ferrule-top atomic force microscope. Ferrule-top cantilevers are a new generation of all-optical miniaturized devices for utilization in liquids, harsh environments, and small volumes [G. Gruca et al., Meas. Sci. Technol. 21, 094033 (2010)]. They are obtained by carving the end of a ferruled fiber in the form of a mechanical beam. Light coupled from the opposite side of the fiber allows detection of cantilever deflections. In this paper, we demonstrate that ferrule-top cantilevers can be used to develop ultra compact AFMs for contact mode imaging in air and in liquids with sensitivity comparable to that of commercial AFMs. The probes do not require any alignment procedure and are easy to handle, favoring applications also outside research laboratories.
{ "pile_set_name": "PubMed Abstracts" }
[Comparison with growth hormone responses to various drugs or substances in patients with active acromegaly (author's transl)]. Growth hormone (GH) responses to L-dopa, 2-Br-alpha-ergocryptine (CB-154), thyrotropine-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH), glucagon and glucose were investigated in six patients with active acromegaly. The following results were obtained. 1) Subcutaneous injection of 1 mg glucagon caused a clear-cut decrease in plasma GH levels in 5 out of 6 active acromegalic patients at 30 minutes after the injection. In 2 out of 6 patients a rebound of plasma GH was observed. 2) In three out of six patients with active acromegaly, oral administration of 0.5 g L-dopa caused a significant suppression of plasma GH levels. 3) CB-154 (2.5mg) administered orally elicited a marked decrease in plasma GH levels in the same three patients who showed a significant suppressive GH reponse to L-dopa, and the inhibitory effect of CB-154 on GH secretion lasted for 6 hours. These patients who had a GH response to L-dopa or CB-154 were named "responders". 4) Intravenous administration of TRH resulted in a significant increase in plasma GH in 4 patients 3 of whom were responders and the other a non-responder. 5) Pretreatment with CB-154 did not modify the TRH-induced GH increase in all patients who had a positive response to TRH. 6) A significant increase in plasma GH was elicited by the intravenous injection of 100 mug LH-RH in 3 out of 6 patients with acromegaly. 7) When oral administration of CB-154 had been given 2 hours before LH-RH, the GH response to LH-RH was blunted in two of three patients who had a LH-RH-induced increase in plasma GH levels.
{ "pile_set_name": "PubMed Abstracts" }
Cardiohemodynamic and electrophysiological effects of a selective EP4 receptor agonist ONO--AE1--329 in the halothane-anesthetized dogs. Cardiovascular effects of a highly selective prostaglandin E2 type 4 (EP4) receptor agonist ONO-AE1-329 were assessed with the halothane-anesthetized dogs (n=6). ONO-AE1-329 was intravenously infused in three escalating doses of 0.3, 1 and 3ng/kg/min for 10min with a pause of 20min between the doses. The low dose of 0.3ng/kg/min significantly increased maximum upstroke velocity of left ventricular pressure by 18% at 20min, indicating increase of ventricular contractility. The middle dose of 1ng/kg/min significantly decreased total peripheral resistance by 24% and left ventricular end-diastolic pressure by 32% at 10min, indicating dilation of arteriolar resistance vessels and venous capacitance ones, respectively; and increased cardiac output by 25% at 10min in addition to the change induced by the low dose. The high dose of 3ng/kg/min increased heart rate by 34% at 10min; decreased mean blood pressure by 14% at 10min and atrioventricular nodal conduction time by 13% at 5min; and shortened left ventricular systolic period by 8% at 10min and electromechanical coupling defined as an interval from completion of repolarization to the start of ventricular diastole by 39% at 10min in addition to the changes induced by the middle dose. No significant change was detected in a ventricular repolarization period. These results indicate that ONO-AE1-329 may possess a similar cardiovascular profile to typical phosphodiesterase 3 inhibitors as an inodilator, and suggest that EP4 receptor stimulation can become an alternative strategy for the treatment of congestive heart failure.
{ "pile_set_name": "PubMed Abstracts" }
SODIUM GLUCOSE COTRANSPORTER 2 AND DIPEPTIDYL PEPTIDASE-4 INHIBITION: PROMISE OF A DYNAMIC DUO. This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). We conducted a nonsystematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiologic abnormalities present in T2DM without overlapping toxicities. The combination of these 2 agents has several advantages including a low risk of hypoglycemia, the potential for weight loss, the ability to coformulate into a pill with once-daily administration, and the possibility to use with other classes of glucose-lowering agents. Cardiovascular outcomes trials reported to date support the safety of the DPP-4 class and suggest possible cardioprotective effects for SGLT2 inhibitors - at least based on the first reported study that used empagliflozin. Recent clinical evidence shows that SGLT2 inhibitor/DPP-4 inhibitor therapy is an effective combination for T2DM treatment, providing glycated hemoglobin (HbA1c) reductions of 1.1 to 1.5%, and weight reductions of approximately 2 kg when added to metformin, which is its primary place in therapy. The combination of an SGLT2 inhibitor/DPP-4 inhibitor is a safe and effective treatment choice for patients with T2DM who are unable to obtain adequate glycemic control with metformin therapy, cannot use metformin, or have a higher baseline HbA1c. BP = blood pressure; CI = confidence interval; CVOT = cardiovascular outcomes; DKA = diabetic ketoacidosis; DPP-4 = dipeptidyl peptidase-4; EXAMINE = EXamination of cArdiovascular outcoMes with alogliptiN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome; FDA = Food and Drug Administration; HbA1c = glycated hemoglobin; HR = hazard ratio; MACE = major adverse cardiovascular events; SAVOR-TIMI 53 = Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Type 2 Diabetes Mellitus; SBP = systolic blood pressure; SGLT2 = sodium glucose cotransporter 2; TECOS = Trial to Evaluate Cardiovascular Outcomes after Treatment with Sitagliptin; T2DM = type 2 diabetes mellitus; XR = extended release.
{ "pile_set_name": "PubMed Abstracts" }
The efficacy of fine needle aspiration cytology in the preoperative evaluation of parakeratotic odontogenic keratocysts. To assess the performance of fine needle aspiration cytology (FNAC) in preoperative diagnosis of parakeratotic odontogenic keratocyst. Twenty-three cases of odontogenic keratocyst which were evaluated with FNAC prior to enucleation were included in the study. Aspiration smears were stained with Papanicolaou and hematoxylin-eosin stain. Results obtained from FNAC were compared with histopathologic data obtained from the excisional biopsies. Keratotic cell clusters with or without inflammation were identified in all the cytologic smears. No dysplastic changes were seen. The evaluation of the excisional biopsies revealed cystic epithelium which is characterized by palisaded basal cells, a corrugated surface with a lumen containing keratin debris. Two of the cases which revealed satellite cysts were not associated with Gorlin-Goltz syndrome due to the absence of other findings. Parakeratotic odontogenic keratocyst can be substantially diagnosed preoperatively utilizing FNAC with a careful evaluation.
{ "pile_set_name": "PubMed Abstracts" }
Alternatively spliced MHC class I mRNAs show specific deletion of sequences encoding the extracellular polymorphic domains. Analysis of structural diversity at the 5' end of H-2 class I mRNAs showed that a small fraction of Kd mRNA from L1210 lymphoma (approximately 10%) or from various normal tissue (2-3%) of DBA/2 mice carries a precise deletion of the sequences encoding the second extracellular domain. Nucleotide sequence of the coding region of the second domain-lacking Kd mRNA was found to be identical to the known sequence of the Kd gene from DBA/2 liver with the exception of the above deletion and a single nucleotide silent substitution at position 150, suggesting that the novel Kd RNA is a product of the functional Kd gene. In addition, various normal tissues that are known to express varying levels of Kd antigen did not show changes in the expression levels of the second domain-lacking Kd mRNA thus ruling out the possibility that synthesis of this RNA is coupled to control the expression levels of the canonical Kd mRNA, hence the Kd antigen. Analysis by polymerase chain reaction showed that all normal tissues including the testis and sperm express this RNA. Preliminary analysis of the Kb mRNA from the spleen and thymus of C57BL/6 mouse also showed the presence of second domain-lacking Kb mRNA in these mice. Furthermore, preliminary structural analysis of the Dd and Ld mRNAs has revealed additional polymorphic extracellular domain-lacking mRNA species including a first domain-lacking Dd mRNA and two Ld mRNAs that lack sequences encoding either the first extracellular domain or the second extracellular domain respectively. These results together show that H-2 mRNAs lacking sequences that specify individual extracellular polymorphic domains are a frequent feature of the structural diversity at the 5' ends of these mRNAs. Potential significance of these domain-lacking H-2 mRNAs is discussed, particularly with regard to the function of the putative encoded peptides as targets of natural killer cells.
{ "pile_set_name": "PubMed Abstracts" }
Citric acid modification of a polymer exhibits antioxidant and anti-inflammatory properties in stem cells and tissues. Biomaterials can be used as carriers of antioxidant or drug to the oxidative injury site of tissue and decrease intracellular oxidative stress levels, however, low dosage delivery or unstable molecular structure of antioxidant or drug limited the long-term sustained release. A chemically stable antioxidant molecule is essential to serve as antioxidant structure components of biomaterials that may provide the relatively high antioxidant content and persisting local antioxidant release with the degradation of materials. In this study, we used citric acid modified polyvinyl alcohol (PVA-C) as a model biomaterial to investigate the role of citric acid on the material stimulated antioxidant and anti-inflammatory effects. In cellular-based assays, PVA-C extracts showed a protective effects on bone marrow mesenchymal stem cells (BMSCs) under oxidative stress. It could enhance the antiapoptotic ability of stem cells by inhibiting reactive oxygen species. Further studies revealed that PVA-C extracts upregulated the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) and superoxide dismutase [Mn] (SOD2). in vivo animal assays, PVA-C extracts showed significant inhibitory effects on the oxidative stress and inflammatory reaction which were induced by lipopolysaccharide (LPS). These findings suggest that the citric acid modified polymer can regulate the redox signaling of stem cells and tissues by the release of citric acid from materials, leading to enhanced oxidative stress-induced degenerative diseases and inflammatory diseases therapy.
{ "pile_set_name": "PubMed Abstracts" }
Idiopathic post-operative pulmonary hypertension in the newborn. A case of severe pulmonary hypertension following the primary repair of an omphalocele in a term infant is reported. There were no pre-disposing factors known to contribute to the postoperative pulmonary hypertension (PPH). Therapy was successful first by using hyperventilation, and then subsequently with tolazoline. Upper gastrointestinal bleeding limited the use of tolazoline after the first fourty-eight hours. Complete recovery ensued. The occurrence of PPH and the current therapy of this unpredictable condition is discussed.
{ "pile_set_name": "PubMed Abstracts" }
[Postoperative treatment of patients after pancreatectomy. Closely meshed monitoring of blood sugar (author's transl)]. A report is presented on the postoperative treatment of 4 patients who had undergone duodeno-pancreatectomy because of chronic pancreatitis. When the patients co-operate well satisfactory metabolic compensation can be achieved with small doses of insulin. Replacement of the pancreatic enzymes with the appropriate preparations can be particularly well monitored by means of the fat content of the faeces. The substitution of vitamins A, D, K, and B12 parenterally at intervals of several weeks is also advisable as a safety measure. A method is described for the closely meshed monitoring of the blood sugar. This method is suitable in co-operative patients who are capable of collecting capillary blood for achieving a particularly good control of the metabolic state.
{ "pile_set_name": "PubMed Abstracts" }
Metabolomics and lipidomics study unveils the impact of polybrominated diphenyl ether-47 on breast cancer mice. Polybrominated diphenyl ether-47 (BDE-47) is a congener of polybrominated diphenyl ethers (PBDEs) and relates to different health risks. However, in vivo study of the association between BDE-47 and breast cancer was scarce. In this study, we performed in vivo exposure of BDE-47 to breast cancer nude mice and conducted mass spectrometry-based metabolomics and lipidomics analysis to investigate the metabolic changes in mice. Results showed that the tumor sizes were positively associated with the dosage of BDE-47. Metabolomics and lipidomics profiling analysis indicated that BDE-47 induced significant alterations of metabolic pathways in livers, including glutathione metabolism, ascorbate and aldarate metabolism, and lipids metabolism, etc. The upregulations of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) suggested the membrane remodeling, and the downregulations of Lyso-PCs and Lyso-PEs might be associated with the tumor growth. Targeted metabolomics analysis revealed that BDE-47 inhibited fatty acid β-oxidation (FAO) and induced incomplete FAO. The inhibition of FAO and downregulation of PPARγ would contribute to inflammation, which could promote tumor growth. In addition, BDE-47 elevated the expression of the cytokines TNFRSF12A, TNF-α, IL-1β and IL-6, and lowered the cytokines SOCS3 and the nuclear receptor PPARα. The changes of cytokines and receptor may contribute to the tumor growth of mice.
{ "pile_set_name": "PubMed Abstracts" }
HtrA1 Down-regulation Induces Cisplatin Resistance in Colon Cancer by Increasing XIAP and Activating PI3K/Akt Pathway. The high temperature requirement factor A1 (HtrA1), a member of serine protease family, has been reported to be down-regulated in various cancer types and correlate with chemoresistance. However, the function of HtrA1 in colon cancer remains unclear. This study investigated the role of HtrA1 in cisplatin (CDDP) resistance of colon cancer. We found that HtrA1 was up-regulated in colon cancer cell line SW480 incubated with CDDP. By treating SW480 cells to a continuous exposure to CDDP, we developed CDDP-resistant SW480/CDDP cells and found that the mRNA and protein levels of HtrA1 were reduced. Besides, the stable knock-down of HtrA1 in SW480 transfected with HtrA1 shRNA could also induce chemoresistance against CDDP. To the contrary, ectopic expression of HtrA1 in SW480/CDDP cells abrogated CDDP resistance. The mechanism underlying HtrA-1 down-regulation induced chemoresisance was also investigated. In SW480/CDDP cells and SW480 cells with HtrA1 knock-down, X-linked inhibitor of apoptosis protein (XIAP) was increased, while the interfering of XIAP impeded CDDP resistance in SW480/CDDP cells. We also found that Akt was activated in SW480/CDDP cells and SW480 cells with HtrA1 knock-down. The inhibition of Akt activation reversed CDDP resistance. In conclusion, our results indicate that HtrA1 down-regulation induces CDDP resistance in colon cancer by increasing XIAP and activating PI3K/Akt pathway. This study provides evidence that HtrA1 might be a therapeutic target for overcoming CDDP resistance in colon cancer.
{ "pile_set_name": "PubMed Abstracts" }
Photochemistry of Thin Solid Films of the Neonicotinoid Imidacloprid on Surfaces. Imidacloprid (IMD) is the most widely used neonicotinoid insecticide found on environmental surfaces and in water. Analysis of surface-bound IMD photolysis products was performed using attenuated total reflectance Fourier transfer infrared (ATR-FTIR) analysis, electrospray ionization (ESI-MS), direct analysis in real time mass spectrometry (DART-MS), and transmission FTIR for gas-phase products. Photolysis quantum yields (ϕ) for loss of IMD were determined to be (1.6 ± 0.6) × 10-3 (1s) at 305 nm and (8.5 ± 2.1) × 10-3 (1s) at 254 nm. The major product is the imidacloprid urea derivative (IMD-UR, 84% yield), with smaller amounts of the desnitro-imidacloprid (DN-IMD, 16% yield) product, and gaseous nitrous oxide (N2O). Theoretical calculations show that the first step of the main mechanism is the photodissociation of NO2, which then recombines with the ground electronic state of IMD radical to form IMD-UR and N2O in a thermally driven process. The photolytic lifetime of IMD at a solar zenith angle of 35° is calculated to be 16 h, indicating the significant reaction of IMD over the course of a day. Desnitro-imidacloprid has been identified by others as having increased binding to target receptors compared to IMD, suggesting that photolysis on environmental surfaces increases toxicity.
{ "pile_set_name": "PubMed Abstracts" }
[Problem of sirenomelia]. Two cases of a rare type of the sirenal developmental abnormality, dipodal sympodia, were studied. In both cases, elements of the rudimental kidney were found. The analysis of the literature and a comparative study of our own cases suggest a correlation between the degree of fusion of the lower extremity rudiments and the intensity of underdevelopment of the urogenital organs.
{ "pile_set_name": "PubMed Abstracts" }
18F-radiopharmacokinetics of [18F]-5-fluorouracil in a mouse bearing two colon tumors with a different 5-fluorouracil sensitivity: a study for a correlation with oncological results. The tissue distribution and biodynamics of 18F-labelled 5-fluorouracil (FU) are described and studied for correlation with its in vivo antitumor activity. The in vivo model consisted of Balb/c mice bearing a FU sensitive (Colon 26-10 carcinoma) tumor in the left and a less responsive (Colon 26 carcinoma) tumor in the right abdominal side of the animal. Distribution and efflux of 18F-label from tumor, blood, and other tissues were determined by obduction at 0.5, 1, 2, 4, and 6 h postintravenous injection. For a comparison, the 18F-labeled 5-fluoro-6-hydroxy and cis-5-fluoro-6-ethoxy uracil adducts were studied in the same in vivo model. For 18F-FU it was found that the 18F-label tumor kinetics rapidly fell into a biphasic mode: a relatively short 18F beta phase (18F t1/2 beta 21 +/- 3 min), linked with the total body metabolic capacity and clearance of the animal, and a longer 18F gamma phase, linked with the intrinsic intratumoral FU metabolism (Colon 26-10: 18F t1/2 gamma 10.3 h; Colon 26: 18F t1/2 gamma 5.6 h). It is proposed that the observed faster 18F efflux of the less responsive Colon 26 corresponds to an enhanced breakdown of 5-fluoronucleotides to 5-fluoronucleosides and subsequent elimination from the tumor cells. It is concluded that on PET scanning, measurement of the dynamic 18F t1/2 gamma and 18F t1/2 beta parameter is of prime importance for an insight in the in vivo tumor biology of a patient.
{ "pile_set_name": "PubMed Abstracts" }
Patient understanding of commonly used oral medicine terminology. Introduction Communication within the doctor-patient relationship is complex due to a variety of reasons; a patient's understanding may not correspond with the clinician's vocabulary, resulting in misunderstanding, anxiety and ill-informed decision making. We investigated the understanding of terminology commonly used in oral and maxillofacial surgery and oral medicine clinics.Methods We investigated patients' understanding using a questionnaire-based study in the out-patient setting. Age, gender, first language and highest educational level were recorded. The questionnaire included multiple choice questions regarding patients' understanding of words as well as asking patients to define certain terms. Vocabulary included 'ulcer', 'blister', 'cancer', 'malignant' and 'benign'.Results and conclusions Many patients have difficulty in understanding and explaining commonly used terminology. 'Blister' was the most commonly understood term, while 'benign' and 'lesion' were the least well understood. 'Tumour' was mistakenly thought of as synonymous with 'malignancy' by over a third of patients. Understanding was better among those for whom English was their first language. It is essential that all clinicians modify their language appropriately during consultations in order to deliver information in a comprehensive manner, to educate patients on their condition thus enabling informed decision making by patients.
{ "pile_set_name": "PubMed Abstracts" }
Modulating the electronic structure of lanthanum manganite by ruthenium doping for enhanced photocatalytic water oxidation. To the best of our knowledge this is the first report in which ruthenium doped polycrystalline lanthanum manganite, LaMn1-xRuxO3 (x = 0.0-0.4), having high efficacy for oxygen production from water without the use of any sacrificial reagent or co-catalyst and as an efficient photocatalyst for dye degradation is reported. Ruthenium doping alters the crystal structure of the parent LaMnO3 (LMO) due to the induced chemical pressure of the larger Ru4+ ion, which facilitates a bond angle of 180° in the Mn3+-O-Mn4+ plane resulting in the easy extraction of a photo-generated charge carrier population leading to enhanced photocatalytic activity. Rietveld refinements reveal that the parent compound LMO crystallizes in the rhombohedral phase, while upon an increase in the doping concentration of ruthenium, the phase of the compounds changes from the rhombohedral to the cubic phase. The percentage contribution of each phase has been estimated using the sixth-order polynomial and pseudo-Voigt function. Typically, all the compositions, LaMn1-xRuxO3 (x = 0.0-0.4), were prepared by a conventional solid state route and studied for their photocatalytic activity. The synthesized compounds were investigated by powder X-ray diffraction (PXRD), UV-visible diffuse reflectance spectroscopy (DRS), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) analysis. The structure-property correlation of the compound is presented based on Rietveld refinement combined with the experimental data. The as-prepared compounds show efficient photocatalytic oxygen gas production from water without the use of any co-catalyst or sacrificial reagents. Among the five compositions, LaMn0.7Ru0.3O3 shows the highest O2 production efficiency (4.73 mmol g-1 h-1) with an apparent quantum yield (AQY) of 7.43%. These ruthenium doped compositions also exhibit superior dye degradation properties, studied by taking the industrial dye methyl orange (MO) as the model compound.
{ "pile_set_name": "PubMed Abstracts" }
Thyrotropin-releasing hormone effects on phosphatidylinositol metabolism and binding in rat pituitary and retina. This paper reveals possible similarities in the thyrotropin-releasing hormone (TRH) effects on phospholipid metabolism in pituitary and retina of the rat central nervous system. Addition of the methylated analog (MeTRH) resulted in 171 +/- 16% and 88 +/- 10% increase in 32PO4 incorporation into phosphatidylinositol (PI) in pituitary (20 min incubation) and retina (60 min incubation), respectively. There was a similar significant increase in phosphatidic cid, but with no change in phosphatidylcholine or other classes of phospholipids. The effect was concentration-dependent and the ED50 also was close to KD, suggesting the response was regulated by MeTRH receptors in membranes of both pituitary and retina.
{ "pile_set_name": "PubMed Abstracts" }
Selective enumeration of probiotic microorganisms in cheese. Cheese is a dairy product which has a good potential for delivery of probiotic microorganisms into the human intestine. To be considered to offer probiotic health benefits, probiotics must remain viable in food products above a threshold level (e.g., 10(6) cfu g(-1)) until the time of consumption. In order to ensure that a minimal number of probiotic bacteria is present in the cheese, reliable methods for enumeration are required. The choice of culture medium for selective enumeration of probiotic strains in combination with starters depends on the product matrix, the target group and the taxonomic diversity of the bacterial background flora in the product. Enumeration protocol should be designed as a function of the target microorganism(s) to be quantified in the cheese. An overview of some series of culture media for selective enumeration of commercial probiotic cultures is presented in this review.
{ "pile_set_name": "PubMed Abstracts" }
A case of Hodgkin's disease presenting with recurrent laryngeal nerve palsy and tracheoesophageal fistula. Malignancy is the most common cause of tracheoesophageal fistulas. The malignancies commonly implicated in the development of tracheoesophageal fistulas are primary bronchial or esophageal carcinomas. Hodgkins disease rarely leads to such a fistula. We report a case of Hodgkin's disease with a tracheoesophageal fistula as well as a left recurrent nerve palsy at presentation. This presentation has no precedent in literature. The patient was treated with systemic chemotherapy and involved field radiotherapy. On follow up 1 year after the completion of treatment, he was clinically and radiologically disease free.
{ "pile_set_name": "PubMed Abstracts" }
Teratogenic potential of valproic acid. Valproic acid administration in pregnancy may be a potential teratogen to the developing fetus. Numerous animal studies have linked valproic acid to vertebral anomalies and renal agenesis. Recent European data have suggested valproic acid as a causal agent of neural tube defects in human offspring. Research relative to teratogenicity of valproic acid administration for petit mal epilepsy is reviewed. Conclusions indicate that the benefits of valproic acid administration outweigh the hazards of teratogenicity.
{ "pile_set_name": "PubMed Abstracts" }
Impact-driven effects in thin-film growth: steering and transient mobility at the Ag(110) surface. Low-energy atomic impacts on the Ag(110) surface are investigated by molecular dynamics simulations based on reliable many-body semiempirical potentials. Trajectory deflections (steering) caused by the atom-surface interaction are observed, together with impact-following, transient-mobility effects. Such processes are quantitatively analysed and their dependence on the initial kinetic energy and on the impinging direction is discussed. A clear influence of the surface anisotropy on both steering and transient mobility effects is revealed by our simulations for the simple isolated-atom case and in the submonolayer-growth regime. For the latter case, we illustrate how steering and transient mobility affect the film morphology at the nanoscale.
{ "pile_set_name": "PubMed Abstracts" }
A novel FES control paradigm based on muscle synergies for postural rehabilitation therapy with hybrid exoskeletons. Hybrid exoskeletons combine robotic orthoses and motor neuroprosthetic devices to compensate for motor disabilities and assist rehabilitation. The basic idea is to take benefits from the strength of each technology, primarily the power of robotic actuators and the clinical advantages of using patient's muscles, while compensating for the respective weaknesses: weight and autonomy for the former, fatigue and stability for the latter. While a wide repertory of solutions have been proposed in literature for the control of robotic orthoses and simple motor neuroprosthesis, the same problem on a complex hybrid architecture, involving a wide number of muscles distributed on multiple articulations, still waits for a practical solution. In this article we present a general algorithm for the control of the neuroprosthesis in the execution of functional coordinated movements. The method extracts muscle synergies as a mean to diagnose residual neuromotor capabilities, and adapts the rehabilitation exercise to patient requirements in a dynamic way. Fatigue effects and unexpected perturbations are compensated by monitoring functional state variables estimated from sensors in the robot. The proposed concept is applied to a case-study scenario, in which a postural balance rehabilitation therapy is presented.
{ "pile_set_name": "PubMed Abstracts" }
Interaction of glyceraldehyde-3-phosphate dehydrogenase with the cytoplasmic pole of band 3 from bovine erythrocyte membrane: the mode of association and identification of the binding site of band 3 polypeptide. Four fragments derived from the cytoplasmic pole of bovine band 3 were isolated, and their ability to bind glyceraldehyde-3-phosphate dehydrogenase from bovine erythrocyte and their amino-terminal primary structure were examined. It was suggested that the 50-kDa fragment, an entire cytoplasmic pole of band 3, contained the blocked amino-terminal end of band 3. Three other fragments, 45-, 39-, and 38-kDa fragments, were produced by cleavage at distances of molecular weight 5000, 11,000, and 12,000 respectively, from the amino-terminus of the 50-kDa fragment. Among these, the 50- and 45-kDa fragments complexed with the enzyme to inhibit its catalytic activity under conditions of low ionic strength, in a fashion similar to that in humans. Affinity for the enzyme was not significantly affected by disruption of the higher order structure of the fragments. The enzyme was found to be inactivated by association with synthetic polyanions, accompanied by conformational alteration. This supports participation of electrostatic interactions as the holding force between the enzyme and band 3, as suggested by I-H. Tsai et al. [1982) J. Biol. Chem. 257, 1438-1442). The 45-kDa fragment was just as potent an inhibitor of the enzyme as the parent fragment, and its amino-terminal region displayed a polyanionic character. These results allow us to map the enzyme binding site of bovine band 3 to a distance of molecular weight approximately 5000 from the amino-terminal end of band 3. Furthermore, comparison of sequence data from different species showed that the species-specific region of band 3 polypeptide centers around the amino-terminal portion.
{ "pile_set_name": "PubMed Abstracts" }
[Allergic pathology due to enzymes: a case report of asthma due to pectinase (polygalacturonase)]. The paper described the case of a worker handling pectinase, an enzyme used in the manufacture of food additives. This enzyme is a carbohydrase (polygalacturonase) obtained by extraction, and consists of three active phases. After little more than a year at the job, the subject complained of bouts of asthma, especially when she had to weigh the enzyme in dust form. Symptoms appeared even when this operation was performed by others near her work station. An allergological examination revealed skin hypersensitivity to the enzyme, without atopy. The methods of preparing the tests performed are described. The authors stress the need to perform similar investigations on other exposed workers in order to assess the allergogenic potential of the substance and adjust environmental preventive measures accordingly.
{ "pile_set_name": "PubMed Abstracts" }
Classification and comparison of capillary columns by determination of the solution enthalpy of polar and non polar probes. The behaviour and separation characteristics of capillary columns containing different stationary phases (bonded methyl- and methylphenylsiloxanes and polyglycols, and carbon layer and porous polymer) were classified and compared by measuring the values of the solution enthalpy DeltaHs of n-alkanes and 1-alcohols at various temperatures. The difference in DeltaHs values between straight-chain 1-alcohols and n-alkanes with the same number of carbon atom (DeltaDeltaHs) does not change with changing temperature when gas-liquid partition stationary phases are used, but depends on the column composition and polarity and therefore permits to evaluate the influence of polarity on the solute-solvent interaction. The trend of the DeltaDeltaHs values is correlated with that of the DeltaC parameter and with the McReynolds' polarity constants.
{ "pile_set_name": "PubMed Abstracts" }
[Surgical managements of peripheral intracranial aneurysms]. To explore the clinical characteristics and treatment strategies of peripheral intracranial aneurysms. A total of 24 patients of peripheral aneurysms from October 2008 to October 2011 were retrospectively analyzed. There were 11 females and 13 males with a mean age of 46 (38-38) years. Of the 24 patients, 11 were female and 13 were male, mean age was 46 years (ranged 38-68). The distributions of the lesions included 12 peripheral anterior cerebral artery (n = 12), aneurysms, 3 peripheral middle cerebral artery (n = 3) aneurysms, 2 peripheral posterior cerebral artery (n = 2) aneurysms, 1 peripheral superior cerebellar artery (n = 1) aneurysm, 2 anterior inferior cerebellar artery (n = 2) aneurysms, 2 posterior inferior cerebellar artery (n = 2) aneurysms, and 2 medial posterior choroidal artery (n = 2) aneurysm. Eight procedures were performed by under neuro-navigation, and another 2 under were performed by intraoperative magnetic resonance imaging (MRI) and navigation. The procedures included Sixteen peripheral aneurysms were simple y clipping (n = 16)ed, 4 were clipping plus reconstruction of ed and parent arteries (n = 4) reconstructed, resection (n = 2) and resection plus reanastomosis 2 were resected, 1 was resected and of parent artery (n = 1) and EC-IC bypass (n = 1) was reanastomosed, and 1 was trapped with EC-IC bypass. At discharge, 20 of them out of the 24 patients had a Glasgow Outcome Scale (GOS) score of 5, and another 4 patients had yielded a score of 4. Two oculomotor nerve palsies occurred postoperatively and , with both improved in during a 3-month follow-ing up period. One patient case had postoperative partial visual field defect. The Peripheral intracranial aneurysms are a rare in clinical practices kind of entity. Precise intraoperative localization of the lesions is the of key importance for management to the procedure. Different treatment strategies should be taken based on their diverse different characteristics of the aneurysm.
{ "pile_set_name": "PubMed Abstracts" }
[Determination of salidroside in eight Rhodiola species by TLC-UV spectrometry]. Quantitative determination of the salidroside in eight Rhodiola species by TLC-UV spectrometry is reported. The salidroside was separated on a silica GF254 TLC plate using CHCl3-CH3OH-H2O(26:14:3) as developing solvent and determined at wavelength 223.8 nm. The results show that this method in simple and convenient.
{ "pile_set_name": "PubMed Abstracts" }
Diabetic peripheral neuropathy: a correlation of nerve conduction studies and clinical findings. The electrophysiologic and clinical characteristics of diabetes were studied in 56 patients having diabetes of adult onset. Historical data including age, duration of diabetes, treatment type, family history and clinical symptoms were noted. Nerve conduction studies of the median, ulnar, peroneal, tibial and sural nerves were performed, and the H reflex was determined. Clinical sensory function of vibration, light touch, and two-point discrimination, muscle stretch reflexes in all four extremities and skin temperatures in the lower extremities were recorded. The data indicated a close correlation of clinical and electrophysiologic findings. The data supported the concept that diabetic peripheral neuropathy is progressive. It was concluded that diabetic peripheral neuropathy was present if two of the following three determinations were abnormal: median motor or sensory latency, ulnar sensory latency and sural latency.
{ "pile_set_name": "PubMed Abstracts" }
[Evaluation of the diagnostic role of the carcinoembryonic antigen in ascitic fluid]. The diagnostic role of carcinoembryonic antigen (CEA) in ascitic fluid was evaluated in order to assess whether or not ascitic haemorrhage is related to cancer. A total of 30 patients with ascitic haemorrhage were analysed (17 had cirrhosis, 5 non-metastasised cancers and 8 metastasised cancers). CEA radioimmunoassay was performed in serum and ascitic fluid. The results showed that CEA in the ascitic fluid highlighted a clear distinction between the average values of the 3 groups examined serum assay did not. Results were respectively: cirrhotic patients 6.11, non-metastasised cancers 38 and metastasised cancers 204.12. Ascitic fluid measurement revealed considerable variation, especially between the first and third groups examined (p = .00000004). Although CEA must be regarded as an aspecific laboratory test for malignancy, these results suggest that CEA determination in the ascitic fluid may be useful for screening patients with ascitic haemorrhage.
{ "pile_set_name": "PubMed Abstracts" }
Isolation and identification of the toxic peptides from Lophyrotoma zonalis (Pergidae) sawfly larvae. The broad-leaved paper bark tree Melaleuca quinquenervia (Cav) (Myrtaceae) was introduced into Florida (USA) early in this century it has proliferated to such an extent that urgent measures are now required to control it. The sawfly Lophyrotoma zonalis (Pergidae) has been introduced as a possible biological control agent due to its ability to defoliate M. quinquenervia. Because toxic D-amino acid- containing peptides have been isolated from some sawfly species, L. zonalis larvae were processed using the previously reported method for the recovery of these compounds. The toxins lophyrotomin (as the free C-terminal acid) and a mixture of pergidin and Val (4)-pergidin were isolated at 0.36 and 0.43% yield of the dried larvae, respectively. Both compounds when dosed intraperitoneally to C57/Bl6 male mice were hepatotoxic with lowest lethal doses of 8 and 32 mg/kg, respectively. The pathology of the liver was different for each compound, with the lophyrotomin free acid causing a periportal haemorrhagic necrosis and the pergidin causing a periacinar coagulative necrosis.
{ "pile_set_name": "PubMed Abstracts" }
Money matters: students' perceptions of the costs associated with placements. Placements are an integral component of the medical, nursing and allied health curricula. However, apart from the relocation costs associated with placements, little research on students' understandings and experiences of the financial implications of placements has been carried out. We report on students' financial concerns associated with placements, which emerged as a main theme in a broader study we conducted on the impact of undergraduate student placement experiences on graduate practice. We conducted a qualitative study which included focus group discussions (n = 17), individual interviews (n = 48) and written responses (n = 2) with undergraduate students (n = 103) and graduates (n = 27) from a tertiary institution in Victoria, Australia. Students identified that income generation and the costs associated with transport and placement location contributed to the financial burden of placements. Students also spoke of the implications of high financial strain impacting on their accumulation of debt as well as on their health and wellbeing. Our study advances our understanding of the implications of financial hardship experienced by medical, nursing and allied health students. In our study, students, regardless of their placement location, experienced increased demands and associated stress as a result of managing placements, paid employment and limited financial resources. We recommend that further quantitative research be conducted to measure the variables identified as emerging themes in this study.
{ "pile_set_name": "PubMed Abstracts" }
Multi-segmental neurofibromatosis. Neurofibromatosis (NF), one of the commonest phakomatoses, is characterized by varied clinical manifestations. Segmental NF is one of the uncommon subtypes of NF. We report a young adult presenting with asymptomatic skin lesions- neurofibromas and café-au-lait macules- over localized areas of the lower back, affecting more than one segment. None of the family members were found to have features of segmental NF. Segmental NF may be misdiagnosed as a birthmark or remain undiagnosed for long periods of time, as the patients are often asymptomatic. Moreover, the clinical features are highly variable and range from a small area of skin involvement to involvement over the entire half of the body. This variation is explained by the fact that segmental NF is thought to arise from a postzygotic NF1 gene mutation, leading to somatic mosaicism. We have also reviewed the relevant literature on this subject.
{ "pile_set_name": "PubMed Abstracts" }
Delayed pneumothorax after laparoscopic ovarian cystectomy. We describe a case that developed a delayed pneumothorax after laparoscopic surgery. A 40-year-old woman (BMI: 19.1) underwent a laparoscopic ovarian cystectomy. On the first postoperative day, she developed a pneumothorax. The subcutaneous CO2 tracked up through the fascial planes, and ruptured into the pleural space, where delayed pneumothorax developed. Gynecologists should be aware of pneumothorax after laparoscopic surgery and should also keep in mind its possible delayed development.
{ "pile_set_name": "PubMed Abstracts" }
Morphological and cytochemical changes of peripheral blood lymphocyte lysosomes in chronic lymphocytic leukemia. Morphological changes of lysosomes (according to Blum) and the activity of acid phosphatase (by the method of Barka and Andersen) were investigated in peripheral blood lymphocytes in patients with chronic lymphocytic leukemia non-treated or treated with Leukeran. The division into groups was carried out according to Rai. Pathological lymphocytes in relation to lymphocytes of healthy subjects showed a decreased number of lysosomes and an increased number of cells with diffuse type of reaction to acid phosphatase. A relation was found between the intensity of morphological changes of lysosomes in pathological lymphocytes and the clinical state of the patients. Morphological evaluation of lysosomes in lymphocytes is a good diagnostic criterion of treatment effectiveness providing prognostic cues.
{ "pile_set_name": "PubMed Abstracts" }
Current status of the treatment of epidermoid cancer of the vulva. Epidermoid cancer accounts for 81% of the malignancies of the vulva. Although the etiology has not been delineated, chronic vulvitis is associated with cancer in almost one-third of the patients. The staging system should utilize the most precise and accurate parameters delineated for improved treatment. A new staging system is utilized. Proven treatment is primarily surgical.
{ "pile_set_name": "PubMed Abstracts" }
Natural course of treated and untreated chronic HCV infection: results of the nationwide Hepnet.Greece cohort study. Interferon (IFN-alpha)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results. To investigate the natural course of IFNalpha-based-treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study. We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNalpha-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively. During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit. IFNalpha-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR.
{ "pile_set_name": "PubMed Abstracts" }
Impact of depressive mixed state in an emergency psychiatry setting: a marker of bipolar disorder and a possible risk factor for emergency hospitalization. Depressive mixed state (DMX) has been reported to be one of the most useful clinical markers for bipolar II disorder (BP-II) in the outpatient setting. However, the significance of DMX in emergency psychiatry has not been well studied. A chart review study of 139 patients who were hospitalized in an emergency psychiatric ward with an initial diagnosis of major depressive disorder (MDD). In 42 (30.2%) patients, the diagnosis was changed to bipolar disorder after a median observation period of 189 days from hospitalization, and of these, 34 were diagnosed as having BP-II. DMX was observed in 56 (40.3%) patients at the time of hospitalization. Compared with patients who remained in MDD, significantly more patients who later developed bipolar disorder had experienced DMX (59.5% vs. 32.0%, p = 0.0044). In multivariate analysis, DMX was one of the independent predictors of conversion to bipolar disorder (OR 2.45, p = 0.037), and the independent predictors for DMX were chronic depression and atypical features (OR 2.85, p = 0.010; OR 3.67, p = 0.046, respectively). In addition, DMX was significantly more frequently observed at emergency hospitalization than at non-emergency hospitalization (48.6% vs. 29.1%, p = 0.0065). A single reviewer evaluated DMX by chart review. DMX is a useful marker of bipolar disorder (mainly BP-II) in the emergency psychiatric setting and is closely related to emergency hospitalization for mood disorders. To confirm these findings, a prospective study that systematically evaluates DMX is needed.
{ "pile_set_name": "PubMed Abstracts" }
A heat-labile serine proteinase from Penicillium citrinum. A serine proteinase from Penicillium citrinum was purified. The M(r) and isoelectric point were determined as about 26,000 and 9.5, respectively. Activity was retained up to above 40 degrees at pH 7 for 30 min, but the enzyme was completely inactivated at 50 degrees. The first amino acids in the N-terminal region were ANVVQSNVPSWGLARISSKRPGTTSYTYDSTAGEGVVFYGVDTG. The specificity differs from that of other serine proteinases. Kinetic studies on fluorogenic substrates were determined.
{ "pile_set_name": "PubMed Abstracts" }
Induction of apoptosis and expression of cell cycle regulatory proteins in response to a phytosphingosine derivative in HaCaT human keratinocyte cells. Ceramide, a compound derived from sphingomyelin, a sphingolipid precursor, affects cell functions such as growth, differentiation, cell division and apoptosis. We have shown that the phytosphingosine derivative, tetra-acetyl phytosphingosine (TAPS), inhibits the growth of HaCaT cells mainly by inducing apoptosis. In this study, we investigated its effect on the cell cycle and on cell cycle regulatory proteins. We showed by flow cytometry and staining for BrdU and phosphorylated histone H3 that the cells accumulated in S phase and arrested in G2 phase and did not divide before undergoing apoptosis. The level of the pro-apoptotic regulator Bax peaked after 6 h and then returned to normal, whereas the level of the anti-apoptotic regulator Bcl-xL, which is presumably induced in order to inhibit apoptosis, started to increase at 6 h, and remained high for 24 h. Phosphorylation of Cdc2 on Tyr-15 greatly increased while p21 rose to a plateau at 8 h. Levels of p53 and Mad2 proteins were unchanged. Our observations suggest that TAPS induces apoptosis of the HaCaT cells at least in part via transient G2 arrest.
{ "pile_set_name": "PubMed Abstracts" }
PEGylated insulin Lispro (LY2605541): clinical overview of a new long-acting basal insulin analog in the treatment of Type 2 diabetes mellitus. Neutral Protamine Hagedorn insulin with an intermediate action profile has been in use for many years for the treatment of Type 1 diabetes and as an option for Type 2 diabetes. It is efficacious in reducing blood sugars, but shows substantial variability and risk of hypoglycemia. Basal insulin analogs have been developed in recent years to overcome these issues. Three basal insulin analogs are currently in the market in Europe. PEGylated insulin lispro is a new second-generation basal insulin analog which most likely will undergo review in 2016 by the US FDA and EMA in Europe for possible approval for marketing. Phase III trials are finalized, but not yet published. Phase II studies suggest antiglycemic efficacy, possible with a preferential hepato-specific action, a low rate of hypoglycemia, minor weight loss and acceptable tolerability. The benefit-risk profile needs, however, to be established.
{ "pile_set_name": "PubMed Abstracts" }
[Fatal gunshot injuries in Hamburg 1966-1991]. Deaths by fire-arms investigated at the Institute for Legal Medicine of the University of Hamburg were analyzed retrospectively since 1966. Among 70,000 deaths (33,000 autopsies) there were 838 fatalities caused by gunshots (about 30 cases per year). One third were classified as homicides, the others as suicides, only 3% as accidents. Almost the entire number of suicides was committed by men (relation male:female 20:1), whereas the proportion of women was higher among the homicides (ratio male:female 3:1). Details referring to the age of the victims, profession-coherence, alcohol-influence, capacity to act and survival-time are analyzed. The kinds of arms, and bullets (with special reference to self-made firearms), criminalistical aspects (i.e. differentiation between homicide and suicide, gun in the hand), morphological findings (i.e. nuchal and oral shots or bullet-related embolism) are introduced.
{ "pile_set_name": "PubMed Abstracts" }
Caffeine attenuates seizure and brain mitochondrial disruption induced by Tramadol: the role of adenosinergic pathway. Tramadol (TR) is an analgesic drug used to treat moderate-to-severe pain but it induces seizure even at therapeutic doses. The exact mechanism of TR-inducing seizure is not clear but inhibition of the serotonin, GABA, and nitrous oxide (NOS) pathways are the commonly proposed mechanisms. Adenosinergic system has a crucial function in the modulation of seizure. Also, oxidative damage is an unavoidable effect of the seizure. This study was conducted to evaluate the role of the adenosinergic system on the seizure and oxidative stress biomarkers induced by TR using antagonist of the adenosinergic receptors in the Albino mice. For that purpose, generated clonic seizure, as seizure threshold, was evaluated by TR. Caffeine (CAF; 8 mg/kg, i.p.), a nonselective antagonist of adenosine receptors, was administered 1 hour before the seizure induction. The seizure threshold significantly increased by CAF-treated group when compared to TR group (p < 0.001). Oxidative stress biomarkers such as reactive oxygen species, protein carbonyl content, and lipid peroxidation significantly decreased and glutathione content significantly increased by CAF in brain mitochondria compared to the TR group, whereas oxidative biomarkers significantly increased in the TR group compared to the control group. The results of the present study suggested that the adenosinergic system is involved in seizure induced by TR and meanwhile, inhibition of adenosine receptors can decrease the TR seizure threshold and also decrease the induced oxidative damage in the brain mitochondria.
{ "pile_set_name": "PubMed Abstracts" }
Combining canonical correlation analysis and infinite reference for frequency recognition of steady-state visual evoked potential recordings: a comparison with periodogram method. Steady-state visual evoked potentials (SSVEP) are the visual system responses to a repetitive visual stimulus flickering with the constant frequency and of great importance in the study of brain activity using scalp electroencephalography (EEG) recordings. However, the reference influence for the investigation of SSVEP is generally not considered in previous work. In this study a new approach that combined the canonical correlation analysis with infinite reference (ICCA) was proposed to enhance the accuracy of frequency recognition of SSVEP recordings. Compared with the widely used periodogram method (PM), ICCA is able to achieve higher recognition accuracy when extracts frequency within a short span. Further, the recognition results suggested that ICCA is a very robust tool to study the brain computer interface (BCI) based on SSVEP.
{ "pile_set_name": "PubMed Abstracts" }
Toxic shock syndrome toxin-1-induced death is prevented by CTLA4Ig. Lethal toxic shock syndrome (TSS) results from the MHC class II presentation of bacterial superantigens, most commonly toxic shock syndrome-1 (TSST-1), to specific TCR Vbeta-bearing T cells. This superantigen-induced stimulation of whole T cell subsets leads to the exuberant cytokine production that in turn causes the shock syndrome. Since T cell activation and cytokine production are known to be dependent upon costimulatory signals, we reasoned that interfering with costimulation could effect TSS outcome. To test that hypothesis, we evaluated the effect of CTLA4Ig, a fusion protein known to block costimulatory signaling, on TSST-1-induced responses. CTLA4Ig not only blocked TSST-1-stimulated T cell proliferation by 90% in vitro, it also strikingly ameliorated TSST-1 induced TSS in vivo. While all mice co-administered TSST-1 and control Ig died, 75% of the CTLA4Ig plus TSST-1-treated mice survived. This salutary CTLA4Ig effect correlated with markedly diminished TSST-1 induced serum levels of TNF-alpha and IFN-gamma, but TSST-1-triggered IL-2 release was not affected. Surprisingly, while CTLA4Ig treatment group survivors remained sensitive to TSS induced by an unrelated superantigen (staphylococcal enterotoxin B), they were completely resistant to a second TSST-1 challenge. Furthermore, this TSST-1 resistance could be transferred to naive C57BL/6 mice using CD8+ T cells from CTLA4Ig plus TSST-1-primed mice. These data suggest several novel interpretations: 1) that the release of TNF-alpha and IL-2 have a different costimulatory signal dependence in vivo, 2) that the TSS resistance conferred by CTLA4Ig was superantigen specific, and 3) that the delayed and transferable resistance to TSST-1 was due, at least in part, to CD8+ T cells with suppressor function.
{ "pile_set_name": "PubMed Abstracts" }
Multiplane transesophageal echocardiographic assessment of mitral regurgitation by Doppler color flow mapping of the vena contracta. Assessment of the severity of mitral regurgitation (MR) by Doppler color flow mapping is limited by dependence of jet area on hemodynamic and technical variables. The width of the MR jet at its origin may be less dependent on hemodynamic variables, and thus should more accurately reflect the severity of MR. Doppler color flow mapping was performed in 80 subjects by transesophageal echocardiography (TEE) within 48 hours of catheterization. Width of the MR jet at its vena contracta was measured by both single plane and multiplane TEE and compared with the angiographic grade of MR and regurgitant volume. The width of the MR jet correlated closely with angiographic grade by both methods. A jet width > or = 6 mm identified angiographically severe MR with a sensitivity and specificity of 100% and 83% by single-plane TEE, and 95% and 98% by multiplane TEE. The sensitivity and specificity for detecting a regurgitant volume > or = 80 ml was 93% and 76% for single-plane TEE, and 86% and 95% for multiplane TEE. Thus, the width of the MR jet at its vena contracta by Doppler color flow mapping is an accurate marker of the severity of MR. By virtue of its ability to obtain orthogonal views specifically oriented to mitral leaflet coaptation, multiplane TEE is superior to single-plane TEE in assessing MR jet width.
{ "pile_set_name": "PubMed Abstracts" }
Bilateral facet dislocations in the thoracolumbar spine. Bilateral facet dislocation represents approximately 11% of all thoracolumbar spine injuries requiring surgical stabilization. The injury can be caused by either flexion distraction (29/30 cases) or by pure distraction (1/30). Recognition of the injury is possible on plain radiographs, and confirmed by the empty facet sign on the computed tomography (CT) scan. In contradistinction to other major spine injuries, the majority of patients present with complete neurologic lesions (21/30). Recovery of patients with incomplete lesions is frequent (5/6); however, recovery from complete lesions did not occur. Compression instrumentation is recommended for patients with complete lesions because it is stable and requires no external immobilization. Distraction instrumentation that imparts significant extension is advised for patients with incomplete lesions. It is safe and reliable, and eliminates the posterior bulging of the injured disc that can occur with compression. For low lumbar injuries where compression is desirable in order to achieve the shortest possible instrumentation, a discectomy is recommended.
{ "pile_set_name": "PubMed Abstracts" }
Therapeutic hypothermia for acute stroke. Hypothermia is the most potent neuroprotective therapy available. Clinical use of hypothermia is limited by technology and homeostatic mechanisms that maintain core body temperature. Recent advances in intravascular cooling catheters and successful trials of hypothermia for cardiac arrest revivified interest in hypothermia for stroke, resulting in Phase 1 clinical trials and plans for further development. Given the recent spate of neuroprotective therapy failures, we sought to clarify whether clinical trials of therapeutic hypothermia should be mounted in stroke patients. We reviewed the preclinical and early clinical trials of hypothermia for a variety of indications, the putative mechanisms for neuroprotection with hypothermia, and offer several hypotheses that remain to be tested in clinical trials. Therapeutic hypothermia is promising, but further Phase 1 and Phase 2 development efforts are needed to ensure that cooling of stroke patients is safe, before definitive efficacy trials.
{ "pile_set_name": "PubMed Abstracts" }
Assessing the environmental health relevance of cooling towers--a systematic review of legionellosis outbreaks. Bioaerosols from cooling towers are often suspected to cause community-acquired legionellosis outbreaks. Although Legionella infections can mostly be assigned to the emission sources, uncertainty exists about the release and distribution into the air, the occurrence of the respirable virulent form and the level of the infective concentration. Our study aimed to evaluate studies on legionellosis outbreaks attributed to cooling towers published within the last 11 years by means of a systematic review of the literature. 19 legionellosis outbreaks were identified affecting 12 countries. Recurring events were observed in Spain and Great Britain. In total, 1609 confirmed cases of legionellosis and a case-fatality rate of approximately 6% were reported. Duration of outbreaks was 65 days on average. For diagnosis the urinary antigen test was mainly used. Age, smoking, male sex and underlying diseases (diabetes, immunodeficiency) could be confirmed as risk factors. Smoking and underlying diseases were the most frequent risk factors associated with legionellosis in 11 and 10 of the 19 studies, respectively. The meteorological conditions varied strongly. Several studies reported a temporal association of outbreaks with inadequate maintenance of the cooling systems. A match of clinical and environmental isolates by serotyping and/or molecular subtyping could be confirmed in 84% of outbreaks. Legionella-contaminated cooling towers as environmental trigger, in particular in the neighbourhood of susceptible individuals, can cause severe health problems and even death. To prevent and control Legionella contamination of cooling towers, maintenance actions should focus on low-emission cleaning procedures of cooling towers combined with control measurements of water and air samples. Procedures allowing rapid detection and risk assessment in the case of outbreaks are essential for adequate public health measures. Systematic registration of cooling towers will facilitate the identification of the source of outbreaks and help to shorten their duration.
{ "pile_set_name": "PubMed Abstracts" }
[Natural history of intestinal lesions in inflammatory bowel disease]. Crohn's disease may involve any part of the digestive tract from mouth to anus, but affects mainly the distal ileum and the,colon. At diagnosis, perianal lesions are observed in 20% of the cases. During the disease course, strictures develop in the majority of patients with ileal disease, while penetrating lesions (fistulas and abscesses) develop in half of the patients. Only one third of patients with colonic involvement will develop structuring or penetrating lesions. Intestinal lesions of ulcerative colitis involve constantly the rectum and may extend continuously throughout the colon. At diagnosis, lesions involve the rectum, the left colon and most of the colon in similar proportions. Subsequent extension of the lesions over 20 years is observed in half of the patients. In Crohn's disease, 40%-50% of the patients require intestinal resection at 10 years. The risk of colectomy in ulcerative colitis is about 1% per year Dysplasia and cancer may complicate longstanding extensive colonic lesions in Crohn's disease and ulcerative colitis. Malignant transformation of chronic inflammatory lesions may also occur in patients with longstanding lesions of the small bowel in Crohn's disease.
{ "pile_set_name": "PubMed Abstracts" }
C3G overexpression promotes the survival of rat-derived H9C2 cardiomyocytes by p-ERK1/2. Integrin β1 subunit and its downstream molecules, such as integrin-linked kinase and focal adhesion kinase, are imperative for promotion of cell proliferation, survival and anti-apoptosis in cardiomyocytes by activation of their downstream pro-survival signalling molecules, such as the phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2). As a component of the integrin pathway, C3G (Crk-SH3 domain guanine nucleotide exchange factor) protein may be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes. Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hC3G, a human C3G overexpression eukaryotic recombinant plasmid. Apoptosis, cell proliferation and survival were analysed in the H9C2 cardiomyocytes either treated with hypoxia/reoxygenation (H/R). Human C3G mRNA overexpression significantly elevated C3G protein expression in H9C2 cardiomyocytes whether treated with H/R or not. C3G overexpression promoted proliferation and survival and anti-apoptosis, and attenuated the proliferative and survival inhibition, and apoptosis induced by H/R by activation of its downstream pro-survival signalling molecule, p-ERK1/2. The results suggest that C3G acts as a pro-survival molecule in H9C2 cardiomyocytes by activation of p-ERK1/2.
{ "pile_set_name": "PubMed Abstracts" }
Anomalous venous system in the human heart. In a 2002 cadaveric dissection course, a complex manner of rare variation was found in the abnormal venous system of the heart of an 88-year-old Japanese man who died of acute pneumonia. The superior vena cava and the left and right brachiocephalic veins were normal. In this case, a complex venous system existed as follows. (1) A left superior vena cava was persistent. (2) The innominate vein was present. It went upward between the ascending aorta and the pulmonary trunk, passed through the ventral side of the bifurcation of the pulmonary trunk, and then anastomosed with the left superior vena cava. The oblique vein of the left atrium, as a fibrous bundle, was connected to the junction of the left superior vena cava and the innominate vein in the pericardium. (3) The great cardiac vein was divided into two branches. One was located at the right side of the left coronary artery, forming the origin of the innominate vein. The other extended to the coronary sinus as a normal great cardiac vein. (4) The orifice of the coronary sinus on the right atrium was obliterated. (5) The abnormal orifice existed between the left atrium and the coronary sinus. The formation process and functional significance of such venous variations are discussed.
{ "pile_set_name": "PubMed Abstracts" }
Expression and contribution of three different isoforms of prostaglandin E synthase in the bovine endometrium. Prostaglandins are involved in the regulation of several reproductive processes such as ovulation, luteolysis, and establishment of pregnancy. Prostaglandin E(2) (PGE(2)) appears to favor establishment of pregnancy in most mammals studied so far. The primary enzymes involved in the production of PGE(2) from arachidonic acid are cyclooxygenases and prostaglandin E synthases (PGES). Three PGES have been identified in humans, but in the bovine, microsomal PGES2 and cytosolic PGES genes have neither been cloned nor associated to any physiological processes. The present study was undertaken to clone bovine MPGES2 and CPGES and to report on their regulation in the endometrium during the estrous cycle. CPGES mRNA expression declines progressively during the cycle; its protein is not modulated according to a precise pattern. MPGES2 mRNA and protein expression decrease from the beginning of the cycle until Days 13-15 and then increase until ovulation. Immunohistochemical analysis reveals that both enzymes are located in luminal epithelial and glandular epithelial cells and at a lower level in stromal cells. In addition, using the bovine endometrial cell line BEND, where higher accumulation of PGE(2) is observed following treatment with phorbol 12-myristate 13-actetate (PMA) and tumor necrosis factor-alpha (TNF-alpha), we have found an associated increase of MPGES1 and COX2 but not CPGES or MPGES2 protein expression. Together, our results suggest that MPGES1 is not the only PGES present in the bovine endometrium but is the main enzyme associated with increased PGE(2) production in vitro.
{ "pile_set_name": "PubMed Abstracts" }
On the ecology of the harbour seal Phoca vitulina in the Wadden Sea: population dynamics, residue levels, and management . The harbour seal population in the Dutch Wadden Sea decreased significantly during the last decades. Calculations based on bounty data revealed that the population decreased from about 2700 in 1950 to about 900 in 1959. Annual aerial surveys--which were carried out since that time--showed a slight increase due to the stop of hunting. However, after 1964 a new decline occurred and since 1974 the population stays at a level of about 450 specimens. During 1974 to 1978 the population dynamics of the population have been studied Frequent aerial surveys provided data on the size of the population. These data have been used in a simulation model and the birth rate and the initial juvenile mortality were calculated. During boat trips an indication of the age composition was obtained by measuring track widths. By comparing these results with similar results from a stable population in Schleswig Holstein it appeared: (1) that juvenile mortality in the first weeks in the Dutch population is higher than that in Schleswig Holstein but the overall mortality of pups in both areas in their first three months of life is of the same order; (2) that pup production in the Dutch population is low compared to the population in Schleswig Holstein; (3) that apparently immigration from elsewhere occurs. To investigate the contribution of environmental pollution to the decline of the Dutch seal population tissues of dead, stranded animals originating from Schleswig Holstein, Denmark and the Netherlands were collected and analyzed for PCBs, o,p'-DDT, p,p'-(DDT, DDE, TDE), dieldrin, aldrin, endrin, endosulfan, alpha, beta, gamma,-HCH, HCB, QCB (pentachlorobenzene), HEPO, total mercury, methyl-mercury, selenium and bromium. Considering epidemiological and experimental data on the effects of PCBs on mammalian reproduction, strong support is obtained for the hypothesis that PCBs are responsible for the decreased reproduction in seals from the Dutch Wadden Sea. if PBCs are responsible for the decrease of the Dutch seal population, measure of all North Sea countries are urgently required because these PCBs may not only be a hazard to seals but also to other animals and even man. Production and use of PCBs should be limited and used PCBs should be collected and destroyed. However, even if an immediate ban on PCB's would be effected, the effects of PCBs because of their persistent character are likely to last many years. For that reason it may be assumed that the seal population in the western Wadden Sea still faces a difficult period in the years to come. In order to lead this population through this difficult period, all possible measures enhancing its continued existence should be taken. Since the seals in the Wadden Sea form one population maximum result may be expected from measures applying to all seals in the Wadden Sea. Thus international cooperation is necessary. The following measures are proposed: Continued interdiction of hunting in order to obtain a maximum number of animals taking part in reproduction. Establishment of seal reserves and, additionally supporting seal nursery stations in order to guarantee a maximum reproductive output. However, it has to be stressed that these measures are not effective if at the same time the main cause of the decrease is not found and brought under control.
{ "pile_set_name": "PubMed Abstracts" }
Elevated 18F-FDG levels in blood and organs after angiotensin II receptor blocker administration: experiment in mice administered telmisartan. Angiotensin II receptor blockers (ARBs) are a common treatment for hypertensive patients but affect renal function. In this study, the effects of ARB on (18)F-FDG distribution and excretion were examined in mice treated with telmisartan at different doses. Male C57BL/6J mice were given telmisartan (low-dose group, 0.33 mg/kg/d; moderate-dose group, 0.66 mg/kg/d; high-dose group, 3 mg/kg/d) mixed in a high-fat diet for 20 wk. Mice on a telmisartan-free diet served as the control. At designated time points, the mice were injected with (18)F-FDG (18.5 MBq/mouse, n = 5-10/time point for each group) to examine its biodistribution. Autoradiography using kidney sections was performed to visualize (18)F-FDG excretion. Plasma blood urea nitrogen (BUN) and creatinine levels were also measured to evaluate renal function. Twenty-week telmisartan treatment significantly and dose-dependently increased (18)F-FDG levels in the blood (percentage injected dose per gram of tissue normalized by animal body weight: low, 0.13 ± 0.03 [P < 0.0083]; moderate, 0.15 ± 0.01 [P < 0.0083]; high, 0.15 ± 0.03 [P < 0.0083], vs. control, 0.09 ± 0.01). Significantly increased (18)F-FDG levels in organs were observed in mice in the moderate- and high-dose groups but not in the low-dose group. The plasma BUN and creatinine levels also dose-dependently increased, but they were within the reference ranges (for BUN: low, 27.00 ± 4.42 mg/dL; moderate, 28.40 ± 2.70 mg/dL; high, 39.22 ± 6.91 mg/dL [P < 0.0083], vs. control, 22.40 ± 2.80 mg/dL. For creatinine: low, 0.28 ± 0.11 mg/dL; moderate, 0.40 ± 0.07 mg/dL [P < 0.0083]; high, 0.51 ± 0.09 mg/dL [P < 0.0083], vs. control, 0.18 ± 0.04 mg/dL). The blood (18)F-FDG level positively correlated with plasma BUN (r = 0.48, P < 0.01) and creatinine (r = 0.61, P < 0.01) levels. The (18)F-FDG levels in the blood and organs returned to baseline 3 wk after cessation of telmisartan treatment. Autoradiography indicated that renal (18)F-FDG excretion was attenuated by telmisartan treatment and was reversed after treatment cessation. (18)F-FDG levels in the blood and organs were significantly increased by telmisartan treatment, indicating a potential increase in background activity on PET imaging of patients treated with ARBs. Our findings indicate the need for a careful assessment of (18)F-FDG uptake in patients treated with ARBs. A brief cessation of ARB treatment may be a potential method to avoid these effects and solve this problem.
{ "pile_set_name": "PubMed Abstracts" }
Noncompetitive inhibition of inositol monophosphatase by K-76 monocarboxylic acid. K-76COONa, a fungal product that was previously isolated for its inhibition of complement activation, was found to inhibit myo-inositol monophosphatase activity. K-76COONa was slightly more potent than lithium, with a Ki of approximately 0.5 mM. Kinetic analyses with D-myo-inositol 1-phosphate as the substrate showed that myo-inositol monophosphatase inhibition by K-76COONa was noncompetitive relative to substrate but competitive with activation by magnesium. Higher concentrations of K-76COONa were necessary to inhibit myo-[3H]inositol 1,4-bisphosphate hydrolysis by inositol 1,4-bisphosphate/inositol 1,3,4-trisphosphate 1-phosphatase (IC50 = approximately 7.5 mM). K-76COONa may be useful for further investigation of the mechanism of myo-inositol monophosphatase and for determination of whether inhibition of this enzyme plays a role in the therapeutic effectiveness of lithium in treatment of affective disorders.
{ "pile_set_name": "PubMed Abstracts" }
The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of stresses, it was of interest to determine what effect cellular senescence in vitro and cells cultured in vitro from young and old human donors have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionary conserved of the heat shock proteins. The ability of early and late passage IMR-90 lung fibroblasts and epidermal melanocytes and skin fibroblasts obtained from young and old human donors to express hsp70 was determined after a brief heat shock. We found that the levels of hsp70 protein and mRNA were lower in late passage cells and cells from old donors than in early passage cells and cells from young donors. The binding activity of the heat shock transcription factor HSF1, as measured by a gel shift assay, was significantly higher in early passage cells and cells from young donors in comparison to late passage cells and cells from old donors. In addition, the levels of HSF1 decreased significantly in late passage cells and cells from old donors in comparison to early passage cells and cells from young donors. Thus, our study demonstrates that the induction of hsp70 by hyperthermia in fibroblasts is significantly lower in late passage fibroblasts and in fibroblasts from old donors. In addition, our study shows that the decline in hsp70 expression during cellular senescence in vitro and in cells derived from old human subjects is paralleled by a decrease in the levels of HSF1.
{ "pile_set_name": "PubMed Abstracts" }
Reproductive toxicology of the new antitussive moguisteine. Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non narcotic peripherally acting antitussive drug, was examined for effects in the rat on general reproductive performance (at 0, 50, 212, 900 mg/kg/d,) for embryotoxicity (at 0, 25, 75, 225, 900 mg/kg/d) and for peri-postnatal toxicity (at 0, 62.5, 250, 1000 mg/kg/d). Embryotoxicity (at 0, 75, 225, 900 mg/kg/d) was also examined in the New Zealand White rabbit. In all the studies, moguisteine was administered orally as a suspension by gavage. At the tested doses, moguisteine did not interfere with general reproductive performance, either in the F0 or in the F1 generation. The drug did not show any toxic effect on the dams and their fetuses, nor did it have any teratogenic effect in either of the tested species. Finally, moguisteine had no adverse effects, either on parturition or on peri-and postnatal survival and/or development of the offspring.
{ "pile_set_name": "PubMed Abstracts" }
A computer-assisted emergency department chart audit. We present a method for a microcomputer-assisted emergency department daily chart audit using a spreadsheet format. Computer technology allows the extraction of a large amount of information from audit data with a minimum of clerical time. The software automatically tabulates, sorts, and updates audit data, and depicts physician performance in a quantitative manner. The software is able to generate a variety of graphics that visually depict physician and departmental performance. The spreadsheet model is flexible, and can be adapted to the needs of various emergency departments or quality assurance activities. The audit has a rapid turnaround time, with charts audited and returned to physicians for feedback within 24 hours of the patient being discharged. Individual physician confidentiality is maintained throughout.
{ "pile_set_name": "PubMed Abstracts" }
Max Linde, MD, a Luebeck ophthalmologist and patron of Edvard Munch. Ophthalmologist Maximilian Linde (1862-1940) had a passion for contemporary art and owned one of the most important private collections in Europe. He first met little known Norwegian expressionist Edvard Munch in 1903, recognized special talent, and welcomed him into his family. With Linde's encouragement, patronage, and friendship, Munich became one of the most important artists of his time. Many of Munch's works were commissioned by Linde and many featured Linde and his family as subjects.
{ "pile_set_name": "PubMed Abstracts" }
Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis. Although the molecular basis of variability of hemoglobin (Hb) F has been extensively examined in β-thalassemia and sickle cell diseases, less study has been done on Hb E disorder. To address the variability of Hb F expression in Hb EE disease, we have examined multiple single nucleotide polymorphisms (SNPs) in the β-globin gene cluster, BCL11A and HBS1L-MYB genes and determined their associations with Hb F levels in this syndrome. Study was done on 141 adult Thai individuals with homozygous Hb E. Hematological parameters were recorded and Hb F measured using Hb-HPLC analyzer. It was found in 26 cases that co-inheritance of α-thalassemia could lead to significant lower production of Hb F. Association of Hb F expression with the (G)γ-Xmn I polymorphism and other SNPs including rs2297339, rs2838513, rs4895441 and rs9399137 in HBS1L-MYB gene and rs4671393 and rs11886868 in BCL11A gene was therefore analyzed in the remaining 115 cases without α-thalassemia. It was found that 4 of these 7 SNPs including (G)γ-XmnI polymorphism (rs7482144), HBS1L-MYB (rs4895441) and (rs9399137) and BCL11A (rs4671393) were significantly associated with higher proportions of subjects with high Hb F (Hb F≥5%). The result demonstrated that multiple genetic modifying factors including T allele of (G)γ-XmnI polymorphism (rs7482144), G allele of HBS1L-MYB (rs489441), C allele of HBS1L-MYB (rs9399137) and C allele of BCL11A (rs4671393) are associated with increased Hb F and in combination could explain approximately 80% of the variation of Hb F in Hb EE disease in Thai population. Other genetic factors regulating Hb F expression in this common genetic disorder remains to be elucidated.
{ "pile_set_name": "PubMed Abstracts" }
Therapeutic footwear can reduce plantar pressures in patients with diabetes and transmetatarsal amputation. To compare how footwear (full-length shoe or short shoe), a total contact insert, a rigid rocker-bottom (RRB) sole, and an ankle-foot orthosis (AFO) affect peak plantar pressure (PPP) on the distal residuum and contralateral extremity of patients with diabetes and transmetatarsal amputation (TMA). Thirty patients with diabetes and TMA participated (mean age 62 +/- 4 years). In-shoe plantar pressures during walking were measured in six types of footwear. Each measurement occurred after a 1-month adjustment period. Repeated measure analysis of variance (ANOVA) was used to compare treatments. All five types of therapeutic footwear reduced plantar pressures compared with regular shoes with a toe-filler (P < 0.05). A full-length shoe, total contact insert, and RRB sole resulted in lower pressures on the distal residuum (222 vs. 284 kPa) and forefoot of the contralateral extremity (197 vs. 239 kPa), compared with a regular shoe and toe-filler. Footwear with an AFO showed reduced PPP on the residuum, but most patients complained of reduced ankle motion during walking. A short shoe reduced pressures on the residuum, but not on the contralateral extremity, and many patients had complaints regarding cosmesis of the shoe. The full-length shoe, total contact insert, and an RRB sole provided the best pressure reduction for the residuum and contralateral foot, with the optimal compromise for cosmetic acceptance and function.
{ "pile_set_name": "PubMed Abstracts" }
Cell surface receptors for extracellular matrix molecules. Table 2 lists most of the extracellular matrix and related receptors identified to date. The wide range of binding affinities of these receptors for their ligands may be important to their function. The affinity of integrins for fibronectin is moderate, with a dissociation constant in the micromolar range. This affinity level leads to relatively rapid dissociation and reformation of receptor-ligand complexes. Thus changes in component concentration can shift binding equilibria within minutes (the time scale of many biologic phenomena) and change the number or organization of adhesive complexes. This type of interaction would be useful in motile cells, in which adhesions must form and dissociate rapidly. In contrast, the affinity of the 68-kDa laminin receptor for its ligand is three orders of magnitude higher. Such levels of affinity would be useful in stabilizing tissue. Members of the integrin family appear to recognize an RGD sequence on the ligands to which they bind. Since there are many ligands containing the RGD sequence, the question of specificity arises. Avian integrin shows little specificity and appears to behave as a multifunctional, promiscuous receptor for extracellular matrix molecules. Figure 1 summarizes our current view of the structural and functional features of avian integrin. In contrast, the mammalian receptors for vitronectin and fibronectin are specific for their respective ligands. More than one of these receptors may be present simultaneously on a cell surface, e.g. fibroblasts express receptors for fibronectin, laminin, and vitronectin at the same time. This multiplicity of receptors provides potential mechanisms for generating the adhesive differences among cells believed to play a prominent role in morphogenesis. Further adhesive differences may stem from the formation of different combinations of various alpha- and beta-subunits expressed in the cell. The mechanism of regulation of adhesive interactions with the extracellular matrix is only beginning to be explored. There are several levels at which this regulation might occur. Integrin appears to be more regionalized in more developed cells that are integral parts of tissue structures. Changes in receptor distribution could alter the relative strength of adhesive interactions. In certain instances, avian integrin disappears, or its concentration is reduced, e.g. during the development of embryonic lung (Chen et al 1986) and erythroid cells (Patel & Lodish 1985). Post-translational modifications provide yet another mechanism for regulating integrin-ligand binding.(ABSTRACT TRUNCATED AT 400 WORDS)
{ "pile_set_name": "PubMed Abstracts" }
With time changes of T-lymphocytes after Babesia infection in mice pretreated with Toxoplasma lysate antigen. Adult female mice of the ICR/JCL strain were injected intraperitoneally with an emulsion of Toxoplasma lysate antigen (TLA; 100 micrograms per head) in light mineral oil (LMO) twice at 2 weeks' interval. Each mouse was inoculated intraperitoneally with 10(2) erythrocytes infected with Babesia rodhaini 2 weeks after the second injection of the emulsion. The rates of decrease in the erythrocyte count, hemoglobin concentration, and hematocrit value 10 days after inoculation, as compared with the counterparts determined 1 day before inoculation, were distinctly lower in these treated mice than in untreated control mice. In the course of Babesia inoculations, substantial reduction in size and weight of the thymus became higher in untreated control than in TLA-treated mice as the infection progressed. In untreated controls, the number of Thy-1 positive (Thy-1 (+) ) cells was about 91.9% of the normal value being 3.7 X 10(7) cells in the whole thymus 1 day before inoculation while those in TLA-treated mice were 6.5 X 10(7) and 0.9 X 10(7) cells 1 day before inoculation and 10 days after inoculation, respectively. The size and weight of the spleen increased in both groups by day 10 after inoculation. The total number of Thy-1 (+) cells in the spleen was 3.9 X 10(7) and 11.7 X 10(7) 1 day before and 10 days after inoculations, respectively in untreated and 12.9 X 10(7) and 15.6 X 10(7), respectively in TLA-treated mice. The number of Thy-1 (+) cells in the liver was 0.5 X 10(7) and 1.2 X 10(7) 1 day before and 10 days after inoculations, respectively in untreated and 0.3 X 10(7) and 3.4 X 10(7), respectively, showing a rate increase of 1033.3% in TLA-treated mice. The rate of increase in count of Thy-1 (+) cells contained in the peripheral blood was 61.4% in the former and 64.1% in the latter. In untreated mice, degeneration and destruction of lymphocytes in the thymus and spleen follicles and aggregation of lymphocytes, which were not found in Thy-1 (+) staining, around pericapillary ducts in the liver were seen histopathologically 10 days after inoculation. In TLA-treated mice, however, perivascular infiltration by Thy-1 (+) lymphocytes and activation of Kupffer cells in the liver and activation of spleen follicles were observed locally 10 days after inoculation.
{ "pile_set_name": "PubMed Abstracts" }
Second hernia repairs in children-a nationwide study. Second inguinal hernia repairs may be needed either owing to contralateral metachronous hernia (MH) or ipsilateral recurrent hernia (RH). In this study, we estimated the incidence rates of MH and RH from a large nationwide database. The information was obtained from the National Health Insurance Database (with 23 million insurants). Subjects with hernia repairs were identified, and information such as age, gender, unilateral/bilateral procedures in the first and second hernia repairs were analyzed. Among the 92,308 newborns observed from their births to the end of 6th year, 3881 had first hernia repairs. Among the 3068 subjects with first unilateral repairs, 307 had second repairs, and among the 813 with first bilateral repairs, 15 had second repairs. The incidence of second repairs was 10.85% (13.71% if <1year old) after first unilateral repairs and was 1.23% (0.63% if <1year old) after first bilateral repairs. The incidence of RH (estimated from second hernia repairs after first bilateral repairs) was 1.23%. The incidence of MH (from second repairs after first unilateral repairs) was 9.62%. These incidence rates are consistent with other published reports.
{ "pile_set_name": "PubMed Abstracts" }
Prevalence of HBV-genotypes in immigrants affected by HBV-related chronic active hepatitis. The genetic heterogeneity of the HBV genome has been established and eight genotypes can be classified according to the criterion of >8% differences in the complete nucleotide sequence of the viral genome. To evaluate the prevalence of HBV-infection in a population of immigrants and to determine in patients with detectable serum HBV-DNA the HBV-genotypes. Between January 2005 and December 2005 a total of 556 immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV-genotype was determined by INNOLiPA. Among the 556 subjects tested, 60 (10.7%) resulted HBsAg positive. All were men, and 42 (70%) come from Africa, 10 (16.6%) from Asia and 9 (14.4%) from East-Europe. 28/60 (46.6%) patients presented normal ALT levels (<40 IU/L) and undetectable serum HBV DNA (<100 copies/mL in real-time PCR), while 32 (53.4%) patients had ALT levels above laboratory normal values and detectable serum HBV DNA. Genotype distribution was as follow: genotype E, 16 (50%), genotype D, 9 (28.1%), genotype A, 7 (21.9%). Our study evidences a moderate prevalence of HBV-infection in immigrants, particularly in sub-Saharan African people, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus, potentially characterized by a different natural history and, possibly, a different response to antiviral treatment.
{ "pile_set_name": "PubMed Abstracts" }
Vaginal birth after cesarean: a meta-analysis of indicators for success. The cesarean birth rate has continued to climb despite efforts to counteract this trend. A major reason for this rise is the practice of doing an elective repeat cesarean. Our study used a statistical model of meta-analysis to analyze the findings of 29 individual studies that looked at the association between the success of a trial of labor and various preexisting conditions. We hypothesized that various preexisting factors, including cephalopelvic disproportion, previous breech, previous vaginal delivery, more than one previous cesarean, use of oxytocin, and the length of labor and extent of dilatation in the previous cesarean, would affect the prediction of the outcome of a trial of labor. After determining odds ratios for the individual preexisting factors from the individual studies, we calculated overall odds ratios which incorporated the findings from all of the studies. For previous cephalopelvic disproportion, the odds were 0.5 for a successful trial of labor; for prior breech, 2.1; for women with a previous vaginal delivery, 2.1; for women who had had more than one cesarean, 0.7; and for women receiving oxytocin, 0.3. We were unable to analyze other preexisting factors because the data were not available, but short discussions of some of these other factors are offered. Even though the success rates do vary with the different preexisting factors, the clinician may anticipate a greater than 50% chance for success in any individual labor.
{ "pile_set_name": "PubMed Abstracts" }
Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. The purpose of this study was to determine the prevalence, cause, severity, and patterns of associated injuries of limb peripheral nerve injuries sustained by patients with multiple injuries seen at a regional Level 1 trauma center. Patients sustaining injuries to the radial, median, ulnar, sciatic, femoral, peroneal, or tibial nerves were identified using a prospectively collected computerized database, maintained by Sunnybrook Health Science Centre, and a detailed chart review was undertaken. From a trauma population of 5,777 patients treated between January 1, 1986, and November 30, 1996, 162 patients were identified as having an injury to at least one of the peripheral nerves of interest, yielding a prevalence of 2.8%. These 162 patients sustained a total of 200 peripheral nerve injuries, 121 of which were in the upper extremity. The mean patient age was 34.6 years (SEM +/- 1.1 year), and 83% of patients were male. The mean injury severity score was 23.1 (+/-0.90), and the mean length of hospital stay was 28 days (+/-1.8). Motor vehicles crashes predominated (46%) as the cause of injury. The most frequently injured nerve was the radial nerve (58 injuries), and in the lower limb, the peroneal nerve was most commonly injured (39 injuries). Diagnosis of a peripheral nerve injury was made within 4 days of admission to Sunnybrook Health Science Centre in 78% of the cases. Surgery was required to treat 54% of patients. Head injuries were the most common associated injury, occurring in 60% of patients. Other common associated injuries included fractures and dislocations. The present report aims to aid in identification and treatment of peripheral nerve injuries.
{ "pile_set_name": "PubMed Abstracts" }
Single and multiple administration of a new triphasic oral contraceptive to women: pharmacokinetics of ethinyl estradiol and free and total testosterone levels in serum. Ethinyl estradiol is part of almost every combined oral contraceptive, and its pharmacokinetic characteristics have been thoroughly investigated in numerous studies. However, little is known about its pharmacokinetics during long-term administration, as compared with single-dose administration. In this study 10 women received a triphasic formulation that contained ethinyl estradiol together with the progestin gestodene over one treatment cycle. Mean area under the curve values of ethinyl estradiol were significantly higher on the last treatment day, as compared with the corresponding values obtained from the same women after single-dose administration. However, the observed increase in area under the curve was within the range of pharmacokinetic accumulation, to be expected on the basis of dosing interval and terminal half-life. Another point of interest was the effect of the triphasic preparation on testosterone concentrations in serum. Both total and free testosterone levels were suppressed by about 60% as compared with pretreatment values, and there was no correlation with corresponding sex hormone-binding globulin levels in the serum.
{ "pile_set_name": "PubMed Abstracts" }
A procedure to study unscheduled DNA synthesis in rat spermatogenic cells in vivo: strain differences between Fisher-344 and Sprague-Dawley rats. A liquid scintillation counting (LSC) procedure was used to study unscheduled DNA synthesis (UDS) in pachytene spermatocytes and spermatids from Fisher-344 (F344) and Sprague-Dawley (SPD) rats treated with methyl methanesulfonate (MMS). MMS induced a large, dose-dependent, UDS response in pachytene spermatocytes from both rat strains. On average, F344 pachytene spermatocytes showed a larger UDS response than those of SPD rats. The lowest dose of MMS that elicited a significant UDS response was 1 mg/kg in F344 rats but 5 mg/kg in SPD rats. Early spermatid stages from F344 rats also showed a larger UDS response than those from SPD rats. The time interval at which spermatid stages showed the maximum UDS response was between 20 and 24 days after MMS treatment. It is concluded that UDS can be measured quantitatively in rat spermatogenic cells in vivo by using the LSC procedure.
{ "pile_set_name": "PubMed Abstracts" }
The effect of chronic diazepam treatment on discrimination performance and 3H-flunitrazepam binding in the brains of shocked and nonshocked rats. The purpose of the present study was: (1) to investigate the effects of unavoidable shock on an appetitively motivated discrimination task; (2) to evaluate the effect of chronic diazepam treatment on the performance of a previously learned discrimination task in shocked and nonshocked animals; (3) to measure the binding of 3H-flunitrazepam (an analogue of diazepam) to selected brain regions of chronically diazepam-treated shocked and nonshocked rats, in comparison to saline-treated controls. Results indicated that unavoidable shock significantly interfered with the learning of a new, nonshock-related discrimination task. The effect of chronic diazepam treatment on the performance depended on the previous experience of the animal; chronic diazepam treatment significantly improved the maze performance of shocked animals. On the other hand, chronic diazepam treatment in the nonshocked animals tended to interfere with the performance of the discrimination task. Neurochemical data showed significant reduction in 3H-flunitrazepam binding to diazepam receptors in membranes from the brains of a nonshocked diazepam-treated (CD) group in comparison to a nonshocked saline-treated (CS) group. In contrast, the unavoidable shock-treated diazepam group (SD) showed opposite effects, the binding of 3H-flunitrazepam increasing significantly. A significant increase in the maximal binding sites in the frontal cortex from shocked rats treated with diazepam, compared to the nonshocked diazepam-treated rats, was detected by Scatchard analysis.
{ "pile_set_name": "PubMed Abstracts" }
Clinical observation on the effects of Bo's abdominal acupuncture in 40 cases of chronic fatigue syndrome. To observe the curative effect of Bo's abdominal acupuncture on chronic fatigue syndrome (CFS). Forty cases with CFS were treated by Bo's abdominal acupuncture at the points for conducting qi back to its origin and 4 points on the abdomen once a day for 2 weeks. Scores for symptoms and scores for fatigue questionnaires were compared before and after treatment. After treatment, the clinical symptoms of patients were differently alleviated, and scores for symptoms, mental condition and neural feeling in questionnaires on fatigue were obviously reduced (P<0.01-0.05). Bo's abdominal acupuncture has a good curative effect on general disease with complex symptoms, especially on lassitude, anorexia, insomnia, amnesia, diarrhea, and general pain.
{ "pile_set_name": "PubMed Abstracts" }