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PDT experience in Brazil: A regional profile.
The success of PDT and its establishment into the existent hall of therapeutic modalities depends on the collection of reported experiences from around the world. In that sense, it is important to report approaches taken by different countries and what their views are on the future of PDT. Following this idea, we present our clinical experience in photodynamic therapy (PDT) in Brazil, as well as the experimental advances coming up in parallel with clinical implementation. This report is a consequence of pioneering work in a collaborative program involving the Physics Institute in São Carlos, São Paulo State (SP), Brazil, the Medical School of the University of São Paulo, Ribeirão Preto, SP, Brazil and the Cancer Hospital Amaral Carvalho, Jaú, SP, Brazil. This collaborative program, begun in 1997, with the first patient treated in 1999, has treated over 400 patients by late 2004. About 80% of lesions were located in the head and neck or skin, but experience is being built in esophagus, bladder, gynecology, and cutaneous recurrence of breast cancer, among others. The overall results have shown to be compatible with previously reported data. Modifications, whose goal is to improve patient benefit and optimize results, are being implemented as we gain experience. In parallel with the clinical development, several laboratories have started studying experimental whose purpose is to analyze the clinical results and to contribute to the worldwide effort to bring PDT to the forefront of therapies offered to patients. We present the overall results of our 5 years experience as well as the whole implementation process. | {
"pile_set_name": "PubMed Abstracts"
} |
Good communication.
We are writing to draw senior nurses' attention to the latest report published by the National Confidential Enquiry into Patient Outcome and Death. | {
"pile_set_name": "PubMed Abstracts"
} |
Primary hyperparathyroidism diagnosed at autopsy. A study of eight cases.
This paper describes the clinical and pathological findings of eight cases of primary hyperparathyroidism first diagnosed at autopsy. The eight cases were obtained from the autopsy files of the Western General Hospital, Edinburgh over a decade (1971-80). The duration of the final hospital admission was very short in the majority of cases but analysis of the clinical history, in which gastro-intestinal and neuro-psychiatric disturbances figured prominently, showed that symptoms of the disease may have been present for very much longer--perhaps years in some instances. Details of the main autopsy findings and cause of death are also presented. | {
"pile_set_name": "PubMed Abstracts"
} |
[Prevalence and role of psychiatric disorders in disability].
Common risk factors for the receipt of disability income (DI) are psychiatric diagnosis at the time of conscription, showing low personal responsibility and job satisfication, unemployment after graduation, low rating on an "IQ" test, low educational level, part-time employment, isolation, separation, smoking, problem drinking, poor subjective state of health and well-being. Psychiatric diagnoses are considered to be the main reason for disability income in women and rank third in men. With average retirement age of 39 for males and 42 for females, schizophrenia is the most important single reason for early retirement before age 40. Major depression has been shown to be the fourth leading cause of DI worldwide. Personality disorders, which display primarily antisocial, histrionic, emotionally unstable and narcissistic behaviour (Cluster B personality disorders) have been associated with an earlier age of work disability, and borderline personality has been associated with failure to return to work. A dependent, schizoid, paranoid and antisocial personality tends to be associated with an increased risk of developing disability. A subtype of adaptation disorder that is characterised primarily by lasting embitterment after exceptional life events, which violate basic beliefs, namely post-traumatic embitterment disorder, shows up highly the development of DI. However, most of the patients applying for a DI have neither been sufficiently diagnosed nor received adequate psychiatric and/or psychotherapeutic treatment when they claim on their DI policy. Thus, the prognosis of the diseases listed above could well be improved at least for some patients depending on their disease (10-80 %). | {
"pile_set_name": "PubMed Abstracts"
} |
Existential and psychopathological evaluation of group psychotherapy of neurotic and psychotic patients.
General problems in researching group psychotherapy are reviewed, especially for those with similar theoretical and methodological approaches. The sample consisted of 100 subjects, 26 of whom were neurotic and 24 of whom were psychotic. They were treated in small groups, headed by the author (the experimental group). An equal number and the same categories of patient attended control psychiatric sessions (the control group). All subjects were tested twice. With three instruments: the semantic differential (with twelve existential categories, five general therapy, and three ego psychology categories), the Kotchen test, and MMPI (midiform). A discriminative analysis of tests and the repeated test data, statistically significant, revealed experiential changes in existential categories, such as "Freedom," "Sex," and "Love" amongst psychotics; and in the case of both psychotic and neurotic patients, treated in groups and compared with the controls, such categories as "Understanding among people." With the help of MMPI, a statistically significant reduction of hysteria in neurotic subjects was established, as well as the preventive effects of group psychotherapy regarding the emergence of psychopathy in psychotic patients. Correlation calculations indicated a greater discrimination in the perception of changes using existential categories in the experiencing of psychotic and depressive patients. Finally, the results obtained are discussed from the viewpoints of clinical experience, results obtained in similar research studies, and unanswered questions resulting from such research. | {
"pile_set_name": "PubMed Abstracts"
} |
Prospective studies on a lithium cohort. 2. Renal function. Water and electrolyte metabolism.
A cohort of manic-depressive patients given prophylactic lithium treatment were examined before treatment started and at intervals during treatment for up to 7 years. The mean lithium dosage was 23.2 mmol/d and the mean serum lithium concentration 0.68 mmol/l. The treatment did not affect glomerulus function. Urine volume rose by 10-20% and renal concentrating ability fell by 7-10% during the treatment. These changes were markedly smaller than those found in patients treated previously with higher lithium doses and serum lithium concentrations. High urine volumes and low renal concentrating abilities were not more frequent during than before lithium treatment. Complaints of increased thirst, frequent urination, and nycturia were presented more often during than before lithium treatment. Serum concentrations, urinary excretions and renal clearances of sodium and potassium were not altered by the treatment. | {
"pile_set_name": "PubMed Abstracts"
} |
Bacterial pneumonia in the elderly.
A retrospective study was made of patients having community-acquired pneumonia and treated at a large municipal hospital in 1973. Patients from nursing homes or other paramedical facilities were excluded. The incidence of Gram-negative bacillary pneumonia was significantly higher in elderly patients compared to two younger groups, and mortality from this type of pneumonia was higher than from pneumococcal or staphylococcal types or from pneumonia of unknown cause. Recommendations are made for the initial treatment of elderly patients with community-acquired pneumonia. | {
"pile_set_name": "PubMed Abstracts"
} |
Intracellular expression of Vitreoscilla haemoglobin improves lipid production in Yarrowia lipolytica.
Genetic modification by overexpressing Vitreoscilla haemoglobin (VHb) is an efficient and economic method for improving O2 utilization for microbial fermentation. In this study, VHb was expressed in oleaginous yeast, Yarrowia lipolytica, and its effect on lipid accumulation was analysed. During fermentation, the dissolved oxygen (DO) concentration was controlled at 5, 10, 20 and 30 of full O2 saturation and also uncontrolled by varying the stirring speed and aeration rate. Yarrowia lipolytica harbouring the VHb gene (VHb+ strain) displayed more pseudomycelium than the control strain (VHb- strain), and VHb expression also enhanced the cell density. When DO level was controlled at 30%, the biomass of VHb+ strains reached about 19 g l-1 and increased by 27% compared to VHb- strains. Total fatty acid contents, although, were higher in VHb+ strains than in VHb- strains under all DO levels, and maximally increased by c. 40% (from 10·5 to 14·5% of the biomass) when the DO concentration was controlled at 30%. VHb overexpression, however, markedly suppressed citrate secretion. In addition, expression of VHb also induced significant changes in fatty acid composition and increased the oleic acid content. SIGNIFICANCE AND IMPACT OF THE STUDY: Genetic modification by overexpressing Vitreoscilla haemoglobin (VHb) is an efficient and economic method for improving O2 utilization for microbial fermentation. In this study, VHb was expressed in Yarrowia lipolytica, which is a most attractive model for microbial oil production because of its excellent lipid accumulation capacity and convenient genetic tools. Expression of VHb resulted in lipid accumulation increased and cell morphology shift, however, markedly suppressed citrate secretion. This study provided the new strategy for fermentation technology to improve lipid production in oleaginous micro-organisms. | {
"pile_set_name": "PubMed Abstracts"
} |
Preventing nosocomial pneumonia: state of the art and perspectives for the 1990s.
In the 1980s, nosocomial pneumonia became the second most common nosocomial infection in the United States. Gram-negative bacilli and Staphylococcus aureus were the most frequently isolated bacteria. Methods to improve the diagnostic sensitivity and specificity included transtracheal aspirates and bronchoscopy with protected specimen brush or bronchoalveolar lavage. Multivariate analysis was used to identify independent risk factors for pneumonia and fatality in different subsets of high-risk patients. Gastric pH and colonization were evaluated as risk factors for pneumonia in mechanically ventilated patients. Colonized respiratory therapy equipment and contaminated tubing condensate and in-line medication nebulizers were suggested as possible sources of nosocomial pathogens. Staff education programs, the use of barrier precautions, and selective decontamination of the digestive tract were associated with reduced rates of lower respiratory tract infection. Despite a decade of progress in our understanding of nosocomial pneumonia, progress in the 1990s will undoubtedly include molecular epidemiologic techniques, appropriate application of risk factor data, and the use of new methods for the diagnosis of pneumonia. Prevention strategies should focus on more effective infection control techniques, improved invasive devices/equipment, and the judicious use of antibiotics for treatment and prophylaxis. | {
"pile_set_name": "PubMed Abstracts"
} |
[Advanced in studies on anxiolytic effects of natural flavonoids].
Anxiety is one of the most common diseases endangering human health. Its pathogenesis is complex, the studies on the mechanisms of anxiety disorder are concentrated on neurotransmitter, neuroendocrine, immunologic system. Flavonoids are a kind of compounds which possess a variety of physiological activity, used in plenty of diseases. In recent years, researches of natural flavonoids on anti-anxiety were increasing, but contents were incomplete. It was just involved several neurotransmitters in research area. This paper is based on different anxiolytic effect mechanisms and structure-activity relationships of natural flavonoids, summarizing the researches of domestic and foreign, which can serve as a reference for further studies on anxiolytic effects of natural flavonoids. | {
"pile_set_name": "PubMed Abstracts"
} |
Causes of death after blunt chest injury.
During the 10 years from 1968 a total of 1119 patients with chest and associated injuries were admitted to the Royal Newcastle Hospital (RNH); 530 of these needed ICU treatment and fifty-nine died. Common causes of death included irreparable associated injuries to brain and exsanguination due to major vessel injury. However, the commonest cause encountered was refractory respiratory failure due to pulmonary sepsis. This condition was associated with hypovolaemic shock, intra-abdominal injuries, failure of conservative treatment and injuries in the older age groups. | {
"pile_set_name": "PubMed Abstracts"
} |
The measurement of stress-inducing life events and life styles: questions of conceptual independence and discriminant validity.
Research on psycho-social sources of coronary heart disease (CHD) has focused on two basic ideas: on the one hand that CHD is the result of the accumulation of stress-inducing events and, on the other hand, that CHD stems from the way in which individuals live their lives and respond to events that do occur. While it is relatively easy to separate these ideas at the conceptual level, the research reported here indicates that the two most prominent operationalizations of life situation and life style share some degree of commonality in their domains. Specifically, a comparison of the responses of 205 individuals indicate that variations in scores on the Jenkins Activity Survey are associated with variations in scores on subjective but not objective items on the Recent Life Changes Questionnaire. The implications of these results for the study of psycho-social factors in CHD are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Purification and characterization of two serine protease inhibitors from the hemolymph of Mythimna unipuncta.
Two serine protease inhibitors, trypsin inhibitor and alpha-chymotrypsin inhibitor, were isolated from the hemolymph of Mythimna unipuncta. Mythimna trypsin and alpha-chymotrypsin inhibitors were purified by gel filtration and anion-exchange chromatography. They displayed molecular masses of 52 kDa and 43 kDa, respectively, as determined by electrophoresis under reducing and non-reducing conditions on denaturing polyacrylamide gels. Their isoelectric points were evaluated by isoelectric focusing and two-dimensional electrophoresis. Their N-terminal sequences have been analyzed as APSDTTIAETLTITEEFFPD and FDESFGFQGPSTYEKTPLGEP, respectively. The role of these inhibitors in the regulation of the defense reaction of the insect is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Simple and efficient immobilization of lipase B from Candida antarctica on porous styrene-divinylbenzene beads.
Two commercial porous styrene-divinylbenzene beads (Diaion HP20LX and MCI GEL CHP20P) have been evaluated as supports to immobilize lipase B from Candida antarctica (CALB). MCI GEL CHP20P rapidly immobilized the enzyme, permitting a very high loading capacity: around 110mgCALB/wetg of support compared to the 50mg obtained using decaoctyl Sepabeads. Although enzyme specificity of the enzyme immobilized on different supports was quite altered by the support used in the immobilization, specific activity of the enzyme immobilized on MCI GEL CHP20P was always higher than those found using decaoctyl Sepabeads for all assayed substrates. Thus, a CALB biocatalyst having 3-8 folds (depending on the substrate) higher activity/wet gram of support than the commercial Novozym 435 was obtained. Half-live of CAL-Diaion HP20LX at 60°C was 2-3 higher than the one of Novozym 435, it was 30-40 higher in the presence of 50% acetonitrile and it was around 100 folds greater in the presence of 10M hydrogen peroxide. Results indicate that styrene-divinylbenzene supports may be promising alternatives as supports to immobilize CALB. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of Cinnamomum zeylanicum on third stage larvae and adult fecundity of Musca domestica and Anopheles pharoensis.
The insecticidal activity of Cinnamomum zeylanicum against the larval maturation and adult emergency of Anopheles pharoensis and Musca domestica 3rd stage was evaluated under controlled laboratory conditions. A. pharoensis with concentrations (conc.) of 100%, 70%, 50%, 25%, 5%, 2%, 1%, 0.9%, 0.7% & 0.5% showed 100% larval mortality. Conc. of 0.3%, 0.2% & 0.1% caused mortality of 77.8%, 44.4% & 33.3% respectively. The fecundity of emerged adults was 0%, 60% & 50%. In M. domestica the conc. from 50%-100% completely killed the larvae. Conc. of 25%, 5%, 2% & 1% caused mortality of 88.9%, 55.6%, 33.3% & 22.2% respectively. Less conc. of C. zeylanicum was not tested. The fecundity of the emerged adults was 0%, 66.7%, 66.7% & 83.3%. Only one control larva died and the nine emerged adults were fertile in the two cases. | {
"pile_set_name": "PubMed Abstracts"
} |
Health and nutrition effects of cash crop production in developing countries: a comparative analysis.
The paper presents results of a comparative analysis of the health and nutritional effects of cash crop production in 6 countries--The Gambia, Guatemala, Kenya, Malawi, the Philippines, and Rwanda. The 6 country case studies were conducted during the same time period and used a similar, although not identical, research protocol. Participation in cash crop schemes resulted in increases in household income. Short-term increases in household income did not result in a decrease in the incidence of illness in preschool-aged children nor in the total time that preschoolers were ill. Increases in household income did result in increases in the preschooler's energy consumption; however, the income/calorie consumption links, although significant, were weak. The household income gains did not have an immediate or large impact on preschooler nutritional status. While, in the longer term, increases in income may bring about improvements in preschooler health, in the short term, it appears that increases in income must be accompanied by improvements in the health environment in order to have a significant effect in reducing preschooler morbidity and improving child nutritional status. | {
"pile_set_name": "PubMed Abstracts"
} |
[Use of nitrates in hypertension. Cardiac and peripheral effects before and during antihypertensive therapy at rest and during stress].
The acute effects of 1.6 mg glycerol trinitrate (2 x 0.8 mg) on the hemodynamic function were compared in 11 healthy subjects and 25 hypertensive patients (WHO stages I and II), at rest and during exercise. The nitrate testing was performed before the beginning of antihypertensive treatment, during nonmedical therapy, as well as under additional oral therapy with diisopropylamin. Right-heart-catheterization, echocardiography, radionuclide-ventriculography and venous occlusion plethysmography were performed. Nitroglycerin consistently led to a reduction of blood pressure in the systemic and pulmonary circulation both at rest and during exercise. There was a small decrease of peripheral arterial resistance (TPR) at rest and a more pronounced decrease of pulmonary arteriolar resistance (PAR) at rest and during exercise. The documented effects may be important with regard to combined antihypertensive treatment. In addition, the application of nitrates in hypertensive crises may be useful. | {
"pile_set_name": "PubMed Abstracts"
} |
Traumatogenicity: effects of self-reported noncombat trauma on MMPIs of male Vietnam combat and noncombat veterans treated for substance abuse.
A recent review of the literature on Post-Traumatic Stress Disorder (PTSD) and the MMPI has shown that all previously published studies have been limited to clinical groups whose trauma occurred in Vietnam combat. The purpose of this study was to test hypotheses that predict higher MMPI and PTSD scale scores among combat veterans who differ in degrees of noncombat traumas. Results support predictions. Those who reported more noncombat traumas attain significantly higher MMPI scores for scales F, Hypochondriasis, Hysteria, Psychopathic Deviate, Psychasthenia, Schizophrenia, Mania, Social Introversion, and an MMPI PTSD score (Keane, Malloy, & Fairbank, 1984). Moreover, noncombat effects are manifested differentially: Combat veterans with higher noncombat trauma evidence greater social withdrawal, whereas noncombat veterans who report higher noncombat trauma are characterized by higher anxiety. MMPI elevations were progressively higher as groups increased in degrees of combat and noncombat trauma: noncombat and low combat trauma veterans were the better adjusted, and combat veterans with higher noncombat trauma were the worst adjusted. Results provide descriptive validity for PTSD as a construct and underscore the importance of assessing frequency and intensity, as well as types of traumas and stresses, in the background histories of substance abusers and other clinical groups as well. | {
"pile_set_name": "PubMed Abstracts"
} |
Total mesorectal excision with radiofrequency in rectal cancer: open versus laparoscopy approach.
The aim of this study was to compare the safety, efficacy and oncologic results in the low rectal resection with total mesorectal excision with radiofrequency (Ligasure™, Covidien, Boulder, CO, USA) in laparoscopic surgery. From July 2005 to December 2008, 227 patients underwent colorectal resection for cancer at S. Martino Hospital in Genoa. Sixty-one patients underwent curative rectal resection for mid or low rectal cancer using Ligasure™ device applied on smaller vessels and for the execution of total mesorectal excision. Forty-six patients underwent open laparotomy (OL), 15 laparoscopic surgery. There were no differences concerning demographics data and diagnosis, but only regarding staging (P=0.009). Primary goal was to evaluate major complications, operating time, hospital stay, distal margin of the tumor and number of nodes harvested in specimen. Secondary goal was to assess the average time of survival in the short period. The mean operative times were shorter in the OL group (188 vs. 246 min) overall. This difference was significant (P=0.004). In particular two parameters of specimens were analyzed: the total number of nodes and distal clearing from cancer, excluding abdominoperineal resection. An average number of 16.6 nodes in the OL group and 13.9 in the VL group (P=ns) were detected; mean distal clearing in the OL group was 30.7 mm and 48.1 mm in the VL group (P=ns). There were no differences concerning major complications in either group. The hospital stay in the VL group was shorter than in the OL group, but the differences were not significant. The Ligasure™ device does not reduce operating time in laparoscopy rectal cancer resection but it allows to get correct oncologic results in patients submitted to total mesorectal excision. | {
"pile_set_name": "PubMed Abstracts"
} |
Human thyroxine absorption: age effects and methodological analyses.
Experience with the use of simultaneous oral and iv radioiodine tracers of thyroxine (T4) to measure T4 absorption was reviewed to determine the effect of advanced age on T4 absorption and to search for acceptable simplifications in the measurement methodology. (1) Age effect: In control subjects, T4 absorption did not differ with age between 21 and 69 years; it averaged 62.8 +/- 13.5% (SD) in subjects over age 70 compared with 69.3 +/- 11.9% in subjects aged 21-69 (p < 0.001). We conclude that, because of this small but significant reduction in T4 absorption efficiency in the elderly, it is especially important to monitor individual response to replacement T4 doses in this age group. (2) Methodology studies: Intrasubject coefficient of variation for T4 absorption in triplicate studies averaged 8.9%, when an identical method was used at weekly intervals (n = 3). When the 3 studies were done by 3 separate methods (sequential po and i.v. 123I-labeled T4, sequential 125I-labeled T4 po and i.v., and simultaneous po and i.v. doses of different tracers), the intrasubject coefficient of variation averaged 9.8% (n = 8). When the absorption calculation used only one serum sample, taken after isotopic equilibrium was achieved at 24 h [the double isotope (eq) method], calculated T4 absorption differed little from that calculated in the same subjects using a full serum time-activity curve and a noncompartmental analysis [the double isotope (AUC) method]. Compared with a compartmental model solution, both methods slightly overestimated T4 absorption. In 4 subjects given i.v. radioiodide as a third tracer at the same time demonstrated that, as long as radioiodide contamination of the T4 tracers is measured and accounted for in the standards, contaminating radioiodide has no clinically significant effect on T4 absorption measurements. When an oral tracer of T4 was considered alone, without an i.v. tracer to correct for T4 metabolism, the estimates of T4 absorption correlated in a curvilinear fashion with T4 absorption as measured by the double isotope method. Except at very low absorption levels, the oral tracer alone is a poor predictor of T4 absorption. We conclude that, when using a double isotope method to measure T4 absorption, it is acceptable to rely on a single serum sample taken at 24 h, a time when isotopic equilibrium between the two tracers has been reached.(ABSTRACT TRUNCATED AT 400 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Successful liver transplantation in a patient with a thrombosed portomesenteric system after multiple failed shunts.
Combined portal and mesenteric vein thrombosis preventing restoration of adequate portal venous flow has been considered a contraindication to liver transplantation. We report a patient with failed splenorenal (SR), portocaval (PC), and mesocaval (MC) shunts, who despite the absence of any obvious means for supplying portal venous inflow to a hepatic graft, successfully underwent orthotopic liver transplantation. A method of reconstruction of the portal vein with the use of vein grafts anastomosed to a large splanchnic venous collateral is described. This technique can be used in selected patients in whom orthotopic liver transplantation might otherwise be considered technically impossible. | {
"pile_set_name": "PubMed Abstracts"
} |
Atomic force microscopy studies of a floating-bilayer lipid membrane on a Au(111) surface modified with a hydrophilic monolayer.
The surface of a gold electrode was functionalized with a hydrophilic monolayer of 1-thio-β-D-glucose formed by spontaneous self-assembly. The Langmuir-Blodgett/Langmuir-Schaefer (LB/LS) method was then used to assemble a bilayer onto the modified Au(111) surface. The bilayer lipid membrane (BLM) was separated from the Au(111) electrode surface by incorporating the monosialoganglioside GM1 into the inner leaflet of a bilayer composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol. To make the inner leaflet, monolayers of GM1/DMPC/cholesterol with mole ratios of 1:6:3, 2:5:3, and 3:4:3 were used. The outer leaflet was composed of a 7:3 mole ratio of DMPC/cholesterol. Because of the amphiphilic properties of GM1, the hydrophobic acyl chains were incorporated into the BLM, whereas the large hydrophilic carbohydrate headgroups were physically adsorbed to the Au(111) electrode surface, creating a "floating" BLM (fBLM). This model contained a water-rich reservoir between the BLM and the gold surface. In addition, because of the bilayer being physically adsorbed onto the support, the fluidity of the BLM was maintained. The compression isotherms were measured at the air/water interface to determine the phase behavior and optimal transfer conditions. The images acquired using atomic force microscopy (AFM) and the force-distance measurements showed that the structure of the fBLM evolved with increasing GM1 content from 10 to 30 mol %, undergoing a transition from a corrugated to a homogeneous phase. This change was associated with a significant increase in bilayer thickness (from ∼5.3 to 7.3 nm). The highest-quality fBLM was produced with 30 mol % GM1. | {
"pile_set_name": "PubMed Abstracts"
} |
Traffic of interacting ribosomes: effects of single-machine mechanochemistry on protein synthesis.
Many ribosomes simultaneously move on the same messenger RNA (mRNA), each synthesizing separately a copy of the same protein. In contrast to the earlier models, here we develop a "unified" theoretical model that not only incorporates the mutual exclusions of the interacting ribosomes, but also describes explicitly the mechanochemistry of each of these macromolecular machines during protein synthesis. Using analytical and numerical techniques of nonequilibrium statistical mechanics, we analyze the rates of protein synthesis and the spatiotemporal organization of the ribosomes in this model. We also predict how these properties would change with the changes in the rates of the various chemomechanical processes in each ribosome. Finally, we illustrate the power of this model by making experimentally testable predictions on the rates of protein synthesis and the density profiles of the ribosomes on some mRNAs in E-coli. | {
"pile_set_name": "PubMed Abstracts"
} |
Biology and treatment of chronic lymphocytic leukemia.
Major advances have occurred in our understanding of the biology, immunology, and opportunities for treatment of chronic lymphocytic leukemia (CLL) in recent times. Surface antigen analysis has helped us define classical CLL and differentiate it from variants such as marginal zone leukemia, mantle cell leukemia, and prolymphocytic leukemia. An important observation has been that the B-cells in indolent types of CLL, which do not require therapy, have undergone somatic hypermutation and function as memory B-lymphocytes whereas those more likely to progress have not undergone this process. Section I by Dr. Nicholas Chiorazzi encompasses emerging elements of the new biology of CLL and will address the types of somatic hypermutation that occur in CLL cells and their correlation with other parameters such as telomere length and ZAP70 status. In addition he addresses the concept of which cells are proliferating in CLL and how we can quantitate the proliferative thrust using novel methods. The interaction between these parameters is also explored. Section II by Dr. Thomas Kipps focuses on immune biology and immunotherapy of CLL and discusses new animal models in CLL, which can be exploited to increase understanding of the disease and create new opportunities for testing the interaction of the CLL cells with a variety of elements of the immune system. It is obvious that immunotherapy is emerging as a major therapeutic modality in chronic lymphocytic leukemia. Dr. Kipps addresses the present understanding of the immune status of CLL and the role of passive immunotherapy with monoclonal antibodies such as rituximab, alemtuzumab, and emerging new antibodies. In addition the interaction between the CLL cells and the immune system, which has been exploited in gene therapy with transfection of CLL cells by CD40 ligand, is discussed. In Section III, Dr. Michael Keating examines the question "Do we have the tools to cure CLL?" and focuses on the fact that we now have three distinct modalities, which are able to achieve high quality remissions with polymerase chain reaction (PCR) negativity for the immunoglobulin heavy chain in CLL. These modalities include initial chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, the use of alemtuzumab for marrow cytoreduction in minimal residual disease and allogeneic bone marrow transplants. The emergence of non-ablative marrow transplants in CLL has led to the broadening of the range of opportunities to treat older patients. The addition of rituximab to the chemotherapy preparative regimens appears to be a significant advance. The combination of our increased understanding of the biology, immune status, and therapy of CLL provides for the first time the opportunity for curative strategies. | {
"pile_set_name": "PubMed Abstracts"
} |
HLA-G functions as a restriction element and a transplantation antigen in mice.
HLA-G, a human MHC class I molecule expressed on the trophoblast during pregnancy, was expressed in transgenic mice by recombining the HLA-G gene with a transcriptional promoter from a murine H-2 MHC class I gene. Skin grafts from HLA-G transgenic mice were rejected by non-transgenic mice showing that HLA-G behaves as a xenotransplantation antigen in mice. Further investigation revealed that murine T cells recognize native HLA-G directly as a xenoantigen or they recognize processed peptides derived from HLA-G presented in the context of murine MHC molecules. HLA-G molecules also function as restriction elements capable of presenting peptides to murine T cells since immunization of HLA-G transgenic mice with peptide that binds specifically to HLA-G molecules elicited HLA-G-restricted, cytotoxic T cell responses. In addition, murine T cell responses to human xenoantigens are enhanced when responder cells originated from HLA-G transgenic mice. Based on these observations, we conclude that expression of HLA-G molecules influences selection of the murine T cell repertoire and that HLA-G exhibits immunological properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice. Thus, any unique immunological functions mediated by HLA-G must arise from the distinctive, trophoblast-specific pattern of HLA-G expression in humans and not from structural peculiarities of HLA-G molecules. | {
"pile_set_name": "PubMed Abstracts"
} |
Single-center review of fluoroscopy-guided percutaneous nephrostomy performed by urologic surgeons.
To review the success rate and complications of radiologically guided percutaneous nephrostomies (PCNs) performed by urologists and compare the complication rates with the standards recommended by the Society of Interventional Radiology (SIR) and the American College of Radiology (ACR). From January 1996 to December 2005, 667 patients had 765 PCNs performed by three urologists, with 74 patients having simultaneous bilateral PCNs. The mean age of the patients was 29 years (range 8 months-95 years). The medical records were reviewed for underlying diseases, success rate, and complications of PCN; and the results were assessed in comparison with recommendations made by SIR and ACR. The PCN was successful in 742 renal units (97%). A total of 26 of the 667 patients (3.89%) had major complications: 12 (1.79%) had sepsis, 10 (1.49%) had hemorrhage sufficient to necessitate transfusion, 1 (0.14%) had pleural injury that was managed conservatively, and another patient had a vascular complication necessitating nephrectomy. None of the patients had bowel transgression. Minor complications occurred in 61 patients (9.1%): urinary-tract infection in 17, PCN tube dislodgement in 11, catheter obstruction by clot or debris in 12, urine leakage around the PCN site in 8, and loss of the PCN catheter in 13. Percutaneous nephrostomy is a relatively safe, minimally invasive, and effective procedure with a low rate of morbidity. Our overall results in term of success rate and major complications are within the threshold limits set by the SIR and ACR. Hence, trained urologists can produce results similar to those of interventional radiologists. Learning of PCN should be mandatory in the training curriculum for all urology residents. | {
"pile_set_name": "PubMed Abstracts"
} |
Opposite ability of pre-TCR and alpha beta TCR to induce apoptosis.
In early CD4(-)CD8(-) pro-thymocytes, signaling through the pre-TCR is crucial for survival and differentiation into CD4(+)CD8(+) cells. At this more mature stage, interactions between alphabetaTCR and self-Ag/MHC complexes in turn lead either to cell survival and differentiation (positive selection) or to cell death (negative selection). Intrinsic differences must therefore exist between pre-TCR signals in CD4(-)CD8(-) thymocytes and alphabetaTCR signals in CD4(+)CD8(+) cells, since only the latter can mediate a death signal. In this work, we directly compared the capability of pre-TCR and alphabetaTCR to induce apoptosis in a CD4(-)CD8(-) thymoma cell line following receptor cross-linking with mAbs. Cross-linking of alphabetaTCR triggered high levels of programmed cell death, mimicking the negative selection signal usually induced in CD4(+)CD8(+) thymocytes. In contrast, pre-TCR was very inefficient at inducing apoptosis upon cross-linking, despite similar levels of surface receptor expression. Importantly, inefficient apoptosis induction by the pre-TCR did not result from its weak association with TCRzeta chain, since TCRs containing alpha-pTalpha chimeric chains, binding weakly to TCRzeta, were still able to induce apoptosis. Although similar tyrosine phosphorylation and calcium influx were induced after either pre-TCR or alphabetaTCR cross-linking, the two pathways diverged at the level of Fas ligand induction. Among putative transcription factors involved in Fas ligand mRNA induction, Nur77 and NFAT transcriptional activities were readily induced after alphabetaTCR, but not pre-TCR, stimulation. Together, these results support the view that the structure of the pre-TCR and alphabetaTCR directly influences their apoptosis-inducing capabilities by activating distinct signaling pathways. | {
"pile_set_name": "PubMed Abstracts"
} |
Fxralpha gene is a target gene of hCG signaling pathway and represses hCG induced steroidogenesis.
The bile acid receptor Farnesoid-X-Receptor alpha (FXRα), a member of the nuclear receptor superfamily, is well known for its roles in the enterohepatic tract. In addition, FXRα regulates testicular physiology through the control of both endocrine and exocrine functions. The endocrine function of the Leydig cells is mainly controlled by the hypothalamo-pituitary axis viaLH/chorionic gonadotropin (CG). If FXRα was demonstrated to control the expression of the Lhcgr gene, encoding the LH receptor; the impact of the LH/CG signaling on the Fxrα expression has not been defined so far. Here, we demonstrate that hCG increases the Fxrα gene expression through the protein kinase-A signaling pathway. Fxrα is then involved in a negative feedback of steroid synthesis. These data improve our knowledge of the local control of the testicular steroidogenesis with the identification of the link between the hypothalamo-pituitary axis and the FXRα signaling pathway. | {
"pile_set_name": "PubMed Abstracts"
} |
Cyclic AMP dependent positive feedback signaling pathways in the cortex contributes to visceral pain.
Cortical areas including the anterior cingulate cortex (ACC) play critical roles in different types of chronic pain. Most of previous studies focus on the sensory inputs from somatic areas, and less information about plastic changes in the cortex for visceral pain. In this study, chronic visceral pain animal model was established by injection with zymosan into the colon of adult male C57/BL6 mice. Whole cell patch-clamp recording, behavioral tests, Western blot, and Cannulation and ACC microinjection were employed to explore the role of adenylyl cyclase 1 (AC1) in the ACC of C57/BL6 and AC1 knock out (AC1 KO) mice. Integrative approaches were used to investigate possible changes of neuronal adenylyl cyclase 1 (AC1) in the ACC after the injury. We found that AC1, a key enzyme for pain-related cortical plasticity, was significantly increased in the ACC in an animal model of irritable bowel syndrome. Inhibiting AC1 activity by a selective AC1 inhibitor NB001 significantly reduced the upregulation of AC1 protein in the ACC. Furthermore, we found that AC1 is required for NMDA GluN2B receptor upregulation and increases of NMDA receptor-mediated currents. These results suggest that AC1 may form a positive regulation in the cortex during chronic visceral pain. Our findings demonstrate that the upregulation of AC1 protein in the cortex may underlie the pathology of chronic visceral pain; and inhibiting AC1 activity may be beneficial for the treatment of visceral pain. | {
"pile_set_name": "PubMed Abstracts"
} |
Therapists' perception of benefits and costs of using virtual reality treatments.
Research indicates that virtual reality is effective in the treatment of many psychological difficulties and is being used more frequently. However, little is known about therapists' perception of the benefits and costs related to the use of virtual therapy in treatment delivery. In the present study, 271 therapists completed an online questionnaire that assessed their perceptions about the potential benefits and costs of using virtual reality in psychotherapy. Results indicated that therapists perceived the potential benefits as outweighing the potential costs. Therapists' self-reported knowledge of virtual reality, theoretical orientation, and interest in using virtual reality were found to be associated with perceptual measures. These findings contribute to the current knowledge of the perception of virtual reality amongst psychotherapists. | {
"pile_set_name": "PubMed Abstracts"
} |
Isolation of hydrophobic membrane proteins by perfusion chromatography--purification of photosystem II reaction centers from spinach chloroplasts.
Ion exchange perfusion chromatography has been introduced for the isolation of hydrophobic membrane protein complexes from thylakoid membranes of spinach chloroplasts. By using this chromatographic technique, previously shown to be useful for the rapid isolation of soluble proteins (Regnier, F. E. (1991) Nature 350, 634-635), we have been able to isolate oxygen evolving photosystem II core complexes and photosystem II reaction center particles. Pure reaction centers could be isolated from photosystem II core complexes after a chromatographic step requiring only 6.5 mm, which is a substantial improvement in comparisons with previous procedures. The entire preparation of photosystem II core complexes and reaction center II particles could be completed in less than 2 h. The use of perfusion chromatography, as a versatile method for the isolation of hydrophobic membrane proteins from photosynthetic membranes, as well as for other biological membranes, will be discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Duplex imaging of the renal arteries with contrast enhancement.
Duplex ultrasound evaluation of the renal arteries is a technically challenging procedure. Its accuracy is significantly influenced by operator expertise and patient factors, such as overlying bowel gas and obesity. Intravenous microbubble contrast agents enhance vascular reflective acoustic signals and may improve ultrasound diagnostic accuracy. The clinical usefulness of such a contrast agent in the renal vasculature was examined prospectively. A total of 22 patients (16 males and 6 females) with mean age of 63 +/-3 years with suspected abdominal vascular disease were studied prospectively. A complete color flow duplex imaging study of the renal vasculature was performed. This was then followed by an identical examination during which an ultrasound contrast agent (Definity, DuPont Pharmaceutical) was infused intravenously at a rate of 2 to 4 mL/min. In addition to imaging of the vessels, the peak systolic velocity and Doppler waveforms of the aorta and renal arteries were examined. These results were independently compared to results with contrast angiography. A mean of 67 mL of contrast was used per patient. Of the total of 43 renal arteries examined, the accuracy for the detection of occlusions was 75% (3 of 4) for both standard and contrast-enhanced duplex ultrasound. The accuracy for the detection of hemodynamically significant stenosis was 50% (6 of 12) for standard and 75% (9 of 12) for contrast-enhanced duplex ultrasound. Visualization of normal or minimally diseased arteries was 94% (30 of 32) for standard and 97% (31 of 32) for contrast-enhanced ultrasound. Although overall accuracy was not enhanced by the infusion of ultrasound contrast, 5 of 7 arteries not visualized by color flow duplex were detected following the infusion of contrast agent, resulting in an additional 10% (5 of 48) of vessels visualized. Peak systolic velocities were increased by an average of 10% in normal or minimally diseased vessels and 12% in stenotic vessels following contrast administration but these differences were not statistically significant. Contrast-enhanced duplex imaging of the renal arteries is safe but not routinely required when performed by an experienced sonographer. However, it may increase visualization and accuracy in patients with stenoses or when the vessels are not initially visualized. Although increased velocities are seen when contrast agent is used, this does not appear to necessitate different Doppler criteria at this time. | {
"pile_set_name": "PubMed Abstracts"
} |
Next generation adoptive immunotherapy--human T cells as carriers of therapeutic nanoparticles.
An important step in adoptive immunotherapy in general and specifically with respect to cancer treatment is the initiation of an inflammatory T cell response at the tumor site. Here we suggest a new concept for a controlled inflammatory response in which the intrinsic cytotoxic properties of T cells are upgraded with the properties of nanoparticles transfected into the T cells during the ex vivo expansion process. We report in vitro upgrading of human T cells using PEGylated boron carbide nanoparticles functionalised with a translocation peptide aimed at Boron Neutron Capture Therapy (BNCT). A key finding is that the metabolism of such upgraded human T cells were not affected by a payload of 0.13 pg boron per cell and that the nanoparticles were retained in the cell population after several cell divisions. This is vital for transporting nanoparticles by T cells to the tumor site. | {
"pile_set_name": "PubMed Abstracts"
} |
Prognostic role of dobutamine stress echocardiography in myocardial viability.
The aim of this review is to provide a perspective on the role of dobutamine stress echocardiography to evaluate myocardial viability and assess prognosis in patients with ischemic left ventricular dysfunction. Pooled analysis of currently available data demonstrates that dobutamine stress echocardiography provides useful information on recovery of dysfunctional but viable myocardium and prognosis. In fact, improvement of long-term prognosis may be the ultimate clinical challenge in the management of patients with ischemic left ventricular dysfunction. Dobutamine stress echocardiography can be used to assess residual ischemia and contractile reserve, which are significant determinants of prognosis. Additionally, other echocardiographic variables, such as end-diastolic wall thickness, end-systolic volume, and extent of viability, affect outcome after revascularization in patients with ischemic cardiomyopathy. Dobutamine stress echocardiography provides information on myocardial ischemia, contractile reserve, and other prognostically relevant parameters in patients with ischemic left ventricular dysfunction. This information can be used to select the optimal treatment strategy for these patients and to estimate and improve clinical outcome. | {
"pile_set_name": "PubMed Abstracts"
} |
Hearing loss in white South African goldminers.
Hearing thresholds of 2,667 white South African goldminers were determined in a cross-sectional survey. Median hearing thresholds at 1,000 Hz were comparable to those expected for men living in a developed society. For the frequencies 3,000-6,000 Hz, which are most affected by industrial noise, hearing thresholds were greater than expected and worsened with age relative to expected losses. The percentage of social impairment of hearing ranged from 0% in the youngest age group to 21.6% among those 58 years of age and over. Data from two surveys on the use of hearing protection indicate that it increased from 13.2% in 1979 to 17.2% in 1982. This level is probably still too low given the pervasiveness of noise in the goldmining industry. Some of the difficulties associated with a hearing conservation programme in the industry are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Nitrate and sulfate: Effective alternative hydrogen sinks for mitigation of ruminal methane production in sheep.
Twenty male crossbred Texel lambs were used in a 2 × 2 factorial design experiment to assess the effect of dietary addition of nitrate (2.6% of dry matter) and sulfate (2.6% of dry matter) on enteric methane emissions, rumen volatile fatty acid concentrations, rumen microbial composition, and the occurrence of methemoglobinemia. Lambs were gradually introduced to nitrate and sulfate in a corn silage-based diet over a period of 4 wk, and methane production was subsequently determined in respiration chambers. Diets were given at 95% of the lowest ad libitum intake observed within one block in the week before methane yield was measured to ensure equal feed intake of animals between treatments. All diets were formulated to be isonitrogenous. Methane production decreased with both supplements (nitrate: -32%, sulfate: -16%, and nitrate+sulfate: -47% relative to control). The decrease in methane production due to nitrate feeding was most pronounced in the period immediately after feeding, whereas the decrease in methane yield due to sulfate feeding was observed during the entire day. Methane-suppressing effects of nitrate and sulfate were independent and additive. The highest methemoglobin value observed in the blood of the nitrate-fed animals was 7% of hemoglobin. When nitrate was fed in combination with sulfate, methemoglobin remained below the detection limit of 2% of hemoglobin. Dietary nitrate decreased heat production (-7%), whereas supplementation with sulfate increased heat production (+3%). Feeding nitrate or sulfate had no effects on volatile fatty acid concentrations in rumen fluid samples taken 24h after feeding, except for the molar proportion of branched-chain volatile fatty acids, which was higher when sulfate was fed and lower when nitrate was fed, but not different when both products were included in the diet. The total number of rumen bacteria increased as a result of sulfate inclusion in the diet. The number of methanogens was reduced when nitrate was fed. Enhanced levels of sulfate in the diet increased the number of sulfate-reducing bacteria. The number of protozoa was not affected by nitrate or sulfate addition. Supplementation of a diet with nitrate and sulfate is an effective means for mitigating enteric methane emissions from sheep. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery.
Propofol and sevoflurane are suitable agents for maintenance of anaesthesia during neurosurgical procedures. We have prospectively compared these agents in combination with the short-acting opioid, remifentanil. Fifty unpremedicated patients undergoing elective craniotomy received remifentanil 1 microg kg(-1) followed by an infusion commencing at 0.5 microg kg(-1) min(-1) reducing to 0.25 microg kg(-1) min(-1) after craniotomy. Anaesthesia was induced with propofol, and maintained with either a target-controlled infusion of propofol, minimum target 2 microg ml(-1) or sevoflurane, initial concentration 2%(ET). Episodes of mean arterial pressure (MAP) more than 100 mm Hg or less than 60 mm Hg for more than 1 min were defined as hypertensive or hypotensive events, respectively. A surgical assessment of operating conditions and times to spontaneous respiration, extubation, obey commands and eye opening were recorded. Drug acquisition costs were calculated. Twenty-four and twenty-six patients were assigned to propofol (Group P) and sevoflurane anaesthesia (Group S), respectively. The number of hypertensive events was comparable, whilst more hypotensive events were observed in Group S than in Group P (P=0.053, chi-squared test). As rescue therapy, more labetolol [45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21) vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between group differences in recovery times were small and clinically unimportant. The combined hourly acquisition costs of hypnotic, analgesic, and vasoactive drugs appeared to be lower in patients maintained with sevoflurane than with propofol. Propofol/remifentanil and sevoflurane/remifentanil both provided satisfactory anaesthesia for intracranial surgery. | {
"pile_set_name": "PubMed Abstracts"
} |
Conversion chemotherapy using cetuximab plus FOLFIRI followed by bevacizumab plus mFOLFOX6 in patients with unresectable liver metastases from colorectal cancer.
Recently, in patients with unresectable colorectal liver metastasis, liver resection sometimes becomes possible by intensive systemic chemotherapy, i.e. conversion therapy. However, among cases that do not respond well to first-line chemotherapy, it is rare that second-line chemotherapy results in a marked response allowing liver resection. We consider that the liver resection rate may be increased by initiating second-line treatment at an earlier stage before progression subsequent to first-line chemotherapy. We are conducting a multicentre Phase II study to evaluate the efficacy and safety of sequential chemotherapy using six cycles of cetuximab plus FOLFIRI (5-fluorouracil, folinic acid and irinotecan) followed by six cycles of bevacizumab plus FOLFOX (5-fluorouracil, folinic acid and oxaliplatin) as conversion chemotherapy. The primary endpoint is the liver resection rate during the bevacizumab + FOLFOX phase. Fifty patients are required for this study. | {
"pile_set_name": "PubMed Abstracts"
} |
Endotoxin priming of neutrophils requires NADPH oxidase-generated oxidants and is regulated by the anion transporter ClC-3.
Several soluble mediators, including endotoxin, prime neutrophils for an enhanced respiratory burst in response to subsequent stimulation. Priming of neutrophils occurs in vitro, and primed neutrophils are found in vivo. We previously localized the anion transporter ClC-3 to polymorphonuclear leukocytes (PMN) secretory vesicles and demonstrated that it is required for normal NADPH oxidase activation in response to both particulate and soluble stimuli. We now explore the contribution of the NADPH oxidase and ClC-3 to endotoxin-mediated priming. Lipooligosaccharide (LOS) from Neisseria meningitidis enhances the respiratory burst in response to formyl-Met-Leu-Phe, an effect that was impaired in PMNs lacking functional ClC-3 and under anaerobic conditions. Mobilization of receptors to the cell surface and phosphorylation of p38 MAPK by LOS were both impaired in PMN with the NADPH oxidase chemically inhibited or genetically absent and in cells lacking functional ClC-3. Furthermore, inhibition of the NADPH oxidase or ClC-3 in otherwise unstimulated cells elicited a phenotype similar to that seen after endotoxin priming, suggesting that basal oxidant production helps to maintain cellular quiescence. In summary, NADPH oxidase activation was required for LOS-mediated priming, but basal oxidants kept unstimulated cells from becoming primed. ClC-3 contributes to both of these processes. | {
"pile_set_name": "PubMed Abstracts"
} |
Acute Mastoiditis Before Pneumococcal Vaccination: The Experience of a Large Tertiary Care Pediatric Hospital.
To report the experience of a large tertiary care pediatric center during a period of increasing Streptococcus pneumoniae antimicrobial resistance before the introduction of pneumococcal vaccine in Israel. Retrospective chart review of children diagnosed acute mastoiditis (AM) between January 1997 and December 2007. The children were divided into 4 age groups (6-11, 12-23, 24-35, and 36-40 months), and each group was compared with the others. A total of 198 AM episodes were recorded during the 10-year study period. The most prevalent pathogen was S. pneumonia, with a very low (15%) penicillin resistance rate (minimal inhibitory concentration ≥ 2). Complications were more prevalent in the 12- to 23-month age group. The number of AM cases increased during the study period. Penicillin resistance did not play an important role in determining the morbidity before the introduction of pneumococcal conjugate vaccine. | {
"pile_set_name": "PubMed Abstracts"
} |
Malignant transformation in vestibular schwannoma: report of a single case, literature search, and debate.
The significance of radiation in the induction of malignancy in vestibular schwannomas (VSs) after radiosurgery is unclear despite an increasing number of case reports. The authors describe a new case of verified malignant transformation in a vestibular schwannoma (MTVS) and provide a new evaluation of such cases previously reported in the literature. A 46-year-old woman underwent subtotal resection of a right-sided VS in 2004. The histological characteristics of the lesion were typical and benign. In early 2007 Gamma Knife surgery (GKS) was performed to treat a residual enlarging remnant. The radiosurgery parameters included the following: target volume 3.5 cm(3), prescription dose 12 Gy, prescription isodose 45%, maximum dose 26.7 Gy, and coverage 97%. At 2 years' follow-up the lesion was enlarged to 5.2 cm(3), but by 5 years it had decreased to 2.3 cm(3). Six months later the lesion was 8.4 cm(3). Repeated surgery was performed, and a histological analysis revealed a malignant peripheral nerve sheath tumor. The case was further managed with repeated GKS performed in the spring of 2013. At that time, the radiosurgery parameters included the following: target volume 3.5 cm(3), prescription dose 16 Gy, prescription isodose 45%, maximum dose 35.6 Gy, and coverage 91%. This Gamma Knife Department has treated a total of 205 patients with VS (local incidence of MTVS 0.49%). A search of the literature published up to and including 2013 was performed using PubMed as well as more informal search methods. This patient is the 29th reported case of MTVS after radiation therapy. Of these cases, 40.7% were patients with neurofibromatosis (NF). In those cases in which histology showed tumors with previously benign characteristics, totally conforming to the criteria for MTVS, the mean delay to malignant expression was 68 months (median delay 72 months). The authors also retrieved papers reporting 30 cases of malignant VS in patients who had not undergone radiation treatment. Five of those cases were malignant transformation of a benign entity, and in 4 of them histology had verified that the initial disease was benign. In those 4 cases, there was a mean delay to malignant expression of 7.2 months (median delay 8 months). Despite more frequent reports of MTVS after radiation treatment recently, there has been no accurate quantification of the risk, except in patients with NF, in whom the incidence of malignancy is high in relation to the numbers treated. The present analysis indicates that the risk of malignancy over 20 years in cases in which no radiation treatment has occurred is 1.32-2.08 per 100,000, and this risk decreases to 1.09-1.74 per 100,000 if cases of NF are excluded. After radiation treatment, the overall risk over 20 years is 25.1 per 100,000, and this risk decreases to 15.6 per 100,000 if cases of NF are excluded. Radiation treatment increases the risk by approximately 10 times in non-NF cases. | {
"pile_set_name": "PubMed Abstracts"
} |
[Two types of diaphragmatic plication; therapeutic plication and prophylactic plication].
Plication of the hemidiaphragm is effective to relieve respiratory symptoms such as exertional dyspnea and orthopnea of the patients with unilateral diaphragmatic paralysis. We have experiences of 2 types of diaphragmatic plication;one for the symptomatic patients with unilateral diaphragmatic paralysis, and the other for the patients who underwent phrenicotomy during extended surgery for a recurrent thymoma. The former plication was performed for a therapeutic purpose to alleviate the patient's symptoms. The latter was performed for a prophylactic purpose to keep the patient free from possible symptoms or postoperative morbidity after phrenicotomy. Case 1:A 65-year-old female with an eventration of the right diaphragm underwent a sternal resection and reconstruction for a large desmoid tumor. After continuous mechanical ventilation for 3 months, she was still under noninvasive positive pressure ventilation( NPPV) for 24 hours a day. Plication of the right hemidiaphragm was performed and the patient was successfully weaned from NPPV. Case 2:A 41-year-old female with myasthenia gravis underwent a surgery for a recurrent thymoma. Left phrenicotomy was necessary to achieve a complete resection of the tumor. Plication of the left diaphragm was performed during the tumor resection to prevent possible respiratory complications. Postoperative course was uneventful, and her vital capacity was well maintained. | {
"pile_set_name": "PubMed Abstracts"
} |
Inference of transcriptional regulatory network by two-stage constrained space factor analysis.
Microarray gene expression and cross-linking chromatin immunoprecipitation data contain voluminous information that can help the identification of transcriptional regulatory networks at the full genome scale. Such high-throughput data are noisy however. In contrast, from the biomedical literature, we can find many evidenced transcription factor (TF)-target gene binding relationships that have been elucidated at the molecular level. But such sporadically generated knowledge only offers glimpses on limited patches of the network. How to incorporate this valuable knowledge resource to build more reliable network models remains a question. We present a modified factor analysis approach. Our algorithm starts with the evidenced TF-gene linkages. It iterates between the network configuration estimation step and the connection strength estimation step, using the high-throughput data, till convergence. We report two comprehensive regulatory networks obtained for Saccharomyces cerevisiae, one under the normal growth condition and the other under the environmental stress condition. http://kiefer.stat.ucla.edu/lap2/download/bti656_supplement.pdf. | {
"pile_set_name": "PubMed Abstracts"
} |
Polybrominated, polychlorinated and monobromo-polychlorinated dibenzo-p-dioxins/dibenzofurans and dioxin-like polychlorinated biphenyls in marine surface sediments from Hong Kong and Korea.
In this study we investigated occurrences and distribution patterns of dioxin-related compounds (DRCs) such as polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs), polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs), monobromo-polychlorinated dibenzo-p-dioxins/dibenzofurans (MoBPCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in marine surface sediments collected from the coastal waters of Hong Kong and Korea. In most sampling sites, concentrations of PCDDs were the highest, followed by DL-PCBs, PCDFs, PBDFs, PBDDs, MoBPCDDs and MoBPCDFs in this order. Levels of PBDD/Fs were generally 1-2 orders of magnitude lower than chlorinated analogues. Levels of PCDDs are higher than PCDFs in Hong Kong while levels of PBDFs are higher than PBDDs in Korea (p<0.05). Report of PBDD/Fs and MoBPCDD/Fs in sediments from East Asian countries is novel and original. Environmental levels of PBDD/Fs are supposed to start increasing in accordance with rising production, use and disposal of brominated flame retardants (BFRs) and recycling processes of e-waste in Asian developing countries. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficient disproportionation of formic acid to methanol using molecular ruthenium catalysts.
The disproportionation of formic acid to methanol was unveiled in 2013 using iridium catalysts. Although attractive, this transformation suffers from very low yields; methanol was produced in less than 2% yield, because the competitive dehydrogenation of formic acid (to CO2 and H2) is favored. We report herein the efficient and selective conversion of HCOOH to methanol in 50% yield, utilizing ruthenium(II) phosphine complexes under mild conditions. Experimental and theoretical (DFT) results show that different convergent pathways are involved in the production of methanol, depending on the nature of the catalyst. Reaction intermediates have been isolated and fully characterized and the reaction chemistry of the resulting ruthenium complexes has been studied. | {
"pile_set_name": "PubMed Abstracts"
} |
The synthesis of a DNA duplex corresponding to the icosanucleotide sequence at the 5' end of messenger RNA from the gene N of bacteriophage lambda.
In connection with work on the nucleotide sequence of the promoter for the gene N of bacteriophage lambda as well as a study of the mechanism of transcription, a 20-unit long DNA duplex corresponding to the known sequence at the 5' end of the above gene transcript has been synthesized. For synthesis, the required duplex was divided into the following deoxyribooligonucleotides: a) the dodecanucleotide, d-A-T-C-A-G-C-A-G-G-A-C-G (II); b) the octanucleotide, d-C-A-C-T-G-A-C-C- (IV); c) the hexanucleotide, d-G-C-T-G-A-rU (I); and d) dodecanucleotide, d-T-C-A-G-T-G-C-G-T-C-C-T (III). All of the four olignucleotides were chemically synthesized and characterized by extensive chromatographic and fingerprinting methods (after labeling the 5' ends with[32P]phosphate group). Longer polynucleotides (an icosa- and an octadecanucleotide) were prepared by polynucleotide ligase-catalyzed joining of segments I and III and by joining segments II and IV. The use of the octadecanucleotide, d-T-C-A-G-T-G-C-G-T-C-C-T-G-C-T-G-A-rU, in work on the sequence analysis of the promoter is described in the accompanying paper. The octadecanucleotide and icosanucleotide were hybridized together to give the double-stranded duplex. | {
"pile_set_name": "PubMed Abstracts"
} |
Novel naphthalene derivatives as inhibitors of human immunoglobulin E antibody production.
A series of naphthalene derivatives with a variety of substituents at the 2-position was prepared in order to evaluate their suppressive effect on immunoglobulin E (IgE) antibody production by human peripheral blood mononuclear cells provoked with anti-CD40 antibody (alpha-CD40), interleukin-4 (IL-4), and interleukin-10 (IL-10). Compounds having a 1,4-phenylene spacer moiety tethered between the 2-naphthyl nucleus and anthranilic acid suppressed IgE antibody production in vitro in preference to that of IgG antibody without affecting cell viability. Deletion of the anthranilic acid moiety diminished the inhibitory activities. Changing the 2-naphthyl to a 1-naphthyl or phenyl nucleus led to no change in the potency, indicating that the aromatic group at this position is indispensable for the inhibitory activities. On the other hand, changing the 1,4-phenylene spacer to a 1,3-phenylene one resulted in reduced potency. Similarly, inhibitory activities were lost when the CO2H moiety at the 2-position was moved to the 3- or 4-position on the terminal benzene. These observations suggest that the conformation around the anthranilic acid moiety affects the inhibitory activities toward IgE biosynthesis. 2-(4-(2-Naphthyloxy)benzamido)benzoic acid (29) seemed to be a more potent inhibitor of IgE production than of IgG production. Insertion of a methylene between the inter-phenylene and the amide moiety resulted in 2-((4-(2-naphthyloxy)phenyl)acetamido)benzoic acid (31), which provided a stronger inhibition of both IgE and IgG production, although the selectivity toward IgE was lower than that of 29. Introduction of a benzyl group at the 6-position on the naphthalene ring considerably increased the inhibitory activity toward IgE production with an IC50 of 8.3 nM (36). The potency of 31 and 36 was retained when hydrocortisone or lipopolysaccharide was used instead of alpha-CD40 and IL-10 as costimulatory factors with IL-4, implying that these compounds may interfere with signal transduction between IL-4/IL-4 receptor cognition and genetic transcription that induce class-switching of immunoglobulin in B cells. These novel naphthalene derivatives are thus excellent candidates for further investigation with a view toward a therapeutic remedy against IgE-mediated allergic diseases. | {
"pile_set_name": "PubMed Abstracts"
} |
Energy metabolism and in vivo cytochrome c oxidase redox relationships in hypoxic rat brain.
Rats were subjected to graded arterial hypoxia while we measured changes in the oxidation level of cytochrome c oxidase (cytochrome aa3) in the brain by a non-invasive, optical technique. The experiments were terminated at different arterial oxygen tensions (hypoxic levels) and the in vivo observations were compared with in vitro measured changes in metabolites known to reflect limitations in cellular aerobic energy production, e.g. glucose, pyruvate, lactate, phosphocreatine, ATP and ADP. Using absorption changes at 605 nm, in vivo cytochrome aa3 was 46% reduced in normoxia as determined by the range between the maximal oxidation level attained with animals breathing 85% O2 + 15% CO2 and maximal reduction with anoxia (100% N2). Hypoxia reduced cytochrome aa3 to levels of 52, 67, 76, and 84% at mean PaO2 values of 53, 39, 35 and 28 mm Hg, respectively. These increases in reduced cytochrome correlated significantly (r = 0.94) with cortical phosphocreatine depletion, lactate production, and increases in the lactate/pyruvate ratio. However, there were no significant changes in ATP or ADP. Rats did not survive below an FIO2 of 7% because of a precipitous fall in arterial blood pressure. Hypoxically-induced cerebral isoelectricity was coincident with a 50% increase in the cytochrome reduction level (to 73% of the total range defined above). Our results indicate that in vivo monitoring of the reduction level of cytochrome aa3 provides an early, continuous, and direct measure of intracellular oxygen insufficiency at levels which adversely affect aerobic energy production. | {
"pile_set_name": "PubMed Abstracts"
} |
Histamine stability in Rihaakuru at -80, 4 and 30°C.
Rihaakuru is a shelf stable fish paste product formed from a fish soup prepared from tuna. Histamine contamination is a food safety issue with this product that is manufactured from tuna fish that has been temperature abused. Histamine concentrations decreased between 31% and 73% in Rihaakuru stored for 10months at either -80, 4 or 30°C. This appears to be a property of the product as histamine solutions are reported to be stable, at least under frozen storage. The risk of histamine food poisoning due to Rihaakuru may reduce during the storage of the product. | {
"pile_set_name": "PubMed Abstracts"
} |
Reconstruction of a sagittal band and extensor tendon centralization using a palmaris longus tendon graft.
A technique of delayed extensor tendon reconstruction and centralization using a palmaris longus tendon graft is presented. The tendon graft is woven through the base of the proximal phalanx and up and over the reconstructed extensor tendon to simulate the natural sagittal bands. As described, the technique allows gliding of the extensor tendon while maintaining its vitally important central location. | {
"pile_set_name": "PubMed Abstracts"
} |
A new species of the genus Eurhadina Haupt (Hemiptera: Auchenorrhyncha: Cicadellidae: Typhlocybinae) from Korea, with a key to Korean species.
The leafhopper genus Eurhadina Haupt, 1929 belongs to the tribe Typhlocybini of subfamily Typhlocybinae (Hemiptera: Auchenorrhyncha: Cicadellidae). Currently, genus Eurhadina includes 3 subgenera, Eurhadina Haupt 1929, Singhardina Mahmood 1967, Zhihadina Yang & Li 1991. A total of 20 valid species of subgenus Eurhadina have been described in the Nearctic and Palaearctic region and the subgenus Singhardina includes 57 species in the Oriental and Palaearctic region (Huang & Zhang 1999, Dworakowska 2002). The subgenus Zhihadina includes only 1 species from China (Yang & Lee, 1991). So far, four species of subgenus Eurhadina were recorded in the Korean Peninsula (Kwon & Huh 2001): Eurhadina (Eurhadina) betularia Anufriev, 1969, E. (E.) koreana Dworakowska, 1971, E. (E.) pulchella (Fallen, 1806), and E. (E.) wagneri Dworakowska, 1969. The majority of species belonging to the subgenus Eurhadina are difficult to distinguish by external appearance because the color patterns of the forewings are very similar among species. | {
"pile_set_name": "PubMed Abstracts"
} |
[Evaluation of care quality in the ICU through a computerized nursing care plan].
The computerized systems that are being implemented for the recording of the Nursing Care Plan may facilitate the performance of continuing follow-up of the care quality. This retrospective descriptive study has been performed in a polyvalent Intensive Care Unit with the following objectives: a) describe the evaluation of the care quality, performed through the computerized record of the Nursing Care Plan; and 2) compare this evaluation with that performed in 1998, when the Nursing Care Plan had not yet been computerized. In the 98 revised computerized Nursing Care Plans, corresponding to the same number of patients with a mean stay of 13.8 days, the following results were obtained. Artificial airway. 74 patients had an endotracheal tube with a mean stay of 5.4 days, 11 patients had a cannula tracheotomy (time period of 45.7 days); no events occurred. Central venous lines: 91 patients were carriers of 163 catheters, the mean presence time was 9.9 days; three with withdrawn due to obstruction, there was one accident withdrawal and two were self-removed. Arterial catheter: the total number of arterial lines, corresponding to 87 patients, was 101 with a mean presence of 6.7 days; 15 obstructions, six accidental withdrawals and four self-removals were recorded. Bladder catheter: 91 patients had a bladder catheter (mean presence 12.9 days); no event occurred. Nasogastric tube: 83 patients were carriers of 98 tubes (63 Salem type and 35 for nutrition), with a mean presence of 10.1 days; five were withdrawn due to obstruction, three accidental withdrawals and 40 self-removed (23 in one patient). Skin integrity: nine patients developed bedsores, eight grade II and two grade III, the mean stay was 26.6 days. No patients had an accidental fall. As study conclusions, it stands out that the preestablished standards for the evaluation of the care were achieved in most and the care quality is maintained in relationship with our 1998 study, remaining within a level considered as good. | {
"pile_set_name": "PubMed Abstracts"
} |
Electronic and steric effects in thermal denitrosation of N-nitrosoamides.
N-Alkyl-N-nitrosoamides undergo competitive reactions whose rates are dependent upon the interplay of a number of factors. There already exists a significant body of work delineating the effects of pH on the partitioning of the nitrosoamides along their deaminative (-N(2)) and denitrosative (-"NO(+)") pathways. In this paper, the issue of pH dependence is discussed with particular attention to nitrosoamide decompositions in nonaqueous media. The role of the acidity of the medium in the partitioning of the nitrosoamide between deamination and denitrosation and in the choice of deaminative pathways is revisited. In nonaqueous media under near-neutral conditions, the partitioning's pH dependence is evidently accompanied by a sensitivity to structural features in the nitrosoamide. Thus, diminution of steric crowding around the N-nitroso moiety as well as the presence of strongly electron-withdrawing acyl units (i.e., those derived from strong acids, e.g., tosyl and trifyl) increase the relative yield of amides by encouraging the denitrosative pathway. A mechanism for thermal denitrosation of nitrosoamides under near-neutral conditions is proposed in which rapid protonation at the acyl O rather than slow protonation at the amidic N is the first step in the reaction profile. A rate-limiting, bimolecular reaction between the O-conjugate acid and adventitious nucleophiles at the nitrosyl group then occurs followed by rapid tautomerization to amide. | {
"pile_set_name": "PubMed Abstracts"
} |
Serum CA125 level modifications in women undergoing repeated IVF cycles.
In the present paper, serum CA125 modifications in patients undergoing their first IVF cycle were compared with those of patients in their second attempt. A significant increase of this marker was detected in each group of patients at day 14 after embryo transfer. However, the level of CA125 monitored in the patients in their second attempt was significantly higher than that determined in patients undergoing their first ovarian stimulation. This condition does not influence either ovarian response or oocyte and embryo quality. Moreover similar IVF outcome was obtained. Therefore we propose that patients undergoing repeated assisted reproductive technology (ART) cycles may suffer from ovarian surface epithelial damage and/or altered cellular growth rate. | {
"pile_set_name": "PubMed Abstracts"
} |
Does writing a list help cancer patients ask relevant questions?
We examined the use of written lists to give patients an opportunity to have their questions answered. Patients undergoing radical radiotherapy for cancer were given a sheet of paper with the simple prompt to write questions and give to the hospital doctor at their appointment 3 weeks later. At 3 months, patients were asked about their use and opinions of the written list. About half of the 478 patients attended with a written list. Fewer patients living in deprived areas used the list compared to more affluent areas. Doctors thought that 34% of patients would not otherwise have asked those questions and 91% of prompted discussions were a worthwhile use of time. | {
"pile_set_name": "PubMed Abstracts"
} |
Exosome-like Nanoparticles from Ginger Rhizomes Inhibited NLRP3 Inflammasome Activation.
The nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immune responses, and its aberrant activation is implicated in the pathogenesis of many diseases such as Alzheimer's disease and type 2 diabetes. Targeting the NLRP3 inflammasome could hold promise to combat these complex diseases, but therapies specifically inhibiting the NLRP3 inflammasome have not been developed for patient treatment. The current study aimed to identify food-borne exosome-like nanoparticles (ELNs) that inhibit NLRP3 inflammasome activity. Nine vegetables or fruits were selected to extract ELNs, which were examined for their inhibitory effects on activation of the NLRP3 inflammasome in primary macrophages. Although most of the tested ELNs posed minimal impacts, the ELNs from ginger rhizomes (G-ELNs) strongly inhibited NLRP3 inflammasome activation. The G-ELNs contained lipids, proteins, and RNAs and were easily taken up by macrophages. G-ELN treatment suppressed pathways downstream of inflammasome activation including caspase1 autocleavage, interleukin (IL)-1β and IL-18 secretion, and pyroptotic cell death. Apoptotic speck protein containing a caspase recruitment domain (ASC) oligomerization and speck formation assays indicated that G-ELNs blocked assembly of the NLRP3 inflammasome. The lipids in G-ELNs, rather than the RNAs or proteins, were responsible for the inhibitory activity observed. Together, the data suggested G-ELNs as new potent agents that block NLRP3 inflammasome assembly and activation. The unique features of G-ELNs including biomolecule protection and tissue bioavailability should facilitate the development of G-ELN-based therapy to target the NLRP3 inflammasome in the disease settings. | {
"pile_set_name": "PubMed Abstracts"
} |
Breast Cancer Screening For Women Ages 40-49--NIH Consensus Statement.
For 2 days, January 21 and 22, a panel of experts representing specialties in women's health, oncology, radiology, epidemiology, and public health listened to presentations by researchers and to public discussion and debate designed to reach a consensus on 5 questions: (1) Is there a reduction in breast cancer mortality due to screening women ages 40-49 with mammography, with or without physical examination? (2) What are the risks associated with screening women ages 40-49 with mammography and with physical examination? (3) Are there other benefits? If so, what and how do they change with age? (4) What is known about how the benefits and risks of breast cancer screening differ based on known risk factors for breast cancer? (5) What are the directions for future research? On January 23, the panel issued a consensus statement concluding that, while mammography has been shown to be clearly effective in reducing cancer mortality in women ages 50-69, there is no difference in breast cancer death within 7 years between 40- to 49-year-old women assigned to receive or not receive screening. For women in their 40s, the potential benefits of earlier diagnosis and breast-conserving therapy must be weighed against the potential risks of mammograms, including discomfort, inconvenience, radiation, and false reassurance given to women with false-negative screens. At the present time, the available data do not warrant a single recommendation for mammography for all women in their 40s. Each woman should decide for herself whether to undergo mammography. | {
"pile_set_name": "PubMed Abstracts"
} |
Proteomic biomarkers of endometrial cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.
There is a need for research studies into the molecular mechanisms underpinning the link between polycystic ovary syndrome (PCOS) and endometrial cancer (EC) to facilitate screening and to encourage the development of novel strategies to prevent disease progression. The objective of this review was to identify proteomic biomarkers of EC risk in women with PCOS. All eligible published studies on proteomic biomarkers for EC identified through the literature were evaluated. Proteomic biomarkers for EC were then integrated with an updated previously published database of all proteomic biomarkers identified so far in PCOS women. Nine protein biomarkers were similarly either under or over expressed in women with EC and PCOS in various tissues. These include transgelin, pyruvate kinase M1/M2, gelsolin-like capping protein (macrophage capping protein), glutathione S-transferase P, leucine aminopeptidase (cytosol aminopeptidase), peptidyl-prolyl cis-transisomerase, cyclophilin A, complement component C4A and manganese-superoxide dismutase. If validated, these biomarkers may provide a useful framework on which the knowledge base in this area could be developed and will facilitate future mathematical modelling to enhance screening and prevention of EC in women with PCOS who have been shown to be at increased risk. | {
"pile_set_name": "PubMed Abstracts"
} |
Ganglioside composition in human meningiomas.
The ganglioside composition in meningioma specimens from 20 patients was analyzed to find potential meningioma-associated structures. The characterization was performed by immunological staining with specific monoclonal antibodies to ganglioside antigens and fast atom bombardment-mass spectrometry. The major gangliosides were GM3 and GD3, and most of the meningioma specimens could be divided into a "GM3-rich" or a "GD3-rich" group. Gangliosides of the gangliotetraose series were represented by GM1, GD1a, GD1b, and GT1b, which were found in minor amounts in all the specimens. The ratios of GM1/GD1a and GD1a/GD1b differed from that in normal brain, and therefore existence of this series could not be explained by contamination with brain material. Ganglioside 3'-isoLM1, found in human malignant glioma, could not be detected in any meningioma specimen. | {
"pile_set_name": "PubMed Abstracts"
} |
The glucagon-like peptide 1 receptor agonist Exendin-4 decreases relapse-like drinking in socially housed mice.
Glucagon-like peptide-1 (GLP-1) is a gut peptide that regulates food intake and glucose metabolism. GLP-1 is also produced and released in the brain, and GLP-1 receptors are expressed in brain regions important for alcohol and drug reward, and for the development of addiction. GLP-1 receptor agonists can decrease alcohol intake acutely in rodents. However, alcohol use disorder is a chronic condition that requires treatments to be effective in promoting abstinence from excessive alcohol consumption over time. Here, we assessed the effect of daily treatment with the GLP-1 receptor agonist Exendin-4 in an assay of relapse-like drinking in socially housed mice. Male C57BL/6NTac mice were allowed continuous access to alcohol without tastant in the home cage for 37days. Then, alcohol bottles were removed and Exendin-4 (1.5μg/kg/day) or saline was administered subcutaneously for 8days during alcohol deprivation. Treatment continued for 8 additional days after reintroducing access to alcohol. A high-precision automated fluid consumption system was used to monitor intake of alcohol and water, drinking kinetics, and locomotor activity. Exendin-4 prevented the deprivation-induced increase in alcohol intake observed in control mice, without significantly affecting total fluid intake, body weight, or locomotor activity. The reduced alcohol intake was caused by a protracted latency to the first drink of alcohol and a reduced number of drinking bouts, while bout size and duration were not affected. The effect was maintained undiminished throughout the treatment period. These findings support the possible use of GLP-1 receptor agonists in the treatment of alcohol use disorder. | {
"pile_set_name": "PubMed Abstracts"
} |
Mitochondrial DNA sequence of the hybrid of Duroc (♂) × [Landrace (♂) × Yorshire (♀)] pig.
Duroc (♂) × [Landrace (♂) × Yorshire (♀)] (D × LY) pig is the popular hybrid pigs in order to make the most use of the heterosis in the world. In this study, the complete nucleotide sequence of D × LY pig mitochondrial genome was determined for the first time. Sequence analysis showed that the genome structure was in accordance with other pig breeds. It contained 22 tRNA genes, 2 ribosomal RNA genes, 13 protein-coding genes and 1 control region (D-loop region). The complete mitochondrial genome sequence of the D × LY pig provides an important data set for further study in genetic mechanism. | {
"pile_set_name": "PubMed Abstracts"
} |
Examples of Fourier transform ion cyclotron resonance mass spectrometry developments: from ion physics to remote access biochemical mass spectrometry.
The application of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) for high resolution biomolecular analysis has increased greatly after 30 years of innovation since its conception in 1974. FT- ICR-MS can now routinely be used for the analysis of complex organic mixtures such as biological or petrochemical samples. Many of these new possibilities have been the results of many different instrumental developments. This paper provides a mini review of selected instrumental developments that now allow these measurements. The development of soft ionization techniques such as electrospray ionization and matrix assisted laser desorption and ionisation was crucial for the analysis of biological macromolecules. Improved ion transport optics led to an increase in sensitivity. New ICR cell designs complement the capabilities of FT-ICR-MS by allowing a more thorough study of the mechanism and kinetics of ion reactions in the gas-phase. A selected example of electron capture dissociation (ECD) employs these developments to investigate the role of peptide conformation in ECD. Improved electronics and software allow faster and more flexible experiments. All these improvements led to an increase in speed and sensitivity that are necessary to couple FT-MS to fast separation techniques such as nano-high performance liquid chromatography. The modern FT-ICR-MS instruments can be incorporated in virtual organizations allowing remote access to unique infrastructure. This concept of remote experimentation opens new possibilities for scientific collaborations between expert scientists at different locations and allows the efficient use of this expensive instrumentation. | {
"pile_set_name": "PubMed Abstracts"
} |
Upregulation of interleukin-10 and inhibition of alloantigen responses by transferrin and transferrin-derived glycans.
Previous studies have shown that critically timed administration of transferrin (Tf) facilitates induction of immunologic unresponsiveness. Here, we determined in mixed leukocyte culture (MLC) and in concanavalin A (ConA)-driven cultures the effect of exogenous Tf and Tf-derived glycans (Tf-Gly) on lymphocyte proliferation. In cultures of human blood lymphocytes, Tf inhibited selectively alloantigen-driven proliferation in MLC, but not ConA-stimulated lymphocyte proliferation. Deglycosylation of Tf abrogated the inhibitory effect of Tf on alloantigen-induced lymphocyte proliferation, and, consistent with a role for glycans, an effect qualitatively and quantitatively similar to Tf was exerted by purified Tf-Gly. Glycans isolated from other proteins, for example, immunoglobulin G (IgG) or fibrinogen, failed to inhibit alloantigen-induced proliferation selectively. Rather, they suppressed lymphocyte proliferation in a non-specific manner. Determination of cytokines in MLC supernatant showed a downregulation of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-2, and IL-12 (p40), along with an upregulation of IL-10, a pattern entirely consistent with the observed effects of Tf and Tf-Gly on alloantigen-induced lymphocyte proliferation. The effect of Tf on MLC was directly IL-10-dependent. IL-10 levels were inversely correlated with lymphocyte proliferation and CD86 expression. Neutralization of IL-10 by anti-IL-10 monoclonal antibody (mAb) blocked the effect of Tf. The MLC-modulating effect of Tf (or Tf-Gly) was not dependent upon the Tf receptor CD71 but appeared to be mediated by a Gly-responsive receptor. These data suggest a role of Tf, and, in particular, Tf-Gly, in allo-interactions that is independent from the role of Tf in iron metabolism, and appears to involve co-stimulatory signals. | {
"pile_set_name": "PubMed Abstracts"
} |
Fluoro-deoxy-glucose positron emission tomography correlates of impaired activities of daily living in dementia with Lewy bodies: implications for cognitive reserve.
1) To investigate the neural substrate of impaired activities of daily living (ADL) in dementia with Lewy bodies (DLB) and 2) to explore, in the context of cognitive reserve, if hypometabolism was more pronounced in well-educated patients at the same level of everyday impairment. Twenty-one patients with DLB underwent an extensive clinical evaluation including cerebral positron emission tomography with F-fluoro-2-deoxy-glucose scanning. First, brain areas were identified, where ADL performance and glucose metabolism were significantly correlated, controlling for individual differences in cognitive and motor dysfunction. Second, it was tested if there was a significant negative association between metabolism and years of education in brain regions associated with ADL performance. Again, a correction for cognitive and motor impairment was deployed. There was a significant association between glucose hypometabolism and impaired ADL performance in an extensive brain cluster located in the right temporoparietal cortex. Furthermore, schooling and metabolic rate were inversely associated in the right Brodmann area 19, controlling for ADL performance. The study suggests that 1) certain brain metabolic alterations are specifically associated with the loss of everyday competence, even if differences in cognition and motor function are taken into consideration and 2) well-educated patients can offset more brain damage until reaching the same degree of ADL impairment as their less educated counterparts. These results extend the literature on cognitive reserve to a region-specific effect on ADL performance. | {
"pile_set_name": "PubMed Abstracts"
} |
Computerized interactive morphometry as an aid in the diagnosis of pleural effusions.
A morphometric study of cytologic preparations from patients with benign and malignant (mesothelioma and carcinoma) pleural effusions is reported. The routine cytologic smears from these specimens were studied with a new system of video-based computerized interactive morphometry (CIM) that allows the measurements of real-time images of cell profiles by the simple procedure of touching the two extreme points of a diameter of interest on a touch-sensitive screen. For each cell, the nuclear profile diameter (NPD) and the cytoplasmic profile diameter (CPD) are measured and categorized into classes with 2-microns intervals; the NPD/CPD ratio is also calculated. The mean NPD is calculated for the specimen after measurement of 100 cells. The data were interpreted by two independent methods: a statistical method of discriminant analysis that classifies the lesions as benign, carcinoma or mesothelioma and provides a probability statement of membership in a particular diagnostic class and an ad-hoc algorithm that categorizes the effusions as benign or malignant based on hierarchic analysis. A data base derived from study of the first 24 cases was constructed and utilized for the test classification of the second 24 cases, which were treated as specimens of unknown diagnosis. The discriminant analysis correctly classified 21 of the 24 test cases into their proper diagnostic groups. The algorithm for a computer-generated pathologic diagnosis correctly identified 47 of the 48 cases as benign or malignant. The technical advantages of video-based CIM over the existing morphometric methods are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Teaching complementary and alternative medicine in a reform curriculum.
The increasing utilization of complementary and alternative medicine (CAM) contrasts with a lack of CAM in medical school education. Therefore, CAM therapies were introduced to the Charité University Medical School (Berlin, Germany) reform curriculum. Teaching concept: A CAM seminar provides basic knowledge about naturopathy, homeopathy, and Traditional Chinese medicine (TCM), plus their utilization, empirical research, and underlying philosophies. Experiential and dialogical didactic techniques are employed. Students evaluated one of the seminars using the 'Heidelberg Inventory for Educational EVALUATION' (Heidelberger Inventar zur Lehrveranstaltungs-EVALUATION, HILVE). Student participation and classroom atmosphere were rated as very good. All other categories were rated above average, except workload and excessive demands. Demand for Education: 69% of all 3rd- and 7th-semester students (n = 74) answered a questionnaire about their opinions on CAM, and the extent and sources of their knowledge. Acupuncture and homeopathy were the best-known methods, primarily from courses or seminars. Personal experience with CAM was reported by 44% of the students. Depending on the method 73-96% of the respondents supported the inclusion of CAM therapies into the medical school curriculum. Acknowledged advantages of CAM were its use as an alternative or additional treatment (73-82%), fewer side effects (44%), and cost reduction (37%). The presented concept helps medical students develop a reflected opinion on CAM. The students rated the quality of the seminar as above average. The high support for university CAM education reflects the students' desire for more knowledge. Interest in other philosophies of disease and therapy may prepare them for a more integrative and pluralistic approach to medicine. | {
"pile_set_name": "PubMed Abstracts"
} |
Reference-Free Quality Assessment of Sonar Images via Contour Degradation Measurement.
Sonar imagery plays a significant role in oceanic applications since there is little natural light underwater, and light is irrelevant to sonar imaging. Sonar images are very likely to be affected by various distortions during the process of transmission via the underwater acoustic channel for further analysis. At the receiving end, the reference image is unavailable due to the complex and changing underwater environment and our unfamiliarity with it. To the best of our knowledge, one of the important usages of sonar images is target recognition on the basis of contour information. The contour degradation degree for a sonar image is relevant to the distortions contained in it. To this end, we developed a new no-reference contour degradation measurement for perceiving the quality of sonar images. The sparsities of a series of transform coefficient matrices, which are descriptive of contour information, are first extracted as features from the frequency and spatial domains. The contour degradation degree for a sonar image is then measured by calculating the ratios of extracted features before and after filtering this sonar image. Finally, a bootstrap aggregating (bagging)-based support vector regression module is learned to capture the relationship between the contour degradation degree and the sonar image quality. The results of experiments validate that the proposed metric is competitive with the state-of-the-art reference-based quality metrics and outperforms the latest reference-free competitors. | {
"pile_set_name": "PubMed Abstracts"
} |
Effects of three combined oral contraceptive preparations containing desogestrel plus ethinyl estradiol on lipid metabolism in comparison with two levonorgestrel preparations.
The effects of three different desogestrel-containing combined oral contraceptive preparations on lipid metabolism were compared with those of two levonorgestrel preparations. The following preparations were studied: (1) monophasic desogestrel (150/30), (2) monophasic desogestrel (150/20, containing 20 micrograms of ethinyl estradiol instead of 30 micrograms of ethinyl estradiol, (3) biphasic desogestrel, (4) monophasic levonorgestrel (150/30), and (5) triphasic levonorgestrel. The effects of these preparations were assessed on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B, the ratio of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol, and the ratio of apolipoprotein A-I to apolipoprotein B after 3 months of treatment, and the percentage changes with regard to pretreatment were calculated. The monophasic desogestrel (150/30) and biphasic desogestrel preparations induced higher high-density lipoprotein cholesterol and apolipoprotein A-I levels than did their levonorgestrel-containing counterparts. Low-density lipoprotein cholesterol levels were increased in monophasic levonorgestrel and clearly decreased in the lowest ethinyl estradiol-containing monophasic desogestrel (150/20) and biphasic desogestrel preparations. Apolipoprotein B increased in all preparations. The antiatherogenic indexes (ratios of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol and apolipoprotein A-I to apolipoprotein B were higher for monophasic desogestrel (150/30) and biphasic desogestrel than for comparable levonorgestrel-containing preparations. The differences seen between the desogestrel and levonorgestrel preparations can best be explained by the lower intrinsic androgenicity of 3-keto-desogestrel (active metabolite of desogestrel) than that of levonorgestrel. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of virulence between clinical and environmental Pseudomonas aeruginosa isolates.
New strains of Pseudomonas aeruginosa were isolated from clinical and environmental settings in order to characterize the virulence properties of this opportunistic pathogen. P. aeruginosa was frequently recovered from oil-contaminated samples but not from non-oil-contaminated soils. The virulence of five environmental and five clinical strains of P. aeruginosa was tested using two different models, Drosophila melanogaster and Lactuca sativa var. capitata L. There was no difference in the virulence between the two groups of isolates in either of the models. Since environmental P. aeruginosa strains are used for bioaugmentation in bioremediation programs, the results presented here should be taken into account in the future design of degradative consortia and/or in establishing containment measures. | {
"pile_set_name": "PubMed Abstracts"
} |
Materials Informatics: Statistical Modeling in Material Science.
Material informatics is engaged with the application of informatic principles to materials science in order to assist in the discovery and development of new materials. Central to the field is the application of data mining techniques and in particular machine learning approaches, often referred to as Quantitative Structure Activity Relationship (QSAR) modeling, to derive predictive models for a variety of materials-related "activities". Such models can accelerate the development of new materials with favorable properties and provide insight into the factors governing these properties. Here we provide a comparison between medicinal chemistry/drug design and materials-related QSAR modeling and highlight the importance of developing new, materials-specific descriptors. We survey some of the most recent QSAR models developed in materials science with focus on energetic materials and on solar cells. Finally we present new examples of material-informatic analyses of solar cells libraries produced from metal oxides using combinatorial material synthesis. Different analyses lead to interesting physical insights as well as to the design of new cells with potentially improved photovoltaic parameters. | {
"pile_set_name": "PubMed Abstracts"
} |
[Morphologic correlates of the electrical interactions between neurons in the limbic system].
Electron microscopical results on "special structural relations" between neighbouring neuronal elements (pericarya, dendrites) are demonstrated in different regions of the rat limbic system: field CA3 and field CA1 of the hippocamp, dentate gyrus, area entorhinalis (L V) and area retrosplenialis granularis (L III). The "special structural relations" are to be characterized as follows: direct apposition of membranes of the neighbouring neurons including an extracellular space of relatively constant width over a larger distance without neuroglia intervening this space. Areas of membrane appositions have been observed between neuronal somata ("soma-somatic appositions"), between dendrites ("dendro-dendritic appositions") and between both, somata and dendrites ("dendro-somatic appositions"). In the elmigraphs their length varied between 1 and 6 microns. In the entorhinal cortex and in the retrosplenial cortex soma-somatic appositions were in the majority, whereas in the hippocampal regions dendrodendritic appositions, in the dentate gyrus all types seem to be predominant. In the literature such direct appositions of neuronal membrane often have been described in the CNS of different species. They are considered as a possible morphological correlate of the ephaptic interaction, which is caused by field effects between neighbouring neurons. Following the literature the results of the ephaptic interactions vary between a weak facilitation and synchronous discharge of an unstimulated neuron by a stimulated one. Although such direct appositions are present in different groups of neurons in the limbic system, especially in the hippocamp, up to now their functional meaning is unclear. No correlation seem to exist between neuronal membrane appositions/ephaptic interactions and such a phenomenon like the hippocampal longterm potentiation; mechanisms of cooperativity included in the LTP like coactivation effects of pre- or postsynaptic elements still remain to be clarified. | {
"pile_set_name": "PubMed Abstracts"
} |
Hypoxia-induced activation of epidermal growth factor receptor (EGFR) kinase in the cerebral cortex of newborn piglets: the role of nitric oxide.
The present study aims to investigate the mechanism of EGFR kinase activation during hypoxia and tests the hypothesis that hypoxia-induced increased activation of EGFR kinase in the cerebral cortical membrane fraction of newborn piglets is mediated by nitric oxide (NO) derived from neuronal nitric oxide synthase (nNOS). Fifteen newborn piglets were divided into normoxic (Nx, n = 5), hypoxic (Hx, n = 5) and hypoxic-treated with nNOS inhibitor (Hx-nNOSi, n = 5). Hypoxia was induced by an FiO2 of 0.07 for 60 min. nNOS inhibitor I (selectivity >2,500 vs. endothelial NOS, eNOS, and >500 vs. inducible NOS, iNOS) was administered (0.4 mg/kg, i. v.) 30 min prior to hypoxia. EGFR kinase tyrosine phosphorylation at Tyr1173, an index of activation of EGFR kinase, was determined by Western blot analysis using an anti-phospho (pTyr(1173))-EGFR kinase antibody. Protein bands were analyzed by imaging densitometry and expressed as absorbance (OD x mm(2)). EGFR kinase activity was determined radiochemically using immunopurified enzyme. EGFR kinase activity was expressed as pmols/mg protein/hr. Density of phosphor (pTyr(1173))-EGFR kinase (OD x mm(2)) was 60.2 +/- 9.8 in Nx, 177.0 +/- 26.9 in Hx (P < 0.05 vs. Nx) and 79.9 +/- 15.7 in Hx-nNOSi (P < 0.05 vs. Hx, P = NS vs. Nx). Activity of EGFR kinase (pmoles/mg protein/hr) was 4,603 +/- 155 in Nx, 8,493 +/- 427 in Hx (P < 0.05 vs. Nx) and 4,516 +/- 104 in Hx-nNOSi (P < 0.05 vs. Hx, P = NS vs. Nx). Pretreatment with nNOS inhibitor prevented the hypoxia-induced increased phosphorylation and increased activity of EGFR kinase. We conclude that the mechanism of hypoxia-induced increased activation of EGFR kinase is mediated by nNOS-derived NO. | {
"pile_set_name": "PubMed Abstracts"
} |
Sustainability of a biobehavioral intervention implemented by therapists and sustainment in community settings.
The ultimate aim of dissemination and implementation of empirically supported treatments (ESTs) in behavioral medicine is (a) sustainability of the therapist/provider's EST usage and (b) sustainment of EST delivery in the setting. Thus far, sustainability has been understudied, and the therapist and setting variables that may be influential are unclear. The purpose of the study was to test the therapists' sustainability of a cancer-specific EST using a prospective longitudinal design and examine its predictors. Oncology mental health therapists (N = 134) from diverse settings (N = 110) completed training in the biobehavioral intervention (BBI) and were provided with 6 months of support for implementation, with no support thereafter. BBI usage (percent of patients treated) was reported at 2, 4, 6, and 12 months. Using a generalized estimating equation with a logistic link function, 12-month sustainability (a nonsignificant change in usage from 6 to 12 months) was studied along with therapist, supervisor, and setting variables as predictors. BBI usage increased through 6 months and, importantly, usage was sustained from 6 (68.4% [95% CI = 62.2%-73.9%]) to 12 months (70.9% [95% CI = 63.6%-77.3%]), with sustainment in 66 settings (60.0%). Predictors of implementation-to-sustainability usage were therapists' early intentions to use the BBI (p < .001) and from the setting, supervisors' positive attitudes toward ESTs (p = .016). Adding to the DI literature, a health psychology intervention was disseminated, implemented, and found sustainable across diverse therapists and settings. Therapists and setting predictors of usage, if modified, might facilitate future sustainability/sustainment of ESTs. | {
"pile_set_name": "PubMed Abstracts"
} |
[Distribution and abundance of the ascidian Ecteinascidia turbinata (Ascidiacea: Perophoridae) in Cuba].
Permanently submerged mangrove roots (Rhizophora mangle) are the main habitat of the ascidian Ecteinascidia turbinata in Cuba. It was occasionally found on black coral (Antiphates caribeana) between 22 and 38 meters deep. This species exhibits a wide distribution in all the mangrove keys surrounding the Island of Cuba but does not occur in riparian or fringing mangroves. Populations of this species are abundant in Cuba: in 75% of the 58 localities sampled the species was present and in 57% more than 50% of the roots held at least one colony. The highest colony densities were found in the northern coast of Pinar del Rio province with values near one colony per lineal meter of mangrove root. We found the highest density (1.46 col/m) and greatest biomass at Jutías Key, with values between 25 and 660 g/m. The average of wet biomass in the studied mangroves was 73.63 g/m. | {
"pile_set_name": "PubMed Abstracts"
} |
Stein-type shrinkage estimators in gamma regression model with application to prostate cancer data.
Gamma regression is applied in several areas such as life testing, forecasting cancer incidences, genomics, rainfall prediction, experimental designs, and quality control. Gamma regression models allow for a monotone and no constant hazard in survival models. Owing to the broad applicability of gamma regression, we propose some novel and improved methods to estimate the coefficients of gamma regression model. We combine the unrestricted maximum likelihood (ML) estimators and the estimators that are restricted by linear hypothesis, and we present Stein-type shrinkage estimators (SEs). We then develop an asymptotic theory for SEs and obtain their asymptotic quadratic risks. In addition, we conduct Monte Carlo simulations to study the performance of the estimators in terms of their simulated relative efficiencies. It is evident from our studies that the proposed SEs outperform the usual ML estimators. Furthermore, some tabular and graphical representations are given as proofs of our assertions. This study is finally ended by appraising the performance of our estimators for a real prostate cancer data. | {
"pile_set_name": "PubMed Abstracts"
} |
The regulation of FOXO1 and its role in disease progression.
Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators. In addition, oxidative stress, high glucose and other stimulations induce the regulation of FOXO1 activity via PI3k-Akt, JNK, CBP, Sirtuins, ubiquitin E3 ligases, etc., which mediate multiple signalling pathways. Subsequent post-transcriptional modifications, including phosphorylation, ubiquitination, acetylation, deacetylation, arginine methylation and O-GlcNAcylation, activate or inhibit FOXO1. The regulation of FOXO1 and its role might provide a significant avenue for the prevention and treatment of diseases. However, the subtle mechanisms of the post-transcriptional modifications and the effect of FOXO1 remain elusive and even conflicting in the development of many diseases. The determination of these questions potentially has implications for further research regarding FOXO1 signalling and the identification of targeted drugs. | {
"pile_set_name": "PubMed Abstracts"
} |
Delayed sexual development.
Sexual maturation can occur at an early age, at the expected or average time, or late. In adolescents who mature late, osseous development may be delayed. A variety of causes for delayed growth and sexual development should be evaluated. Constitutional delay is a nonpathogenic variation within normal growth parameters. The Tanner criteria should be used in assessing sexual maturation and bone age evaluation for skeletal growth. These criteria are based on the fact that sexual growth follows predictable patterns. Children need reassurance about their developmental growth, and subsequent growth should be monitored carefully. | {
"pile_set_name": "PubMed Abstracts"
} |
Malignant smooth muscle tumors of the epididymis.
We report 2 cases of primary leiomyosarcoma of the epididymis. There is no evidence of tumor recurrence in 1 patient 21 years postoperatively and prophylactic chemotherapy has been started in 1 patient because of a high mitotic rate in the tumor. The 9 cases reported previously are reviewed briefly. | {
"pile_set_name": "PubMed Abstracts"
} |
Application of the random forest classification method to peaks detected from mass spectrometric proteomic profiles of cancer patients and controls.
The random forest classification method was applied to classify samples from 76 breast cancer patients and 77 controls whose proteomic profile had been obtained using mass spectrometry. The analysis consisted of two stages, the detection of peaks from the profiles and the construction of a classification rule using random forests. Using a peak detection method based on finding common local maxima in the smoothed sample spectra, 444 peaks were detected, reducing to 365 robust peaks found in at least 7 out of 10 random subsets of samples. Subjects were classified as cases or controls using the random forest algorithm applied to the 365 peaks. Based on the prediction of the status of out-of-bag samples, the total error rate was 16.3%, with a sensitivity of 81.6% and a specificity of 85.7%. Measures of importance of each of the peaks were calculated to identify regions of the spectrum influencing the classification, and the four most important peaks were identified as mz3863_13, mz2943_12, mz3193_44 and mz8925_94. Combining initial peak detection with the random forest algorithm provides a high-performance classification system for proteomic data, with unbiased estimates of future performance. | {
"pile_set_name": "PubMed Abstracts"
} |
Transcatheter Valve SELECTion in Patients With Right Bundle Branch Block and Impact on Pacemaker Implantations.
This study sought to evaluate the impact of the ACURATE neo (NEO) (Boston Scientific, Marlborough, Massachusetts) versus SAPIEN 3 (S3) (Edwards Lifesciences, Irvine, California) on permanent pacemaker implantation (PPI) in patients with pre-existing right bundle branch block (RBBB) after transcatheter aortic valve replacement. Pre-existing RBBB is the strongest patient-related predictor for PPI after transcatheter aortic valve replacement. No comparison of newer-generation transcatheter heart valves with regard to PPI in these patients exists. This multicenter registry includes 4,305 patients; 296 (6.9%) had pre-existent RBBB and no pacemaker at baseline and formed the study population. The primary endpoint was new PPI at 30 days. The association of NEO versus S3 with PPI was assessed using binary logistic regression analyses and inverse probability treatment weighting in a propensity-matched population. The 30-day PPI rate was 39.2%. The S3 and NEO were used in 66.9% and 33.1%, respectively. The NEO was associated with lower rates of PPI compared with the S3 (29.6% vs. 43.9%; p = 0.025; odds ratio [OR]: 0.54; 95% confidence interval [CI]: 0.32 to 0.89; p = 0.018), after multivariable adjustment (OR: 0.48; 95% CI: 0.26 to 0.86; p = 0.014), and in the inverse probability treatment weighting analysis (OR: 0.37; 95% CI: 0.25 to 0.55; p < 0.001). There was no difference in device failure (8.2% vs. 6.6%; p = 0.792) or in-hospital course. In the propensity-matched population, PPI rate was also lower in the NEO versus S3 (23.1% vs. 44.6%; p = 0.016; OR: 0.37; 95% CI: 0.17 to 0.78; p = 0.010), with no difference in device failure (9.2% vs. 6.2%; p = 0.742). In patients with RBBB, risk of PPI was significantly lower with the NEO compared with the S3, suggesting the possibility of a patient tailored transcatheter heart valve therapy. | {
"pile_set_name": "PubMed Abstracts"
} |
[Genetic and cytogenetic predictors of human chromosomal radiosensitivity].
We studied association between the frequencies of gamma-induced (1 Gy in vitro) chromosome aberrations in blood lymphocytes and polymorphism of 45 repair candidate genes, detoxification and oxidative stress genes (53 sites) for 99 healthy volunteers. The levels of chromosome-type aberrations correlated with carriage of the minor alleles of the genes OGG1 Ser326Cys, ABCB1 Ile1145 = and NQO1 Pro187Ser (p = 0.0002). We have shown that all the revealed genetic associations were less effective in predicting chromosomal radiosensitivity as compared to the correlations between spontaneous and gamma-induced aberrations (p = 1.0 x 10(-6)). The addition of genetic markers to cytogenetic predictors improved the predictive accuracy for chromosomal radiosensitivity with the multiple correlation coefficient reaching R = 0.58 (p = 3.1 x 10(-8)). Thereby we were able to explain more than 30% of the population variability in chromosomal radiosensitivity. | {
"pile_set_name": "PubMed Abstracts"
} |
Renal tubular epithelial and T cell interactions in autoimmune renal disease.
Interaction between epithelial cells and T cells may initiate autoimmune tissue destruction. Renal tubular epithelial cells may participate in such immune interactions since they: (1) can be induced to express surface molecules which facilitate engagement with T cells; (2) secrete and express membrane bound cytokines; (3) are exposed to peptides from blood and the glomerular filtrate and are capable of processing these potentially immunogenic peptides. We have recently established T cell clones captured from the interstitium of MRL-lpr mice with lupus nephritis. These T cell clones are unique and are regulated by the lpr gene. They express the alpha/beta T cell receptor, and beta cell markers, but do not display CD4 or CD8 on their surface. These T cell clones proliferate to renal tubular cells but not to cells from other tissues and secrete IFN-gamma which induces class II and ICAM-1 on renal tubular epithelial cells. Expression of class II and ICAM-1 induced by IFN-gamma renders these epithelial cells capable of triggering T cell hybridomas to proliferate and secrete IL-2. Therefore, renal tubular epithelial cells are capable of processing and presenting antigen. This review will focus on the dynamic interaction of renal epithelial cells and T cells and discuss its importance in the initiation of autoimmune renal injury. | {
"pile_set_name": "PubMed Abstracts"
} |
Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial.
Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. Patients were randomized to sitagliptin vs placebo added to standard care. Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death. Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups. clinicaltrials.gov Identifier: NCT00790205. | {
"pile_set_name": "PubMed Abstracts"
} |
Irreversible ligands with high selectivity toward delta and mu opiate receptors.
Alkylating agents that display strong selectivity for opiate receptor types delta or mu were prepared by appropriate modification of the structures of the strong analgesics fentanyl, etonitazene, and endoethenotetrahydrooripavine. The availability of these substances should facilitate studies of the structural basis of receptor specificity and of the physiologic roles of these receptors. | {
"pile_set_name": "PubMed Abstracts"
} |
Upper respiratory tract infection and serum antibody responses in nursing home patients.
Residents of a Veterans Administration nursing home care unit (NHCU) were observed for the development of upper respiratory tract infection (URI) during 12 consecutive months to determine the frequency of sporadic cases or outbreaks of URI and to characterize them clinically and by laboratory means. Fifty-nine episodes of URI occurred in 56 residents during the study period. Serologic testing or virus isolation proved or suggested an etiologic agent on 22 occasions. URI was more common in late Fall and Winter and was caused by various agents, including influenza, Mycoplasma pneumoniae, respiratory syncytial virus, and parainfluenza viruses. A minor outbreak of influenza B in February 1986 contrasted with previous cases of URI in that the patients had a higher mean temperature and abnormal breath sounds, and they were clinically sicker. This suggests that clinical and epidemiologic surveillance during the influenza season may allow the early recognition of influenza in elderly nursing home residents. Over a 4-year period 147 serum antibody responses after influenza infection or influenza vaccination were compiled. Antibody responses to individual influenza vaccine components were measured 75 to 90 days after vaccination. The geometric mean titer (GMT) and the percentage of samples with antibody levels greater than 1:40 were determined for each of the three antigenic subtypes on 3 consecutive years. The GMT to individual vaccine components was consistently greater than 1:40, except to influenza B/Singapore in 1984 and A/Chile and B/U.S.S.R. in 1985, when these subtypes were first included in the vaccine, suggesting the NHCU residents responded less vigorously to unfamiliar vaccine subtypes.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Determination and potential importance of diterpene (kaur-16-ene) emitted from dominant coniferous trees in Japan.
Reactive volatile organic compounds (VOCs) are known to affect atmospheric chemistry. Biogenic VOCs (BVOCs) have a significant impact on regional air quality due to their large emission rates and high reactivities. Diterpenes (most particularly, kaur-16-ene) were detected in all of the 205 enclosure air samples collected over multiple seasons at two different sites from Cryptomeria japonica and Chamaecyparis obtusa trees, the dominant coniferous trees in Japan,. The emission rate of kaur-16-ene, was determined to be from 0.01 to 7.1 μg dwg(-1) h(-1) (average: 0.61 μg dwg(-1) h(-1)) employing branch enclosure measurements using adsorbent sampling followed by solid phase-liquid extraction techniques. The emission rate was comparable to that of monoterpenes, which is known major BVOC emissions, collected from the same branches. In addition, total emission of kaur-16-ene at 30°C was estimated to exceed that of total anthropogenic VOC emissions. | {
"pile_set_name": "PubMed Abstracts"
} |
Product development in tissue engineering.
Tissue engineering may be defined as the application of the principles and techniques of biomedical engineering to products and processes involving living cells. As such it is located at the confluence of traditional medical device technology, molecular pharmacology, and cell biology. Effective function at this interface has proven both elusive and critical in tissue engineering research and is likely to remain a determinant of success or failure as products move from research through development and into clinical practice. As a further challenge, regulatory processes, traditions, and approval pathways are rather different for medical devices than for Pharmaceuticals and biologies, and commercialization of hybrid products will require knowledge and expertise in both areas. This review compares and contrasts the development cycle for medical devices and pharmaceutical products and highlights the major development issues facing emerging tissue engineering products. | {
"pile_set_name": "PubMed Abstracts"
} |
Early chorionic activity in women bearing inert IUD, copper IUD and levonorgestrel-releasing IUD.
Early chorionic activity was assessed in the premenstrual days by means of serum HCG beta-fraction. As control, a group of women with no contraceptive use was studied; early chorionic activity was detected in 31.8% of the cycles. In the group bearing an inert IUD the incidence was 20%, which did not differ from the control; while in the medicated IUD groups (Cu-IUD and LNG-IUD) the incidences were 4.8% and nil, respectively. Both medicated IUD groups showed a significant difference when compared with the control, as well as the inert IUD groups. The meaning of these findings, pointing out differences in the main mechanism of action between inert and medicated IUDs, is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Na+-K+ pump activation inhibits endothelium-dependent relaxation by activating the forward mode of Na+/Ca2+ exchanger in mouse aorta.
The effect of Na+-K+ pump activation on endothelium-dependent relaxation (EDR) and on intracellular Ca2+ concentration ([Ca2+]i) was examined in mouse aorta and mouse aortic endothelial cells (MAECs). The Na+-K+ pump was activated by increasing extracellular K+ concentration ([K+]o) from 6 to 12 mM. In aortic rings, the Na+ ionophore monensin evoked EDR, and this EDR was inhibited by the Na+/Ca2+ exchanger (NCX; reverse mode) inhibitor KB-R7943. Monensin-induced Na+ loading or extracellular Na+ depletion (Na+ replaced by Li+) increased [Ca2+]i in MAECs, and this increase was inhibited by KB-R7943. Na+-K+ pump activation inhibited EDR and [Ca2+]i increase (K+-induced inhibition of EDR and [Ca2+]i increase). The Na+-K+ pump inhibitor ouabain inhibited K+-induced inhibition of EDR. Monensin (>0.1 microM) and the NCX (forward and reverse mode) inhibitors 2'4'-dichlorobenzamil (>10 microM) or Ni2+ (>100 microM) inhibited K+-induced inhibition of EDR and [Ca2+]i increase. KB-R7943 did not inhibit K+-induced inhibition at up to 10 microM but did at 30 microM. In current-clamped MAECs, an increase in [K+]o from 6 to 12 mM depolarized the membrane potential, which was inhibited by ouabain, Ni2+, or KB-R7943. In aortic rings, the concentration of cGMP was significantly increased by acetylcholine and decreased on increasing [K+]o from 6 to 12 mM. This decrease in cGMP was significantly inhibited by pretreating with ouabain (100 microM), Ni2+ (300 microM), or KB-R7943 (30 microM). These results suggest that activation of the forward mode of NCX after Na+-K+ pump activation inhibits Ca2+ mobilization in endothelial cells, thereby modulating vasomotor tone. | {
"pile_set_name": "PubMed Abstracts"
} |
Comparison of medical management and genetic counseling options pre- and post-whole exome sequencing for patients with positive and negative results.
Whole exome sequencing (WES) is expected to impact patient management, but data surrounding the types of downstream effects and how frequently these effects are observed depending on the type of WES results received is limited. This study investigated changes to medical management and genetic counseling (GC) options following WES for individuals with positive and negative results. Electronic medical records of patients who had positive (n = 37) or negative (n = 41) WES results from Cincinnati Children's Hospital were retrospectively reviewed. Pre- and post-WES management and GC options were analyzed as were differences between positive and negative results. Almost all participants (97%) were observed to have at least one difference in medical management and/or GC options following WES. Comparing pre- and post-WES detected significant differences (p ≤ 0.05) in genetic testing, imaging, and metabolic testing regardless of WES results. Participants with positive results also had significant differences in recurrence risk, reproductive options, testing for family members, and support groups. Pre- to post-WES differences were significantly different between participants with positive and negative results in specialist referrals, lifestyle recommendations, recurrence risk, and all GC options (p ≤ 0.05); specifically, participants with positive results were more likely to have differences in these categories. Overall, differences in medical management and/or GC options were observed for participants with both types of WES results (positive and negative). Results from this study may contribute to the understanding of how WES impacts patients and their care and thus improve its utilization. | {
"pile_set_name": "PubMed Abstracts"
} |
Upregulation of protein-tyrosine nitration in the anterior horn cells of amyotrophic lateral sclerosis.
Spinal cords of sporadic cases with amyotrophic lateral sclerosis (ALS) and normal controls were immunohistochemically examined using antibodies for nitrotyrosine (NT), Cu/Zn superoxide dismutase (SOD), and nitric oxide synthase (NOS) of brain, endothelial, and inducible forms. Immunoreactivity for NT was densely detected in the motor neurons of ALS while it was not or was only minimally detected in those of controls. The staining was also found in the axons of motor neurons of ALS, but was not found in the controls. In contrast, although immunoreactivity for Cu/Zn SOD of the motor neurons was dense in the motor neurons, it was not different between the ALS and controls. Immunoreactivities for bNOS and eNOS in the motor neurons of ALS were stronger than those of controls, and were also found in degenerated axons in the anterior horn of ALS. However, the immunoreactivity for inducible NOS was only minimally detected in the motor neurons of ALS and controls, and was not detected in the degenerated axons of ALS. These results suggest that nitration of protein-tyrosine residue is upregulated in motor neurons of the spinal cord of ALS with selective increases of brain NOS- and endothelial NOS-like immunoreactivities. | {
"pile_set_name": "PubMed Abstracts"
} |
[Glucose and galactose absorption in the small intestine of rats in vivo].
In mathematical models, competition between glucose and galactose in the course of their active transport across the apical membrane of the erythrocytes, was studied. Both substances seem to share the same means of transmembrane transport, although the affinity of glucose in 6-fold higher. | {
"pile_set_name": "PubMed Abstracts"
} |
Integration of the DNA of a novel filamentous bacteriophage VSK from Vibrio cholerae 0139 into the host chromosomal DNA.
An unusual filamentous bacteriophage, VSK, containing single-stranded, circular DNA as its genome was isolated from Vibrio cholerae 0139 strains P07 and B04. Unlike other single-stranded DNA phages, VSK can integrate its genome into the chromosome of the host and enter into a lysogenic state. The double-stranded replicative form (RF) of the single-stranded phage DNA was isolated. A restriction map of the VSK RF DNA was constructed using HaeII, AvaII, ClaI and XbaI. By Southern blot analysis of the chromosomal DNA of the lysogen using labeled phage DNA as probe, the attachment site (attP) on the viral genome was also identified. | {
"pile_set_name": "PubMed Abstracts"
} |
TNF-induced anorexia and learned food aversions are attenuated by area postrema lesions.
Tumor necrosis factor (TNF) or cachectin has been proposed as an important mediator of cancer anorexia and cachexia. The present studies examined the extent to which TNF administration generates symptoms similar to those produced by tumor growth. Like the growth of certain tumors, TNF administration was found to be associated with the development of strong aversions to a novel diet. Area postrema lesions were found to significantly attenuate the effects of TNF on intake of a novel diet, a finding previously reported for tumor anorexia. In addition, the anorexic effects of TNF differed considerably as a function of the novelty of the diet. When the available diet was novel, effects of TNF in lowering food intake were substantial, whereas more modest effects were seen when the diet was familiar. These findings provide evidence for parallels between TNF- and tumor-induced anorexias. Nonetheless, these studies also confirm previous observations of the rapid development of tolerance to the anorexic effects of TNF, a finding that is not consistent with a role for TNF as a critical mediator of tumor anorexia. | {
"pile_set_name": "PubMed Abstracts"
} |
Decreased expression of signal-transducing CD3 zeta chains in T cells from the joints and peripheral blood of rheumatoid arthritis patients.
Although T cells from patients with rheumatoid arthritis (RA) have previously been determined to have poor proliferative responses to a variety of stimuli, the underlying mechanism is not known. We have investigated the expression of the signal-transducing zeta molecule in subsets of T cells and natural killer (NK) cells derived from the peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) of RA patients using quantitative flow cytometry, Western blot analysis and immunohistochemistry. A decrease of zeta expression was apparent in all investigated lymphocyte subsets from the PBMC and SFMC of RA patients, as compared to the corresponding subsets from healthy age- and sex-matched controls. A less pronounced reduction of cell surface-located CD3 epsilon, CD4 and CD8 was also located in T cells from SFMC as compared to PBMC from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image analysis also confirmed the low expression of zeta chains in synovial tissue of RA patients. The possibility that the decreased expression of zeta and of immune functions of T cells from RA patients may be related to the presence of free oxygen radicals, as we have previously reported in cancer patients, should be considered. | {
"pile_set_name": "PubMed Abstracts"
} |
2B4, a new member of the immunoglobulin gene superfamily, is expressed on murine dendritic epidermal T cells and plays a functional role in their killing of skin tumors.
Dendritic epidermal T cells (DETC), which are skin-specific members of the tissue-resident gamma delta T-cell family, are characterized by their potential to kill selected tumor targets by a non-major histocompatibility complex (MHC)-restricted mechanism. We have recently identified a new receptor molecule, 2B4, that appears to be associated with non-MHC-restricted recognition of tumor targets by natural killer cells. The purpose of this study was to determine whether DETC express 2B4 molecules, and, if so, to assess their functional roles in DETC-mediated killing of tumor targets. Short-term DETC lines as well as DETC freshly procured from skin expressed surface 2B4, as detected with a specific monoclonal antibody. Removal of interleukin (IL)-2 from DETC cultures caused substantial reduction in 2B4 expression levels as well as a reduction in cytotoxic capacity against YAC-1 targets in a standard 51Cr-release assay. Conversely, exposure to IL-2, but not to IL-7, elevated both 2B4 expression and cytotoxicity. To assess the functional roles played by surface 2B4, we pretreated DETC lines with anti-2B4 antibody and then tested for their killing potential. Anti-2B4, but not the control antibody, augmented their capacity to lyse YAC-1 targets (51Cr-release assays) and to disrupt the monolayers of Pam-212-transformed keratinocytes (visual assessment). Thus, we conclude that DETC express, in an IL-2-dependent manner, 2B4 molecules, which may play a unique role in the killing of skin-derived tumors. | {
"pile_set_name": "PubMed Abstracts"
} |
The need for repeated urological evaluation in low-risk patients with microscopic hematuria after negative diagnostic work-up.
To evaluate the role of repeated urological evaluation after negative initial diagnostic work-up of asymptomatic microhematuria (AMH) in low-risk patients. Criteria for patient inclusion were a complete negative initial diagnostic assessment including ultrasound (US), cystoscopy, upper urinary tract (UUT) imaging using intravenous urography (IVU) or multiphasic computed tomography (CT), absence of risk factors and a follow-up period of at least three years. Based on our institutional practice, urinalysis was repeated yearly; cystoscopy with US was repeated three years after initial work-up. The oncological outcome was evaluated across a mean follow-up of 8 (range: 3.7-10.2) years. A case series of 87 (32.2% of 270) low-risk patients, 56 women and 31 men, with a mean age of 52.4 (range: 19-87) years was studied. Three years after initial work-up, cystoscopy confirmed no bladder carcinoma in any of these 87 patients. Prostate cancer was diagnosed in one (1.1%) patient. In five (5.6%) patients, nephrological evaluation due to concomitant proteinuria on follow-up demonstrated chronic renal insufficiency (n=3), IgA nephropathy (n=1) and papillary necrosis of the kidney (n=1). Low-risk patients with persistent AMH after negative urological evaluation have a neglectable risk of developing bladder cancer on follow-up. Newly-discovered proteinuria on follow-up should be clarified by a nephrologist, as proteinuria could be a sign of significant glomerular disease. | {
"pile_set_name": "PubMed Abstracts"
} |
Increased expression of transgene in stably transformed cells of Dunaliella salina by matrix attachment regions.
Nuclear matrix attachment regions (MARs) are known to bind specifically to the nuclear scaffold and are thought to influence expression of the transgenes. In our previous studies, a new deoxyribonucleic acid fragment isolated from Dunaliella salina could bind to the nuclear matrix in vitro and had the typical characteristics of MARs. In this study, to investigate effects of MARs on expression of transgenes in the stably transformed cells of D. salina, expression vectors with and without MARs, which contained chloramphenicol acetyltransferase (CAT) reporter gene driven by D. salina ribulose 1,5-bisphosphate carboxylase/oxygenase promoter, were constructed and delivered, respectively, into cells of D. salina by electroporation. Twenty stably transformed colonies of D. salina were randomly picked out, and CAT gene expression was assayed. The results showed that the CAT enzyme of the colonies of D. salina transformed with the expression vector containing MARs averaged out about 4.5-fold higher than those without MARs, while the transgene expression variation among individuals of transformants decreased threefold. The CAT enzyme in the stably transformed lines was not significantly proportional to the gene copy numbers, suggesting that the effects of MARs on transgene expression may not be through increasing the transgene copy numbers. | {
"pile_set_name": "PubMed Abstracts"
} |
The family as the object of care in family practice.
Family practice as a specialty is based upon the continuing and comprehensive care of families. Much emphasis has been placed upon care of the "whole-person" and the family, but actual practice still reflects a predominant focus on the individual, rather than the family, as the object care. There is an important conceptual and practical difference between caring for the individual in the context of the family and caring for the family itself as the patient. Both approaches are required for family medicine to realize its potential in the ongoing care of families. This paper outlines some useful concepts and principles which can help to increase the capability of family physicians to deal with the common problems of individuals and their families. | {
"pile_set_name": "PubMed Abstracts"
} |
GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position.
GPR34 is a G protein-coupled receptor belonging to the P2Y family. Here, we attempted to resolve conflicting reports about whether it is a functional lysophosphatidylserine (LysoPS) receptor. In HEK293 cells expressing human, mouse or rat GPR34 and Gα chimera between Gαq and Gαi1(Gq/i1), LysoPS quickly elevated intracellular Ca(2+) ion levels ([Ca(2+)](i)). LysoPS also stimulated alkaline phosphatase (AP)-tagged TGFα (AP-TGFα) release in GPR34-expressing HEK293 cells and induced the migration of CHO-K1 cells expressing GPR34. Other lysophospholipids did not induce these actions. Replacement of the serine residue of LysoPS abolished the reactivity of LysoPS with GPR34, indicating that GPR34 strictly recognizes the serine head group of LysoPS. Recombinant phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)) that deacylates fatty acid at the sn-1 position of PS and produces 2-acyl-LysoPS, but not catalytically inactive mutant PS-PLA(1), stimulated the release of AP-TGFα from GPR34-expressing cells. Consistent with the result, LysoPS was detected in the cells treated with wild-type PS-PLA(1) but not with the mutant PS-PLA(1). PS treated with PLA(1) was much more effective at stimulating AP-TGFα release than PS treated with PLA(2). In addition, migration-resistant 2-acyl-1-deoxy-LysoPS, a 2-acyl-LysoPS analogue, was much more potent than 1-acyl-2-deoxy-LysoPS. The present studies confirm that GPR34 is a cellular receptor for LysoPS, especially with a fatty acid at the sn-2 position. | {
"pile_set_name": "PubMed Abstracts"
} |
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