tbuckley/cabot-search huggingface dataset:
Interleukin‐33 amplifies <scp>I</scp>g<scp>E</scp> synthesis and triggers mast cell degranulation via interleukin‐4 in naïve mice
Authors: M. Komai‐Koma, F. Brombacher, P. N. Pushparaj, B. Arendse, C. McSharry, J. Alexander, R. Chaudhuri, N. C. Thomson, A. N. J. McKenzie, I. McInnes, F. Y. Liew, D. Xu
Journal: Allergy (2012)

The regulation and function of IgE in healthy individuals and in antigen-naïve animals is not well understood. IL-33 administration increases serum IgE in mice with unknown mechanism. We tested the hypothesis that IL-33 provides an antigen-independent stimulus for IgE production and mast cell degranulation.IL-33 was administered to naïve wild-type (WT), nude and ST2(-/-) , IL-4(-/-) , IL4Rα(-/-) and T-or B-cell-specific IL-4Rα(-/-) mice. IgE and cytokines were quantified by ELISA. T- and B-lymphocyte numbers and CD40L expression were determined by flow cytometry. Anaphylaxis was measured by temperature, mast cell degranulation and histamine release.IL-33 enhanced IgE production in naïve WT, T-IL-4Rα(-/-) but not in ST2(-/-) , IL-4(-/-) , IL-4Rα(-/-) or B-cell-specific IL-4Rα(-/-) mice, demonstrating IL-33 specificity and IL-4 dependency. Moreover, IL-4 was required for IL-33-induced B-cell proliferation and T-cell CD40L expression, which promotes IgE production. IL-33-induced IL-4 production was mainly from innate cells including mast cells and eosinophils. IL-33 increased mast cell surface IgE and triggered degranulation and systemic anaphylaxis in allergen-naïve WT but not in IL-4Rα(-/-) mice.IL-33 amplifies IgE synthesis and triggers anaphylaxis in naïve mice via IL-4, independent of allergen. IL-33 may play an important role in nonatopic allergy and idiopathic anaphylaxis.
Nucleosomes possess a high affinity for glomerular laminin and collagen IV and bind nephritogenic antibodies in murine lupus-like nephritis
Authors: J E Mjelle, O P Rekvig, K A Fenton
Journal: Annals of the Rheumatic Diseases (2007)

Lupus nephritis is closely associated with in vivo autoantibody-binding to glomerular membrane-associated electron-dense structures (EDS). The biochemical nature and cellular origin of EDS are controversial, and definitive characterisation needs to be performed.By using the terminal transferase biotin-dUTP nick end-labelling (TUNEL) assay at the electron microscopic level, we have traced extracellular chromatin within the glomerular basement membranes of nephritic (NZBxNZW)F1 mice. The TUNEL assay was subsequently used in combination with standard immune electron microscopy (IEM). To analyse why chromatin particles associate with membranes, we determined the affinity of nucleosomes and DNA for glomerular laminin, collagen IV and the mesangial matrix proteoglycan perlecan by surface plasmon resonance.This intra-assay colocalisation TUNEL IEM demonstrated that autoantibodies fully colocalised with extracellular TUNEL-positive chromatin observed as EDS in glomerular membranes, similar to results obtained by the same technique applied to human lupus nephritis. Most importantly, these data validate the murine variant of lupus nephritis as a model to study origin of extracellular chromatin as a key element in human lupus nephritis. Kinetic analyses demonstrated that nucleosomes had a high affinity for collagen IV and laminin, but not for perlecan.Collectively, these results provide firm evidence that dominant target structures for nephritogenic autoantibodies are constituted by TUNEL-positive chromatin associated with glomerular capillary and mesangial matrix membranes at high affinity.
Tubal ligation and the risk of ovarian cancer: review and meta-analysis
Authors: D. Cibula, M. Widschwendter, O. Majek, L. Dusek
Journal: Human Reproduction Update (2010)

BACKGROUNDThe reduction of ovarian cancer (OC) risk in women with a history of tubal ligation (TL) has been reported repeatedly, mostly on small populations. We have aimed to provide a critical overview of the studies available to date and to conduct a meta-analysis.
A SYSTEM OF COMBINED INDIVIDUAL AND GROUP THERAPY AS USED IN THE MEDICAL PROGRAM FOR MERCHANT SEAMEN
Authors: STEPHEN SHERMAN
Journal: American Journal of Psychiatry (1943)

In summing up, it may be reaffirmed that the widely varying personality pictures offerred by merchant seamen necessitates diversity of therapeutic approach. This diversity is likewise demanded by the pressure of time, the need to cover a deal of ground with limited hours at one's disposal. Individual therapy cannot, so far as we have been able to determine to date, be cut short or swayed very radically from its classical form. Allowance must always be made for the spontaneous healing tendency of the acute war neuroses. Many of the acute cases in primarily healthy individuals do best if not tampered with too much. These cases get a great deal out of the contact with the rest home in the simplest sense. Many of them heal and go back to sea in three weeks or less. With those cases complicated by a preexisting neurosis, the task is of course more severe. In the light of our present knowledge, there seems to be no escape from a prolonged and orthodox form of individual therapy with these latter cases. It is possible that some realignment in the therapeutic scheme may ultimately be necessary, enabling us to care for these cases in some special way. Whatever the therapeutic method may be, work with war neurosis among merchant seamen brings its own unique rewards. One would need to travel far to find a group of men more appealing as to personality, more eager to accept what is offered them, and more grateful for help given. It is hoped that work with these seamen will vouchsafe, at the conclusion of the war, a body of clinical data of very special interest and value to medicine.
Targeting Epithelial-to-Mesenchymal Transition with Met Inhibitors Reverts Chemoresistance in Small Cell Lung Cancer
Authors: Israel Cañadas, Federico Rojo, Álvaro Taus, Oriol Arpí, Montserrat Arumí-Uría, Lara Pijuan, Silvia Menéndez, Sandra Zazo, Manuel Dómine, Marta Salido, Sergi Mojal, Antonio García de Herreros, Ana Rovira, Joan Albanell, Edurne Arriola
Journal: Clinical Cancer Research (2013)

Met receptor phosphorylation is associated with poor prognosis in human small cell lung cancer (SCLC). The aim of our work was to investigate the effects of hepatocyte growth factor (HGF)/Met-mediated epithelial-to-mesenchymal transition (EMT) in SCLC and to evaluate the role of Met inhibition in mesenchymal/chemorefractory SCLC models.SCLC models of HGF-induced EMT were evaluated in vitro and in vivo (subcutaneous xenografts in BALB/c nude mice) for chemosensitivity and response to Met inhibition with PF-2341066 (crizotinib). Human SCLC samples at diagnosis (N = 87) and relapse (N = 5) were evaluated by immunohistochemistry and immunofluorescence for EMT markers and Met status and these were correlated with patient outcome.We identified that the activation of the Met receptor through HGF induced expression of mesenchymal markers, an aggressive phenotype, and chemoresistance. Blockade of this process with the Met inhibitor resensitized cells to chemotherapy in vitro and in vivo. Moreover, mesenchymal markers in human SCLC specimens were associated with Met activation, predicted worse survival, and were upregulated in chemorefractory disease.These results provide novel evidence on an important role of Met-dependent EMT in the adverse clinical behavior of SCLC and support clinical trials of Met inhibitors and chemotherapy in this fatal disease.
Recurrence of recipient Langerhans' cell histiocytosis following bilateral lung transplantation
Authors: S B Habib, J Congleton, D Carr, J Partridge, B Corrin, D M Geddes, N Banner, M Yacoub, M Burke
Journal: Thorax (1998)

Langerhans' cell histiocytosis may cause irreversible respiratory failure due to progressive destruction of lung parenchyma and widespread cystic change. Transplantation offers a therapeutic option. A case is described of recurrence of Langerhans' cell histiocytosis which was associated with deterioration in lung function four years following bilateral lung transplantation. Patients transplanted for Langerhans' cell histiocytosis should be followed up with this complication in mind.
Sudan's media laws frustrate drives on AIDS and genital mutilation
Authors: P. Moszynski
Journal: BMJ (2002)

A growing clampdown on the press is affecting public health campaigns in Sudan, just as a breakdown in peace talks dashed hopes of ending one of the world's most intractable civil wars.

On 11 September the campaigning group Human Rights Watch wrote to President Omar al Bashir, condemning the recent crackdown. The group said, “In the past week, following the government's withdrawal from peace talks in Nairobi with rebel forces, the governmental National Press Council has confiscated newspapers for publishing allegedly subversive articles and security forces have detained, harassed, and interrogated newspaper editors and journalists.”

“Subversion” includes criticism of the breakdown of the peace talks—“threatening the unity of the state”—and discussing female …
Health Care and Patient-Reported Outcomes
Authors: Richard R. Rubin, Mark Peyrot, Linda M. Siminerio
Journal: Diabetes Care (2006)

The purpose of this study was to assess the relationship of patients' self-reported well-being, self-management, and diabetes control with factors related to the patient's health care.This was a cross-sectional survey of national samples of patients with diabetes (n = 5,104) from the multinational study of Diabetes Attitudes, Wishes and Needs (DAWN). Patients from 13 countries in Asia, Australia, Europe, and North America reported their level of well-being, self-management, and diabetes control. Hierarchical multiple regression analysis (blocks are countries, respondent characteristics, and health care features) was used to examine predictors of diabetes-related distress and general well-being, adherence to lifestyle and medical treatment recommendations, and perceived diabetes control and hyperglycemic symptoms.Country, respondent demographic and disease characteristics, and health care features were all associated with patient-reported outcomes. Better patient-provider collaboration was associated with more favorable ratings on all outcomes, and better access to the provider and availability of team care were associated with some positive outcomes. Country differences were only partly accounted for by patient and health care factors. Relationships between health care factors and outcomes varied across countries.Patients' reports of well-being, self-management, and diabetes control were related to the countries in which they live, their demographic and disease characteristics, and features of their health care. Opportunities to enhance patient-provider collaboration, access to care, and availability of team care should be pursued.
An in vivo microperfusion study of distal tubule bicarbonate reabsorption in normal and ammonium chloride rats.
Authors: D Z Levine
Journal: Journal of Clinical Investigation (1985)

For many years it has been thought that distal nephron hydrogen ion secretion can be importantly modulated by factors such as sodium delivery, sodium avidity, and potassium stores. Free flow micropuncture studies have also indicated that the rate of bicarbonate delivery may also alter the rate of bicarbonate reabsorption. The present studies were undertaken to examine possible luminal influences on total CO2 reabsorption in microperfused distal tubules in the rat in vivo. Tubules from normal and acidotic rats were perfused with five solutions in a manner that induced changes in bicarbonate load, sodium and potassium fluxes (JNa, JK), and luminal sulfate concentration. in each collected perfusate, simultaneous analyses were undertaken to determine water reabsorption, Na, and K concentrations using graphite furnace atomic absorption spectroscopy and total CO2 by microcalorimetry. Using factorial analysis of covariance to account for confounding effects on total CO2 flux (JtCO2) such as water reabsorption, distal tubules of acidotic rats reabsorbed CO2 in the range of 50-112 pmol X min-1 X mm-1 X These JtCO2 values were not significantly correlated with HCO3 load, JNa, or JK despite changes in the latter from net reabsorption to net secretion. Distal tubules of rats with normal acid-base status had JtCO2 values which were neither significantly different from zero nor correlated with changes in JK and JNa. Further, doubling the load from 250-500 pmol/min (by doubling the perfusion rate of 25-mM HCO3 solutions) did not stimulate JtCO2 in these normal animals. Accordingly, these acute in vivo microperfusion studies indicate for the first time that neither load nor potassium or sodium fluxes are important modulators of distal tubule bicarbonate reabsorption.
Antiretroviral Solid Drug Nanoparticles with Enhanced Oral Bioavailability: Production, Characterization, and In Vitro–In Vivo Correlation
Authors: Tom O. McDonald, Marco Giardiello, Philip Martin, Marco Siccardi, Neill J. Liptrott, Darren Smith, Phill Roberts, Paul Curley, Alessandro Schipani, Saye H. Khoo, James Long, Alison J. Foster, Steven P. Rannard, Andrew Owen
Journal: Advanced Healthcare Materials (2013)

Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving &gt;25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion‐templated freeze‐drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non‐nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z ‐average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four‐fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible.
Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro.
Authors: K L Moore, S P Andreoli, N L Esmon, C T Esmon, N U Bang
Journal: Journal of Clinical Investigation (1987)

Endotoxemia is frequently associated clinically with disseminated intravascular coagulation (DIC); however, the mechanism of endotoxin action in vivo is unclear. Modulation of tissue factor (TF) and thrombomodulin (TM) expression on the endothelial surface may be relevant pathophysiologic mechanisms. Stimulation of human umbilical vein endothelial cells with endotoxin (1 microgram/ml) increased surface TF activity from 1.52 +/- 0.84 to 11.89 +/- 8.12 mU/ml-10(6) cells at 6 h (n = 11) which returned to baseline by 24 h. Repeated stimulation at 24 h resulted in renewed TF expression. Endotoxin (1 microgram/ml) also caused a decrease in TM expression to 55.0 +/- 6.4% of control levels at 24 h (n = 10) that remained depressed at 48 h. Both effects were dose and serum dependent. A temporary rise in TF expression accompanied by a sustained fall in TM expression comprise a shift in the hemostatic properties of the endothelium that would favor intravascular coagulation and may contribute to the pathogenesis of DIC in gram-negative septicemia.
Public health in the NHS
Authors: P D O Davies
Journal: Journal of the Royal Society of Medicine (2002)

The May issue of JRSM reports a further debate on public health in the UK1. As a chest physician working in Liverpool I am becoming increasingly frustrated by the arguments around public health while my patients and I are daily subjected to extensive tobacco advertising on our television screens and on enormous billboards all around the city. Any debate on public health reorganization seems completely irrelevant in the face of the overwhelming advertising to which we are still subjected by the tobacco industry.
Identification of Amadori-Modified Plasma Proteins in Type 2 Diabetes and the Effect of Short-Term Intensive Insulin Treatment
Authors: Abdul Jaleel, Panagiotis Halvatsiotis, Brian Williamson, Peter Juhasz, Stephen Martin, K. Sreekumaran Nair
Journal: Diabetes Care (2005)

OBJECTIVE—Growing evidence supports that nonenzymatic glycation products may cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are the intermediate products of nonenzymatic glycation and constitute the forms of glycated proteins in diabetes. The objective of the current study was to utilize two-dimensional gel electrophoresis, Western blot, and mass spectrometry to identify Amadori-modified plasma proteins in type 2 diabetic patients with poor glycemic control and assess the impact of short-term insulin treatment on the glycation of these proteins. RESEARCH DESIGN AND METHODS—We compared eight type 2 diabetic subjects (aged 56 ± 3 years and BMI 29.7 ± 0.9 kg/m2) with an average diabetes duration of 8.5 years (range 3–19) with equal numbers of weight-matched (aged 56 ± 2 years and BMI 30.1 ± 10.0 kg/m2) and lean (aged 58 ± 2 years and BMI 25 ± 00.5 kg/m2) nondiabetic subjects who have no first-degree relatives with diabetes. Two separate blood samples were collected from the type 2 diabetic subjects, one following 2 weeks of withdrawal of all antidiabetic medications (T2D−; plasma glucose 12.6 ± 1.0 mmol/l) and another following 10 days of intensive insulin treatment (T2D+; plasma glucose 5.5 ± 0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel electrophoresis. Western blot analysis was performed, and several proteins, which reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by tandem mass spectrometry. RESULTS—No significant differences in the glycation of proteins between the obese and lean groups were noted, but type 2 diabetic patients had several proteins with higher glycation than the control groups. We identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody upon intensive insulin treatment. A significant (P &amp;lt; 0.03) difference in Amadori modification was observed between the T2D− and control subjects for all these proteins except the Ig light chain. Insulin treatment reduced Amadori modification of albumin (23.2%, P &amp;lt; 0.02), fibrin (34.6%, P &amp;lt; 0.001), Ig heavy chain constant region (20.7%, P &amp;lt; 0.05), transferrin (25.4%, P &amp;lt; 0.04), and Ig light chain (13%, P &amp;lt; 0.02). In addition, Western blot analysis of two-dimensional gel electrophoresis identified α-fibrinogen precursor, β-fibrinogen precursor, fibrinogen γ-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment. CONCLUSIONS—The current approach offers the opportunity to identify Amadori modification of many proteins that may cause functional alterations and offers the potential for monitoring short-term glycemic control in diabetic patients.
Quantitative Assessment of Severity of Ventricular Septal Defect by Three-Dimensional Reconstruction of Color Doppler–Imaged Vena Contracta and Flow Convergence Region
Authors: Masahiro Ishii, Kanoko Hashino, Genjyu Eto, Takahiro Tsutsumi, Wakako Himeno, Yoko Sugahara, Hiromi Muta, Jun Furui, Teiji Akagi, Yuhei Ito, Hirohisa Kato
Journal: Circulation (2001)

The aim of the present study was to investigate the feasibility and potential value of the computer-controlled, 3D, echocardiographic reconstruction of the color Doppler-imaged vena contracta (CDVC) and the flow convergence (FC) region as a means of accurately and quantitatively estimating the severity of a ventricular septal defect (VSD).We performed a 3D reconstruction of the CDVC and the FC region in 19 patients with an isolated VSD using an ultrasound system interfaced with a Tomtec computer. The variable asymmetric geometry of the CDVC and the FC region could be 3D-visualized in all patients. The 3D-measured areas of CDVC correlated well with volumetric measurements of the severity of VSD (r=0.97, P:<0.001). Regression analysis between the shunt flow rate (calculated from the product of the area of CDVC and the continuous Doppler-derived velocity time integral) and the corresponding reference results (calculated by cardiac catheterization) demonstrated a close correlation (r=0.95, P:<0.001). There was also a good correlation between shunt flow rates calculated using the conventional 2D, 1-axis measurement of the FC isovelocity surface area with the hemispheric assumption (r=0.95, P:<0.001); shunt flow rates calculated using 3D, 3-axis measurements of the FC region (r=0.97, P:<0.01); and reference results by cardiac catheterization. However, the 2D method substantially underestimated the actual shunt flow rate.The 3D reconstruction of the CDVC and the FC region may aid in quantifying the severity of VSD.
References that anyone can edit: review of Wikipedia citations in peer reviewed health science literature
Authors: M. D. Bould, E. S. Hladkowicz, A.-A. E. Pigford, L.-A. Ufholz, T. Postonogova, E. Shin, S. Boet
Journal: BMJ (2014)

Objectives To examine indexed health science journals to evaluate the prevalence of Wikipedia citations, identify the journals that publish articles with Wikipedia citations, and determine how Wikipedia is being cited. Design Bibliometric analysis. Study selection Publications in the English language that included citations to Wikipedia were retrieved using the online databases Scopus and Web of Science. Data sources To identify health science journals, results were refined using Ulrich's database, selecting for citations from journals indexed in Medline, PubMed, or Embase. Using Thomson Reuters Journal Citation Reports, 2011 impact factors were collected for all journals included in the search. Data extraction Resulting citations were thematically coded, and descriptive statistics were calculated. Results 1433 full text articles from 1008 journals indexed in Medline, PubMed, or Embase with 2049 Wikipedia citations were accessed. The frequency of Wikipedia citations has increased over time; most citations occurred after December 2010. More than half of the citations were coded as definitions (n=648; 31.6%) or descriptions (n=482; 23.5%). Citations were not limited to journals with a low or no impact factor; the search found Wikipedia citations in many journals with high impact factors. Conclusions Many publications are citing information from a tertiary source that can be edited by anyone, although permanent, evidence based sources are available. We encourage journal editors and reviewers to use caution when publishing articles that cite Wikipedia.