tbuckley/cabot-search huggingface dataset:
Polymorphisms in the CPB2 Gene Are Maintained by Balancing Selection and Result in Haplotype-Preferential Splicing of Exon 7
Authors: R. Cagliani, M. Fumagalli, S. Riva, U. Pozzoli, M. Fracassetti, N. Bresolin, G. P. Comi, M. Sironi
Journal: Molecular Biology and Evolution (2010)

The CPB2 gene encodes thrombin-activatable fibrinolysis inhibitor (TAFI), a hepatically secreted zymogen acting as a molecular link among coagulation, fibrinolysis, and inflammation. Variants in CPB2 have been associated with several human conditions. We resequenced and analyzed the two regions carrying previously known nonsynonimous single-nucleotide polymorphisms (Ala147Thr and Ile325Thr) and variants affecting transcript stability. Our data indicate that whereas the gene portion extending from exon 9 to the 3′ untranslated region fits a model of neutral evolution, variants in the region encompassing exons 6–7 have been maintained by balancing selection. Indeed, we verified that the region displays high nucleotide diversity, many intermediate frequency variants, and an excess of polymorphism compared with interspecific divergence. Consistently, haplotype analysis indicated the presence of two major haplotype clades separated by deep branches. Transcript analysis revealed that in both HepG2 cells and human liver samples, CPB2 exon 7 undergoes haplotype-preferential skipping. Therefore, we indicate that balancing selection has been maintaining functional variants that promote alternative exon 7 splicing. Although transcripts lacking exon 7 represent a minority of total CPB2 products, the effect on antifibrinolytic activity might be much greater as the intrinsic instability of TAFI is a major determinant of its antifibrinolytic potential. These data highlight the contribution of population genetics approaches to the analysis of functional genetic variation and may orient further biochemical and genetics studies on the pathophysiolgic role of CPB2 gene products.
A refractory case of secondary erythermalgia successfully treated with lumbar sympathetic ganglion block
Authors: M. Seishima, H. Kanoh, T. Izumi, M. Niwa, Y. Matsuzaki, A. Takasu, M. Ban, Y. Kitajima
Journal: British Journal of Dermatology (2000)

Journal Article A refractory case of secondary erythermalgia successfully treated with lumbar sympathetic ganglion block Get access M. Seishima, M. Seishima Departments of Dermatology and Mariko Seishima. E‐mail: seimarik@gumail.cc.gifu‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Kanoh, H. Kanoh Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar T. Izumi, T. Izumi Departments of Dermatology and Search for other works by this author on: Oxford Academic Google Scholar M. Niwa, M. Niwa Anaesthesiology, Ogaki Municipal Hospital, Minaminokawa‐cho 4–86, Ogaki 503–8502, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Matsuzaki, Y. Matsuzaki Anaesthesiology, Ogaki Municipal Hospital, Minaminokawa‐cho 4–86, Ogaki 503–8502, Japan Search for other works by this author on: Oxford Academic Google Scholar A. Takasu, A. Takasu Anaesthesiology, Ogaki Municipal Hospital, Minaminokawa‐cho 4–86, Ogaki 503–8502, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Ban, M. Ban Department of Dermatology, Hashima City Hospital, Hashima, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Kitajima Y. Kitajima Department of Dermatology, Gifu University School of Medicine, Gifu, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 4, 1 October 2000, Pages 868–872, https://doi.org/10.1046/j.1365-2133.2000.03795.x Published: 01 October 2000
When does rheumatoid arthritis start and can it be stopped before it does?
Authors: Vivian P Bykerk, Johanna M Hazes
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) is characterised by a persistent and often destructive polyarticular synovitis involving large and small joints not infrequently associated with extra-articular features. This construct was classified by the American Rheumatism Association (ARA) 1987 classification criteria for RA.1 However, RA probably has a long prodrome with an asymptomatic phase followed by a period of unclassifiable musculoskeletal symptoms and signs before fully manifesting four out of seven of these criteria. Current concepts of pathogenesis presume that environmental triggers interact with genes such as those from the histocompatibility complex where an arthritogenic peptide triggers the innate immune response followed by upregulation of adaptive immunity.2 This would represent the preclinical phase of RA during which anti-citrullinated peptide antibodies (ACPAs) and then IgM-rheumatoid factor (IgM-RF) are generated. During this adaptive immune response, profound changes occur in the synovial membrane, leading to an influx of immune and inflammatory cells and increased vascularity of the joints followed by a destructive synovitis.2

Ultimately, patients develop a sufficient burden of synovitis that it is classifiable as RA. It is not easy to identify when RA actually starts clinically but it may be important to recognise preclinical RA at a much earlier time point in order to prevent progression to full-blown classifiable disease which becomes persistent and destructive. Starting from the presence of early arthritis or undifferentiated arthritis (UA) several prediction models to predict the development of RA—however, defined—have been derived. In all models the presence of ACPAs is an independent strong predictor of the development of RA.3,–,6

Recently, researchers have attempted to identify patients in the prodromal phase during a period of very early inflammatory arthritis (VEIA) to determine if there are predictors that may indicate which patients go on to develop RA and if there is any treatment …
Hormonal and metabolic reactions evoked by acute myocardial infarction.
Authors: L Ceremuzyński
Journal: Circulation Research (1981)

RECOGNITION of the importance of humoral balance in the body originated in the work of Claude Bernard (1855) and was developed later mainly by Cannon (1915) andSelye (1950).Recent myocardial infarction (MI) has been reported to elicit humoral disturbances which, a little more than a decade ago, were not considered of importance.The recognition that they may influence the clinical course of the disease came in recent years as a consequence of better understanding of the complex character of MI and the nature of its complications.In this review I intend to show briefly the accumulated data on the pattern of humoral, mainly hormonal, disorders accompanying MI which have been relatively well elucidated.Their interrelations and the mechanism of their possible influence on the clinical course of the disease also will be outlined.The therapeutic implications of this knowledge will be discussed briefly and some areas which require further research will be suggested.
Controlled trial of psychiatric nurse therapists in primary care.
Authors: I Marks
Journal: BMJ (1985)

In a randomised controlled clinical trial neurotic patients (mainly phobic and obsessive-compulsive) did significantly better up to one year follow up after receiving behavioural psychotherapy from a nurse therapist rather than routine treatment from a general practitioner. At the end of the year control patients who had not improved had crossover behavioural treatment from the nurse and then improved. Those who dropped out or refused therapy did not show worthwhile gains. Patients preferred being treated in the primary care setting rather than in hospital. Placing nurse therapists in primary care is not only viable but may save more health care resources than it consumes.
Molecular Interactions Between Inhaled Anesthetics and Proteins
Authors: R G Eckenhoff, J S Johansson
Journal: Pharmacological Reviews (1997)

The fundamental interactions of inhalational anesthetics with proteins have been considered in some detail, using specific examples where appropriate to illustrate these interactions and demonstrate progress. It is now clear that these low-affinity volatile molecules with rapid kinetics can specifically bind to discrete sites in some proteins at reasonable pharmacological concentrations, and some general features of these sites are beginning to emerge. The structural or dynamic consequences of anesthetic binding, however, are still vague at best. The remaining challenge is to define which interactions produce anesthetic binding to relevant targets and what the features of this relevant anesthetic binding site are. Finally, and most importantly, how does the occupancy of these pockets, patches, or cavities result in the subtle alterations in protein conformation and dynamics that confound their function and ultimately produce the behavioral response that we term "anesthesia"?
Nephrectomy in Infancy
Authors: A. C. Morson
Journal: BMJ (1926)

movemenits of the stomach have started on their course.This w-ould explain the interval between eatinig and the oi-set of pain in gastric ulcers.In duodenal ulcer the percentage of acid in the gastrio jti;ice is nearly always hiigh.The pyloric sphincter relaxes in the presence of acid oii its proximal side, and contracts if acid remains unneutralized on its distal side.If the strength of the acid is excessive the conitraction of the sphincter is overdone and prolonged.The\ results of gastro- jejunostomy are said to be the most satisfactory in cases of duodenal ulcer.Perhaps this is because the operation allows a more free regurgitation of alkaline juice into the stomach, and provides an exit that is niot guarded by a sl hincter.So that in gastric and duodenal ulcers the explanation of pain and its time-table is the behaviour of the smooth nLuscle under the influence of acid.In one case'the acid stimulates the base of the ulcer, and in the other a highly acid juice produces a cramp of the sphincter.
Postural Control Mechanisms During Quiet Standing in Patients With Diabetic Sensory Neuropathy
Authors: Danik Lafond, Hélène Corriveau, Francois Prince
Journal: Diabetes Care (2004)

The objective of the present study was to compare postural mechanisms identified by using dual force platform in healthy elderly community-dwelling subjects and diabetic sensory neuropathy (DSN) patients under different visual conditions.The presence and the severity of the sensory neuropathy was evaluated with a clinical scale. Postural mechanisms and motor strategies of the ankle and hip joints were quantified by testing subjects in quiet stance on a dual force platform under two visual conditions (eyes open and eyes closed). Root mean square (RMS) values of the center of pressure (COP) time-varying signals and normalized cross-correlation function were used to estimate the contribution and the interdependence of postural control mechanisms.DSN patients show larger RMS values of the COP(net) displacement in both anteroposterior and mediolateral (ML) directions. Motor strategies at the ankle joints are altered in DSN patients compared with healthy elderly subjects particularly in the ML direction.This experiment is the first to highlight that even with vision, postural mechanisms at the ankle joints are impaired in DSN patients during quiet standing. Our results point out the importance of focusing on postural control instability in ML of DSN patients.
Predicting risk of type 2 diabetes in England and Wales: prospective derivation and validation of QDScore
Authors: J. Hippisley-Cox, C. Coupland, J. Robson, A. Sheikh, P. Brindle
Journal: BMJ (2009)

<b>Objective</b> To develop and validate a new diabetes risk algorithm (the QDScore) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population. <b>Design</b> Prospective open cohort study using routinely collected data from 355 general practices in England and Wales to develop the score and from 176 separate practices to validate the score. <b>Participants</b> 2 540 753 patients aged 25-79 in the derivation cohort, who contributed 16 436 135 person years of observation and of whom 78 081 had an incident diagnosis of type 2 diabetes; 1 232 832 patients (7 643 037 person years) in the validation cohort, with 37 535 incident cases of type 2 diabetes. <b>Outcome measures</b> A Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort and to derive a risk equation in men and women. The predictive variables examined and included in the final model were self assigned ethnicity, age, sex, body mass index, smoking status, family history of diabetes, Townsend deprivation score, treated hypertension, cardiovascular disease, and current use of corticosteroids; the outcome of interest was incident diabetes recorded in general practice records. Measures of calibration and discrimination were calculated in the validation cohort. <b>Results</b> A fourfold to fivefold variation in risk of type 2 diabetes existed between different ethnic groups. Compared with the white reference group, the adjusted hazard ratio was 4.07 (95% confidence interval 3.24 to 5.11) for Bangladeshi women, 4.53 (3.67 to 5.59) for Bangladeshi men, 2.15 (1.84 to 2.52) for Pakistani women, and 2.54 (2.20 to 2.93) for Pakistani men. Pakistani and Bangladeshi men had significantly higher hazard ratios than Indian men. Black African men and Chinese women had an increased risk compared with the corresponding white reference group. In the validation dataset, the model explained 51.53% (95% confidence interval 50.90 to 52.16) of the variation in women and 48.16% (47.52 to 48.80) of that in men. The risk score showed good discrimination, with a D statistic of 2.11 (95% confidence interval 2.08 to 2.14) in women and 1.97 (1.95 to 2.00) in men. The model was well calibrated. <b>Conclusions</b> The QDScore is the first risk prediction algorithm to estimate the 10 year risk of diabetes on the basis of a prospective cohort study and including both social deprivation and ethnicity. The algorithm does not need laboratory tests and can be used in clinical settings and also by the public through a simple web calculator (www.qdscore.org).
Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study
Authors: Katharina Fleischhauer, Bronwen E Shaw, Theodore Gooley, Mari Malkki, Peter Bardy, Jean-Denis Bignon, Valérie Dubois, Mary M Horowitz, J Alejandro Madrigal, Yasuo Morishima, Machteld Oudshoorn, Olle Ringden, Stephen Spellman, Andrea Velardi, Elisabetta Zino, Effie W Petersdorf
Journal: The Lancet Oncology (2012)
Loss of Beta-Catenin Expression in Metastatic Gastric Cancer
Authors: Matthias P.A. Ebert, Jun Yu, Juliane Hoffmann, Alba Rocco, Christoph Röcken, Sabine Kahmann, Oliver Müller, Murray Korc, Joseph J. Sung, Peter Malfertheiner
Journal: Journal of Clinical Oncology (2003)

Purpose: Beta-catenin (β-catenin) participates in intercellular adhesion and is an integral part of the Wnt signaling pathway. The role of β-catenin in the pathogenesis of gastric cancer and its metastasis is largely unknown. Patients and Methods: Immunohistochemistry and Western blot analysis were used to analyze the expression of β-catenin in 87 human gastric cancers, in metastasis and cancer cell lines. The β-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations. Furthermore, methylation of the β-catenin promoter in cell lines was assessed by treatment with 5′-azadeoxycytidine and sodium bisulfite genomic sequencing. Results: β-Catenin expression was present at either the cell membrane or the cytoplasm in 34 of 75 primary gastric cancers. Expression of β-catenin was significantly more frequent in intestinal-type (P = .0049) and well-differentiated gastric cancers (P &lt; .001). There were no quantitative differences between gastric cancers and the nonmalignant gastric tissues, as determined by Western blot analysis. One of 18 metastatic cancer lesions and four of five gastric cancer cell lines expressed β-catenin protein. N87 cells, derived from the liver metastasis of a gastric cancer, did not express β-catenin. Treatment with 5′-azadeoxycytidine restored β-catenin protein levels in this cell line, which exhibited significantly more 5-methylcytosines in the β-catenin promoter compared with the other cell lines. Conclusion: β-Catenin expression is lost in a subgroup of primary gastric cancers, is frequently absent in metastases, and exhibits nuclear localization in cancers with either β-catenin or APC gene mutations. Interestingly, the loss of β-catenin expression in metastatic gastric cancers may result from hypermethylation of the β-catenin promoter.
GreenLight HPS 120-W Laser Vaporization versus Transurethral Resection of the Prostate for the Treatment of Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia: A Randomized Clinical Trial with 2-year Follow-up
Authors: Carlos Capitán, Cristina Blázquez, M. Dolores Martin, Virginia Hernández, Enrique de la Peña, Carlos Llorente
Journal: European Urology (2011)
Dilemmas in the Management of Atrial Fibrillation in Chronic Kidney Disease
Authors: Holger Reinecke, Eva Brand, Rolf Mesters, Wolf-Ru[Combining Diaeresis]diger Scha[Combining Diaeresis]bitz, Marc Fisher, Hermann Pavensta[Combining Diaeresis]dt, Gu[Combining Diaeresis]nter Breithardt
Journal: Journal of the American Society of Nephrology (2008)

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Little attention has been paid to the problem of atrial fibrillation, although this arrhythmia is very frequent with a prevalence of 13 to 27% in patients on long-term hemodialysis. Because of the large number of pathophysiologic mechanisms involved, these patients have a high risk for both thromboembolic events and hemorrhagic complications. Stroke is a frequent complication in CKD: The US Renal Data System reports an incidence of 15.1% in hemodialysis patients compared with 9.6% in patients with other stages of CKD and 2.6% in a control cohort without CKD. The 2-yr mortality rates after stroke in these subgroups were 74, 55, and 28%, respectively. Although oral coumadin is the treatment of choice for atrial fibrillation, its use in patients with CKD is reported only in limited studies, all in hemodialysis patients, and is associated with a markedly increased rate of bleeding compared with patients without CKD. With regard to the high risk for stroke and the conflicting data about oral anticoagulation, an individualized stratification algorithm is presented based on relevant studies.
Ischemia-induced loss of epithelial polarity. Role of the tight junction.
Authors: B A Molitoris, S A Falk, R H Dahl
Journal: Journal of Clinical Investigation (1989)

In proximal tubular cells ischemia is known to result in the redistribution of apical and basolateral domain-specific lipids and proteins into the alternate surface membrane domain. Since tight junctions are required for the maintenance of surface membrane polarity, the effect of ischemia on tight junction functional integrity was investigated. In vivo microperfusion of early loops of proximal tubules with ruthenium red (0.2%) in glutaraldehyde (2%) was used to gain selective access to and outline the apical surface membrane. Under control situations ruthenium red penetrated less than 10% of the tight junctions. After 5, 15, and 30 min of ischemia, however, there was a successive stepwise increase in tight junction penetration by ruthenium red to 29, 50, and 62%, respectively. This was associated with the rapid duration-dependent redistribution of basolateral membrane domain-specific lipids and NaK-ATPase into the apical membrane domain. Taken together, these data indicate that during ischemia proximal tubule tight junctions open, which in turn leads to the lateral intramembranous diffusion of membrane components into the alternate surface membrane domain.
Intimate partner violence and HIV in ten sub-Saharan African countries: what do the Demographic and Health Surveys tell us?
Authors: Dick Durevall, Annika Lindskog
Journal: The Lancet Global Health (2014)

BackgroundMany studies have identified a significant positive relation between intimate partner violence and HIV in women, but adjusted analyses have produced inconsistent results. We systematically assessed the association, and under what condition it holds, using nationally representative data from ten sub-Saharan African countries, focusing on physical, sexual, and emotional violence, and on the role of male controlling behaviour.MethodsWe assessed cross-sectional data from 12 Demographic and Health Surveys from ten countries in sub-Saharan Africa. The data are nationally representative for women aged 15–49 years. We estimated odds ratios using logistic regression with and without controls for demographic and socioeconomic factors and survey–region fixed effects. Exposure was measured using physical, sexual, emotional violence, and male controlling behaviour, and combinations of these. The samples used were ever-married women, married women, and women in their first union. Depending on specification, the sample size varied between 11 231 and 45 550 women.FindingsThere were consistent and strong associations between HIV infection in women and physical violence, emotional violence, and male controlling behaviour (adjusted odds ratios ranged from 1·2 to 1·7; p values ranged from <0·0001 to 0·0058). The evidence for an association between sexual violence and HIV was weaker and only significant in the sample with women in their first union. The associations were dependent on the presence of controlling behaviour and a high regional HIV prevalence rate; when women were exposed to only physical, sexual, or emotional violence, and no controlling behaviour, or when HIV prevalence rates are lower than 5%, the adjusted odds ratios were, in general, close to 1 and insignificant.InterpretationThe findings indicate that male controlling behaviour in its own right, or as an indicator of ongoing or severe violence, puts women at risk of HIV infection. HIV prevention interventions should focus on high-prevalence areas and men with controlling behaviour, in addition to violence.FundingSwedish National Science Foundation and Gothenburg Centre of Globalization and Development, University of Gothenburg, Gothenburg, Sweden.