tbuckley/cabot-search huggingface dataset:
Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic-metabolizing bacterium
Authors: Carlo Selmi, David L. Balkwill, Pietro Invernizzi, Aftab A. Ansari, Ross L. Coppel, Mauro Podda, Patrick S. Leung, Thomas P. Kenny, Judy Van De Water, Michael H. Nantz, Mark J. Kurth, Eric M. Gershwin
Journal: Hepatology (2003)

Infectious and environmental agents have been proposed as immunologic triggers for primary biliary cirrhosis (PBC). Recently, a ubiquitous organism that metabolizes organic compounds and estrogens, Novosphingobium aromaticivorans , has been defined. Importantly, 2 bacterial proteins have homology with the E2 component of the pyruvate dehydrogenase complex (PDC–E2). Sera from 97 patients with PBC, 46 first–degree relatives, 10 spouses, and 195 controls were studied for reactivity against N. aromaticivorans and Escherichia coli . The reactivity was defined by absorption, affinity purification, and using monoclonal antibodies to PDC–E2. Stool samples from 20 patients with PBC and 34 controls were analyzed by polymerase chain reaction (PCR) for the presence of N. aromaticivorans . Sera from 100% of anti–PDC–E2 positive (77/77), 33% of anti–BCOADC E2 positive (1/3), and 12% of antimitochondrial antibody (AMA) negative patients with PBC (2/17) reacted with titers up to 10 -6 against two known lipoylated bacterial proteins (47 and 50 kd) from N. aromaticivorans , including patients with early disease. This titer was approximately 100– to 1,000–fold higher than against E. coli and verified by absorption, use of affinity–purified sera, and monoclonal antibody reagents. Moreover, 78 of 80 AMA–positive and 5 of 17 AMA–negative patients with PBC had antibodies against 3 other N. aromaticivorans proteins. In contrast, 0 of 195 control sera reacted against N. aromaticivorans . Approximately 25% of patients and controls had N. aromaticivorans in their fecal specimens. In conclusion, based on protein homology, capacity to metabolize xenobiotics as well as modulate estrogens, its presence in feces, and specific immunologic response, we propose that N. aromaticivorans is a candidate for the induction of PBC.
Determinants of Incident Hyperglycemia 6 Years After Delivery in Young Rural Indian Mothers
Authors: Smita R. Kulkarni, Caroline H.D. Fall, Niranjan V. Joshi, Himangi G. Lubree, Vaishali U. Deshpande, Rashmi V. Pasarkar, Dattatray S. Bhat, Sadanand S. Naik, Chittaranjan S. Yajnik
Journal: Diabetes Care (2007)

OBJECTIVE—To study determinants of incident hyperglycemia in rural Indian mothers 6 years after delivery. RESEARCH DESIGN AND METHODS—The Pune Maternal Nutrition Study collected information in six villages near Pune on prepregnant characteristics and nutrition, physical activity, and glucose tolerance during pregnancy. An oral glucose tolerance test (OGTT) was repeated 6 years after delivery. RESULTS—A total of 597 mothers had an OGTT at 28 weeks’ gestation; 3 had gestational diabetes (by World Health Organization 1999 criteria). Six years later, 42 of 509 originally normal glucose-tolerant mothers were hyperglycemic (8 diabetic, 20 with impaired glucose tolerance, and 14 with impaired fasting glucose). The hyperglycemic women had shorter legs and thicker skinfolds before pregnancy (P &amp;lt; 0.01, both), were less active and more hyperglycemic (2-h plasma glucose 4.8 vs. 4.4 mmol/l, P &amp;lt; 0.001) during pregnancy, and gained more weight during follow-up (6.0 vs. 2.7 kg, P &amp;lt; 0.001). Multivariate analysis revealed that total leukocyte count and blood pressure during pregnancy were additional independent predictors of 2-h glucose concentration at follow-up. CONCLUSIONS—Our results suggest that compromised linear growth, adiposity, inflammation, and less physical activity predispose to hyperglycemia in young rural Indian women. International cut points of diabetes risk factors are largely irrelevant in these women.
In vitro and in vivo protective effect of atriopeptin III on ischemic acute renal failure.
Authors: M Nakamoto, J I Shapiro, P F Shanley, L Chan, R W Schrier
Journal: Journal of Clinical Investigation (1987)

The effect of atriopeptin III (AP-III) on ameliorate ischemic acute renal failure was first examined in the isolated perfused kidney. Isolated rat kidneys were clamped for 1 h and reperfused for 30 min without therapy and then perfused with either 0 (control) or 100 micrograms/dl AP-III. In this system AP-III significantly improved renal plasma flow (39.6 +/- 2.4 vs. 32.2 +/- 2.1 ml/min per g; P less than 0.05) inulin clearance (182.6 +/- 49.2 vs. 24.6 +/- 6.2 microliters/min per g; P less than 0.05), urine flow (52.9 +/- 12.1 vs. 7.1 +/- 0.8 microliters/min per g, P less than 0.01), and net tubular sodium reabsorption (21.2 +/- 6.6 vs. 2.9 +/- 0.9 mumol/min per g, P less than 0.05) as compared with control. A second series of in vivo studies experiments were performed using 1 h of bilateral renal artery clamping followed by an intravenous infusion of either saline alone (control) or AP-III (0.20 microgram/kg per min) for 60 min. The results demonstrated that inulin clearance (244.4 +/- 25.1 vs. 15.8 +/- 8.2 microliters/min per 100 g; P less than 0.01), urine flow (23.1 +/- 5.9 vs. 1.1 +/- 0.5 microliters/min per 100 g; P less than 0.01), and net tubular sodium reabsorption (38.9 +/- 4.7 vs. 4.3 +/- 1.6 mumol/min per 100 g; P less than 0.01) were significantly higher in AP-III-treated rats than controls during the hour of AP-III infusion. In 1 h posttreatment study this significant protective effect of AP-III was documented to persist. In more chronic studies animals treated acutely with AP-III had lower serum creatinine concentration at 24 h (1.8 +/- 0.3 vs. 3.3 +/- 0.4 mg/dl; P less than 0.01) and 48 (1.0 +/- 0.2 vs. 2.4 +/- 4.0 mg/dl; P less than 0.01) after the 60 min of ischemia than controls. Renal adenosine triphosphate regeneration as assessed by P-31 nuclear magnetic resonance during reflow was also significantly improved in AP-III-treated animals at 1 h (3.03 +/- 0.30 vs. 1.45 +/- 0.40 mumol/g dry wt; P less than 0.05) and 2 h (3.98 +/- 0.46 vs. 1.80 +/- 0.05 mumol/g dry wt; P less than 0.01) or reflow as compared with control rats. Thus, AP-III significantly ameliorates ischemic acute renal failure both in vitro and in vivo in the rat.
E-cadherin autoantibody profile in patients with pemphigus vulgaris
Authors: M.E.F. Oliveira, D.A. Culton, P. Prisayanh, B.F. Qaqish, L.A. Diaz
Journal: British Journal of Dermatology (2013)

Pemphigus vulgaris (PV) is an autoimmune skin blistering disease. The main targets of autoantibodies are the desmosomal proteins desmoglein (Dsg)3 and Dsg1. Anti-E-cadherin antibody is the second most frequent antibody found in pemphigus foliaceus (fogo selvagem), but the frequency in PV is unknown.To determine the anti-E-cadherin antibody profile in the two major subtypes of PV: mucosal PV (mPV) and mucocutaneous PV (mcPV).Sera from 80 patients with PV and 80 controls were tested. Patients with PV were subdivided into mPV (n = 18) and mcPV (n = 62). Samples were tested by E-cadherin, Dsg1 and Dsg3 enzyme-linked immunosorbent assays (ELISAs), and immunoprecipitation coupled with Western blotting (IP-WB).Both mPV and mcPV sera have antibodies against E-cadherin as demonstrated by ELISA and IP-WB. Both subtypes of PV have low levels of anti-E-cadherin antibodies, but significantly higher levels than healthy controls by ELISA (P < 0·0001). No difference exists in antibody levels between subgroups (P = 0·82). By IP-WB, 78% of mcPV sera reacted to E-cadherin, vs. 33% of mPV sera tested. Correlation analysis suggests a moderate correlation between anti-E-cadherin antibodies and Dsg1 antibodies (average r = 0·61), but no correlation with Dsg3 antibodies (average r = 0·19). Patients with mPV can have lower levels of Dsg1 antibodies compared with controls by ELISA (P < 0·0001). A few mPV sera also reacted to Dsg1 protein by IP-WB (17%).Anti-E-cadherin antibodies are present in both major subtypes of PV. A moderate correlation exists between E-cadherin and Dsg1 antibodies. Patients with mPV can have low levels of both E-cadherin and Dsg1 antibodies.
Serial echocardiographic assessment of left ventricular function and gene analysis of contractile protein and collagen after myocardial infarction
Authors: Akihisa Hanatani, Minoru Yoshiyama, Iku Toda, Kaname Akioka, Masakazu Teragaki, Kazuhide Takeuchi, Jyunichi Yoshikawa
Journal: Journal of the American College of Cardiology (1996)
Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a <i>Diabetes Care</i> Editors’ Expert Forum
Authors: William T. Cefalu, George A. Bray, Philip D. Home, W. Timothy Garvey, Samuel Klein, F. Xavier Pi-Sunyer, Frank B. Hu, Itamar Raz, Luc Van Gaal, Bruce M. Wolfe, Donna H. Ryan
Journal: Diabetes Care (2015)

As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors’ Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease.
Evolution of extensively drug-resistant Mycobacterium tuberculosisfrom a susceptible ancestor in a single patient
Authors: Vegard Eldholm, Gunnstein Norheim, Bent von der Lippe, Wibeke Kinander, Ulf R Dahle, Dominique A Caugant, Turid Mannsåker, Anne Torunn Mengshoel, Anne Ma Dyrhol-Riise, Francois Balloux
Journal: Genome biology (2014)

Abstract Background Mycobacterium tuberculosis is characterized by a low mutation rate and a lack of genetic recombination. Yet, the rise of extensively resistant strains paints a picture of a microbe with an impressive adaptive potential. Here we describe the first documented case of extensively drug-resistant tuberculosis evolved from a susceptible ancestor within a single patient. Results Genome sequences of nine serial M. tuberculosis isolates from the same patient uncovered a dramatic turnover of competing lineages driven by the emergence, and subsequent fixation or loss of single nucleotide polymorphisms. For most drugs, resistance arose through independent emergence of mutations in more than one clone, of which only one ultimately prevailed as the clone carrying it expanded, displacing the other clones in the process. The vast majority of mutations identified over 3.5 years were either involved in drug resistance or hitchhiking in the genetic background of these. Additionally, RNA-sequencing of isolates grown in the absence of drug challenge revealed that the efflux-associated iniBAC operon was up-regulated over time, whereas down-regulated genes include those involved in mycolic acid synthesis. Conclusions We observed both rapid acquisitions of resistance to antimicrobial compounds mediated by individual mutations as well as a gradual increase in fitness in the presence of antibiotics, likely driven by stable gene expression reprogramming. The rapid turnover of resistance mutations and hitchhiking neutral mutations has major implications for inferring tuberculosis transmission events in situations where drug resistance evolves within transmission chains.
The impact of illness perception and fear avoidance on disability in COPD
Authors: Nikola Stenzel, Winfried Rief, Klaus Kenn
Journal: European Respiratory Journal (2014)

Introduction   Various studies have demonstrated the relevance of anxiety in COPD. First studies show that anxiety can impact patient9s illness behaviour and fear avoidance can influence disability and quality of life. Another well studied psychological concept in COPD is illness perception. Several studies showed its importance for health-related outcomes. So far, these concepts have never been tested simultaneously in COPD.  Aim of this study was to examine illness perception and fear avoidance in COPD and their mutual impact on disability and quality of life.   Method   1025 COPD-patients (M=59.7 years; GOLD I–IV) completed an online-survey. Fear Avoidance was assessed by the newly developed Fear Avoidance Questionnaire for COPD, illness perception wasassessed by the Brief Illness Perception Questionnaire. Outcome measures included COPD-related disability (CAT) and quality of life (SF-12). To test the impact of illness perception and fear avoidance on the outcome variables, hierarchical regression analyses and multiple mediation analyses were conducted.   Results   Results of the two regressions showed that, after controlling for demographics and illness severity, both fear avoidance and illness perception predicted disability (FA:  s  = .31;  p   s  = .20;  p   s  = -.28;  p   s  = -.26;  p     Conclusion   Fear avoidance and illness perception both play an important role for disability in COPD and should receive further attention.
In silico analysis of regulatory networks underlines the role of miR-10b-5p and its target BDNF in huntington’s disease
Authors: Sören Müller
Journal: Translational Neurodegeneration (2014)

Non-coding RNAs (ncRNAs) play various roles during central nervous system development. MicroRNAs (miRNAs) are a class of ncRNAs that exert their function together with argonaute proteins by post-transcriptional gene silencing of messenger RNAs (mRNAs). Several studies provide evidence for alterations in miRNA expression in patients with neurodegenerative diseases. Among these is huntington's disease (HD), a dominantly inherited fatal disorder characterized by deregulation of neuronal-specific mRNAs as well as miRNAs. Recently, next-generation sequencing (NGS) miRNA profiles from human HD and neurologically normal control brain tissues were reported. Five consistently upregulated miRNAs affect the expression of genes involved in neuronal differentiation, neurite outgrowth, cell death and survival. We re-analyzed the NGS data publicly available in array express and detected nineteen additional differentially expressed miRNAs. Subsequently, we connected these miRNAs to genes implicated in HD development and network analysis pointed to miRNA-mediated downregulation of twenty-two genes with roles in the pathogenesis as well as treatment of the disease. In silico prediction and reporter systems prove that levels of BDNF, a central node in the miRNA-mRNA regulatory network, can be post-transcriptionally controlled by upregulated miR-10b-5p and miR-30a-5p. Reduced BDNF expression is associated with neuronal dysfunction and death in HD. Moreover, the 3'UTR of CREB1 harbors a predicted binding site for these two miRNAs. CREB1 is similarly downregulated in HD and overexpression decreased susceptibility to 3-nitropropionic-induced toxicity in a cell model. In contradiction to these observations, it is presumed that miR-10b-5p upregulation in HD exerts a neuroprotective role in response to the mutation in the huntingtin gene. Therefore, the function of miR-10b-5p and especially its effect on BDNF expression in HD requires further academic research.
Multiuse 10-g Monofilament Contamination
Authors: Anne M. Sharkey, Adam Goldkind, Raymond Yong, William Chagares, James S. Wrobel
Journal: Diabetes Care (2010)

Growing interest has been given to the contamination of commonly used instruments in the physical exam (1,2). We are unaware of such scrutiny being given to the 10-g monofilament. The 10-g monofilament is a common screening test used to identify patients with loss of protective sensation and is part of recommended practice for the comprehensive foot exam for patients with diabetes (3). The instrument is typically used on feet with no open lesions or other breaks in the integument.

With the growing prevalence and concern associated with resistant organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci , many preventative measures are now being used by clinics and hospitals around the country, including normal screening for these bacteria. …
Focal and Segmental Glomerulosclerosis
Authors: Stéphan Troyanov, Catherine A. Wall, Judith A. Miller, James W. Scholey, Daniel C. Cattran
Journal: Journal of the American Society of Nephrology (2005)

Focal and segmental glomerulosclerosis (FSGS) is one of the most common primary glomerular diseases to terminate in ESRD. A complete remission (CR) confers an excellent long-term prognosis, but the quantitative benefits of partial remissions (PR) have not been defined. This study evaluated the rate of renal function decline (slope of creatinine clearance) and renal survival in nephrotic FSGS patients with CR, PR, or no remission. It also examined relapse rate from remission and its impact on outcome. Multivariate analysis included clinical and laboratory data at presentation and over follow-up, BP control, the agents used, and immunosuppressive therapy. The study cohort was 281 nephrotic FSGS patients who had a minimum of 12 mo of observation and were identified from the Toronto Glomerulonephritis Registry. Over a median follow-up of 65 mo, 55 experienced a CR, 117 had a PR, and 109 had no remission. A PR was independently predictive of slope and survival from renal failure by multivariate analysis (adjusted time-dependent hazard ratio, 0.48; 95% confidence interval, 0.24 to 0.96; P = 0.04). Immunosuppression with high-dose prednisone was associated with a higher rate of PR and CR. Relapse from PR was frequent (56%) and associated with a more rapid rate of renal function decline and worse renal survival compared with relapse-free partial remitters. Only female gender and the nadir of proteinuria during remission were associated with a sustained remission. A PR in proteinuria and its maintenance are important therapeutic targets in FSGS, with implications for both slowing progression rate and improving renal survival.
Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma
Authors: C. Manegold, J. Symanowski, U. Gatzemeier, M. Reck, J. von Pawel, C. Kortsik, K. Nackaerts, P. Lianes, N.J. Vogelzang
Journal: Annals of Oncology (2005)
The Vienna classification of gastrointestinal epithelial neoplasia
Authors: R J Schlemper
Journal: Gut (2000)

<h3>BACKGROUND</h3> Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. <h3>AIM</h3> To develop common worldwide terminology for gastrointestinal epithelial neoplasia. <h3>METHODS</h3> Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. <h3>RESULTS</h3> The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). <h3>CONCLUSION</h3> The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.
Management of antenatally diagnosed pulmonary sequestration associated with congenital cystic adenomatoid malformation
Authors: M. Samuel, D. M Burge
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Sequestration with associated cystic adenomatoid malformation is rare. A study was undertaken to determine whether pulmonary sequestration associated with congenital cystic adenomatoid malformation has a more favourable natural history than that of sequestration without associated cystic adenomatoid malformation. <h3>METHODS</h3> An outline of the postnatal work up leading to the management of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation diagnosed antenatally as pulmonary malformation is presented and the indications for surgical intervention are discussed. <h3>RESULTS</h3> In five infants in whom an antenatal ultrasound scan had detected a congenital lung malformation at 18–19 weeks gestation a final diagnosis of extralobar or intralobar pulmonary sequestration with congenital cystic adenomatoid malformation was made postnatally. Postnatal ultrasound and computerised axial tomographic scans confirmed the diagnosis of sequestration by delineating anomalous vascular supply. Cystic changes were also observed in the basal area of the sequestration in all patients. Four children remained asymptomatic and one infant presented at 10 months of age with pneumonia. The mean age at surgical resection was 6.8 months (range 2–10). Histopathological examination confirmed intralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in two patients and extralobar pulmonary sequestration with associated Stocker type 2 congenital cystic adenomatoid malformation in three patients. The mean period of follow up was four years (range 1–8). The children remain well and are developing normally. <h3>CONCLUSIONS</h3> The importance of seeking an anomalous blood supply in children with congenital lung lesions is emphasised. Pulmonary sequestration and congenital cystic adenomatoid malformation probably share a common embryogenesis despite diverse morphology. The natural history of antenatally diagnosed lung masses is variable. Early postnatal surgical resection of pulmonary sequestration with cystic adenomatoid malformation is recommended. Surgical excision should be conservative, sparing the normal lung parenchyma.