tbuckley/cabot-search huggingface dataset:
Nullius In Verba
Authors: Richard S. Lehman
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Effect of childhood adversity on health related quality of life in patients with upper abdominal or chest pain
Authors: A-M Biggs, Q Aziz, B Tomenson, F Creed
Journal: Gut (2004)

<b>Background and aims:</b> This study assessed whether childhood and current adversities: (a) were more prevalent in patients with functional dyspepsia (FD) or non-cardiac chest pain (NCCP) than in patients with gastro-oesophageal reflux disease (GORD) or ischaemic heart disease (IHD); and (b) predicted health related quality of life in these disorders. <b>Patients:</b> Cohort study of consecutive attenders to gastroenterology and cardiology clinics in a secondary/tertiary referral centre. <b>Methods:</b> Patients were interviewed using the childhood experience of care and abuse and life events and difficulties schedules. Distress was assessed by questionnaire. Outcome was assessed using SF36 at the index clinic visit and six months later. <b>Results:</b> A total of 133 patients were included (40 NCCP, 43 FD, 29 GORD, and 21 IHD) (67% response rate). The diagnostic groups did not differ significantly in the proportion reporting childhood adversity (30%), ongoing social stress (40%), lack of a close confidant (14%), or level of psychological distress. Reported childhood adversity was associated with poor outcome at the index visit (SF36 physical component score: 36.6 (SEM 1.8) <i>v</i> 42.3 (SEM 1.2) for the remainder; p = 0.014). In multiple regression analysis, childhood adversity was a significant independent predictor for patients with functional disorders (NCCP and FD) but not organic disorders (GORD or IHD). Change in SF36 score at six months was determined by age and distress score at the index visit in both groups. <b>Conclusion:</b> Childhood adversity was common among this consecutive sample but was associated directly with poor outcome only in patients with functional gastrointestinal syndromes. Distress is an important predictor of outcome in all patients. Greatest impairment occurs when lack of social support accompanies reported childhood adversity.
Cancer Incidence and Mortality in England and Wales: Trends and Risk Factors
Authors: Cyril Fisher
Journal: Journal of the Royal Society of Medicine (2003)

In the past century in the UK, there has been a 50% improvement in life expectancy at birth and more than this at 65 years of age. Many formerly common and fatal infectious diseases have been controlled, chronic obstructive lung disease has been effectively reduced and cardiovascular disease has either declined in incidence or is less often fatal. But the prevalence of cancer is increasing despite major improvements in treatment. Part of the reason is detection of early cancer which might never have caused symptoms, but there have also been some real changes. Swerdlow and his coauthors here collate information on trends in cancer in England and Wales, based on mortality and cancer registration statistics. They concentrate on data since 1960, although for certain cancers trends in earlier years are analysed. For each tumour, trends are discussed by region, by birth cohort and with associated or presumed aetiological factors. The data are presented in figures and tables. There is a separate chapter on general trends in factors that may cause or prevent cancer, including such contemporary issues as AIDS, alcohol consumption, diet, Helicobacter pylori, oral contraceptives and mobile telephones as well as occupation, reproduction related variables and sexual behaviour and sexually transmitted diseases. A 62-page appendix, comprising just over one-fifth of the book, presents incidence and mortality data in tabular form. The most notable trends are the rise in tumours in younger people, the decline in lung cancer and the increase in prostate cancer compared with thirty years ago (the last perhaps not being as much as might be expected). There is also an increase in lung cancer in women. A decreasing trend in cancer deaths in organ transplant recipients is revealed and explained by possible improvement in control of immunosuppression as well, perhaps, as more successful treatment of incident cases.

Although primarily a statistical analysis, this book is packed with information that will be of value not only to epidemiologists but also to clinicians, pathologists and others with an interest in cancer.
Dysregulated fibulin-5 expression and elastogenesis in COPD lungs: pyromaniac or fire fighter?
Authors: Guy Brusselle
Journal: Thorax (2014)

COPD is characterised functionally by a persistent airflow limitation, which is not fully reversible and is usually progressive. The pathological hallmarks of COPD are, on the one hand chronic inflammation and remodelling of the small airways (ie, bronchiolitis) and, on the other hand enlargement of alveolar spaces due to destruction of alveolar lung tissue (ie, emphysema).1 Fibrosis of the small airways and loss of elastic recoil due to emphysematous destruction contribute to chronic airflow limitation in COPD. Elastic fibres, principal components of the extracellular matrix (ECM) of alveolar septa, provide mechanical elasticity to the lungs and interconnect the lung parenchyma with small airways via alveolar attachments. An imbalance between proteases (such as neutrophil elastase) and antiproteases (such as α1-antitrypsin, the main inhibitor of neutrophil elastase), leading to a net increase in proteolytic activity, has been implicated in the pathophysiology of COPD.2 However, two opposing processes are supposed to drive the pathogenesis of small airway fibrosis and emphysema: the thickening of the small airway walls results from an exaggerated repair process leading to a marked increase in deposition of ECM, whereas the emphysematous destruction of the lung tissue is indicative of an insufficient production of ECM and, thus, a defective repair. Since small airway fibrosis and emphysema occur in close proximity to each other in COPD, the underlying mechanisms of their pathogenesis remain enigmatic. …
A New Therapeutic Strategy against Hormone-Dependent Breast Cancer: The Preclinical Development of a Dual Aromatase and Sulfatase Inhibitor
Authors: Paul A. Foster, Surinder K. Chander, Simon P. Newman, L.W. Lawrence Woo, Oliver B. Sutcliffe, Christian Bubert, Dujin Zhou, Shiuan Chen, Barry V.L. Potter, Michael J. Reed, Atul Purohit
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The production of E2 is paramount for the growth of estrogen receptor–positive breast cancer. Various strategies have been used, including the use of enzyme inhibitors against either aromatase (AROM) or steroid sulfatase (STS), in an attempt to ablate E2 levels. Both these enzymes play a critical role in the formation of estrogenic steroids and their inhibitors are now showing success in the clinic. Experimental Design: We show here, in a xenograft nude mouse model, that the inhibition of both enzymes using STX681, a dual AROM and STS inhibitor (DASI), is a potential new therapeutic strategy against HDBC. MCF-7 cells stably expressing either AROM cDNA (MCF-7AROM) or STS cDNA (MCF-7STS) were generated. Ovariectomized MF-1 female nude mice receiving s.c. injections of either androstenedione (A4) or E2 sulfate and bearing either MCF-7AROM or MCF-7STS tumors were orally treated with STX64, letrozole, or STX681. Treatment was administered for 28 days. Mice were weighed and tumor measurements were taken weekly. Results: STX64, a potent STS inhibitor, completely blocked MCF-7STS tumor growth but failed to attenuate MCF-7AROM tumor growth. In contrast, letrozole inhibited MCF-7AROM tumors but had no effect on MCF-7STS tumors. STX681 completely inhibited the growth of both tumors. AROM and STS activity was also completely inhibited by STX681, which was accompanied by a significant reduction in plasma E2 levels. Conclusions: This study indicates that targeting both the AROM and the STS enzyme with a DASI inhibits HDBC growth and is therefore a potentially novel treatment for this malignancy.
Differential Behaviors of Atrial Versus Ventricular Fibroblasts
Authors: Brett Burstein, Eric Libby, Angelino Calderone, Stanley Nattel
Journal: Circulation (2008)

In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined.We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater alpha-smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([(3)H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-beta(1). Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congestive heart failure atria showed larger fractions of fibroblasts in mitotic phases compared with ventricles and displayed enhanced gene expression of fibroblast-selective markers (collagen-1, collagen-3, fibronectin-1). Gene microarrays revealed 225 differentially expressed transcript probe sets between paired atrial and ventricular fibroblast samples, including extracellular matrix (eg, fibronectin, laminin, fibulin), cell signaling (PDGF, PDGF receptor, angiopoietin, vascular endothelial growth factor), structure (keratin), and metabolism (xanthine dehydrogenase) genes, identifying PDGF as a candidate contributor to atrial-ventricular fibroblast differences. PDGF receptor gene expression was greater in normal atrium compared with ventricle, and congestive heart failure differentially enhanced atrial versus ventricular PDGF and PDGF receptor gene expression. PDGF receptor protein expression and alpha-smooth muscle actin protein expression were enhanced in isolated congestive heart failure fibroblasts. The PDGF receptor tyrosine kinase inhibitor AG1295 eliminated fetal bovine serum- and transforming growth factor-beta(1)-stimulated atrial-ventricular fibroblast proliferative response differences.Atrial fibroblasts behave differently than ventricular fibroblasts over a range of in vitro and in vivo paradigms, with atrial fibroblasts showing enhanced reactivity that may explain greater atrial fibrotic responses. PDGF signaling is particularly important for atrium-selective fibroblast responses and may represent a novel target for arrhythmogenic atrial structural remodeling prevention.
Crohn's Disease and Genetic Hitchhiking at IBD5
Authors: C. D. Huff, D. J. Witherspoon, Y. Zhang, C. Gatenbee, L. A. Denson, S. Kugathasan, H. Hakonarson, A. Whiting, C. T. Davis, W. Wu, J. Xing, W. S. Watkins, M. J. Bamshad, J. P. Bradfield, K. Bulayeva, T. S. Simonson, L. B. Jorde, S. L. Guthery
Journal: Molecular Biology and Evolution (2011)

Inflammatory bowel disease 5 (IBD5) is a 250 kb haplotype on chromosome 5 that is associated with an increased risk of Crohn's disease in Europeans. The OCTN1 gene is centrally located on IBD5 and encodes a transporter of the antioxidant ergothioneine (ET). The 503F variant of OCTN1 is strongly associated with IBD5 and is a gain-of-function mutation that increases absorption of ET. Although 503F has been implicated as the variant potentially responsible for Crohn's disease susceptibility at IBD5, there is little evidence beyond statistical association to support its role in disease causation. We hypothesize that 503F is a recent adaptation in Europeans that swept to relatively high frequency and that disease association at IBD5 results not from 503F itself, but from one or more nearby hitchhiking variants, in the genes IRF1 or IL5. To test for evidence of recent positive selection on the 503F allele, we employed the iHS statistic, which was significant in the European CEU HapMap population (P = 0.0007) and European Human Genome Diversity Panel populations (P ≤ 0.01). To evaluate the hypothesis of disease-variant hitchhiking, we performed haplotype association tests on high-density microarray data in a sample of 1,868 Crohn's disease cases and 5,550 controls. We found that 503F haplotypes with recombination breakpoints between OCTN1 and IRF1 or IL5 were not associated with disease (odds ratio [OR]: 1.05, P = 0.21). In contrast, we observed strong disease association for 503F haplotypes with no recombination between these three genes (OR: 1.24, P = 2.6 × 10−8), as expected if the sweeping haplotype harbored one or more disease-causing mutations in IRF1 or IL5. To further evaluate these disease-gene candidates, we obtained expression data from lower gastrointestinal biopsies of healthy individuals and Crohn's disease patients. We observed a 72% increase in gene expression of IRF1 among Crohn's disease patients (P = 0.0006) and no significant difference in expression of OCTN1. Collectively, these data indicate that the 503F variant has increased in frequency due to recent positive selection and that disease-causing variants in linkage disequilibrium with 503F have hitchhiked to relatively high frequency, thus forming the IBD5 risk haplotype. Finally, our association results and expression data support IRF1 as a strong candidate for Crohn's disease causation.
Insulin restores neuronal nitric oxide synthase expression and function that is lost in diabetic gastropathy
Authors: Crystal C. Watkins, Akira Sawa, Samie Jaffrey, Seth Blackshaw, Roxanne K. Barrow, Solomon H. Snyder, Christopher D. Ferris
Journal: Journal of Clinical Investigation (2000)

Gastrointestinal dysfunction is common in diabetic patients. In genetic (nonobese diabetic) and toxin-elicited (streptozotocin) models of diabetes in mice, we demonstrate defects in gastric emptying and nonadrenergic, noncholinergic relaxation of pyloric muscle, which resemble defects in mice harboring a deletion of the neuronal nitric oxide synthase gene (nNOS). The diabetic mice manifest pronounced reduction in pyloric nNOS protein and mRNA. The decline of nNOS in diabetic mice does not result from loss of myenteric neurons. nNOS expression and pyloric function are restored to normal levels by insulin treatment. Thus diabetic gastropathy in mice reflects an insulin-sensitive reversible loss of nNOS. In diabetic animals, delayed gastric emptying can be reversed with a phosphodiesterase inhibitor, sildenafil. These findings have implications for novel therapeutic approaches and may clarify the etiology of diabetic gastropathy.
Simple aspiration and drainage and intrapleural minocycline pleurodesis versus simple aspiration and drainage for the initial treatment of primary spontaneous pneumothorax: an open-label, parallel-group, prospective, randomised, controlled trial
Authors: Jin-Shing Chen, Wing-Kai Chan, Kung-Tsao Tsai, Hsao-Hsun Hsu, Chien-Yu Lin, Ang Yuan, Wen-Jone Chen, Hong-Shiee Lai, Pan-Chyr Yang
Journal: The Lancet (2013)
Desferrioxamine improves neutrophil phagocytosis in thalassemia major
Authors: Brigitte Cantinieaux, Chantal Hariga, Pierre Fondu, Alina Ferster, Michèle Toppet
Journal: American Journal of Hematology (1990)

The aims of the present study are: first, to assess the toxic role of serum from thalassemic patients in phagocytosis of PMN from healthy controls, and second, to seek to determine whether serum and cellular disturbances of polymorphonuclear neutrophils (PMN) phagocytosis, observed in thalassemic patients, can be prevented and/or corrected by use of desferrioxamine (DFX). Two kinds of in vitro incubations--without or with DFX--were performed. PMN or serum from thalassemic patients or from healthy controls was used. First, a phagocytosis defect of 3 different bacteria species was induced in PMN from healthy controls by incubation in thalassemic serum. Second, DFX could prevent, already at 1 microM, the phagocytic defect induced in normal PMN by the incubation with thalassemic serum, with disappearance of the toxic role of thalassemic serum at higher concentrations. Third, improvement of the phagocytosis defect of PMN from thalassemic patients was also observed at 1 microM of DFX for the 3 bacteria species. Normalization was obtained at higher concentrations for gram-negative bacteria. In vivo studies revealed, after a 3 hr subcutaneous infusion of DFX into 3 thalassemic patients, an improvement of the phagocytosis results and a decrease of the Prussian Blue reactivity of the PMN. It is concluded first that an iron-mediated defect in phagocytosis can be induced in normal neutrophils by incubation in serum from thalassemic patients, and second that a precautious and intensive chelation therapy seems to be advantageous for increasing PMN defense against infectious agents. Special care must nevertheless be taken in order to detect rapidly opportunistic (such as Yersinia) infections.
Calcium-Activated Potassium Channels Contribute to Human Coronary Microvascular Dysfunction After Cardioplegic Arrest
Authors: Jun Feng, Yuhong Liu, Richard T. Clements, Neel R. Sodha, Kamal R. Khabbaz, Venkatachalam Senthilnathan, Katherine K. Nishimura, Seth L. Alper, Frank W. Sellke
Journal: Circulation (2008)

Background— Cardioplegic arrest (CP) followed by reperfusion after cardiopulmonary bypass induces coronary microvascular dysfunction. We investigated the role of calcium-activated potassium (K Ca ) channels in this dysfunction in the human coronary microvasculature. Methods and Results— Human atrial tissue was harvested before CP from a nonischemic segment and after CP from an atrial segment exposed to hyperkalemic cold blood CP (mean CP time, 58 minutes) followed by 10-minute reperfusion. In vitro relaxation responses of precontracted arterioles (80 to 180 μm in diameter) in a pressurized no-flow state were examined in the presence of K Ca channel activators/blockers and several other vasodilators. We also examined expression and localization of K Ca channel gene products in the coronary microvasculature using reverse transcriptase-polymerase chain reaction, immunoblot, and immunofluorescence photomicroscopy. Post-CP reperfusion relaxation responses to the activator of intermediate and small conductance K Ca channels (IK Ca /SK Ca ), NS309 (10 −5 M), and to the endothelium-dependent vasodilators, substance P (10 −8 M) and adenosine 5diphosphate (10 −5 M), were significantly reduced compared with pre-CP responses ( P &lt;0.05, n=8/group). In contrast, relaxation responses to the activator of large conductance K Ca channels (BK Ca ), NS1619 (10 −5 M), and to the endothelium-independent vasodilator, sodium nitroprusside (10 −4 M), were unchanged pre- and post-CP reperfusion (n=8/group). Endothelial denudation significantly diminished NS309-induced vasodilatation and abolished substance P- or adenosine 5 diphosphate-induced relaxation ( P &lt;0.05), but had no effect on relaxation induced by either NS1619 or sodium nitroprusside. The total polypeptide levels of BK Ca , IK Ca , and SK Ca and the expression of IK Ca mRNA were not altered post-CP reperfusion. Conclusion— Cardioplegic arrest followed by reperfusion after cardiopulmonary bypass causes microvascular dysfunction associated with and likely in part due to impaired function of SK Ca and IK Ca channels in the coronary microcirculation. These results suggest novel mechanisms of endothelial and smooth muscle microvascular dysfunction after cardiac surgery.
Estrogens induce cholangiocyte proliferation through the activation of the ERK1/2 system and the adapter proteins Sch, and Src
Authors: Domenico Alvaro, Gianfranco Alpini, Paolo Onori, Antonio Franchitto, Shannon Glaser, Gene Le Sage, Alessandro Gigliozzi, Adolfo Attili, Gianluca Svegliati Baronigaudio, Veronica Drudi Metalli, Maria Grazia Mancino, Eugenio Gaudio
Journal: Journal of Hepatology (2002)
Post-remission therapy of adult acute myeloid leukaemia: One cycle of high-dose versus standard-dose cytarabine
Authors: M. Fopp, M.F. Fey, M. Bacchi, F. Cavalli, J. Gmuer, E. Jacky, L. Schmid, A. Tichelli, A. Tobler, L. Tschopp, V. Von Fliedner, A. Gratwohl
Journal: Annals of Oncology (1997)
Development of a 14C-urea breath test in ferrets colonised with Helicobacter mustelae: effects of treatment with bismuth, antibiotics, and urease inhibitors.
Authors: A A McColm, J A Bagshaw, C F O'Malley
Journal: Gut (1993)

A 14C-urea breath test analogous to its clinical counterpart is described for use in ferrets naturally or experimentally infected with Helicobacter mustelae. The test is performed within a sealed glass metabolism chamber through which air is drawn at a constant rate and expired breath collected into sodium hydroxide. Peak 14CO2 production occurred approximately 1 hour after substrate administration. Both inter- and intra-animal responses were highly reproducible, with mean coefficients of variation less than 10%. Other than enhancing peak 14CO2 levels very slightly, fasting had little influence on the response. In infant animals challenged with H mustelae, breath test activity increased linearly with the total count of culturable bacteria isolated from the antrum. Treatment of established infections with colloidal bismuth subcitrate (DeNol) for 4 weeks resulted in clearance of all detectable bacteria but retention of some breath test activity. Subsequent regrowth of bacteria was parallelled by an increase in the breath test response. Inclusion of amoxycillin and metronidazole in the treatment regimen, however, eradicated all the bacteria and almost totally eliminated 14CO2 production. This response parallels the clinically observed suppressive effect on H pylori achieved with bismuth alone relative to the total eradication seen with triple therapy. A single oral dose of the urease inhibitor, flurofamide, inhibited over 90% of the response for at least 24 hours. Acetohydroxamic acid was less effective. These findings suggest that in the ferret H mustelae model, breath test analysis can be a useful, non-invasive alternative to endoscopy for evaluation of agents affecting either growth of the organism or urease activity.