tbuckley/cabot-search huggingface dataset:
Inflammation in Myocardial Diseases
Authors: David J. Marchant, John H. Boyd, David C. Lin, David J. Granville, Farshid S. Garmaroudi, Bruce M. McManus
Journal: Circulation Research (2012)

Inflammatory processes underlie a broad spectrum of conditions that injure the heart muscle and cause both structural and functional deficits. In this article, we address current knowledge regarding 4 common forms of myocardial inflammation: myocardial ischemia and reperfusion, sepsis, viral myocarditis, and immune rejection. Each of these pathological states has its own unique features in pathogenesis and disease evolution, but all reflect inflammatory mechanisms that are partially shared. From the point of injury to the mobilization of innate and adaptive immune responses and inflammatory amplification, the cellular and soluble mediators and mechanisms examined in this review will be discussed with a view that both beneficial and adverse consequences arise in these human conditions.
Behavioural and new pharmacological treatments for constipation: getting the balance right
Authors: M. Camilleri, A. E. Bharucha
Journal: Gut (2010)

Chronic constipation affects almost one in six adults and is even more frequent in the elderly. In the vast majority of patients, there is no obstructive mucosal or structural cause for constipation and, after excluding relatively rare systemic diseases (commonest of which is hypothyroidism), the differential diagnosis is quickly narrowed down to three processes: evacuation disorder of the spastic (pelvic floor dyssynergia, anismus) or flaccid (descending perineum syndrome) varieties, and normal or slow transit constipation. Treatment of chronic constipation based on identifying the underlying pathophysiology is generally successful with targeted therapy. The aims of this review are to discuss targeted therapy for chronic constipation: behavioural treatment for outlet dysfunction and pharmacological treatment for constipation not associated with outlet dysfunction. In particular, we shall review the evidence that behavioural treatment works for evacuation disorders, describe the new treatment options for constipation not associated with evacuation disorder, and demonstrate how 'targeting therapy' to the underlying diagnosis results in a balanced approach to patients with these common disorders.
Bioassays of Follicle Stimulating Hormone
Authors: CHRISTINA WANG
Journal: Endocrine Reviews (1988)

ANTERIOR pituitary glands of many animal species, including man, secrete FSH in multiple heterogeneous forms. These FSH isohormones exhibit different molecular weights, isoelectric properties, bioactivities, and plasma half-lives (1–4). The heterogeneity of the isoforms is believed to be due to the differences in the carbohydrate moieties of the glycoprotein. Early studies showed that the hormonal milieu influenced not only the amount of FSH secreted but also its biological activity (4–7). Most of the physiological and clinical studies on serum FSH had been measured by specific RIAs. Changes in biological activities of FSH (bio-FSH) are not always associated with similar changes in FSH immunoreactivity (immuno-FSH) (3, 8, 9). Although pituitary and urinary FSH had been measured by bioassays, until recently, serum bio-FSH could not be measured because of the lack of specific and sensitive methods. This review summarizes the recent development of FSH bioassays that can be applied to clinical studies of FSH in serum.
Pectoralis major tendon ruptures: when to operate
Authors: J F Quinlan, M Molloy, B J Hurson
Journal: British Journal of Sports Medicine (2002)

The treatment of pectoralis major tendon ruptures has been the subject of much debate. The classical history of the injury is forced abduction and external rotation. The cases of two patients (an amateur rugby union player and a recreational snowboarder) are reported. The diagnosis was made by clinical examination in both patients, and both were operated on more than two weeks after injury. After surgery and a graduated rehabilitation programme, both men were able to return to their sporting activities. These two cases highlight the advantage of operative management in this uncommon condition.
Functional evidence for an active role of B-type natriuretic peptide in cardiac remodelling and pro-arrhythmogenicity
Authors: Jérôme Thireau, Sarah Karam, Jérémy Fauconnier, Stéphanie Roberge, Cécile Cassan, Olivier Cazorla, Franck Aimond, Alain Lacampagne, Dominique Babuty, Sylvain Richard
Journal: Cardiovascular Research (2012)

During heart failure (HF), the left ventricle (LV) releases B-type natriuretic peptide (BNP), possibly contributing to adverse cardiovascular events including ventricular arrhythmias (VAs) and LV remodelling. We investigated the cardiac effects of chronic BNP elevation in healthy mice and compared the results with a model of HF after myocardial infarction (PMI mice). Healthy mice were exposed to circulating BNP levels (BNP-Sham) similar to those measured in PMI mice. Telemetric surface electrocardiograms showed that in contrast with fibrotic PMI mice, electrical conduction was not affected in BNP-Sham mice. VAs were observed in both BNP-Sham and PMI but not in Sham mice. Analysis of heart rate variability indicated that chronic BNP infusion increased cardiac sympathetic tone. At the cellular level, BNP reduced Ca2+ transients and impaired Ca2+ reuptake in the sarcoplasmic reticulum, in line with blunted SR Ca2+ ATPase 2a and S100A1 expression. BNP increased Ca2+ spark frequency, reflecting Ca2+ leak through ryanodine receptors, elevated diastolic Ca2+, and promoted spontaneous Ca2+ waves. Similar effects were observed in PMI mice. Most of these effects were reduced in BNP-Sham and PMI mice by the selective β1-adrenergic blocker metoprolol. Elevated BNP levels, by inducing sympathetic overdrive and altering Ca2+ handling, promote adverse cardiac remodelling and VAs, which could account in part for the progression of HF after MI. The early use of β-blockers to prevent the deleterious effects of chronic BNP exposure may be beneficial in HF.
Light and electron microscopic studies of antibiotic associated colitis in the hamster
Authors: C. D. Humphrey, W. B. Lushbaugh, C. W. Condon, J. C. Pittman, F. E. Pittman
Journal: Gut (1979)

Lincomycin and its analogue, clindamycin, are capable of producing mild to severe colonic mucosal injury in humans (antibiotic associated colitis).Patients with the disorder may have severe diarrhoea, pseudomembranous plaques, confluent pseudomembranes, and/or a frank, diffuse haemorrhagic colitis.The present study was designed to assess the Golden Syrian hamster as an animal model for antibiotic associated colitis and to describe lesions seen in the animal model by light, transmission electron, and scanning electron microscopy.A colitis was produced in Golden Syrian hamsters by oral or parenteral administration of lincomycin, clindamycin, or N-demethyl clindamycin.Animals were killed at intervals and microscopic studies made of sequential morpho- logical changes in the ileum, caecum, and colon.The microscopic lesions in the early stages of the disorder were abnormalities within the brush border, cellular oedema, and hyperaemia.Changes in the intracellular organelles were observed in more severely damaged epithelial cells.Epithelial hyperplasia resulted in the piling up of cells on the mucosal surfaces.In specimens with the most severe damage, complete loss of epithelium from the mucosal surface was observed.Pseudomembranous plaques were occasionally seen.Comparison of the clinical, gross, and histological features of the animal disease with the human disorder suggest that, although minor differences are present, the hamster model is suitable for experimental studies of antibiotic associated colitis.
Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia
Authors: Maria Pierro, Lavinia Ionescu, Tiziana Montemurro, Arul Vadivel, Gaia Weissmann, Gavin Oudit, Derek Emery, Sreedhar Bodiga, Farah Eaton, Bruno Péault, Fabio Mosca, Lorenza Lazzari, Bernard Thébaud
Journal: Thorax (2012)

<h3>Background</h3> Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown. <h3>Methods</h3> Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model. <h3>Results</h3> Rat pups exposed to hyperoxia showed the characteristic arrest in alveolar growth with air space enlargement and loss of lung capillaries. PCs and MSCs partially prevented and rescued lung function and structure. Despite therapeutic benefit, cell engraftment was low, suggesting that PCs and MSCs act via a paracrine effect. Accordingly, cell free-derived conditioned media from PCs and MSCs also exerted therapeutic benefit when used either prophylactically or therapeutically. Finally, long-term (6 months) assessment of stem cell or conditioned media therapy showed no adverse lung effects of either strategy, with persistent improvement in exercise capacity and lung structure. <h3>Conclusions</h3> Human umbilical cord-derived PCs and MSCs exert short- and long-term therapeutic benefit without adverse lung effects in this experimental model and offer new therapeutic options for lung diseases characterised by alveolar damage.
Declining β-Cell Function Relative to Insulin Sensitivity With Escalating OGTT 2-h Glucose Concentrations in the Nondiabetic Through the Diabetic Range in Overweight Youth
Authors: Stephen F. Burns, Fida Bacha, So Jung Lee, Hala Tfayli, Neslihan Gungor, Silva A. Arslanian
Journal: Diabetes Care (2011)

Overweight in youth is associated with the risk of developing type 2 diabetes. We hypothesized that β-cell function relative to insulin sensitivity decreases with increasing 2-h glucose levels based on an oral glucose tolerance test (OGTT) in overweight youth. RESEARCH DESIGN AND METHODS A total of 147 overweight (BMI ≥85th percentile for age and sex) youth, aged 8 to <20 years, undertook three tests: 1) a 3-h hyperinsulinemic-euglycemic clamp; 2) a 2-h hyperglycemic clamp; and 3) a 2-h OGTT. Participants were categorically assigned to five groups according to their OGTT 2-h plasma glucose level, ranging from <120 to ≥200 mg/dL. β-Cell function relative to insulin sensitivity, assessed by clamp disposition index (DI) and oral disposition index (DI(O)), were compared among groups.Insulin sensitivity, first-phase insulin, and DI declined significantly as 2-h glucose concentrations increased. The highest DI was found in youth with 2-h plasma glucose concentrations <120 mg/dL, with a significant decline of ~40% in those with glucose concentrations between 120 and <140 mg/dL, and an ~75% decline, the lowest DI, in youth with glucose concentrations ≥200 mg/dL. Data were similar with regard to the OGTT DI(O).These data in overweight youth demonstrate that impairment in insulin secretion relative to insulin sensitivity is apparent even with normal glucose tolerance. Below the current cutoff of 140 mg/dL for impaired glucose tolerance, there is a >30% decline in β-cell function relative to insulin sensitivity. Against this back drop of metabolically heightened risk for type 2 diabetes, preventive measures should target the β-cell alongside insulin sensitization.
Access to inhaled corticosteroids is key to improving quality of care for asthma in developing countries
Authors: N. Ait‐Khaled, D. A. Enarson, K. Bissell, N. E. Billo
Journal: Allergy (2007)

Asthma is a worldwide public health problem affecting about 300 million people. The majority of persons living with asthma are in the developing world where there is limited access to essential drugs. The financial burden for persons living with asthma and their families, as well as for healthcare systems and governments, is very high. Inadequate treatment and the high cost of medications leads to disability, absenteeism and poverty. Despite the existence of effective asthma medications and international guidelines, and progress made in the implementation of such guidelines over the last decade, the high cost of essential asthma medications remains a major obstacle for patient access to treatment in developing countries. The International Union Against Tuberculosis and Lung Disease has evaluated this problem and created an Asthma Drug Facility (ADF) so that countries can purchase affordable, good quality essential drugs for asthma. The ADF uses pooled procurement along with other purchasing and supply strategies to obtain the lowest possible prices. Accompanied by the implementation of standardized asthma management, the increased affordability of drugs provided by the ADF should bring rapid and significant health and cost benefits for patients, their communities and governments.
Cyclooxygenase-2 and its role in ovulation: a 2004 account
Authors: Jean Sirois, Khampoune Sayasith, Kristy A. Brown, Angelika E. Stock, Nadine Bouchard, Monique Doré
Journal: Human Reproduction Update (2004)

The pre-ovulatory surge of gonadotrophins triggers a marked and obligatory increase in follicular prostaglandin synthesis prior to ovulation, and the cyclooxygenase (COX) enzyme is a key rate-limiting step in the biosynthesis of prostaglandins. In the early 1990s, the pre-ovulatory rise in follicular prostaglandin synthesis was shown to result from the selective induction of a novel COX isoform, now referred to as COX-2. Differences in the time-course of COX-2 induction in species with a short versus a long ovulatory process suggest that the enzyme could be a molecular determinant that sets the alarm of the mammalian ovulatory clock. Some of the fine molecular mechanisms involved in the transcriptional activation of the COX-2 gene in granulosa cells have also been elucidated. The binding of trans-activating upstream stimulatory factors (USF) to a consensus E-box cis-element in the proximal region of the promoter was shown to play a predominant role in COX-2 transcription. Studies showed that COX-2 expression could also serve as a valuable marker for follicular commitment to ovulation during hyperstimulatory cycles. This paper presents a comprehensive review of the events that led to the characterization of COX-2 in pre-ovulatory follicles, updates current concepts on the control of COX-2 expression in pre-ovulatory follicles, and addresses the consequences of COX-2 inhibition to women fertility and potential implications of COX-2 expression in ovarian cancer.
Perforation of Atrium by Polyethylene CV Catheter
Authors: Bruce A. Friedman
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Embolic pieces of intravenous polyethylene catheters have been noted since Turner and Sommers<sup>1</sup>described a case in which a 4-cm fragment separated and lodged in the right atrium. Brown and Kent<sup>2</sup>recorded perforation of the right ventricle by a segment of a polyethylene catheter, and Johnson<sup>3</sup>subsequently reported a similar perforation of the right atrium by a piece of tubing. Doering et al<sup>4</sup>in a recent review cited 26 cases from the literature and added 23 additional patients in whom embolism of intravenous catheters occurred. One of the latter had perforation of the right atrium. In the following patient there was perforation of the right atrium by an intact indwelling polyethylene catheter used jointly to monitor the central venous pressure and for intravenous fluid therapy. Death was related to hydropericardium produced by fluid conducted into the pericardial sac by the catheter. <h3>Report of</h3>
Age- and Disease-Related Methylation of Multiple Genes in Nonneoplastic Duodenum and in Duodenal Juice
Authors: Hiroyuki Matsubayashi, Norihiro Sato, Kieran Brune, Amanda Lapides Blackford, Ralph H. Hruban, Marcia Canto, Charles J. Yeo, Michael Goggins
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Methylation of CpG islands contributes to gene silencing during cancer development, and although some methylation alterations are promising diagnostic markers of cancer, some CpG islands are also methylated in normal tissues. We have previously observed that some normally unmethylated CpG islands that undergo methylation in pancreatic cancers are normally methylated in the adjacent duodenum. Because duodenal methylation patterns are an important consideration when sampling pancreatic tissues for pancreatic cancer methylation alterations, we determined the DNA methylation patterns of 24 genes in the normal duodenum of patients with pancreatic disease and related these patterns to demographic factors. Experimental Design: The nonneoplastic duodenal mucosa of 158 patients with pancreatic carcinoma and 41 patients with chronic pancreatitis was analyzed using methylation-specific PCR and combined bisulfite restriction analysis. Secretin-stimulated pancreatic/duodenal juice from 15 individuals undergoing endoscopic investigation for upper gastrointestinal disease was also analyzed. Results: Low-level methylation was detectable by methylation-specific PCR in the nonneoplastic duodenum of many patients with pancreatic cancer and chronic pancreatitis as well as in the pancreaticoduodenal secretions of patients without pancreaticobiliary disease. For many genes, the prevalence of methylation increased with age and was more prevalent in patients with pancreatic cancer than in age-matched patients with chronic pancreatitis. Our results indicate that strategies to detect pancreatic cancer using aberrantly methylated genes should rely on analysis of pure pancreatic juice rather than on pancreatic juice collected within the duodenal lumen. Patients who develop pancreatic cancer may have a greater propensity to methylate CpG islands than age-matched controls.
Evidence that endogenous ecotropic virus is not expressed in AKR thymic lymphoid cells of chimeric hosts.
Authors: K J Blank, T Pincus
Journal: The Journal of Experimental Medicine (1980)

AKR/J thymocytes derived from fetal liver cells do not produce virus when they differentiate in lethally irradiated B10.K mice, whereas spleen and bone marrow cells are virus producers. In contrast, B10.K thymocytes that differentiate in lethally irradiated AKR mice become virus producers. These results suggest that infection of the thymus in AKR mice is initiated in thymic stromal cells.
Apparent lack of MHC restriction in binding of class I HLA molecules to solid-phase peptides.
Authors: B P Chen, J Rothbard, P Parham
Journal: The Journal of Experimental Medicine (1990)

The specificity of binding of solubilized, purified HLA-A,B molecules to solid-phase peptides has been examined using the assay described by Bouillet et al. [1989. Nature (Lond.). 339:473.] 64 peptides derived from the sequences of viral antigens, HLA-A,B,C heavy chains, and clathrin light chains were tested for binding to HLA-A2.1, Aw68.1, Aw69, B44, and B5, molecules that differ by 5-17 residues of the peptide binding groove. 15 of the peptides, including those known to be T cell epitopes, gave significant binding. The pattern of peptide binding for each of the five HLA-A,B molecules was not significantly different. Binding was demonstrated to be a property of native beta 2m-associated HLA-A,B molecules that preserved conformational antigenic determinants after binding to peptide. In comparison to our previous results from solution-based assays the proportion of HLA-A,B molecules that can bind solid-phase peptides is very high. This accessibility of solid-phase peptides to the binding site of MHC molecules may be directly related to the observed absence of MHC specificity in the binding.
Induction by topical corticosteroids of skin enzymes metabolizing carcinogenic hydrocarbons
Authors: M.H. BRIGGS, MAXINE BRIGGS
Journal: British Journal of Dermatology (2006)

Epidermal aryl hydrocarbon hydroxylase activity of homogenates from mice treated for 7 days with various topical corticosteroid ointments was significantly higher than in preparations from animals receiving steroid-free ointment bases, or no treatment. As determined by 3,4-benzopyrene oxidation, enzyme activity was also greatly increased 24 h after small doses of various polycyclic hydrocarbons given by the intraperitoneal route. Inhibition of enzyme activity was observed in skin homogenates from both control and treated animals following addition in vitro of 7,8-benzoflavone, but not with dimethylsulphoxide.
Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance
Authors: Adrian R. Kendal, Ye Chen, Frederico S. Regateiro, Jianbo Ma, Elizabeth Adams, Stephen P. Cobbold, Shohei Hori, Herman Waldmann
Journal: The Journal of Experimental Medicine (2011)

A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4+Foxp3+ cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3hCD2 mice to isolate and ablate Foxp3+ T reg cells with an anti-hCD2 antibody, we show for the first time that CD4+Foxp3+ cells are crucial for infectious tolerance induced by nonablative anti–T cell antibodies. In tolerant animals, Foxp3+ T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3+ T reg cells. Finally, Foxp3+ cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3+ cells sustain tolerance by converting naive T cells into the next generation of Foxp3+ cells. Empowering Foxp3+ regulatory T cells in vivo offers a tractable route to avoid and correct tissue immunopathology.
Health protection of the Olympic athlete
Authors: Kathrin Steffen, Torbjørn Soligard, Lars Engebretsen
Journal: British Journal of Sports Medicine (2012)

Protection of the athletes' health is a clearly articulated objective of the International Olympic Committee. Longitudinal surveillance of injuries and illnesses can provide valuable data that may identify high-risk sports and disciplines. This is a foundation for introducing tailored preventive measures. During the XXIX Summer and XXI Winter Games, comprehensive injury and illness recording through the medical staff of the participating National Olympic Committees and the sports medicine clinics revealed that between 7% and 11% of all athletes incurred an injury or suffered from at least one occurrence of illness during the Games. The incidence of injuries and illnesses varied substantially between sports. In the future, risk factor and injury mechanism analyses in high-risk Olympic sports are essential to better direct injury-prevention strategies. Concomitantly, periodic health evaluations of athletes will be instrumental to optimise health protection.