tbuckley/cabot-search huggingface dataset:
Expression of lymphotoxin-αβ on antigen-specific T cells is required for DC function
Authors: Leslie E. Summers-deLuca, Douglas D. McCarthy, Bojana Cosovic, Lesley A. Ward, Calvin C. Lo, Stefanie Scheu, Klaus Pfeffer, Jennifer L. Gommerman
Journal: The Journal of Experimental Medicine (2007)

During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-αβ (LTαβ) in this process because signaling through the LTβ-receptor (LTβR) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs. We report that LTαβ is a critical participant required for optimal DC function, independent of its described role in maintaining lymphoid tissue organization. In the absence of LTαβ or CD40L on Ag-specific T cells, DC dysfunction could be rescued in vivo via CD40 or LTβR stimulation, respectively, suggesting that these two pathways cooperate for optimal DC conditioning.
Regional Expression of Natriuretic Peptide Receptors During the Formation of Arterial Neointima in the Rabbit
Authors: J. Brown, Q. Chen
Journal: Circulation Research (1995)

Abstract In vitro evidence suggests that natriuretic peptide receptors (NPR)-B and NPR-C inhibit vascular smooth muscle (VSM) proliferation. NPR-B is guanylate cyclase-coupled and selectively activated by C-type natriuretic peptide (CNP)-(1-22). NPR-C is not guanylate cyclase-coupled and, unlike NPR-B, avidly binds atrial natriuretic peptide (ANP)-(1-28) as well as CNP-(1-22). Here, we investigate these receptors during the VSM proliferation and neointimal formation found 5, 7, and 20 days after compressing the central ear artery of the rabbit. Receptors were mapped autoradiographically using [ 125 I-Tyr 0 ]CNP-(1-22), which binds NPR-B and NPR-C, and 125 I-ANP-(1-28), which binds NPR-C and NPR-A, another guanylate cyclase-coupled receptor. Normal tunica media had NPR-B–like binding sites, and the level of these did not change significantly after compression. Consistent with this, CNP-(1-22) stimulated cGMP production equally with membranes from normal or damaged arteries and was more effective than ANP-(1-28). Neointima, which became evident 5 to 7 days after arterial damage, expressed NPR-C–like sites and no detectable NPR-B–like binding. NPR-C–like sites also appeared on the media for the first time between 5 and 7 days after compression. Immunohistochemistry for proliferating cell nuclear antigen revealed widespread mitosis in VSM at 5 days after compression, but mitosis was virtually restricted to the neointima at and beyond 7 days after compression. Thus, whereas levels of NPR-B did not change significantly after arterial injury and NPR-A was not detected, NPR-C–like receptors were unregulated as mitosis declined in the media and as a prominent neointima formed.
Inhibition of Histone Deacetylase Activity Suppresses Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Human Renal Epithelial Cells
Authors: Masahiro Yoshikawa, Keiichi Hishikawa, Takeshi Marumo, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2006)

Histone acetylation plays an important role in regulating gene expressions by modulating chromatin structure. Histone deacetylase (HDAC) inhibitors have been reported to have an antifibrogenic effect in some organs, such as the liver, skin, and lung, but the underlying mechanisms remain to be clarified. In the kidney, bone morphologic protein 7 (BMP-7) and hepatocyte growth factor are reported to antagonize TGF-beta1-induced tubular epithelial-to-mesenchymal transition (EMT), but nothing is known concerning the effect of HDAC inhibitors on EMT. It was shown that trichostatin A (TSA), an HDAC inhibitor, prevented TGF-beta1-induced EMT in cultured human renal proximal tubular epithelial cells. Treatment with TGF-beta1 induced morphologic changes such as EMT in human renal proximal tubular epithelial cells. However, co-treatment with TSA completely prevented TGF-beta1-induced morphologic changes and significantly prevented TGF-beta1-induced downregulation of E-cadherin and upregulation of collagen type I. Treatment with TSA did not alter TGF-beta1-induced phosphorylation of Smad2 and Smad3 but induced several inhibitory factors of TGF-beta1 signals, such as inhibitors of DNA binding/differentiation 2 (Id2) and BMP-7. Chromatin immunoprecipitation assay confirmed that histone acetylation was involved in the downregulation of E-cadherin and upregulation of Id2 and BMP-7. These results suggest that TSA and other HDAC inhibitors could be new therapeutic agents for tubular EMT.
Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice
Authors: Partha S. Biswas, Sanjay Gupta, Emily Chang, Li Song, Roslynn A. Stirzaker, James K. Liao, Govind Bhagat, Alessandra B. Pernis
Journal: Journal of Clinical Investigation (2010)

Deregulated production of IL-17 and IL-21 plays a key pathogenic role in many autoimmune disorders. A delineation of the mechanisms that underlie the inappropriate synthesis of IL-17 and IL-21 in autoimmune diseases can thus provide important insights into potential therapies for these disorders. Here we have shown that the serine-threonine kinase Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) becomes activated in mouse T cells under Th17 skewing conditions and phosphorylates interferon regulatory factor 4 (IRF4), a transcription factor that is absolutely required for the production of IL-17 and IL-21. We furthermore demonstrated that ROCK2-mediated phosphorylation of IRF4 regulated the synthesis of IL-17 and IL-21 and the differentiation of Th17 cells. Whereas CD4+ T cells from WT mice activated ROCK2 physiologically under Th17 conditions, CD4+ T cells from 2 different mouse models of spontaneous autoimmunity aberrantly activated ROCK2 under neutral conditions. Moreover, administration of ROCK inhibitors ameliorated the deregulated production of IL-17 and IL-21 and the inflammatory and autoantibody responses observed in these autoimmune mice. Our findings thus uncover a crucial link among ROCK2, IRF4, and the production of IL-17 and IL-21 and support the idea that selective inhibition of ROCK2 could represent an important therapeutic regimen for the treatment of autoimmune disorders.
Introducing the Gastroenterologist-accountable Professionalism in Practice (G-APP) Pathway: Bridging the G-APP-Replacing MOC With a Model for Lifelong Learning and Accountability
Authors: Suzanne Rose, Brijen J. Shah, Jane Onken, Arthur J. DeCross, Maura H. Davis, Rajeev Jain, Lawrence S. Kim, Kim Persley, Sheryl A. Pfeil, Lori N. Marks
Journal: Clinical Gastroenterology and Hepatology (2015)
Efficacy of Dofetilide in the Treatment of Atrial Fibrillation-Flutter in Patients With Reduced Left Ventricular Function
Authors: Ole D. Pedersen, Henning Bagger, Niels Keller, Bradley Marchant, Lars Køber, Christian Torp-Pedersen
Journal: Circulation (2001)

Background In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations. Methods and Results In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo ( P &lt;0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P &lt;0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P ≤0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P ≤0.02) rehospitalization. Conclusions Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm is associated with improved survival.
Urologic Complications of Diabetes
Authors: Jeanette S. Brown, Hunter Wessells, Michael B. Chancellor, Stuart S. Howards, Walter E. Stamm, Ann E. Stapleton, William D. Steers, Stephen K. Van Den Eeden, Kevin T. McVary
Journal: Diabetes Care (2005)

Diabetes and urologic diseases are very common health problems that markedly increase in prevalence and incidence with advancing age (1–3). Diabetes is associated with an earlier onset and increased severity of urologic diseases, resulting in costly and debilitating urologic complications. Urologic complications, including bladder dysfunction, sexual and erectile dysfunction, as well as urinary tract infections (UTIs), have a profound effect on the quality of life of men and women with diabetes. This review presents a comprehensive overview of the current understanding of clinical and basic research on urologic complications of diabetes and recommendations for future directions for research and clinical care.

Over 50% of men and women with diabetes have bladder dysfunction (4,5). Current understanding of bladder dysfunction reflects a progressive condition encompassing a broad spectrum of lower urinary tract symptoms including urinary urgency, frequency, nocturia, and incontinence. Previously, the dysfunction has been classically described as diminished bladder sensation, poor contractility, and increased postvoid residual urine, termed bladder cystopathy (6). However, bladder cystopathy most likely represents end-stage bladder failure with symptoms of infrequent voiding, difficulty initiating voiding, and postvoid fullness and is relatively uncommon.

A number of clinical studies in men and women with diabetes have reported bladder instability or hypersensitivity as the most frequent finding, ranging from 39–61% of subjects (5,7). Diminished bladder contractility or sensation has been found less often (5), and an acontractile bladder appears to be quite uncommon.

### Bladder dysfunction in women

In women, urinary incontinence is estimated to affect nearly 50% of middle aged and older women, leading to significant distress, limitations in daily functioning, and poorer quality of life (8,9). Diabetes has been identified as an important independent risk factor for incontinence in several large observational studies, including the Nurses’ Health Study, and is associated with 30–100% increased risk (9 …
Total lung capacity, residual volume and predicted residual volume in a densitometric study of older men.
Authors: R W Latin, R O Ruhling
Journal: British Journal of Sports Medicine (1986)

Results of investigations using various lung volumes for hydrostatic weighing determinations (HWD) appear to be inconclusive. Often, these lung volumes are predicted and not clinically determined. For this reason, total lung capacity (TLC), a measured residual volume (RV), and a predicted residual volume (PRV) were used during HWDs to compare the techniques. Twenty-five older men, 56 to 70 years (means +/- 62.1 + 4.2 years) performed HWDs at RV (10 trials) and at TLC (3-5 trials). Values for body density and fat free mass were not significantly different between RV and TLC; both values were, however, significantly different from those derived using PRV. There were statistically significant differences (p less than 0.05) between all 3 per cent body fat values but the 1.1 per cent difference between TLC and RV may not be physiologically important. It was concluded that TLC and RV may be used comparably during HWDs, but a PRV may produce significantly different values. Since HWD at TLC is easily performed and circumvents the difficulties associated with the RV technique, it may be the preferred method for older subjects.
PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group (NCCTG) randomized phase II study
Authors: S.R. Alberts, N.R. Foster, R.F. Morton, J. Kugler, P. Schaefer, M. Wiesenfeld, T.R. Fitch, P. Steen, G.P. Kim, S. Gill
Journal: Annals of Oncology (2005)
The pulmonary clock.
Authors: M R Hetzel
Journal: Thorax (1981)

The pulmonary clockMeasurement is fundamental to modern medicine, yet few doctors appreciate the importance of analysing biological data, not only as individual results, but also as a signal related to time.Biological rhythms are predominantly circadian-so called because they have a natural period of approximately 24 hours (circa diem) if allowed to run freely in the absence of external stimuli.They can be further described as diurnal if the peak of the rhythm (acrophase) occurs during daylight and the nadir (bathyphase) is seen during the night.Clinicians are familiar with the rhythm in adrenal cortical function,' but many other rhythms-for example, in body temperature,2 pulse rate,3 or renal function4-are also relevant to medicine, particularly in the design and interpretation of experimental work.Some rhythms have such low amplitude that they are not clinically important.Chronobiology is particularly important in the lung, however, since a circadian rhythm in airway resistance is easily demonstrated and, in asthma, is sometimes of such large amplitude that it is obvious to clinican and patient alike.The implications of this rhythm are threefold.It is relevant to the diagnosis of asthma, to the design and interpretation of trials of bronchodilator drugs, and, in severe cases, nocturnal asthma remains a challenge to pharmacology.Nocturnal asthma was described long before the birth of chronobiology.Aurelianus Caelius (fourth or fifth century AD) noted the frequent nocturnal occurrence of asthma attacks,5 and Maimonides (1135-1204)6 suggested that sleep was dangerous during an attack.Willis (1679)7 attributed it to the bedclothes overheating the blood, necessitating a "more plentiful sucking in of air."Floyer (1698)8 found that his attacks were exclusively nocturnal over seven years and Laennec (1827)9 described a patient whose attacks only occurred if his night light went out.Trousseau (1868)10 described nocturnal asthma in both himself and his mother.In the present century the aetiology of nocturnal asthma remained unknown until the rhythm in air- way calibre was identified in normal subjects.Claims that it was caused by feathers in bedding and
Acute Rheumatism: Hyperpyrexia: Post-Febrile Mania: Recovery
Authors: D. H. Kyle
Journal: BMJ (1901)

the seat " as if in a fit," was at once carried inside and laid on a couch.She was at once seen by the doctor, and found to be dead.Necropsy.-This was performed next day.On opening the pericardium a large amount of clot was found lying in the anterior surface of the heart and distending the pericardium.The heart was fatty as a whole, and sowed two medium-sized milk spots on the left ventricle.At a distance of I inch from the apex, on the anterior aspect of the left ventricle, was an area reddish-purple in colour from effused blood, in the centre of which was a small irregular tear about inch in length.On inserting a probe it was found to lead upwards and inwards into the cavity of the left ventricle, about 2 inch from the interventricular septum.Otherwise there was nothing of note, except that the whole heart showed marked fattv change; it weighed 9 ozs.As regards the other organs.there was little of interest; the lungs were emphysematous, the liver and kidneys were somewhat fatty, and the brain showed signs of degeneration.
Pancreatic Cyst in Infancy: Recovery after Marsupialization
Authors: W. H. Power
Journal: BMJ (1961)

Pancreatic cyst is a very rare condition: Aldis, quoted by Aird (1957), found only 2 in 75,000 patients.Most cysts have occurred in adult females.The condition is exceedingly rare in childhood and infancy.Miles (1959), in a review of the literature, found only eight cases in infants under 2 years of age, and, of these, cysts were demonstrated at birth in only two, and none was operated upon in the neonatal period.His own case was that of a full-term female baby who was operated upon when 8 days old.There had been frequent regurgitation of the baby's feeds with increasing abdominal distension.Examination of the abdomen and chest by x rays, intravenous pyelogram, barium meal, and barium enema showed a homogeneous shadow over most of the abdomen, with upward and medial displacement of the stomach and downward displace- ment of the large and small intestines.Laparotomy revealed a large thin-walled multilocular cyst arising from the head and body of the pancreas: the cyst was excised and the baby made a satisfactory recovery.
Comparative Efficacy of Bisphosphonates in Metastatic Breast and Prostate Cancer and Multiple Myeloma: A Mixed-Treatment Meta-analysis
Authors: Carlo Palmieri, John R. Fullarton, Janet Brown
Journal: Clinical Cancer Research (2013)

Abstract Purpose: A mixed-treatment comparison (MTC) was undertaken to compare the efficacy of zoledronic acid, clodronate, pamidronate, and ibandronate (i.v. and oral) in patients with skeletal-related events (SRE) secondary to metastatic breast and prostate cancer and multiple myeloma. Experimental Design: Studies of bisphosphonates in the three malignancies were identified and SRE data were extracted. Outcomes from the MTC were expressed as the annual SRE rate and as the mean likelihood (probability) ratio for the rate of SREs during treatment with zoledronic acid compared with the other bisphosphonates. Results: A total of 17 studies were identified (7 breast, 3 prostate, and 7 multiple myeloma). Data were available for all bisphosphonates in breast cancer; no data were available for ibandronate (oral or i.v.) in prostate cancer or for oral ibandronate in multiple myeloma. The SRE rates in breast cancer were 1.60 for zoledronic acid, 1.67 for oral ibandronate (excess SRE rate, 4%), 1.70 for i.v. ibandronate (6%), 2.07 for pamidronate (29%), and 2.29 for clodronate (42%). In prostate cancer, the SRE rates were 0.83 for zoledronic acid, 1.11 for clodronate (35%), and 1.41 for pamidronate (71%). In multiple myeloma, the SRE rates were 1.43 for zoledronic acid, 1.64 for pamidronate (15%), 1.90 for clodronate (33%), and 2.49 for i.v. ibandronate (75%). Conclusions: Zoledronic acid seems to be the most efficacious bisphosphonate for reducing the risk of SREs in patients with cancer of the breast or prostate and those with multiple myeloma. Clin Cancer Res; 19(24); 6863–72. ©2013 AACR.
A Road Forward to Improve Public Health
Authors: Robert D. Brook, Jeffrey R. Brook
Journal: Circulation (2011)

A ir quality has improved in many countries, including the United States, during the past few decades. 1,2Importantly, these gains have translated into observable health benefits.Reductions in fine particulate matter (PM) have significantly contributed to the increase in life expectancy in the United States since the 1980s. 2However, the burden of adverse health effects caused by high levels of air pollution continues to grow throughout many regions of the world.Outdoor air pollution ranks as the 8th-leading risk factor for death among high-income countries. 3Estimates are that anthropogenic fine PM contributes to Ϸ3.5 million cardiopulmonary deaths globally per year. 4Perhaps not well appreciated is the reality that cardiovascular (CV) deaths likely constitute the largest portion of this mortality. 1
One-Hour Plasma Glucose Concentration and the Metabolic Syndrome Identify Subjects at High Risk for Future Type 2 Diabetes
Authors: Muhammad A. Abdul-Ghani, Tamam Abdul-Ghani, Nibal Ali, Ralph A. DeFronzo
Journal: Diabetes Care (2008)

OBJECTIVE—To assess the efficacy of 1-h plasma glucose concentration and the metabolic syndrome in predicting future risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 1,611 subjects from the San Antonio Heart Study, who were free of type 2 diabetes at baseline; who had plasma glucose and insulin concentrations measured at time 0, 30, 60, and 120 min during the oral glucose tolerance test (OGTT); and who had their diabetes status determined with an OGTT after 7–8 years of follow-up, were evaluated. Two models, based on glucose tolerance status, 1-h plasma glucose concentration, and presence of the metabolic syndrome, were tested in predicting the risk for type 2 diabetes at 7–8 years of follow-up. RESULTS—A cutoff point of 155 mg/dl for the 1-h plasma glucose concentration during the OGTT was used to stratify subjects in each glucose tolerance group into low, intermediate, and high risk for future type 2 diabetes. A model based upon 1-h plasma glucose concentration, Adult Treatment Panel (ATP) III criteria for the metabolic syndrome, and fasting plasma glucose, independent of 2-h plasma glucose, performed equally well in stratifying nondiabetic subjects into low, intermediate, and high risk for future type 2 diabetes and identified a group of normal glucose-tolerant subjects who were at very high risk for future type 2 diabetes. CONCLUSIONS—The plasma glucose concentration at 1 h during the OGTT is a strong predictor of future risk for type 2 diabetes. A plasma glucose cutoff point of 155 mg/dl and the ATP III criteria for the metabolic syndrome can be used to stratify nondiabetic subjects into three risk groups: low, intermediate, and high risk.
Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany
Authors: C. Frye, J. Heinrich, M. Wjst, H-E. Wichmann
Journal: European Respiratory Journal (2001)

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8–14 yrs from three communities in East Germany were carried out in 1992–1993 and 1995–1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed. The prevalence of BHR increased from 6.4% in 1992–1993 to 11.6% in 1995–1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3–3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95–2.3) after adjustment for several indoor factors. In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.