tbuckley/cabot-search huggingface dataset:
Relationship between lung inflammation, changes in lung function and severity of exposure in victims of the Bhopal tragedy
Authors: VK Vijayan, K Sankaran
Journal: European Respiratory Journal (1996)

The world's worst chemical industrial disaster, which occurred at Bhopal on 2-3 December, 1984, resulted in considerable respiratory morbidity in the exposed population. Therefore, a study was planned to evaluate the relationship between lower respiratory tract inflammation, lung function and severity of exposure. Sixty patients exposed to methyl isocyanate and presenting with respiratory symptoms were studied using bronchoalveolar lavage (BAL) 1-7 yrs after the accident. Pulmonary function tests included forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). An index of severity of exposure was derived retrospectively on the basis of the acute symptoms in the victims themselves or the occurrence of death among their family members. Total lung inflammatory cells (p < 0.01) and absolute numbers of macrophages (p = 0.01) and lymphocytes (p < 0.05) increased as severity of exposure increased. FEV1/FVC % (p = 0.05) was also significantly lower as severity of exposure increased. Moderately exposed subjects had significantly lower FEV1/FVC % (p < 0.05) compared to those mildly exposed. In nonsmokers, BAL neutrophils, both percentage and absolute numbers, showed significant negative correlations with FEV1 % predicted (rs = -0.350, p < 0.05; and rs = -0.374, p < 0.01, respectively). Neutrophil percentage was negatively correlated with FEV1/FVC % (rs = -0.378; p < 0.01). Absolute lymphocytes had significant negative correlations with FVC % pred (rs = -0.318; p < 0.05). Macrophages had significant positive correlations with FVC % pred (rs = 0.322; p < 0.05) and FEV1 % pred (rs = 0.433; p < 0.01). Radiographic abnormalities (International Labour Organization (ILO) classification) were associated with decline in FEV1 % pred (p < 0.05). This study suggests that pulmonary function abnormalities occur in gas-exposed subjects as a consequence of an abnormal accumulation of lung inflammatory cells (lymphocytes and neutrophils), and that the intensity of lung inflammation and reduction in pulmonary function are greater in severely exposed subjects. As it has been observed that decline in pulmonary function is associated with radiographic abnormalities, there is a suggestion that injury following toxic gas exposure can lead to irreversible lung damage.
Dysregulation of miR-15a and miR-214 in human pancreatic cancer
Authors: Xing J Zhang, Hua Ye, Cheng W Zeng, Bo He, Hua Zhang, Yue Q Chen
Journal: Journal of Hematology & Oncology (2010)

Abstract Background Recent reports indicate that microRNAs (miRNAs) play a critical role in malignancies. However, the role that miRNAs play in pancreatic cancer remains to be determined. The purpose of this study was to investigate aberrantly expressed miRNAs in pancreatic cancer tissues and demonstrate their roles in disease progression. Results We detected the expression patterns of miRNAs in 10 pancreatic cancer tissues and their adjacent benign tissues by quantitative real time-PCR (qRT-PCR) and found that miR-15a and miR-214 were dysregulated in the tumor samples. This is the first time that miR-214 has been identified as aberrantly expressed in pancreatic cancer. In vitro experiments showed that overexpression of miR-15a inhibited the viability of pancreatic cancer cells, whereas overexpression of miR-214 decreased the sensitivity of the cells to gemcitabine (GEM). Furthermore, we identified WNT3A and FGF7 as potential targets of miR-15a and ING4 as a target of miR-214. Conclusions Aberrant expression of miRNAs such as miR-15a and miR-214 results in different cellular effects in pancreatic cancer. Downregulation of miR-15a might contribute to proliferation of pancreatic cancer cells, whereas upregulation of miR-214 in pancreatic cancer specimens might be related to the poor response of pancreatic cancer cells to chemotherapy. MiR-15a directly targets multiple genes relevant in pancreatic cancer, suggesting that it may serve as a novel therapeutic target for treatment of the disease.
Predictors of Metabolically Healthy Obesity in Children
Authors: Rhiannon L. Prince, Jennifer L. Kuk, Kathryn A. Ambler, Jasmine Dhaliwal, Geoff D.C. Ball
Journal: Diabetes Care (2014)

To determine the prevalence of metabolically healthy obesity (MHO) in children and examine the demographic, adiposity, and lifestyle predictors of MHO status.This cross-sectional study included 8-17 year olds with a BMI ≥85th percentile who were enrolled in a multidisciplinary pediatric weight management clinic from 2005-2010. Demographic, anthropometric, lifestyle, and cardiometabolic data were retrieved by retrospective medical record review. Participants were dichotomized as either MHO or metabolically unhealthy obese (MUO) according to two separate classification systems based on: 1) insulin resistance (IR) and 2) cardiometabolic risk (CR) factors (blood pressure, serum lipids, and glucose). Multivariable logistic regression was used to determine predictors of MHO using odds ratios (ORs) with 95% CIs.The prevalence of MHO-IR was 31.5% (n = 57 of 181) and MHO-CR was 21.5% (n = 39 of 181). Waist circumference (OR 0.33 [95% CI 0.18-0.59]; P = 0.0002) and dietary fat intake (OR 0.56 [95% CI 0.31-0.95]; P = 0.04) were independent predictors of MHO-IR; moderate-to-vigorous physical activity (OR 1.80 [95% CI 1.24-2.62]; P = 0.002) was the strongest independent predictor of MHO-CR.Up to one in three children with obesity can be classified as MHO. Depending on the definition, adiposity and lifestyle behaviors both play important roles in predicting MHO status. These findings can inform for whom health services for managing pediatric obesity should be prioritized, especially in circumstances when boys and girls present with CR factors.
Characterization of Clinical Cases of Collecting Duct Carcinoma of the Kidney Assessed by Comprehensive Genomic Profiling
Authors: Sumanta K. Pal, Toni K. Choueiri, Kai Wang, Depinder Khaira, Jose A. Karam, Eliezer Van Allen, Norma A. Palma, Mark N. Stein, Adrienne Johnson, Rachel Squillace, Julia A. Elvin, Juliann Chmielecki, Roman Yelensky, Evgeny Yakirevich, Doron Lipson, Douglas I. Lin, Vincent A. Miller, Philip J. Stephens, Siraj M. Ali, Jeffrey S. Ross
Journal: European Urology (2015)
Synergistic Modulation of ATP-Sensitive K <sup>+</sup> Currents by Protein Kinase C and Adenosine
Authors: Yongge Liu, Wei Dong Gao, Brian O’Rourke, Eduardo Marban
Journal: Circulation Research (1996)

Abstract Ischemic preconditioning has been shown to involve the activation of adenosine receptors, protein kinase C (PKC), and ATP-sensitive K + (K ATP ) channels. We investigated the effects of PKC activation and adenosine on K ATP current (I K,ATP ) and action potentials in isolated rabbit ventricular myocytes. Responses to pinacidil (100 to 400 μmol/L), an opener of K ATP channels, were markedly increased by preexposure to the PKC activator phorbol 12-myristate 13-acetate (PMA, 100 nmol/L). I K,ATP measured at 0 mV was increased by PMA pretreatment from 0.55±0.32 to 3.25±0.47 nA (n=6, P &lt;.01). We next determined whether PKC activation abbreviates the time required to turn on I K,ATP during metabolic inhibition (MI). In control cells in which MI was induced by 2 mmol/L cyanide and 0 glucose, I K,ATP developed after an average of 15.1±2.4 minutes (n=8). Ten-minute pretreatment with PMA alone (PMA+MI) did not significantly alter this latency (11.9±2.0 minutes, n=8). Since adenosine receptor activation has been shown to play an important role in the preconditioning response, two groups of myocytes were studied with adenosine (10 μmol/L) included during MI. Without PMA, adenosine alone (MI+Ado) did not affect the latency to develop I K,ATP (12.3±1.5 minutes, n=8). However, if cells were pretreated with PMA and then subjected to MI in the presence of adenosine (PMA+MI+Ado), the latency was greatly shortened to 5.5±1.6 minutes (n=8; P &lt;.02 versus MI, PMA+MI, and MI+Ado groups). This effect could not be reproduced by an inactive phorbol but was completely abolished by the adenosine receptor antagonist 8-( p -sulfophenyl)-theophylline. The opening of K ATP channels may be cardioprotective because of the abbreviation of action potential duration (APD) during ischemia. Therefore, we tested whether PKC activation could modify the time course of APD shortening during MI. Consistent with the ionic current measurements, PMA pretreatment significantly accelerated APD shortening, but only when adenosine (10 μmol/L) was included during MI. The effects were not attributable to accelerated ATP consumption: PMA pretreatment did not alter the time required to induce rigor during MI, whether or not adenosine was included. Our results indicate that PKC activation increases the I K,ATP induced by pinacidil or by MI. The latter effect requires concomitant adenosine receptor activation. The synergistic modulation of I K,ATP by PKC and adenosine provides an explicit basis for current paradigms of ischemic preconditioning.
Drugs in the Treatment of Rheumatic Disorders
Authors: N. Mutch
Journal: Annals of the Rheumatic Diseases (1949)

N. MUTCH and others (1936) reported that often the CO2- carrying power of the blood is not materially affected.Gebert (1931) found that pH values might indeed sometimes be raised so that the administration of alkalis cann6t be expected entirely to alleviate the condition.
Immunological characterisation of hoffa's fat pad in osteoarthritis
Authors: E. Yusuf, K. A. Marijt, G. J. V. M. van Osch, A. Zuurmond, V. Stoianovic-Susulic, R. E. M. Toes, M. Kloppenburg, A. Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2010)

Obesity is an increasing health problem in the western world. Accumulating data indicate that the adipose tissue is not only a lipid storage site, but also secretes a large number of inflammatory mediators that have powerful immunomodulatory effects. Among …
Simple and Accurate Prediction of the Clinical Probability of Pulmonary Embolism
Authors: Massimo Miniati, Matteo Bottai, Simonetta Monti, Marco Salvadori, Luca Serasini, Mirko Passera
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Clinical probability assessment is a fundamental step in the diagnosis of pulmonary embolism.To develop a predictive model for pulmonary embolism based on clinical symptoms, signs, and the interpretation of the electrocardiogram.The model was developed from a database of 1,100 patients with suspected pulmonary embolism, of whom 440 had the disease confirmed by angiography or autopsy findings. It was validated in an independent sample of 400 patients with suspected pulmonary embolism (71% were inpatients). Easy-to-use software was developed for computing the clinical probability on palm computers and mobile phones.The model comprises 16 variables of which 10 (older age, male sex, prolonged immobilization, history of deep vein thrombosis, sudden-onset dyspnea, chest pain, syncope, hemoptysis, unilateral leg swelling, electrocardiographic signs of acute cor pulmonale) are positively associated, and 6 (prior cardiovascular or pulmonary disease, orthopnea, high fever, wheezes, or crackles on chest auscultation) are negatively associated with pulmonary embolism. In the validation sample, 165 (41%) of 400 patients had pulmonary embolism confirmed by angiography. The prevalence of pulmonary embolism was 2% when the predicted clinical probability was slight (0 to 10%), 28% when moderate (11 to 50%), 67% when substantial (51 to 80%), and 94% when high (81 to 100%). There was no significant difference between inpatients and outpatients with respect to the prevalence of pulmonary embolism in the four probability categories.The proposed model is simple and accurate, and it may aid physicians when assessing the clinical probability of pulmonary embolism.
A case of unusual hand pain in general practice
Authors: Faraz Mughal, Ahmed Rashid, Rajnish C Mishra
Journal: BMJ (2015)

A 34 year old white man presented to his general practitioner with a one year history of progressive bilateral hand pain. There was no trauma history or previous arthropathy. He consumed 84 units of alcohol a week, lived alone, and had lost his job as a plasterer owing to reduced hand function. He had three children. On initial examination of the hands and wrists, he had no swelling or bony tenderness and he had normal power, reflexes, and sensation of the upper limbs. Pain was elicited when he unclenched his fists.

Vitamin supplements were prescribed, he was referred to the alcohol team, and a fit note was issued with review planned after a full set of blood tests. Full blood count, renal profile, bone profile, thyroid function, erythrocyte sedimentation rate, and C reactive protein were within normal ranges. Serum alanine aminotransferase was raised (59 U/L; reference range 0-40) and rheumatoid factor was negative.

At follow-up review, bilateral ptosis, frontal balding, and myopathic facies were noted. Bilateral percussion myotonia and distal wasting of the hand muscles were also found on examination. Finger extension was restricted and slowed bilaterally. Cranial nerve examination was otherwise normal, as was cardiorespiratory examination.



### 1. What do these clinical findings suggest?

#### Short answer

These clinical findings suggest a diagnosis of muscular dystrophy, probably myotonic dystrophy.

#### Discussion

Myotonic dystrophy is characterised by progressive myopathy, myotonia, and systemic involvement. Myotonic dystrophy type 1 (DM1), known as Steinert’s disease, is the most common type of muscular dystrophy in adults, with a European prevalence of 3-15 per 100 000. Myotonic dystrophy type 2 (DM2), known as proximal myotonic …
S112 TNF-R1 Ubiquitous Scaffolding and Signalling protein (TRUSS) is a regulator of TNF- induced NF- -B activation
Authors: A. J. Langton, I. Horan, S. Farrow, D. W. Riches, E. R. Chilvers, H. Parfrey
Journal: Thorax (2011)

The pleiotropic cytokine TNFα plays a key role in the pathogenesis of many chronic inflammatory lung diseases, particularly sarcoidosis, asthma and COPD. Due to its broad spectrum of activity however, current anti-TNFα therapies are of limited efficacy in these conditions and are associated with an increased risk of infection and malignancy. Interaction of TNFα with its cognate receptor, TNF-R1 initiates a signalling cascade that leads ultimately to the phosphorylation of the transcription factor NF-kB. This allows NF-kB to shuttle in a co-ordinated manner between the cytoplasm and the nucleus, leading to the up-regulation of genes that are key to cellular inflammatory and apoptotic responses. We propose that the novel TNF-R1 interacting protein TRUSS (TNF-R1 Ubiquitous Scaffolding and Signalling protein), which interacts with members of the TNF-R1 signalling cascade, may regulate this process. A549 cells, which express high levels of endogenous TRUSS, were transfected transiently with siRNA, which resulted in 80±14% (mean±SEM, n=16) knockdown of TRUSS mRNA. TRUSS deficient cells demonstrated a profound early (&lt;1 h) defect in the nuclear translocation of p50/p65 subunits following TNFα stimulation (p&lt;0.05, n=3). As a consequence, in the absence of TRUSS, p50, its precursor phospho-p105, and phospho-p65 were retained in the cytoplasm in these cells following TNFα stimulation. Furthermore, TRUSS depletion caused a reduction in TNFα stimulated NF-kB (p&lt;0.01, n=7) and AP-1 (p&lt;0.01, n=6) luciferase reporter activity; this was associated with a decrease in interleukin 6, RANTES, G-CSF and GM-CSF (p&lt;0.05, n=6) mRNA and protein expression while MCP-1, CXCL5 and IL-8 were not affected. Although TRUSS deplete cells displayed impaired up-regulation of IkBa mRNA in response to TNFα stimulation, the protein response was intact. Upstream signalling molecules TNFR1, TRADD, TRAF2 and RIP were unaffected by TRUSS knockdown. In conclusion, these data suggest a novel role for TRUSS as a scaffold protein involved in the initial nuclear translocation of p50/p65 NF-kB subunits, which regulates the early pro-inflammatory response to TNFα. Hence TRUSS may represent a more selective therapeutic target for modulating TNFα functions.
RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics
Authors: Myron G. Best, Nik Sol, Irsan Kooi, Jihane Tannous, Bart A. Westerman, François Rustenburg, Pepijn Schellen, Heleen Verschueren, Edward Post, Jan Koster, Bauke Ylstra, Najim Ameziane, Josephine Dorsman, Egbert F. Smit, Henk M. Verheul, David P. Noske, Jaap C. Reijneveld, R. Jonas A. Nilsson, Bakhos A. Tannous, Pieter Wesseling, Thomas Wurdinger
Journal: Cancer Cell (2015)
The New York Diabetes Association’s 48th Annual Scientific Meeting, the American Diabetes Association’s 48th Annual Advanced Postgraduate Course, and the Meeting of the Naomi Berry Diabetes Center of Columbia University
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2001)

This report covers the New York Diabetes Association’s 48th Annual Scientific Meeting, October 2000; the Meeting of the Naomi Berry Diabetes Center of Columbia University, December 2000; and the American Diabetes Association’s 48th Annual Advanced Postgraduate Course, January 2001, New York, New York. Topics include diabetic retinopathy, diabetic nephropathy, the cell biology of insulin action, and islet cell transplantation.

At the 48th Annual Scientific Meeting of the Gerald J. Friedman Symposium on October 28, 2000, in New York, NY, Lloyd P. Aiello, Boston, MA, discussed potential pharmacologic treatments of diabetic retinopathy. Diabetic retinopathy is a major cause of blindness and visual loss, acting via two complications, proliferative retinopathy, which leads to retinal hemorrhage and scarring with the inevitable development of traction detachment, and that of macular edema, which is caused by abnormalities of retinal vessels. Panretinal photocoagulation, the existing treatment, is less effective for macular edema and can be expected to lead to some degree of visual loss; it may also lead to severe complications when performed incorrectly. The original hypothesis that diabetic retinopathy is caused by abnormal production of growth factors stimulated by retinal hypoxia was made more than 50 years ago by I.C. Michaelson. Growth hormone and IGFs play a permissive role, fibroblast growth factor may act synergistically, and vascular endothelial growth factor (VEGF) appears to be the major mediator. The expression of this glycoprotein is increased by hypoxia, and its levels are particularly high in patients with active proliferative retinopathy. VEGF increases retinal permeability in a dose-related fashion at levels encountered clinically in patients with retinopathy.

These considerations suggest a number of potential approaches to treatment. Prevention of hypoxia with glycemic control, antioxidants, and AGE inhibitors might directly protect the retinal vessels. Angiotensin II (A2) is an important signal for VEGF secretion, with ACE inhibitors and A2 …
Abnormal Immune Responses to Herpes Simplex in Subjects with Atopic Dermatitis Complicated by Eczema Herpeticum
Authors: D.Y. Leung, M. Boguniewicz, P. Taylor, J.D. Canniff, K.L. Kesler, B.D. Armstrong, A.D. Weinberg
Journal: Journal of Allergy and Clinical Immunology (2009)
Safety of monitoring heart transplant recipients without annual routine coronary angiography
Authors: C.H. Spes, V. Klauss, S.D. Schnaack, A.R. Tammen, K.-H. Henneke, J. Rieber, T.M. Behr, P. Uberfuhr, B. Reichart, K. Theisen, C.E. Angermann, H. Mudra
Journal: Journal of the American College of Cardiology (1998)
Bias in meta-analysis detected by a simple, graphical test
Authors: M. Egger, G. D. Smith, M. Schneider, C. Minder
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. <b>Design:</b> Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the <i>Cochrane Database of Systematic Reviews</i>. <b>Main outcome measure:</b> Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. <b>Results:</b> In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. <b>Conclusions:</b> A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. <h3>Key messages</h3> Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the <i>Cochrane Database of Systematic Reviews</i> Critical examination of systematic reviews for publication and related biases should be considered a routine procedure