tbuckley/cabot-search huggingface dataset:
STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET
Authors: Donald G. McKay, Ting-Chao Wong
Journal: The Journal of Experimental Medicine (1962)

The generalized Shwartzman reaction can be produced in pregnant rats by dietary means in the absence of injection of exogenous bacterial endotoxin. The experiment consists of a period of exposure to a diet low in tocopherol followed by exposure to a diet containing oxidized lipids during the gestation period. Pregnancy near term is an essential requirement for the development of the generalized Shwartzman reaction in these experiments. Fibrin thrombi were found in the renal glomeruli in 88.5 per cent, in the lungs in 94.2 per cent, in the liver in 11.4 per cent, in the spleen in 11.4 per cent, and in the adrenal in 40 per cent of animals that died spontaneously. There were pathologic alterations in the placenta which consisted of degeneration of the trophoblast, thrombosis of maternal blood channels in the giant cell trophoblast layer and in the labyrinth, congestion of the labyrinth, hemorrhage into the uterine cavity, placental separation, intra-uterine fetal death, decidual and uterine vein thrombosis, and placentitis in 10 per cent of the cases. The mechanism by which the diet is instrumental in causing this reaction remains to be demonstrated.
Quality of randomised trials in COPD
Authors: B. Bausch, A. Spaar, J. Kleijnen, M. A. Puhan
Journal: European Respiratory Journal (2009)

Randomised trials can provide high-level evidence to inform treatment decisions. Since their quality in respiratory medicine is largely unknown, we assessed the quality of a large set of chronic obstructive pulmonary disease (COPD) trials. As a marker of trial quality, we assessed the procedure and concealment of random allocation, and the conduct of an intention-to-treat-analysis in 344 randomised trials published between 1957 and 2006. We used ordered logistic regression to assess the association between trial quality and type of intervention, type of journal, journal impact factor and year of publication. 257 (75%) trials assessed pharmacological and 87 (25%) assessed nonpharmacological interventions. The generation of appropriate randomisation was reported in 27.0% of the trials, concealment of random allocation in 11.6% and an intention-to-treat analysis in 21.8% of trials. Significantly higher quality was found in trials on nonpharmacological interventions (OR 2.49, 95% CI 1.56-3.99), and in trials published in general medical journals (versus specialised journals; OR 2.25, 95% CI 1.30-3.90) and after 2000 (versus 1957-2000; OR 2.28, 95% CI 1.45-3.58). The association of quality with a high impact factor was of borderline significance (p = 0.06). The quality of many COPD trials is low but tends to become better since the adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement.
Hepatocyte growth factor leads to recovery from alcohol-induced fatty liver in rats
Authors: Minoru Tahara, Kunio Matsumoto, Toshihiro Nukiwa, Toshikazu Nakamura
Journal: Journal of Clinical Investigation (1999)

A fatty liver is characterized by the hyperaccumulation of lipids within hepatocytes and is often caused by excessive alcohol intake. Rats fed ethanol-containing diets for 37 days showed remarkable increase in hepatic lipids and lipid droplet accumulation in the hepatocytes, indicating the onset of alcoholic fatty liver. Administration of hepatocyte growth factor (HGF) for the last seven days of ethanol treatment markedly decreased hepatic lipids to a level lower than that seen before HGF treatment. In contrast, serum levels of lipids and lipoproteins increased with HGF administration. Primary cultured hepatocytes prepared from the fatty liver retained lipid droplets during a 48-hour culture. However, when cultured in the presence of HGF, intracellular lipid concentrations decreased and lipid secretion was enhanced. Consistent with these events, HGF stimulated the rate of protein synthesis of apolipoprotein B (apoB) and enhanced subsequent mobilization of lipids into the medium. These results indicate that HGF administration induced recovery from the fatty liver, at least in part, by enhancing apoB synthesis and the subsequent mobilization of lipids from hepatocytes with fatty change. The possibility that HGF can be therapeutic for subjects with an alcohol-related fatty liver warrants further attention.
Detection and Staging of Preinvasive Lesions and Occult Lung Cancer in the Central Airways with 18F-Fluorodeoxyglucose Positron Emission Tomography: A Pilot Study
Authors: Arifa Pasic, Hes A. Brokx, Emile F. Comans, Gerarda J. Herder, Elle K. Risse, Otto S. Hoekstra, Pieter E. Postmus, Tom G. Sutedja
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in radiologically occult preinvasive lesions and lung cancer in the central airways. Experimental Design: Twenty-two patients with 24 preinvasive lesions and early squamous cell cancer (SCC) being occult on high-resolution computed tomography were studied. All lesions were diagnosed based on histology sampled using autofluorescence bronchoscopy. FDG-PET findings were correlated with WHO histologic classification. FDG-PET was considered true-positive when the final diagnosis was SCC and true-negative when the lesions were classified as severe dysplasia or less. Results: FDG-PET was true-positive in 8 of 11 and true-negative in 11 of 13 cases corresponding with a sensitivity of 73% [95% confidence interval (CI), 0.43-0.91] and specificity of 85% (95% CI, 0.57-0.97). Positive and negative predictive values were 80% (95% CI, 0.48-0.96) and 79% (95% CI, 0.52-0.93), respectively. Conclusions: Our very preliminary data suggest that FDG-PET might be useful for the evaluation of early central airway lesions, being positive in most SCC and negative in cases of severe dysplasia. Validation in a larger multicenter study is needed.
Abnormal Circulatory Responses to High Altitude in Subjects with a Previous History of High-Altitude Pulmonary Edema
Authors: HERBERT N. HULTGREN, ROBERT F. GROVER, L. HOWARD HARTLEY
Journal: Circulation (1971)

In five men with a history of susceptibility to high-altitude pulmonary edema (HAPE), hemodynamics and pulmonary gas exchange were measured at sea level, and again 24 hours following ascent to an altitude of 3,100 m. At sea level, all findings were essentially normal including a mean pulmonary arterial pressure [See Equation in PDF File] of 13.8 ± 1.9 mm Hg. None of the subjects developed clinically detectable pulmonary edema at altitude. Wedge pressures and cardiac output remained normal. [See Equation in PDF File] increased remarkably, being 38.8 ± 10.3 mm Hg at rest and 53.2 ± 11.6 mm Hg during moderate exercise. Acute relief of hypoxia only partially relieved this pulmonary hypertension. Arterial blood gases were normal at sea level. In spite of hyperventilation at altitude, arterial O 2 pressure was only 50.8 ± 6.1 torr at rest and fell to 41.4 ± 3.3 torr during exercise due to a widening of the alveolar-arterial O 2 pressure difference to 28.0 ± 6.8 torr. Hence, these men susceptible to HAPE developed excessive pulmonary hypertension and impaired pulmonary O 2 exchange without detectable pulmonary edema following ascent to high altitude. The increase in pulmonary vascular resistance is only partially explained by hypoxic pulmonary vasoconstriction.
The Effect of Interview Language on the Evaluation of Psychopathology in Spanish-American Schizophrenic Patients
Authors: LUIS R. MARCOS, MURRAY ALPERT, LEONEL URCUYO, MARTIN KESSELMAN
Journal: American Journal of Psychiatry (1973)

Psychiatric ratings of ten schizophrenic patients whose native language was Spanish disclosed more psychopathology when the patients were interviewed in the English language than when they were interviewed in Spanish. Some evidence suggested that there were clinically important changes in the patient attributable to his problems in speaking in a second language. The clinician's frame of reference must also be taken into account: what is applicable to native English-speaking patients cannot be directly applied to the evaluation of persons from other cultures.
Prevalence of hypovitaminosis D in TB patients in an East London population
Authors: Muhammad Tufail, Philip Coakley, Ashton Harper, Pandina Kwong, Stuart Jones, Bridget Hall, Angela Hauser, Ajitha Jayaratnam, Michael Apps
Journal: European Respiratory Journal (2012)

Introduction:   There is a well-established link between vitamin D (25(OH)D) deficiency and TB, although in vivo association is still contentious.   Aims:   This retrospective case control study aimed to compare the prevalence of hypovitaminosis D in cases diagnosed with TB in 3 East London Boroughs to controls, who were defined as non-respiratory inpatients who were not on vitamin D supplements and in whom 25(OH)D assay was performed during the study period.   Methods:   We compared 25(OH)D levels in patients diagnosed with active TB with controls during a twelve month period from 01/09/10-31/08/11. Hypovitaminosis was defined by two thresholds for 25(OH)D concentrations: deficiency    Results:   There were 211 TB cases of whom 75 (35%) had 25(OH)D levels measured. All 75 had hypovitaminosis D of whom 60 (80%) had 25(OH)D deficiency and 15 (20%) were insufficient in 25(OH)D.  There were 323 controls, 87 of whom were taking supplements and so were excluded. Of the remaining 236 controls, 6.8 % were vitamin D replete (vs. 0 % in TB cases), 52.1 % had vitamin D deficiency (vs. 80% in TB cases) and 41.1 % were vitamin D insufficient (vs. 20% in TB cases). Mean 25(OH)D levels were significantly lower in the study group as compared to the control group (18.11 nmol/L vs 34.98 nmol/L, p    Conclusions:   The prevalence of hypovitaminosis D in both the study as well as the control groups is alarmingly high but importantly 100% of TB cases who had 25(OH)D levels checked were either deficient or insufficient. We hypothesize that this may be a unique finding in our ethnically-diverse population and thus may have implications for nutritional supplementation offered to active TB patients.
Association between Group 2 Innate Lymphoid Cells enrichment, nasal polyps and allergy in Chronic Rhinosinusitis
Authors: D. Miljkovic, A. Bassiouni, C. Cooksley, J. Ou, E. Hauben, P. ‐J. Wormald, S. Vreugde
Journal: Allergy (2014)

Abstract Background Group 2 innate lymphoid cells ( ILC 2s) were shown to be involved in the initiation and coordination of Th2‐type immune responses in allergic disease animal models. Recently, ILC 2s enrichment was noted in chronic rhinosinusitis ( CRS ) patients; however, the role of ILC 2s in coordinating the Th2 response in CRS remains to be elucidated. Here, we characterize the ILC 2 compartment in CRS by investigating the correlations between ILC 2s, Th2 cells and Th2 cytokines expression in CRS patients. Methods We used flow cytometric analysis of sinonasal mucosal tissues of 29 CRS patients and 5 controls to quantify ILC2s and Th2 cells. Messenger RNA expression levels of IL‐5, IL‐13, IL‐25, IL‐33, TSLP and GATA3 were determined using qRT ‐PCR. Results ILC2s were significantly enriched in nasal polyps (CRSwNP) patients. Multivariate linear regression showed a significant positive association of ILC2 numbers with CRSwNP and allergic CRS and a negative association with the number of previous endoscopic sinus surgeries. Group 2 innate lymphoid cell numbers significantly correlated with Th2 cell frequencies. Messenger RNA expression levels of IL‐5 and IL‐13 were increased in CRSwNP compared with controls, while mRNA levels of IL‐25 and GATA3 were significantly reduced. Conclusions Our results characterize the complex interactions between ILC 2s and other Th2 response elements in the context of CRS and suggest that ILC 2 enrichment occurs in CRS w NP and in allergic CRS patients.
Adding docetaxel to cisplatin and fluorouracil in patients with unresectable head and neck cancer: a cost–utility analysis
Authors: N.L. Liberato, C. Rognoni, S. Rubrichi, S. Quaglini, M. Marchetti, T. Gorlia, L. Licitra, J.B. Vermorken
Journal: Annals of Oncology (2011)
The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents: analyses from Phase Three of the ISAAC programme
Authors: Edwin A Mitchell, Richard Beasley, Ulrich Keil, Stephen Montefort, Joseph Odhiambo
Journal: Thorax (2012)

<h3>Background</h3> Exposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between exposure and asthma in childhood and adolescents. <h3>Aims</h3> To examine the association between maternal and paternal smoking and symptoms of asthma, eczema and rhinoconjunctivitis. <h3>Methods</h3> Parents or guardians of children aged 6–7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including maternal smoking in the child9s first year of life, current maternal smoking (and amount) and paternal smoking. Adolescents aged 13–14 years self completed the questionnaires on these symptoms and whether their parents currently smoked. <h3>Results</h3> In the 6–7-year age group there were 220 407 children from 75 centres in 32 countries. In the 13–14-year age group there were 350 654 adolescents from 118 centres in 53 countries. Maternal and paternal smoking was associated with an increased risk of symptoms of asthma, eczema and rhinoconjunctivitis in both age groups, although the magnitude of the OR is higher for symptoms of asthma than the other outcomes. Maternal smoking is associated with higher ORs than paternal smoking. For asthma symptoms there is a clear dose relationship (1–9 cigarettes/day, OR 1.27; 10–19 cigarettes/day, OR 1.35; and 20+ cigarettes/day, OR 1.56). When maternal smoking in the child9s first year of life and current maternal smoking are considered, the main effect is due to maternal smoking in the child9s first year of life. There was no interaction between maternal and paternal smoking. <h3>Conclusions</h3> This study has confirmed the importance of maternal smoking, and the separate and additional effect of paternal smoking. The presence of a dose–response effect relationship with asthma symptoms suggests that the relationship is causal, however for eczema and rhinoconjunctivitis causality is less certain.
Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis
Authors: Adriano G Rossi, Deborah A Sawatzky, Annemieke Walker, Carol Ward, Tara A Sheldrake, Nicola A Riley, Alison Caldicott, Magdalena Martinez-Losa, Trevor R Walker, Rodger Duffin, Mohini Gray, Elvira Crescenzi, Morag C Martin, Hugh J Brady, John S Savill, Ian Dransfield, Christopher Haslett
Journal: Nature Medicine (2006)
Delayed Chemokine Receptor 1 Blockade Prolongs Survival in Collagen 4A3–Deficient Mice with Alport Disease
Authors: Volha Ninichuk, Oliver Gross, Christoph Reichel, Andrej Khandoga, Rahul D. Pawar, Raluca Ciubar, Stephan Segerer, Emilia Belemezova, Ewa Radomska, Bruno Luckow, Guillermo Perez de Lema, Philip M. Murphy, Ji-Liang Gao, Anna Henger, Matthias Kretzler, Richard Horuk, Manfred Weber, Fritz Krombach, Detlef Schlo[Combining Diaeresis]ndorff, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2005)

Human Alport disease is caused by a lack of the alpha3-, 4-, or 5-chain of type IV collagen (COL4A). Affected humans and COL4A3-deficient mice develop glomerulosclerosis and progressive renal fibrosis in the presence of interstitial macrophages, but their contribution to disease progression is under debate. This question was addressed by treating COL4A3-deficient mice with BX471, an antagonist of chemokine receptor 1 (CCR1) that is known to block interstitial leukocyte recruitment. Treatment with BX471 from weeks 6 to 10 of life improved survival of COL4A3-deficient mice, associated with less interstitial macrophages, apoptotic tubular epithelial cells, tubular atrophy, interstitial fibrosis, and less globally sclerotic glomeruli. BX471 reduced total renal Cll5 mRNA expression by reducing the number of interstitial CCL5-positive cells in inflammatory cell infiltrates. Intravital microscopy of the cremaster muscle in male mice identified that BX471 or lack of CCR1 impaired leukocyte adhesion to activated vascular endothelium and transendothelial leukocyte migration, whereas leukocyte rolling and interstitial migration were not affected. Furthermore, in activated murine macrophages, BX471 completely blocked CCL3-induced CCL5 production. Thus, CCR1-mediated recruitment and local activation of macrophages contribute to disease progression in COL4A3-deficient mice. These data identify CCR1 as a potential therapeutic target for Alport disease or other progressive nephropathies associated with interstitial macrophage infiltrates.
Pathogenesis of Idiopathic Pulmonary Fibrosis
Authors: Paul J. Wolters, Harold R. Collard, Kirk D. Jones
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated.
Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine.
Authors: R Schulz, S Miyazaki, M Miller, E Thaulow, G Heusch, J Ross, B D Guth
Journal: Circulation Research (1989)

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.
Roles of the Tumor Suppressor p53 and the Cyclin-dependent Kinase Inhibitor p21WAF1/CIP1 in Receptor-mediated Apoptosis of WEHI 231 B Lymphoma Cells
Authors: Min Wu, Robert E. Bellas, Jian Shen, Gail E. Sonenshein
Journal: The Journal of Experimental Medicine (1998)

Treatment of WEHI 231 immature B lymphoma cells with an antibody against their surface immunoglobulin M (anti-IgM) induces apoptosis and has been studied extensively as a model of self-induced B cell tolerance. Since the tumor suppressor protein p53 has been implicated in apoptosis in a large number of cell types and has been found to be mutated in a variety of B cell tumors, here we sought to determine whether p53 and the p53 target gene cyclin-dependent kinase inhibitor p21WAF1/CIP1 were involved in anti-IgM–induced cell death. Anti-IgM treatment of WEHI 231 cells increased expression of p53 and p21 protein levels. Ectopic expression of wild-type p53 in WEHI 231 cells induced both p21 expression and apoptosis. Ectopic expression of p21 similarly induced apoptosis. Rescue of WEHI 231 cells from apoptosis by costimulation with CD40 ligand ablated the increase in p21 expression. Lastly, a significant decrease in anti-IgM–mediated apoptosis was seen upon downregulation of endogenous p53 activity by expression of a dominant-negative p53 protein or upon microinjection of an antisense p21 expression vector or antibody. Taken together, the above data demonstrate important roles for p53 and p21 proteins in receptor-mediated apoptosis of WEHI 231 B cells.
GP120: Biologic Aspects of Structural Features
Authors: Pascal Poignard, Erica Ollmann Saphire, Paul WHI Parren, Dennis R. Burton
Journal: Annual Review of Immunology (2001)

▪ Abstract HIV-1 particles are decorated with a network of densely arranged envelope spikes on their surface. Each spike is formed of a trimer of heterodimers of the gp120 surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1 entry into target cells, initiating the HIV-1 replication cycle. They are a target for entry-blocking drugs and for neutralizing Abs that could contribute to vaccine protection. The crystal structure of the core of gp120 has been recently solved. It reveals the structure of the conserved HIV-1 receptor binding sites and some of the mechanisms evolved by HIV-1 to escape Ab responses. The gp120 consists of three faces. One is largely inaccessible on the native trimer, and two faces are exposed but apparently have low immunogenicity, particularly on primary viruses. We have modeled HIV-1 neutralization by a CD4 binding site monoclonal Ab, and we propose that neutralization takes place by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance. Knowledge of gp120 structure and function should assist in the design of new drugs as well as of an effective vaccine. In the latter case, circumventing the low immunogenicity of the HIV-1 envelope spike is a major challenge.