tbuckley/cabot-search huggingface dataset:
Infections in asthma and allergy
Authors: S A LEWIS
Journal: Thorax (1998)

The role of infection in asthma is presently a paradox. While respiratory syncytial virus, among others, has long been believed to instigate immunological changes which lead to asthma, and rhinovirus might be an important contributory factor in the exacerbation of asthma symptoms in children and adults, there is increasing speculation that infections in early life have a protective role in the development of allergy and asthma. The motivation for this theory was the observation of a strong relationship between birth order and the risk of allergic disease and generic atopy which has consistently emerged from British cohorts spanning the last 40 years.1-3 One of the appeals of the infection hypothesis is its undoubted capacity to explain the increase in allergic disease in developed societies over recent years as an inevitable consequence of improved hygiene standards, increased immunisation, and reduced contact between children owing to declining family size and less crowded homes. A theory which was once based exclusively on epidemiological associations has now gained support on immunological grounds. As the mechanisms which control the immune response to allergen and the course of the events in early life leading to maturation of this system become better understood, it is evident that the microbial environment of early life is a potential influence on this process.4 Neither epidemiology nor immunology yet provide much evidence on the nature of the infection or infections likely to be involved, but each supplies some useful, though sometimes disparate, clues.

In this issue of Thorax Farooqi and Hopkin have taken a retrospective look at all the available health records of a relatively recent (1975–1984) birth group taken from a single general practice in Oxfordshire, and examined links between a diversity of early childhood infections and the subsequent diagnosis of allergic disease.5 This historical cohort study …
Gestational Diabetes
Authors: Robert G. Moses, Maria T. Mackay
Journal: Diabetes Care (2004)

To assess the relationship between leg length and glucose tolerance in pregnancy.The leg length and leg-to-height percentage were prospectively determined on 161 glucose-tolerant women during pregnancy and 61 women with gestational diabetes mellitus (GDM).Women with GDM were a mean of 2.8 cm shorter than women who were glucose tolerant, due entirely to their leg lengths being a mean of 3.2 cm shorter. With respect to the 2-h result on the glucose tolerance test (GTT), there were negative correlations for height (r = -0.161, P = 0.017), leg length (r = -0.266, P < 0.0005), and the leg-to-height percentage (r = -0.294, P < 0.0005). The correlation between the leg-to-height percentage and the 2-h result on the GTT remained significant after adjustment for age (r = -0.252, P < 0.0005) and for age and BMI (r = -0.224, P = 0.001).Women with GDM are shorter than glucose-tolerant women and have a lower leg-to-height percentage. Consideration of short stature as a risk factor for GDM is not valid without taking into account the leg-to-height percentage.
Gram-negative bacterial lipopolysaccharide impairs hyaluronan clearancein vivo and its uptake by the isolated, perfused rat liver
Authors: Ion V. Deaciuc, Gregory J. Bagby, Charles H. Lang, Nebojsa Skrepnik, John J. Spitzer
Journal: Hepatology (1993)

The purpose of this investigation was to examine the effect of gram-negative bacterial lipopolysaccharide on hyaluronan concentration in blood plasma, hyaluronan removal from the blood and hyaluronan uptake by isolated, perfused rat liver. Intravenous administration of Escherichia coli lipopolysaccharide to rats markedly increased plasma hyaluronan concentration in a dose-dependent manner. One day after lipopolysaccharide challenge (0.1 or 1.0 mg per 100 gm body wt), plasma hyaluronan levels were 570.7 +/- 66.8 ng x ml-1 and 1,951.0 +/- 120.3 ng x ml-1, respectively, as compared with 94.2 +/- 12.2 ng x ml-1 in the time-matched control animals. Removal of intravenously injected hyaluronan (30 micrograms per 100 gm body wt) was suppressed 32% by lipopolysaccharide administration (100 micrograms per 100 gm body wt). At the same dose, lipopolysaccharide induced a severe inhibition (60% to 80%) of hyaluronan uptake by perfused livers isolated 3 or 24 hr after lipopolysaccharide administration. The inhibitory effect of lipopolysaccharide on hyaluronan uptake by the isolated, perfused liver was not abolished by pretreatment with either antibodies to tumor necrosis factor-alpha IgG or indomethacin, an inhibitor of the cyclooxygenase pathway. Continuous intravenous infusion of recombinant murine tumor necrosis factor-alpha for 18 to 20 hr did not affect plasma hyaluronan concentration. These data suggest that neither tumor necrosis factor-alpha, an early cytokine induced by lipopolysaccharide, nor prostaglandins are involved in the mechanism of lipopolysaccharide-induced inhibition of hyaluronan uptake by the perfused rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)
De-SUMOylation Enzyme of Sentrin/SUMO-Specific Protease 2 Regulates Disturbed Flow–Induced SUMOylation of ERK5 and p53 that Leads to Endothelial Dysfunction and Atherosclerosis
Authors: Kyung-Sun Heo, Eugene Chang, Nhat-Tu Le, Hannah Cushman, Edward T.H. Yeh, Keigi Fujiwara, Jun-ichi Abe
Journal: Circulation Research (2013)

Disturbed flow induces proinflammatory and apoptotic responses in endothelial cells, causing them to become dysfunctional and subsequently proatherogenic.Although a possible link between SUMOylation of p53 and ERK5 detected during endothelial apoptosis and inflammation has been suggested, the mechanistic insights, especially under the proatherogenic flow condition, remain largely unknown.SUMOylation of p53 and ERK5 was induced by disturbed flow but not by steady laminar flow. To examine the role of the disturbed flow-induced p53 and ERK5 SUMOylation, we used de-SUMOylation enzyme of sentrin/Small Ubiquitin-like MOdifier (SUMO)-specific protease 2 deficiency (Senp2(+/-)) mice and observed a significant increase in endothelial apoptosis and adhesion molecule expression both in vitro and in vivo. These increases, however, were significantly inhibited in endothelial cells overexpressing p53 and ERK5 SUMOylation site mutants. Senp2(+/-) mice exhibited increased leukocyte rolling along the endothelium, and accelerated formation of atherosclerotic lesions was observed in Senp2(+/-)/Ldlr(-/-), but not in Senp2(+/+)/Ldlr(-/-), mice fed a high-cholesterol diet. Notably, the extent of lesion size in the aortic arch of Senp2(+/-)/Ldlr(-/-) mice was much larger than that in the descending aorta, also suggesting a crucial role of the disturbed flow-induced SUMOylation of proteins, including p53 and ERK5 in atherosclerosis formation.These data show the unique role of sentrin/SUMO-specific protease 2 on endothelial function under disturbed flow and suggest that SUMOylation of p53 and ERK5 by disturbed flow contributes to the atherosclerotic plaque formation. Molecules involved in this newly discovered signaling will be useful targets for controlling endothelial cells dysfunction and consequently atherosclerosis formation.
Montelukast sodium in cystic fibrosis
Authors: A H MORICE
Journal: Thorax (2001)

Many older patients with cystic fibrosis (CF) describe a component of their condition as “asthma” despite a lack of objective bronchial lability. We undertook a therapeutic trial of the leukotriene antagonist montelukast sodium in one such patient and observed a marked improvement in symptoms and peak expiratory flow rate (PEFR). Subsequently we performed an open label study in adult patients attending the Hull Adult Cystic Fibrosis Clinic.

Eleven patients (eight male) of mean (range) age 25.9 (16–44) years with stable CF and no pulmonary infective exacerbations for at least four weeks entered a two week observation period during which they recorded a …
Inflammatory Reaction in Pulmonary Muscular Arteries of Patients with Mild Chronic Obstructive Pulmonary Disease
Authors: VICTOR IVO PEINADO, JOAN ALBERT BARBERÁ, PIETRO ABATE, JOSEP RAMÍREZ, JOSEP ROCA, SALUD SANTOS, ROBERT RODRIGUEZ-ROISIN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Endothelial dysfunction and intimal thickening have been shown in pulmonary arteries (PA) of patients with mild chronic obstructive pulmonary disease (COPD). To investigate whether an inflammatory process related to tobacco smoking might be involved in the development of pulmonary vascular abnormalities in COPD, we characterized the inflammatory cell infiltrate and the endothelium-dependent relaxation in PA of 39 patients who underwent lung resection, divided into three groups: “nonsmokers” (n = 7); “smokers,” with normal lung function (n = 12); and “COPD” (n = 20). Endothelium-dependent relaxation was assessed in vitro by exposing PA rings to adenosine diphosphate (ADP). Inflammatory cell types were identified by immunohistochemistry. PA of COPD patients developed lower relaxation in response to ADP than nonsmokers and smokers. The number of inflammatory cells was increased in PA of COPD compared with the other two groups. This cell infiltrate was largely constituted by T lymphocytes. The CD8+ T-cell subset was increased in both smokers and COPD compared with nonsmokers, yielding a reduction of the CD4+/CD8+ ratio. The intensity of the inflammatory infiltrate correlated with both the endothelium-dependent relaxation and the intimal thickness. We conclude that cigarette smoking induces a CD8+ T-lymphocyte infiltrate in PA, which is associated with the impairment of the vessel's structure and function, suggesting the potential involvement of an inflammatory process in the pathogenesis of pulmonary vascular abnormalities in the early stage of COPD.
A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas
Authors: Sameer Agnihotri, Amparo Wolf, Diana M. Munoz, Christopher J. Smith, Aaron Gajadhar, Andres Restrepo, Ian D. Clarke, Gregory N. Fuller, Santosh Kesari, Peter B. Dirks, C. Jane McGlade, William L. Stanford, Kenneth Aldape, Paul S. Mischel, Cynthia Hawkins, Abhijit Guha
Journal: The Journal of Experimental Medicine (2011)

Glioblastoma Multiforme (GBM), the most common and lethal primary human brain tumor, exhibits multiple molecular aberrations. We report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumor suppressor gene (TSG). Although GATA4 was expressed in normal brain, loss of GATA4 was observed in 94/163 GBM operative samples and was a negative survival prognostic marker. GATA4 loss occurred through promoter hypermethylation or novel somatic mutations. Loss of GATA4 in normal human astrocytes promoted high-grade astrocytoma formation, in cooperation with other relevant genetic alterations such as activated Ras or loss of TP53. Loss of GATA4 with activated Ras in normal astrocytes promoted a progenitor-like phenotype, formation of neurospheres, and the ability to differentiate into astrocytes, neurons, and oligodendrocytes. Re-expression of GATA4 in human GBM cell lines, primary cultures, and brain tumor-initiating cells suppressed tumor growth in vitro and in vivo through direct activation of the cell cycle inhibitor P21(CIP1), independent of TP53. Re-expression of GATA4 also conferred sensitivity of GBM cells to temozolomide, a DNA alkylating agent currently used in GBM therapy. This sensitivity was independent of MGMT (O-6-methylguanine-DNA-methyltransferase), the DNA repair enzyme which is often implicated in temozolomide resistance. Instead, GATA4 reduced expression of APNG (alkylpurine-DNA-N-glycosylase), a DNA repair enzyme which is poorly characterized in GBM-mediated temozolomide resistance. Identification and validation of GATA4 as a TSG and its downstream targets in GBM may yield promising novel therapeutic strategies.
Western Blot Analysis of Antigens on Melanoma Cells Recognized by Cytotoxic T Cells
Authors: P. Hersey, M. MacDonald, H. Werkman
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Western Blot Analysis of Antigens on Melanoma Cells Recognized by Cytotoxic T Cells Get access Peter Hersey, Peter Hersey * 3Immunology and Oncology Unit of the Mater Misericordiae Hospital, Royal Newcastle HospitalNewcastle, Australia *Correspondence to: Dr. Peter Hersey, Immunology and Oncology Unit, 4th Floor, David Maddison Clinical Sciences Building, Royal Newcastle Hospital, Newcastle, NS.W. 2300, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Malcolm MacDonald, Malcolm MacDonald 3Immunology and Oncology Unit of the Mater Misericordiae Hospital, Royal Newcastle HospitalNewcastle, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Harko Werkman Harko Werkman 3Immunology and Oncology Unit of the Mater Misericordiae Hospital, Royal Newcastle HospitalNewcastle, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 11, 3 August 1988, Pages 826–835, https://doi.org/10.1093/jnci/80.11.826 Published: 03 August 1988 Article history Received: 28 December 1987 Revision received: 14 March 1988 Accepted: 30 March 1988 Published: 03 August 1988
Persistence of Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients Predicts Increased Risk for Relapse—A European Pooled Analysis
Authors: Wolfgang Janni, Florian D. Vogl, Gro Wiedswang, Marit Synnestvedt, Tanja Fehm, Julia Jückstock, Elin Borgen, Brigitte Rack, Stephan Braun, Harald Sommer, Erich Solomayer, Klaus Pantel, Jahn Nesland, Klaus Friese, Bjørn Naume
Journal: Clinical Cancer Research (2011)

The prognostic significance of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients at the time of primary diagnosis has been confirmed by a large pooled analysis. In view of the lack of early indicators for secondary adjuvant treatment, we here evaluated whether the persistence of DTCs after adjuvant therapy increases the risk of subsequent relapse and death.Individual patient data from 676 women with primary diagnosis of early breast cancer stages I-III from 3 follow-up studies were pooled. During clinical follow-up, patients underwent BM aspiration (BMA) to determine the presence of DTC. Tumor cells were detected by the standardized immunoassays. Univariate and multivariable proportional hazards models were estimated to assess the prognostic significance of DTC for disease-free survival (DFS) and overall survival (OS).Patients were followed for a median of 89 months. BMA was performed at median 37 months after diagnosis of breast cancer. At follow-up BMA, 15.5% of patients had DTCs. The presence of DTC was an independent indicator of poor prognosis for DFS, distant DFS (DDFS), cancer-specific survival, and OS during the first 5 years following cancer diagnosis (log-rank test P < 0.001 values for all investigated endpoints).Among breast cancer patients, persistent DTCs during follow-up significantly predicted the increased risk for subsequent relapse and death. Analysis of DTC might serve as a clinically useful monitoring tool and should be tested as an indicator for secondary adjuvant treatment intervention within clinical trials.
Upregulation of Bcl-2 Through Caspase-3 Inhibition Ameliorates Ischemia/Reperfusion Injury in Rat Cardiac Allografts
Authors: J Grünenfelder, D N Miniati, S Murata, V Falk, E G Hoyt, M Kown, M L Koransky, R C Robbins
Journal: Circulation (2001)

Oxidative stress after ischemia/reperfusion of cardiac allografts leads to cytokine production. Bcl-2, an inhibitor of apoptosis, also has strong antioxidant properties. Caspase-3 is known to cleave bcl-2. This study tests the hypothesis that bcl-2 is downregulated while tumor necrosis factor-alpha (TNF-alpha) levels increase after cardiac transplantation. Furthermore, the use of caspase-3 inhibition was investigated as a strategy for preserving myocardial bcl-2 and mitochondrial cytochrome c after transplantation.PVG-to-ACI rat heterotopic cardiac transplantations were performed in 4 groups designed with 30 minutes' ischemia and 4 or 8 hours of reperfusion (n=4 per group). Treatment consisted of DEVD-CHO 500 microgram IP per animal to donor and recipient 2 hours before transplantation and 250 microgram IC into allograft. Controls were treated with saline. Grafts were analyzed by reverse transcription-polymerase chain reaction for bcl-2 mRNA, by ELISA for TNF-alpha, for myeloperoxidase activity, and by Western blot for cytochrome c. In untreated groups, bcl-2 mRNA decreased significantly over time, whereas TNF-alpha increased significantly at 4 hours (P=0.003) and returned to baseline after 8 hours' reperfusion (P=NS compared with normal hearts). Treatment with caspase-3 inhibitor showed significant upregulation of bcl-2 mRNA expression after 4 and 8 hours of reperfusion (P<0.001 versus control), with a concomitant decrease in TNF-alpha to baseline levels. Myeloperoxidase activity in all groups was no different from that of normal hearts. Mitochondrial cytochrome c release increased in both control and treatment groups.Bcl-2 is actively downregulated and TNF-alpha is upregulated in this model of cardiac allograft ischemia/reperfusion. Furthermore, the caspase-3 pathway is linked to this process, and blockade of caspase-3 can ameliorate reperfusion injury by upregulating bcl-2 and inhibiting TNF-alpha without affecting cytochrome c release.
miR126-5p repression of ALCAM and SetD5 in endothelial cells regulates leucocyte adhesion and transmigration
Authors: Loïc Poissonnier, Gaëlle Villain, Fabrice Soncin, Virginie Mattot
Journal: Cardiovascular Research (2014)

AimsmiR126-5p is processed from the miR126-3p/-5p duplex, which is expressed in endothelial cells and gives rise to the guide strand miR126-3p and the passenger strand miR126-5p. miR126-3p has prominent roles in vascular development and diseases, whereas the expression and physiological functions of miR126-5p are unknown. The purpose of this study was to evaluate the expression and role of miR126-5p in blood vessel endothelial cells.
Weight Loss Maintenance
Authors: Thomas H. Inge, Robert M. Siegel, Stavra A. Xanthakos
Journal: JAMA Pediatrics (2014)

In 1991, a total of 8 people were sealed for 2 years inside a manmade “Biosphere” consisting of a 3-acre ecologically closed habitat. This crew of 4 men and 4 women voluntarily entered the habitat to learn about the interactions between humans and key ecological systems. However, these scientists serendipitously experienced a hardship that has actually taught the world a great deal more about basic human physiology than ever expected. In the first growing season after entering the Biosphere, an unplanned crop failure resulted in a relative famine in their ecological bubble. This crop failure resulted in a severe calorie imbalance, with an esti
Tumour necrosis factor receptor 2 (TNFRSF1B) association study in Sjogren's syndrome
Authors: Corinne Miceli-Richard, Philippe Dieude, Eric Hachulla, Xavier Puechal, François Cornelis, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2007)

Primary Sjogren’s syndrome (pSS) is a complex disease involving both genetic and environmental factors. Among the genetic susceptibility factors, HLA-DRB1 has been extensively studied as a strong candidate gene and the association of HLA - DRB1*0301 (DR3) with pSS has been frequently reported among Caucasians.1 2 As the Tumour Necrosis Factor α ( TNFα ) gene is located within the HLA region, its contribution to disease susceptibility has also been studied. We have previously reported a significant association of TNF-308A allele with pSS, in strong linkage disequilibrium with HLA-DRB1*03 .3 This association was restricted to patients with anti-SSB antibodies. TNF exerts its action through two cell …
Airway inflammation is augmented by obesity and fatty acids in asthma
Authors: H.A. Scott, P.G. Gibson, M.L. Garg, L.G. Wood
Journal: European Respiratory Journal (2011)

Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma. Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood samples analysed for inflammatory markers. There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (β=1.015, 95% CI 0.258–1.772; p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9% versus 16.2%; p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (β=0.108, 95% CI 0.036–0.180; p=0.004) and negatively with monounsaturated fatty acids (β= -0.068, 95% CI -0.131– -0.005; p=0.035). This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.
Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon γ–Deficient Mice Leads to Exacerbation of Experimental Autoimmune Encephalomyelitis
Authors: Cong-Qiu Chu, Susan Wittmer, Dyana K. Dalton
Journal: The Journal of Experimental Medicine (2000)

Mice deficient in interferon (IFN)-γ or IFN-γ receptor develop progressive and fatal experimental autoimmune encephalomyelitis (EAE). We demonstrate that CD4 T cells lacking IFN-γ production were required to passively transfer EAE, indicating that they were disease-mediating cells in IFN-γ knockout (KO) mice. IFN-γ KO mice accumulated 10–16-fold more activated CD4 T cells (CD4+CD44hi) than wild-type mice in the central nervous system during EAE. CD4+CD44hi T cells in the spleen and central nervous system of IFN-γ KO mice during EAE showed markedly increased in vivo proliferation and significantly decreased ex vivo apoptosis compared with those of wild-type mice. IFN-γ KO CD4+CD44hi T cells proliferated extensively to antigen restimulation in vitro and accumulated larger numbers of live CD4+ CD44hi T cells. IFN-γ completely suppressed proliferation and significantly induced apoptosis of CD4+CD44hi T cells responding to antigen and hence inhibited accumulation of live, activated CD4 T cells. We thus present novel in vivo and in vitro evidence that IFN-γ may limit the extent of EAE by suppressing expansion of activated CD4 T cells.