tbuckley/cabot-search huggingface dataset:
Monitoring exhaled carbon monoxide in COPD exacerbations
Authors: Imre Barta, Orsolya Drozdovszky, Balázs Antus
Journal: European Respiratory Journal (2014)

Aims: Exhaled carbon-monoxide (eCO) has been implicated as a pulmonary biomarker in various respiratory diseases. The aim of this longitudinal study was to investigate whether serious acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring hospitalization is associated with an increase in eCO and to see if recovery is accompanied by a reduction of eCO level.  Methods:Levels of eCO along with routine clinical variables were measured in 29 current smoker and 33 ex-smoker COPD patients at the time of at hospital admission, and also at discharge following regular treatment.  Results:Levels of eCO were increased in current smokers, both during exacerbation (6.0 [2.0-9.5] vs. 1.0 [1.0-2.0] ppm, p  Conclusions: Our results suggest that eCO may be involved in smoking-associated inflammatory processes in the airways, but its monitoring during an episode of AECOPD is of limited clinical value.
Aspects of Blood Pressure, Lipid, and Glycemic Treatment
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the fourth of a series of articles reviewing presentations at the 63rd annual scientific session of the American Diabetes Association, held in New Orleans, Louisiana, June 2003.

William Cushman described the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which had a total of 33,357 hypertensive participants, 36% of whom had diabetes, making it the largest study of blood pressure treatment in diabetes (1). Interestingly, 60% of the population studied satisfied criteria for the metabolic syndrome. In both the diabetic and nondiabetic subgroups, there was no difference in coronary heart disease (CHD) events or mortality between patients randomized to chlorthalidone, amlodipine, and lisinopril. Congestive heart failure (CHF) was less common with chlorthalidone than with the other agents. For those with fasting glucose <126 mg/dl at baseline, the mean glucose was 93 mg/dl at baseline, with levels increasing to 104 mg/dl with chlorthalidone, 103 mg/dl with amlodipine, and 101 mg/dl with lisinopril at 4 years. Similarly, diabetes incidence was highest with chlorthalidone at 11.6 vs. 9.8% with amlodipine and 8.1% with lisinopril. Including those persons who developed diabetes, and those with fasting glucose ≥126 mg/dl who had unrecognized diabetes, 39, 40, and 39% of persons in the three groups actually had diabetes. In each group, 4% had impaired fasting glucose (IFG) at levels of 110–125 mg/dl. The diabetic participants had 36% CVD prevalence, as opposed to 62% of the IFG and nondiabetic groups, based on the differing entry criteria for those with and without diabetes. Initial fasting glucose levels were 169, 116, and 91 mg/dl in the respective groups. Lisinopril did not lower systolic blood pressure as effectively as the two other agents, although it affected diastolic blood pressure similarly. Among persons with diabetes, at 2 years fasting blood glucose decreased 3 and 2 mg/dl with amlodipine …
Molecular Basis for the Cell Type–Specific Induction of SnoN Expression by Hepatocyte Growth Factor
Authors: Ruoyun Tan, Xianghong Zhang, Junwei Yang, Yingjian Li, Youhua Liu
Journal: Journal of the American Society of Nephrology (2007)

Hepatocyte growth factor (HGF) is a potent antifibrotic cytokine that antagonizes the TGF-β1/Smad signaling in diverse types of kidney cells by different mechanisms. HGF is shown to induce Smad co-repressor Sloan-Kettering Institute proto-oncogene–related novel gene, non–Alu-containing (SnoN) expression in proximal tubular epithelial cells (HKC-8) but not in glomerular mesangial cells and interstitial fibroblasts. This study investigated the molecular mechanisms underlying the cell type–specific induction of SnoN by HGF. Treatment of HKC-8 cells with actinomycin D completely abolished HGF-mediated SnoN induction, suggesting its dependence on gene transcription. Although HGF activated several signal pathways in HKC-8 cells, blockade of extracellular signal–regulated kinase-1 and -2 (Erk-1/2) activation but not Akt and p38 mitogen-activated protein kinase abolished SnoN induction. HGF rapidly activated both upstream and downstream signaling of Erk-1/2, which led to the activation of the cAMP response element–binding protein (CREB). In the promoter region of human SnoN gene, two cAMP response elements were located in close proximity to Sp1 sites. Chromatin immunoprecipitation assay revealed that activated CREB and Sp1 bound to their cognate cis-acting elements in SnoN promoter in response to HGF stimulation. Ectopic expression of wild-type CREB promoted SnoN expression, whereas dominant negative mutant CREB abrogated SnoN induction by HGF. Likewise, chemical blockade of Sp1 binding abolished HGF-mediated SnoN induction. Furthermore, HGF selectively induced CREB phosphorylation in HKC-8 cells but not in mesangial cells and fibroblasts. <i>In vivo</i>, administration of HGF gene induced renal Erk-1/2 phosphorylation, CREB activation, and SnoN expression in obstructive nephropathy. Collectively, these results suggest that CREB activation, in concert with Sp1, constitutes a molecular switch that confers the cell type–specific induction of SnoN in response to HGF stimulation.
Hormonal Requirements of Various Strains of Mouse Mammary Gland in Organ Culture&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Dharm Vir Singh
Journal: JNCI Journal of the National Cancer Institute (1972)

With the organ culture method, studies were made to analyze the strain differences in hormone responsiveness to mouse mammary glands. Two principal questions were asked: 1) How many days of pretreatment in vivo are required to allow lobuloalveolar differentiation of mouse mammary gland in response to hormones in vitro; 2) Given the optimal duration of pretreatment, what is the minimal hormonal combination that will induce lobuloalveolar differentiation in vitro in mammary glands of mice of different strains? Four strains of mice were examined in regard to the hormonal requirements for induction of mammary gland lobuloalveolar differentiation in vitro. I8 required 5 days of pretreatment with estradiol and progesterone to show development in vitro; C3H required 9 days; C57BL and A required 15 days. The greater length of pretreatment was correlated with the absence of “inherited hormonal influence” and the minimal hormonal requirements varied with different strains in vitro. The concentration of 0.1 μg aldosterone/ml of medium was adequate for all strains except A, which needed a higher concentration. Insulin requirement ranged from 0.5–2.5 μg/ml; prolactin and growth hormone requirements, from 0.25–5.0 μg/ml. These requirements in vitro and “inherited hormonal influence” were not correlated. All this information will be useful in later attempts to induce neoplastic transformation in vitro.
Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis
Authors: T Neogi, A Soni, S A Doherty, L L Laslett, R A Maciewicz, D J Hart, W Zhang, K R Muir, M Wheeler, C Cooper, T D Spector, F Cicuttini, G Jones, M Nevitt, Y Liu, N K Arden, M Doherty, A M Valdes
Journal: Annals of the Rheumatic Diseases (2013)

There is extensive literature reporting discordance between the presence and severity of symptoms and the degree of radiographic structural osteoarthritis (OA).1–⇓⇓⇓5 Genetic differences may account for some of this discordance. Indeed, certain genetic variants implicated in pain sensitivity have been shown to be significantly different between asymptomatic radiographic cases of OA and symptomatic cases.6–9 

The catechol-O-methyltransferase, encoded by the COMT gene, is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters.10 Genetic variation at the COMT gene has been shown to result in differential pain sensitivity.10–12 Carriers of the Val158Met COMT variant have been reported to have a higher risk (OR=2.9, 95% CI 1.2 to 6.1) of hip pain as compared with carriers of the Val/Val genotype among those with hip OA.9 This result has not been replicated in independent cohorts, nor for OA in other joints.

We assessed whether the Met allele in the COMT gene is involved in increased risk of symptomatic knee OA in seven cohorts: five cohorts from the UK, …
Association of circulating adiponectin levels with progression of radiographic joint destruction in rheumatoid arthritis
Authors: J. T. Giles, D. M. van der Heijde, J. M. Bathon
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Adipokines have inflammatory and immunomodulatory properties that may contribute to erosive joint damage. The association of serum adipokine levels with progression of radiographic joint damage in patients with rheumatoid arthritis (RA) was prospectively explored. <h3>Methods</h3> Patients with RA underwent serum adipokine assessment (adiponectin, resistin, leptin) at three timepoints and hand/feet x-rays, scored using the Sharp-van der Heijde Score (SHS), at baseline and the third study visit, separated by an average of 39±4 months. The associations of baseline and average adipokine levels with change in SHS were explored, adjusting for pertinent confounders. <h3>Results</h3> Of the 152 patients studied, 85 (56%) showed an increase in SHS (defined as &gt;0 SHS units). Among the adipokines studied, only adiponectin was significantly associated with radiographic progression, with average adiponectin levels more strongly associated than baseline levels. After adjusting for average C reactive protein and baseline SHS, patients in the highest quartile of average adiponectin had a SHS progression rate more than double the lowest quartile (1.00 vs 0.48 units/year; p=0.008). Similarly, those in the highest quartile of adiponectin had a more than fivefold greater odds of any radiographic progression compared with the lowest quartile (OR 5.75; p=0.002). The magnitude of the association of average adiponectin levels with radiographic progression was greater in women, those with body mass index &lt;30 kg/m<sup>2</sup> and those receiving baseline biological disease-modifying antirheumatic drugs. <h3>Conclusions</h3> These prospective data provide evidence of temporality and dose-response in the relationship between circulating adiponectin and erosive joint destruction in RA, and highlight subgroups of patients at highest risk for adiponectin-associated radiographic progression.
Update on<i>Epidermal Growth Factor Receptor</i>Mutations in Non–Small Cell Lung Cancer
Authors: Gregory J. Riely, Katerina A. Politi, Vincent A. Miller, William Pao
Journal: Clinical Cancer Research (2006)

Abstract In 2004, several investigators reported that somatic mutations in the epidermal growth factor receptor gene were associated with clinical responses to erlotinib and gefitinib in patients with non–small cell lung cancer. Since then, multiple groups have examined the biological properties that such mutations confer as well as the clinical relevance of these mutations in patients with non–small cell lung cancer. Although a tremendous amount of knowledge has been gained in the past 2 years, there remain a number of important epidemiologic, biological, and clinical questions.
The effect of air pollution on inner-city children with asthma
Authors: K.M. Mortimer, L.M. Neas, D.W. Dockery, S. Redline, I.B. Tager
Journal: European Respiratory Journal (2002)

The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City Asthma Study. Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SO2), nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9 yrs). None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning % PEFR (0.59% decline (95% confidence interval (CI) 0.13-1.05%) per interquartile range (IQR) increase in 5-day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95% CI 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03-1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR increase in 6-day average NO2 and OR=1.26 (95% CI 1.0-1.59) per IQR increase in 2-day average PM10. This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.
Deletion of Microsomal Prostaglandin E Synthase-1 Increases Sensitivity to Salt Loading and Angiotensin II Infusion
Authors: Zhanjun Jia, Aihua Zhang, Hui Zhang, Zheng Dong, Tianxin Yang
Journal: Circulation Research (2006)

Microsomal prostaglandin E synthase-1 (mPGES-1), a membrane-associated protein, is critically involved in the inflammatory response and may be involved in physiological processes as well. The present study examined the role of mPGES-1 in regulation of sodium balance and blood pressure in the settings of salt loading and angiotensin II infusion. mPGES-1 -/- mice developed severe and progressive hypertension associated with an inappropriate increase in sodium balance when fed a high-salt diet. These mice exhibited a significantly impaired ability to excrete an acute enteral load of NaCl. Under these 2 settings of salt loading, urinary excretion of prostaglandin E(2) and nitrate/nitrite were remarkably increased in wild-type animals but not in mPGES-1 -/- mice. The changes of urinary cGMP paralleled that of urinary nitrate/nitrite. mPGES-1 -/- mice exhibited a remarkable inhibition of high salt-induced increase in gene expression of all 3 NO synthase isoforms, whereas these mice had upregulated expression of NO synthase III but not NO synthase I and NO synthase II at basal state. Chronic salt loading remarkably induced mPGES-1 protein expression exclusively in the distal nephron. In primary cultures of CD cells, mPGES-1 expression was significantly increased following exposure to hypertonic NaCl, in parallel with increased prostaglandin E(2) release. These findings have revealed a mPGES-1/prostaglandin E(2)/NO/cGMP pathway that appears to be critically important for salt adaptation. In addition, we provide evidence that mPGES-1 deficiency sensitized the hypertensive effect of angiotensin II. Overall, this study has characterized the natriuretic and antihypertensive role of mPGES-1 that likely contributes to blood pressure homeostasis.
PTU-017 IgG4 +ve autoimmune hepatitis is not observed among patients of non-Asian origin
Authors: A D Yeoman, Y Zen, M A Heneghan
Journal: Gut (2012)

<h3>Introduction</h3> IgG4 mediated autoimmune disease has recently been described in relation to pancreatitis and sclerosing cholangitis. Furthermore recent reports, mainly from Japan, have also identified cases of autoimmune hepatitis (AIH) in which an IgG4 positive hepatic inflammatory infiltrate predominates. <h3>Methods</h3> We set out to establish the frequency with which IgG4 +ve plasma cells are observed in a cohort of patients with AIH without pancreatitis or sclerosing cholangitis. Immuno-histochemical analysis via application of a monoclonal antibody to IgG4 was undertaken on archived liver tissue specimens. Three fields per biopsy specimen were analysed and the number of IgG4 +ve plasma cells per high powered field (HPF) and the proportion of these as a total of the plasma cell infiltrate were recorded. As per recent publications<sup>1 2</sup> a biopsy specimen was determined to be IgG4 +ve if more than 10 IgG4 +ve plasma cells were seen per high powered filed (HPF) AND where this number equated to &gt;40% of the total plasma cell infiltrate. Immunohistochemical and histo-pathological analysis was undertaken by a single, experienced, hepato-pathologist (YZ). <h3>Results</h3> Sixty-three liver tissue specimens underwent immuno-histochemical analysis. These specimens derived from 53 Caucasian and 10 Afro-Caribbean patients. All patients met the revised International Autoimmune Hepatitis Group diagnostic criteria for probable or definite AIH. The median age of patients at diagnosis was 31 years and 78% were female. Among this cohort 44 patients presented with chronic disease and histological evidence of chronic active hepatitis while 19 presented with acute disease in whom histology demonstrated hepatic collapse in 16 and severe lobular hepatitis in three patients. Only 7 of 63 samples (11%) demonstrated &gt;10 IgG4 +ve cells/HPF. While there was a greater number of biopsy specimens with &gt;10 IgG4 +ve plasma cells per HPF in acute vs chronic presentations this did not reach statistical significance (16% vs 9%, p=0.44). Additionally, there was no difference in the frequency of this finding between males and females (males 21% females 8% p=0.4) or between different ethnic groups (11% in Caucasians vs 10% in Afro-Caribbeans, p=0.99). Importantly, in none of the seven cases in which &gt;10 IgG4 +ve plasma cells/HPF were noted did the proportion of IgG4 +ve plasma cells equate to &gt;40% of the total plasma cell infiltrate. <h3>Conclusion</h3> While a small proportion of non-Asian AIH patients demonstrate &gt;10 IgG4 +ve plasma cells/HPF, in no individual did this represent &gt;40% of the total hepatic plasma cell infiltrate. Consequently, significant IgG4 +ve plasma cell infiltrates are not observed among non-Asian patients with AIH presenting to our institution. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Umemura T</b>, <i>et al</i>. <i>Hepatology</i> 2007;<b>46</b>:463–71. 2. <b>Cheuk</b>, <i>et al</i>. <i>Adv Anat Pathol</i> 2010;<b>17</b>:303–32.
Evidence That Serum Levels of the Soluble Receptor for Advanced Glycation End Products Are Inversely Associated with Pancreatic Cancer Risk: A Prospective Study
Authors: Li Jiao, Stephanie J. Weinstein, Demetrius Albanes, Philip R. Taylor, Barry I. Graubard, Jarmo Virtamo, Rachael Z. Stolzenberg-Solomon
Journal: Cancer Research (2011)

Cigarette smoking, obesity, type 2 diabetes, and, to a lesser extent, meat cooked at high temperatures are associated with pancreatic cancer. Cigarette smoke and foods cooked at higher temperatures are major environmental sources of advanced glycation end products (AGE). AGEs accumulate during hyperglycemia and elicit oxidative stress and inflammation through interaction with the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) acts as an anti-inflammatory factor to neutralize AGEs and block the effects mediated by RAGE. In this study, we investigated the associations of prediagnostic measures of N(ε)-(carboxymethyl)-lysine (CML)-AGE and sRAGE with pancreatic cancer in a case-cohort study within a cohort of 29,133 Finnish male smokers. Serum samples and exposure information were collected at baseline (1985-1988). We measured CML-AGE, sRAGE, glucose, and insulin concentrations in fasting serum from 255 incident pancreatic cancer cases that arose through April 2005 and from 485 randomly sampled subcohort participants. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI, adjusted for age, years of smoking, and body mass index. CML-AGE and sRAGE were mutually adjusted. CML-AGE levels were not associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.68 (0.38-1.22), P(trend) = 0.27]. In contrast, sRAGE levels were inversely associated with pancreatic cancer [fifth compared with first quintile, RR (95% CI): 0.46 (0.23-0.73), P(trend) = 0.002]. Further adjustment for glucose or insulin levels did not change the observed associations. Our findings suggest that sRAGE is inversely associated with pancreatic cancer risk among Finnish male smokers.
Hormonal responses during prolonged exercise are influenced by a selective DA/NA reuptake inhibitor
Authors: M F Piacentini, R Meeusen, L Buyse, G De Schutter, K De Meirleir
Journal: British Journal of Sports Medicine (2004)

Objective: A decrease in dopamine activity is thought to lead to a reduction in motivation and arousal and therefore to the “central” component of fatigue. The purpose of the present study was to investigate the effects of a dopamine (DA) noradrenaline (NA) reuptake inhibitor, bupropion (Zyban™), on exercise performance and on the hormonal response to exercise. Methods: Eight healthy well trained male cyclists (Watt max 397±15 W) participated in the study. Subjects completed one maximal exercise test (to determine maximal power output Watt max ), and two endurance performance tests (time trials) in a double blind randomised cross-over design. Subjects took either placebo capsules (lactose) or 2×300 mg bupropion (BUP). Blood samples were collected for adrenocorticotropin (ACTH), prolactin, cortisol, growth hormone, beta-endorphins, and catecholamines. Results: Performance was not influenced by BUP (placebo: 89±1 min; BUP 2×300 mg: 89±0.7 min). All hormones increased during exercise in all trials. Cortisol plasma concentrations were significantly higher in the BUP trial at rest, at min 60, and at the end of exercise, while beta-endorphins were higher in the BUP trial at the end of exercise and during recovery, and ACTH at the end of exercise. Conclusion: From the present results, we can conclude that bupropion had a more marked central noradrenergic effect (compared to dopaminergic) on the hormonal response to exercise, but no effect on the outcome of performance.
Third complementarity-determining-region sequence analysis of lymphocytic interstitial pneumonia: most cases demonstrate a minor monoclonal population hidden among normal lymphocyte clones.
Authors: K Kurosu, N Yumoto, M Furukawa, T Kuriyama, A Mikata
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We analyzed the third complementarity-determining region (CDR3) of the immunoglobulin heavy chain (IgH) gene in five patients with lymphoid interstitial pneumonia (LIP) through a two-step polymerase chain reaction (PCR) and sequencing analysis. By sequencing analysis of the PCR products, morphologic LIP could be divided into two groups: a polyclonal type and a minor monoclonal type. Because of their high frequencies, minor monoclonal clones seemed to be neoplastic clones hidden in normally reactive lymphocyte clones. Consequently, only the polyclonal type might have represented true LIP. Sequencing of the PCR products from open-chest biopsy and transbronchial lung biopsy (TBLB) specimens obtained 8 yr later in one patient with minor monoclonal type LIP confirmed this possibility. In true LIP, six of 20 lymphocyte clones showed 67 to 86% homology with lymphocyte clones derived from fetal tissue. In three of these six clones, the D-region (N-D-N) lengths were very short, whereas four clones showed a high homology with autoreactive lymphocytes (rheumatoid factor, anti-DNA antibody, and G6-positive lymphocytes). Since rheumatoid factors, anti-DNA antibodies, and G6 are autoreactive antibodies, immature B cells stimulated by autoantigens might play some role in the pathogenesis of true LIP.
IL-6/IL-6R Axis Plays a Critical Role in Acute Kidney Injury
Authors: Yael Nechemia-Arbely, Daniel Barkan, Galina Pizov, Anat Shriki, Stefan Rose-John, Eithan Galun, Jonathan H. Axelrod
Journal: Journal of the American Society of Nephrology (2008)

The response to tissue injury involves the coordination of inflammatory and repair processes. IL-6 expression correlates with the onset and severity of acute kidney injury (AKI), but its contribution to pathogenesis remains unclear. This study established a critical role for IL-6 in both the