tbuckley/cabot-search huggingface dataset:
Neonatal Chlamydial Infection Induces Mixed T-Cell Responses That Drive Allergic Airway Disease
Authors: Jay C. Horvat, Kenneth W. Beagley, Margaret A. Wade, Julie A. Preston, Nicole G. Hansbro, Danica K. Hickey, Gerard E. Kaiko, Peter G. Gibson, Paul S. Foster, Philip M. Hansbro
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Chlamydial lung infection has been associated with asthma in children and adults. However, how chlamydial infection influences the development of immune responses that promote asthma remains unknown.To determine the effect of chlamydial infection at various ages on the development of allergic airway disease (AAD).Mouse models of chlamydial lung infection and ovalbumin-induced AAD were established in neonatal and adult BALB/c mice. Neonatal or adult mice were given a chlamydial infection and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Features of AAD and inflammation were compared between uninfected or unsensitized controls.Mild Chlamydia-induced lung disease was observed 10-15 days after infection, as evidenced by increased bacterial numbers and histopathology in the lung and a reduction in weight gain. After 6 weeks, infection and histopathology had resolved and the rate of weight gain had recovered. Neonatal but not adult infection resulted in significant decreases in interleukin-5 production from helper T cells and by the numbers of eosinophils recruited to the lung in response to ovalbumin exposure. Remarkably, the effects of early-life infection were associated with the generation of both type 1 and 2 ovalbumin-specific helper T-cell cytokine and antibody responses. Furthermore, although neonatal infection significantly attenuated eosinophilia, the generation of the mixed T-cell response exacerbated other hallmark features of asthma: mucus hypersecretion and airway hyperresponsiveness. Moreover, infection prolonged the expression of AAD and these effects were restricted to early-life infection.Early-life chlamydial infection induces a mixed type 1 and 2 T-cell response to antigen, which differentially affects the development of key features of AAD in the adult.
Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest
Authors: Esteban Lopez-de-Sa, Juan R. Rey, Eduardo Armada, Pablo Salinas, Ana Viana-Tejedor, Sandra Espinosa-Garcia, Mercedes Martinez-Moreno, Ervigio Corral, Jose Lopez-Sendon
Journal: Circulation (2012)

Background— It is recommended that comatose survivors of out-of-hospital cardiac arrest should be cooled to 32° to 34°C for 12 to 24 hours. However, the optimal level of cooling is unknown. The aim of this pilot study was to obtain initial data on the effect of different levels of hypothermia. We hypothesized that deeper temperatures will be associated with better survival and neurological outcome. Methods and Results— Patients were eligible if they had a witnessed out-of-hospital cardiac arrest from March 2008 to August 2011. Target temperature was randomly assigned to 32°C or 34°C. Enrollment was stratified on the basis of the initial rhythm as shockable or asystole. The target temperature was maintained during 24 hours followed by 12 to 24 hours of controlled rewarming. The primary outcome was survival free from severe dependence (Barthel Index score ≥60 points) at 6 months. Thirty-six patients were enrolled in the trial (26 shockable rhythm, 10 asystole), with 18 assigned to 34°C and 18 to 32°C. Eight of 18 patients in the 32°C group (44.4%) met the primary end point compared with 2 of 18 in the 34°C group (11.1%) (log-rank P =0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients with initial shockable rhythm assigned to 32°C (61.5%) were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P =0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P =0.0002) in patients assigned to 32°C compared with 34°C. On the contrary, there was a trend toward a higher incidence of bradycardia (7 versus 2; P =0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups. Conclusions— The findings of this pilot trial suggest that a lower cooling level may be associated with a better outcome in patients surviving out-of-hospital cardiac arrest secondary to a shockable rhythm. The benefits observed here merit further investigation in a larger trial in out-of-hospital cardiac arrest patients with different presenting rhythms. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01155622.
Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System
Authors: Kar Neng Lai, Sydney C. W. Tang, Jinn-Yuh Guh, Tsai-Der Chuang, Man Fai Lam, Loretta Y. Y. Chan, Anita W. L. Tsang, Joseph C. K. Leung
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-β synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar findings were observed for TGF-β gene and protein expression. The values measured in HMC incubated with pIgA1 were significantly higher than those in HMC incubated with equivalent amounts of mIgA1. When similar experiments were performed with the addition of either captopril or losartan, there was a significant increase in the renin gene expression by HMC, whereas the synthesis of TGF-β was markedly reduced. The TGF-β signal transduction pathways in HMC were studied by measuring the receptor-regulated Smad proteins (Smad 2 and 3) and common-partner Smad proteins (Smad 4). pIgA1 from patients with IgAN upregulated Smad activity in HMC, and the activity observed in HMC that had been preincubated with pIgA1 was readily suppressed with optimal concentrations of captopril or losartan. The effects of pIgA1 on the RAS were further examined in HMC incubated with IgA isolated from 30 patients with IgAN, 30 healthy subjects, and disease control subjects with other diseases. pIgA1 induction of angiotensin II or TGF-β synthesis in HMC was significantly greater with preparations from patients with IgAN, compared with healthy or disease control subjects. The findings support a pathogenetic role of pIgA1 in IgAN through upregulation of the RAS and TGF-β, leading to chronic renal failure with renal fibrosis.
Bronchodilator treatment and deaths from asthma: case-control study
Authors: H Ross Anderson, Jon G Ayres, Patricia M Sturdy, J Martin Bland, Barbara K Butland, Clare Peckitt, Jennifer C Taylor, Christina R Victor
Journal: BMJ (2004)

To investigate the association between bronchodilator treatment and death from asthma.Case-control study.33 health authorities or health boards in Great Britain.532 patients under age 65 who died from asthma and 532 controls with a hospital admission for asthma matched for period, age, and area.Odds ratios for deaths from asthma associated with prescription of bronchodilators and other treatment, with sensitivity analyses adjusting for age at onset, previous hospital admissions, associated chronic obstructive lung disease, and number of other drug categories.After full adjustment, there were no significant associations with drugs prescribed in the 4-12 months before the index date. For prescriptions in the 1-5 years before, mortality was positively associated with inhaled short acting beta2 agonists (odds ratio 2.05, 95% confidence interval 1.26 to 3.33) and inversely associated with antibiotics (0.59, 0.39 to 0.89). The former association seemed to be confined to those aged 45-64, and the association with antibiotics was more pronounced in those under 45. Significant age interactions across all periods suggested inverse associations with oral steroids confined to the under 45 age group. An inverse association with long acting beta2 agonists and a positive association with methylxanthines in the 1-5 year period were non-significant.There was no evidence of adverse effects on mortality with medium to long term use of inhaled long acting beta2 agonist drugs. The association with short acting beta(2) agonists has several explanations, only one of which may be a direct adverse effect.
Pollutant Exposures from Natural Gas Cooking Burners: A Simulation-Based Assessment for Southern California
Authors: Jennifer M. Logue, Neil E. Klepeis, Agnes B. Lobscheid, Brett C. Singer
Journal: Environmental Health Perspectives (2013)

Background: Residential natural gas cooking burners (NGCBs) can emit substantial quantities of pollutants, and they are typically used without venting range hoods.Objective: We quantified pollutant concentrations and occupant exposures resulting from NGCB use in California homes.Methods: A mass-balance model was applied to estimate time-dependent pollutant concentrations throughout homes in Southern California and the exposure concentrations experienced by individual occupants. We estimated nitrogen dioxide (NO2), carbon monoxide (CO), and formaldehyde (HCHO) concentrations for 1 week each in summer and winter for a representative sample of Southern California homes. The model simulated pollutant emissions from NGCBs as well as NO2 and CO entry from outdoors, dilution throughout the home, and removal by ventilation and deposition. Residence characteristics and outdoor concentrations of NO2 and CO were obtained from available databases. We inferred ventilation rates, occupancy patterns, and burner use from household characteristics. We also explored proximity to the burner(s) and the benefits of using venting range hoods. Replicate model executions using independently generated sets of stochastic variable values yielded estimated pollutant concentration distributions with geometric means varying by &lt; 10%.Results: The simulation model estimated that—in homes using NGCBs without coincident use of venting range hoods—62%, 9%, and 53% of occupants are routinely exposed to NO2, CO, and HCHO levels that exceed acute health-based standards and guidelines. NGCB use increased the sample median of the highest simulated 1-hr indoor concentrations by 100, 3,000, and 20 ppb for NO2, CO, and HCHO, respectively.Conclusions: Reducing pollutant exposures from NGCBs should be a public health priority. Simulation results suggest that regular use of even moderately effective venting range hoods would dramatically reduce the percentage of homes in which concentrations exceed health-based standards.Citation: Logue JM, Klepeis NE, Lobscheid AB, Singer BC. 2014. Pollutant exposures from natural gas cooking burners: a simulation-based assessment for Southern California. Environ Health Perspect 122:43–50; http://dx.doi.org/10.1289/ehp.1306673
Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma
Authors: S.M. Rajpara, A.P. Botello, J. Townend, A.D. Ormerod
Journal: British Journal of Dermatology (2009)

Journal Article Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma Get access S.M. Rajpara, S.M. Rajpara Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, U.K. Correspondence: Sanjay Rajpara. E‐mail: sanjay.rajpara@nhs.net Search for other works by this author on: Oxford Academic Google Scholar A.P. Botello, A.P. Botello Department of Public Health, University of Aberdeen, Aberdeen, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. Townend, J. Townend Department of Public Health, University of Aberdeen, Aberdeen, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.D. Ormerod A.D. Ormerod Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, U.K.Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 3, 1 September 2009, Pages 591–604, https://doi.org/10.1111/j.1365-2133.2009.09093.x Published: 01 September 2009
The Endothelin Receptor Blocker Bosentan Inhibits Doxorubicin-Induced Cardiomyopathy
Authors: Sandra Bien, Alexander Riad, Christoph A. Ritter, Matthias Gratz, Florian Olshausen, Dirk Westermann, Markus Grube, Thomas Krieg, Sabine Ciecholewski, Stephan B. Felix, Alexander Staudt, Heinz-Peter Schultheiss, Ralf Ewert, Uwe Völker, Carsten Tschöpe, Heyo K. Kroemer
Journal: Cancer Research (2007)

Abstract Doxorubicin is a frequently used anticancer drug, but its therapeutic benefit is limited by acute and chronic cardiotoxicity, often leading to heart failure. The mechanisms underlying doxorubicin-induced cardiotoxicity remain unclear. It was previously shown in men that doxorubicin leads to increased endothelin-1 plasma levels. In addition, cardiac-specific overexpression of endothelin-1 in mice resulted in a cardiomyopathy resembling the phenotype following doxorubicin administration. We therefore hypothesized that endothelin-1 is involved in the pathogenesis of doxorubicin cardiotoxicity. In mice (C57Bl/10), we found that doxorubicin (20 mg/kg body weight, i.p.) impaired cardiac function with decreased ejection fraction, diminished cardiac output, and decreased end-systolic pressure points recorded by a microconductance catheter. This impaired function was accompanied by the up-regulation of endothelin-1 expression on mRNA and protein level. In vitro investigations confirmed the regulation of endothelin-1 by doxorubicin and indicated that the doxorubicin-mediated increase of endothelin-1 expression involves epidermal growth factor receptor signaling via the MEK1/2-ERK1/2 cascade, which was further confirmed by immunoblotting studies in the left ventricle of treated animals. Pretreatment of mice with the endothelin receptor antagonist bosentan (100 mg/kg body weight, p.o.) strikingly inhibited doxorubicin-induced cardiotoxicity with preserved indices of contractility. Moreover, bosentan pretreatment resulted in reduced tumor necrosis factor-α content, lipid peroxidation, and Bax expression, as well as increased GATA-4 expression. Thus, endothelin-1 plays a key role in mediating the cardiotoxic effects of doxorubicin and its inhibition may be of therapeutic benefit for patients receiving doxorubicin. [Cancer Res 2007;67(21):10428–35]
Cutaneous manifestations of systemic lupus erythematosus
Authors: J.A. YELL, J. MBUAGBAW, S.M. BURGE
Journal: British Journal of Dermatology (1996)

We have assessed the cutaneous signs in 73 patients with systemic lupus erythematosus (SLE), seen during a 5-year period in an English hospital. Most previous information about the cutaneous manifestations of SLE has been obtained from studies performed in the U.S.A. We classified lesions as specific cutaneous and mucosal LE (acute, subacute and chronic) or non-specific LE-related, e.g. photosensitivity, urticaria, erythema, Raynaud's phenomenon or vasculitis. Acute cutaneous LE lesions included a butterfly rash with erythematous macules, telangiectasia or papulosquamous lesions, seen in 37 patients (51%) and facial oedema seen in four patients (5%). Five patients (7%) had psoriasiform subacute cutaneous LE. Chronic cutaneous LE was common: 18 patients (25%) had chronic discoid lesions (DLE) and, in 12 (15%), these had preceded systemic disease. One patient had facial lupus profundus. Ten patients (14%) had scarring alopecia secondary to DLE. Fifteen patients (20.5%) had chronic chilblain lupus. Twenty-three patients (31.5%) had a history of mouth ulceration. Of these, 11 (15%) gave a history of ulcers at the onset of their disease. Three (4%) had erythema and superficial ulceration of the palate, not typical of aphthous ulcers, and three (4%) had chronic buccal plaques. Cheilitis due to DLE was seen in three (4%), episcleritis in three (4%), five (7%) had nasal disease, six (8%) bullous skin eruptions, one 'the bullous eruption of SLE', four bullae associated with cutaneous vasculitis, and one bullae associated with ultraviolet radiation. Forty-six (63%) observed photosensitivity. A non-scarring alopecia occurred in 29 (40%). Vascular phenomena were common: three patients (4%) had chronic palmar erythema, Raynaud's phenomenon occurred in 44 patients (60%), chronic urticaria, worsened by sun exposure, was noted by 32 (44%) (in whom the lesions often lasted more than 36 h), eight (11%) had cutaneous vasculitis and three (4%) livedo reticularis. Skin changes play a prominent part in SLE and may provide helpful diagnostic information. In this British population, chilblains and urticaria were particularly common. Lesions of subacute cutaneous LE were relatively unusual in this group of patients with SLE.
Prehospital Resuscitation
Authors: William A. Gray
Journal: JAMA (1993)

Over the past two decades, the provision of advanced cardiac life support (ACLS) in the prehospital arena has been established and refined in many communities throughout the United States and other industrialized countries. Whereas in the late 1960s no one was given much hope of surviving an out-of-hospital cardiac arrest, today, in cities like Seattle, Milwaukee, and Miami, rates of hospital discharge for cardiac arrest due to ventricular fibrillation hover around 25% to 30%. 1-3 This has been accomplished only by applying the lessons learned from research on the subject, which have been incorporated into the  of survival developed by the American Heart Association. 4 The first link in the chain is establishing systems for rapid public access to emergency medical care (eg, by telephoning 911). The second link is widespread public training in cardiopulmonary resuscitation (CPR) techniques (eg, in Houston, Tex, certification in CPR is a routine part
Pathophysiology and Management of Hypertension in Diabetes
Authors: Michael L. Tuck, Dalila B. Corry
Journal: Annual Review of Medicine (1991)

Arterial hypertension is more common in diabetes mellitus than in nondiabetic subjects, and many metabolic and hemodynamic features of diabetes mellitus contribute to the etiology of hypertension. Control of hypertension in diabetes mellitus is extremely important as high blood pressure accelerates both macrovascular and microvascular complications of this disease. Most classes of antihypertensive agents are effective in blood pressure control in diabetes mellitus, so the choice of antihypertensive therapy is based on the differences in adverse effects of these agents on metabolic control and other cardiovascular risks.
Antigen-induced generation of lyso-phospholipids in human airways.
Authors: F H Chilton, F J Averill, W C Hubbard, A N Fonteh, M Triggiani, M C Liu
Journal: The Journal of Experimental Medicine (1996)

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.
Human Leukocyte Antigen–DQ2 Homozygosity and the Development of Refractory Celiac Disease and Enteropathy-Associated T-Cell Lymphoma
Authors: Abdulbaqi Al–Toma, Marije S. Goerres, Jos W.R. Meijer, A. Salvador Peña, J. Bart A. Crusius, Chris J.J. Mulder
Journal: Clinical Gastroenterology and Hepatology (2006)
Minimizing Unnecessary Surgery for Thyroid Nodules
Authors: J. Larry Jameson
Journal: New England Journal of Medicine (2012)

Thyroid follicles remodel continuously, responding to stimuli such as thyrotropin, growth factors, cytokines, and iodine. Nodules develop when these growth signals drive hyperplasia or when a follicular cell acquires a genetic mutation that confers autonomous growth. Thyroid nodules are commonly seen in clinical practice. With the use of ultrasonography, nodules can be detected in at least 25 to 50% of adults and are more common in women and with increasing age.When a patient presents with a thyroid nodule, the primary concern is whether it is benign or malignant. Findings on fine-needle aspiration, ideally performed with ultrasonographic guidance, are the . . .
Prognostic Variables for Resection of Colorectal Cancer Hepatic Metastases: An Evolving Paradigm
Authors: Anton J. Bilchik, Graeme Poston, Rene Adam, Michael A. Choti
Journal: Journal of Clinical Oncology (2008)

Anton J. Bilchik, California Oncology Research Institute and David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA Graeme Poston, Royal Liverpool and Aintree University Hospitals, Liverpool, United Kingdom Rene Adam, Assistance Publique—Hopitaux de Paris Hopital Paul Brousse, Universite Paris Sud, Paris, France Michael A. Choti, Johns Hopkins School of Medicine, Baltimore, MD