tbuckley/cabot-search huggingface dataset:
Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects
Authors: Elisabetta Bacchi, Carlo Negri, Maria Elisabetta Zanolin, Chiara Milanese, Niccolò Faccioli, Maddalena Trombetta, Giacomo Zoppini, Antonio Cevese, Riccardo C. Bonadonna, Federico Schena, Enzo Bonora, Massimo Lanza, Paolo Moghetti
Journal: Diabetes Care (2012)

OBJECTIVE To assess differences between the effects of aerobic and resistance training on HbA1c (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA1c, glucose clamp–measured insulin sensitivity, and oral glucose tolerance test–assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured. RESULTS After training, increase in peak oxygen consumption (VO2peak) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P &amp;lt; 0.0001). HbA1c was similarly reduced in both groups (−0.40% [95% CI −0.61 to −0.18] vs. −0.35% [−0.59 to −0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA1c after training was independently predicted by baseline HbA1c and by changes in VO2peak and truncal fat. CONCLUSIONS Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in VO2peak and truncal fat may be primary determinants of exercise-induced metabolic improvement.
Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset
Authors: John M Coleman, Chetan Naik, Fernando Holguin, Anuradha Ray, Prabir Ray, John B Trudeau, Sally E Wenzel
Journal: Thorax (2012)

Eosinophilic inflammation is implicated in asthma. Eotaxin 1-3 regulate eosinophil trafficking into the airways along with other chemotactic factors. However, the epithelial and bronchoalveolar lavage (BAL) cell expression of these chemokines in relation to asthma severity and eosinophilic phenotypes has not been addressed.To measure the expression of the three eotaxin isoforms in bronchoscopically obtained samples and compare them with clinically relevant parameters between normal subjects and patients with asthma.Normal subjects and patients with asthma of varying severity recruited through the Severe Asthma Research Program underwent clinical assessment and bronchoscopy with airway brushing and BAL. Eotaxin 1-3 mRNA/protein were measured in epithelial and BAL cells and compared with asthma severity, control and eosinophilic inflammation.Eotaxin-2 and eotaxin-3 mRNA and eotaxin-2 protein were increased in airway epithelial brushings from patients with asthma and were highest in cases of severe asthma (p values 0.0155, 0.0033 and 0.0006, respectively), with eotaxin-2 protein increased with age at onset. BAL cells normally expressed high levels of eotaxin-2 mRNA/protein but BAL fluid levels of eotaxin-2 were lowest in severe asthma. Epithelial eotaxin-2 and eotaxin-3 mRNA/protein was associated with sputum eosinophilia, lower forced expiratory volume in 1 s and more asthma exacerbations. Airway epithelial cell eotaxin-2 protein differed by asthma severity only in those with late onset disease, and tended to be highest in those with late onset eosinophilic asthma.Epithelial eotaxin-2 and 3 are increased in asthma and severe asthma. Their expression may contribute to luminal migration of eosinophils, especially in later onset disease, asthma control and severity.
Response to: ‘The search for size: a doping risk factor in adolescent rugby’: Table 1
Authors: Clint Readhead
Journal: British Journal of Sports Medicine (2015)

I read the editorial,1 ‘The search for size: a doping risk factor in adolescent rugby’, with interest. I agree with the general message of the editorial suggesting that the importance of size in the professional and the international game may prompt schoolboy rugby players to use muscle-building substances such as anabolic androgenic steroids to expedite their growth. I also support the notion of a long-term multidimensional player development approach to counter the risk of adolescent players doping to increase their size.

However, I feel that the data representing anabolic androgenic steroid use by South African schoolboy rugby players was misleading.

The statement, “12 of the 52 South African schoolboy rugby players recently returned positive tests for using anabolic androgenic steroids,” was backed up by a reference2 in the editorial. However, this reference does not have any contextual information about …
Tobacco smoke exposure suppresses radiation-induced inflammation in the lung: a study of bronchoalveolar lavage and ultrastructural morphology in the rat
Authors: L Bjermer, Y Cai, K Nilsson, S Hellstrom, R Henriksson
Journal: European Respiratory Journal (1993)

Previous studies on patients with breast cancer, who received postsurgical irradiation, displayed a markedly suppressed inflammatory response in the lung of smoking patients compared to nonsmokers. The aim of the present study was to investigate further the effect of exposure to tobacco smoke on the development of irradiation-induced pneumonitis in the rat. Four groups of animals were used: controls (C); those exposed to tobacco smoke (S); those irradiated but not exposed to smoke (RNS); and those irradiated and exposed to tobacco smoke (RS). The rats were exposed to a diluted main stream of cigarette smoke, at a concentration of about 0.4 mg.l-1, in a nose-only exposure system for 1 h.day-1, 5 days.week-1 for 10 weeks. Exposure to tobacco smoke started 3 weeks before irradiation. The basal one third of both lungs was exposed to a single radiation dose of 28 Gy (6 MeV photons). All animals were killed 7 weeks after irradiation. We compared findings in bronchoalveolar lavage (BAL) and tissue morphology. The alveolar tissue showed less inflammation in the RS-group than in the RNS-group. Most strikingly, mast cells were increased one hundredfold in the lung interstitium and thirty fold in the peribronchial area in the RNS-group, whereas no increase was found in the RS-group or in the controls. The alveolar septa of the RNS-group were thickened, with occurrence of inflammatory cells and mast cells, whereas the RS-group displayed no difference as compared to the non-irradiated, nonsmoking group (C).(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibility gene
Authors: Steven Gazal, Karim Sacre, Yannick Allanore, Maria Teruel, Alison H Goodall, Shigeto Tohma, Lars Alfredsson, Yukinori Okada, Gang Xie, Arnaud Constantin, Alejandro Balsa, Aya Kawasaki, Pascale Nicaise, Christopher Amos, Luis Rodriguez-Rodriguez, Gilles Chiocchia, Catherine Boileau, Jinyi Zhang, Olivier Vittecoq, Thomas Barnetche, Miguel A Gonzalez-Gay, Hiroshi Furukawa, Alain Cantagrel, Xavier Le Loët, Takayuki Sumida, Margarita Hurtado-Nedelec, Christophe Richez, Sylvie Chollet-Martin, Thierry Schaeverbeke, Bernard Combe, Liliane Khoryati, Baptiste Coustet, Jammel El-Benna, Katherine Siminovitch, Robert Plenge, Leonid Padyukov, Javier Martin, Naoyuki Tsuchiya, Philippe Dieudé
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To evaluate the contribution of the <i>SPP1</i> rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. <h3>Methods</h3> We analysed a total of 11 715 RA cases and 26 493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for <i>SPP1</i> rs11439060 and rs9138. The effect of the <i>SPP1</i> rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated. <h3>Results</h3> We provide evidence for a distinct contribution of <i>SPP1</i> to RA susceptibility according to ACPA status: the combination of ≥3 <i>SPP1</i> rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (p=1.29×10<sup>−5</sup>, OR<sub>ACPA-negative</sub> 1.257 (1.135 to 1.394)) and less with ACPA positivity (p=0.0148, OR<sub>ACPA-positive</sub> 1.072 (1.014 to 1.134)). The ORs between these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed (p=7.33×10<sup>−3</sup>). Expression quantitative trait locus analysis revealed an association of the <i>SPP1</i> risk-allele combination with decreased <i>SPP1</i> expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the <i>SPP1</i> risk-allele combination and low serum level of secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated positively with ACPA production (p=0.005; r=0.483). <h3>Conclusions</h3> We demonstrate a significant contribution of the combination of <i>SPP1</i> rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association being greater in patients negative for ACPAs.
Plasma Carotenoids and Tocopherols and Risk of Myocardial Infarction in a Low-Risk Population of US Male Physicians
Authors: A. Elisabeth Hak, Meir J. Stampfer, Hannia Campos, Howard D. Sesso, J. Michael Gaziano, Walter Willett, Jing Ma
Journal: Circulation (2003)

Background— Increased intake of carotenoids and vitamin E may protect against myocardial infarction (MI). However, prospective data on blood levels of carotenoids other than β-carotene and vitamin E (tocopherol) and risk of MI are sparse. Methods and Results— We conducted a prospective, nested case-control analysis among male physicians without prior history of cardiovascular disease who were followed for up to 13 years in the Physicians’ Health Study. Samples from 531 physicians diagnosed with MI were analyzed together with samples from paired control subjects, matched for age and smoking, for 5 major carotenoids (α- and β-carotene, β-cryptoxanthin, lutein, and lycopene), retinol, and α- and γ-tocopherol. Overall, we found no evidence for a protective effect against MI for higher baseline plasma levels of retinol or any of the carotenoids measured. Among current and former smokers but not among never-smokers, higher baseline plasma levels of β-carotene tended to be associated with lower risk ( P for interaction=0.02). Men with higher plasma levels of γ-tocopherol tended to have an increased risk of MI ( P for trend=0.01). Conclusions— These prospective data do not support an overall protective relation between plasma carotenoids or tocopherols and future MI risk among men without a history of prior cardiovascular disease.
Herpetiform pemphigus showing reactivity with pemphigus vulgaris antigen (desmoglein 3)
Authors: A. KUBO, M. AMAGAL, T. HASHIMOTO, T. DOI, M. HIGASHIYAMA, K. HASHIMOTO, K. YOSHIKAWA
Journal: British Journal of Dermatology (1997)

We report a patient with herpetiform pemphigus (HP) who showed reactivity only with pemphigus vulgaris (PV) antigen but not with pemphigus foliaceus (PF) antigen. Direct and indirect immunofluorescence revealed keratinocyte cell surface staining in the lower layers of the epidermis, where desmoglein 3 (Dsg3) is expressed. Immunoblot analysis, using ethylenediamine tetra-acetic acid-separated human epidermal extracts, revealed that the patient's serum recognized only a 130-kDa polypeptide which co-migrated with Dsg3. By antigen-specific immunoadsorption studies, using desmoglein 1 (Dsg1) and Dsg3 recombinant protein produced by baculovirus expression system, immunoreactivity of the patient's serum was completely adsorbed by Dsg3 alone, but not by Dsg1. These results indicate that this HP patient produced only anti-Dsg3 autoantibodies and no other autoantibodies against components of the keratinocyte cell surface. HP could be a variant of PV, in addition to PF, with unique clinical and histological features.
Ku86 Modulates DNA Topoisomerase I–Mediated Radiosensitization, but not Cytotoxicity, in Mammalian Cells
Authors: Shyh-Jen Shih, Tara Erbele, Allan Y. Chen
Journal: Cancer Research (2005)

Abstract Ku86 is an integral component of the nonhomologous end-joining (NHEJ) pathway of cellular double-strand break repair. In the current study, we investigated the role of Ku86 in DNA topoisomerase I–mediated radiosensitization induced by camptothecin in mammalian cells. Interestingly, as examined by clonogenic survival assay, a 30-minute camptothecin treatment induced significantly higher levels of radiosensitization in the Ku86-deficient Chinese hamster ovary xrs-6 cells than in the hamster Ku86-complemented xrs-6+hamKu86 cells, albeit exhibiting similar drug toxicity in these two cell lines. To confirm these findings, similar studies were conducted in two pairs of transfectant sublines established from the Ku86-deficient Chinese hamster lung fibroblast XR-V15B cells. Compared with the vector-alone sublines, radiation resistance was restored in the human Ku86-complemented sublines without alteration of cell cycle distributions. Again, significantly higher levels of camptothecin-induced radiosensitization were observed in the vector-alone sublines than in the Ku86-complemented XR-V15B sublines. In contrast, camptothecin treatments, ranging from 0.5 to 24 hours, induced similar cytotoxicities in both vector-alone and Ku86-complemented sublines. Because neither the DNA-damaging etoposide and cisplatin nor the tubulin-binder vinblastine induced enhanced levels of radiosensitization in the Ku86-deficient cells, Ku86 seems to uniquely affect topoisomerase I–mediated radiosensitization induced by camptothecin. Furthermore, cotreatment with DNA replication inhibitor aphidicolin abolished both camptothecin-induced cytotoxicity and radiosensitization in the vector-alone, as well as the Ku86-complemented subline cells, indicating both events are initiated by replication-dependent topoisomerase I–mediated DNA damages. Taken together, our data show a novel role of Ku86 in modulating topoisomerase I–mediated radiosensitization, but not cytotoxicity, in mammalian cells.
Inactivation of Integrin-β1 Prevents the Development of Polycystic Kidney Disease after the Loss of Polycystin-1
Authors: Kyung Lee, Sylvia Boctor, Laura M.C. Barisoni, G. Luca Gusella
Journal: Journal of the American Society of Nephrology (2014)

Dysregulation of polycystin-1 (PC1) leads to autosomal dominant polycystic kidney disease (ADPKD), a disorder characterized by the formation of multiple bilateral renal cysts, the progressive accumulation of extracellular matrix (ECM), and the development of tubulointerstitial fibrosis. Correspondingly, cystic epithelia express higher levels of integrins (ECM receptors that control various cellular responses, such as cell proliferation, migration, and survival) that are characteristically altered in cystic cells. To determine whether the altered expression of ECM and integrins could establish a pathologic autostimulatory loop, we tested the role of integrin-β1 in vitro and on the cystic development of ADPKD in vivo. Compared with wild-type cells, PC1-depleted immortalized renal collecting duct cells had higher levels of integrin-β1 and fibronectin and displayed increased integrin-mediated signaling in the presence of Mn(2+). In mice, conditional inactivation of integrin-β1 in collecting ducts resulted in a dramatic inhibition of Pkd1-dependent cystogenesis with a concomitant suppression of fibrosis and preservation of normal renal function. Our data provide genetic evidence that a functional integrin-β1 is required for the early events leading to renal cystogenesis in ADPKD and suggest that the integrin signaling pathway may be an effective therapeutic target for slowing disease progression.
Diet and Health
Authors: S. K. Westman
Journal: BMJ (1947)

<h3>Introduction</h3> Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient‘s cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse. Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer. <h3>Methods and analysis</h3> A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25–70 years will provide the same data. <h3>Ethics and dissemination</h3> The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request. <h3>Trial registration number</h3> NCT04488614.
SLAM Family Receptors Regulate Immunity with and without SAP-related Adaptors
Authors: André Veillette
Journal: The Journal of Experimental Medicine (2004)

Two papers describing mice deficient in signaling lymphocyte activation molecule and 2B4 represent the first accounts of immune phenotypes in animals lacking members of the SLAM family of receptors. The findings provide definitive evidence of the importance of SLAM-related receptors in the regulation of T cell, macrophage, and natural killer cell functions.
Home Resorts for Invalids. On the Climate of Guernsey
Authors: S. E. Hoskins
Journal: BMJ (1852)

IT is satisfactory to observe that the correlation between meteorological, medical, and agricultural science, is no longer the tacit recognition of an abstract theory; recent treatises on medical topography, and the effects of climate on cultivation, prove that the influence of atmospheric phenomena on animal and vegetable life is engaging some degree of attention: not however, as yet, to the full extent which the practical importance of the investigation merits and requires.A powerful impulse was given some years ago to the study of me- teorology, by the publication of the Report of the Committee of Physics of the Royal Society, intended principally for the guidance of persons attached to the Antarctic expedition.The instructions it contained, together with its suggestions as to the advantage of systematic co- operation, were speedily adopted by government and other public observatories, as well as by a number of private individuals; and the anticipations entertained, that uniformity of plan, steadily adhered to for a few years, would furnish the most perfect data for its own correction, have been fully realised.The methods of ascertaining and applying these data are due to James Glaisher, Esq., F.R.8., whose extensive computations and inductions contribute in an eminent degree to advance the science of meteorology many steps in its progress towards maturity.This gentleman's in- valuable tables on diurnal range, reprinted from the Philosophical Tranaction, at the suggestion of the society I have the honour of addressing, afford facilities for reducing a few observations, taken at the most convenient hours of the day and night, to mean monthly values.
Aspergillus niger endocarditis complicating aortic tissue valve replacement.
Authors: R S Moore, P S Hasleton, R A Lawson, T N Stanbridge
Journal: Thorax (1984)

With the increase in valve replacement over the past 20 years has come the problem of fungal endocarditis.Aspergillus in most series is the second commonest cause of iX'.fungal endocarditis1 2 reported on native or mechanical valves and the infection is usually fatal.2Only two cases have been reported on tissue prostheses.We report the 4 third case of aspergillus infection on a tissue valve and the first on the Xenofic tissue valve. Case reportA 63 year old man underwent aortic valve replacement with a Xenofic tissue prosthesis for calcific aortic stenosis and incompetence.Before operation he had had a small varicose ulcer over his right ankle, culture swabs yielding Staphylococcus aureus and Pseudomonas aeruginosa.Sur- gery was delayed until the ulcer was almost healed.Antibiotic prophylaxis for the operation comprised cloxacillin and netilmicin, commencing with the
Genome-wide analysis of estrogen receptor binding sites
Authors: Jason S Carroll, Clifford A Meyer, Jun Song, Wei Li, Timothy R Geistlinger, Jérôme Eeckhoute, Alexander S Brodsky, Erika Krasnickas Keeton, Kirsten C Fertuck, Giles F Hall, Qianben Wang, Stefan Bekiranov, Victor Sementchenko, Edward A Fox, Pamela A Silver, Thomas R Gingeras, X Shirley Liu, Myles Brown
Journal: Nature Genetics (2006)
TNF-alpha mRNA expression in diaphragm muscle after endotoxin administration.
Authors: C Shindoh, W Hida, Y Ohkawara, K Yamauchi, I Ohno, T Takishima, K Shirato
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We studied gene expression and production of TNF-alpha in the diaphragm tissue and changes of muscle contractile properties after endotoxin injection (Escherichia coli, 20 mg/kg) in 88 rats. We assessed the muscle contractile properties by force-frequency curves and twitch kinetics using dissected diaphragm muscle strips. The peak tensions of force-frequency curves decreased from control values (2.15 +/- 0.2 kg/cm2) up to 4 h (0.81 +/- 0.17, p < 0.001), and then increased at 6 h (1.36 +/- 0.19, p < 0.05) after endotoxin injection. The cytotoxic activity on L929 cells in arterial blood samples maximally increased at 2 h (p < 0.001), then decreased to 6 h (p < 0.05). TNF-alpha mRNA in diaphragm tissue was detected by Northern blot method at 1 and 1.5 h, and the immunolocalization of TNF-alpha was evaluated at 2 and 4 h by immunohistochemistry in the muscle tissues. Furthermore, preinjection with anti-m TNF-alpha antibody prevented the decrement of force-frequency curves after endotoxin injection of 10 microliters/kg. From this evidence that TNF-alpha gene expression and production occurred in the diaphragm tissue, but anti-m TNF-alpha antibody preinjection prevented the deterioration of diaphragm muscle contractile properties, we suggest that TNF-alpha may act on muscle cells extracellularly.