tbuckley/cabot-search huggingface dataset:
Lung function reference values in Singaporean children aged 6-18 years.
Authors: G J Connett, S H Quak, M L Wong, J Teo, B W Lee
Journal: Thorax (1994)

BACKGROUND--A study was undertaken to produce reference values of lung function in Chinese children and a means of calculating adjusted standard deviation scores of lung function for Malay and Indian ethnic groups. METHODS--A cross sectional study of lung function (forced expiratory volume in one second and forced vital capacity) measured with a Jaeger spirometer was performed in a representative sample of Singaporean children made up of 1403 Chinese, 335 Malays, and 206 Indians. RESULTS--The relation between natural logarithms of lung function and height was approximately linear until 150 cm in boys and 140 cm in girls. At these heights there were abrupt changes in the gradients of both lines. Separate regression lines were derived for heights above and below these inflection points. Significant differences in lung function were seen in Chinese compared with Malay and Indian children. In particular, values were considerably lower among Indian boys. CONCLUSIONS--The relation between lung function and height in Chinese children is best described by two regression equations over separate height ranges. Information is provided for the calculation of reference values and standard deviation scores, together with the correction factors that need to be applied to derive these values in Malay and Indian children.
Transglutaminase 2 Is Central to Induction of the Arterial Calcification Program by Smooth Muscle Cells
Authors: Kristen A. Johnson, Monika Polewski, Robert A. Terkeltaub
Journal: Circulation Research (2008)

Arterial calcification is a phenotype of vascular repair in atherosclerosis, diabetes, hyperphosphatemic renal failure, and aging. Arterial calcification is modulated by transition of arterial smooth muscle cells (SMCs) from contractile to chondro–osseous differentiation programmed in response to increases in P i , bone morphogenetic protein-2, and certain other stimuli. Transglutaminase (TG)2 release modulates tissue repair, partly by transamidation-catalyzed covalent crosslinking of extracellular matrix substrates. TG2 regulates cultured SMC differentiation, resistance artery remodeling to vasoconstriction, and atherosclerotic lesion size. Here, TG2 expression was required for the majority of TG activity in mouse and human aortic SMCs. TG2 −/− SMCs lost the capacity for P i donor–induced formation of multicellular bone-like nodules and for increased expression of the type III sodium–dependent P i cotransporter Pit-1 and certain osteoblast and chondrocyte genes (tissue-nonspecific alkaline phosphatase, the osteoblast master transcription factor runx2, and chondrocyte-restricted aggrecan), and for P i donor– and bone morphogenetic protein-2–induced calcification. Uniquely in TG2 −/− SMCs, P i donor treatment increased expression of the physiological SMC chondro–osseous differentiation and calcification inhibitors osteoprotegerin, matrix Gla protein, and osteopontin. Conversely, TG2 −/− SMCs, unlike wild-type SMCs, failed to maintain contractile differentiation on laminin. Exogenous catalytically active TG2 augmented calcification by TG2 −/− SMC in response to P i donor treatment. TG2 expression also drove P i -stimulated calcification of mouse aortic ring organ cultures, which was suppressed by the TG2 catalytic site-specific inhibitor Boc-DON-Gln-Ile-Val-OMe (10 μmol/L). Our results suggest that TG2 release in injured arteries is critical for programming chondro–osseous SMC differentiation and calcification in response to increased P i and bone morphogenetic protein-2.
Which patients with cirrhosis should undergo endoscopic screening for esophageal varices (EV) detection?
Authors: F. Schepis, C. Camma, D. Niceforo, A. Magnano, S. Pallio, M. Cinquegrani, G. D'Amico, L. Pasta, A. Craxi, A. Saitta, G. Raimondo
Journal: Journal of Hepatology (2001)
A tale of two global emergencies: tuberculosis control efforts can learn from the Ebola outbreak
Authors: Ruvandhi R. Nathavitharana, Jon S. Friedland
Journal: European Respiratory Journal (2015)

In 1993, the World Health Organization (WHO) issued a press release announcing that tuberculosis (TB) was a global emergency, making it the first infectious disease to be declared as such. Although progress has been made, no country has eliminated TB and there are 3 million missed TB diagnoses each year [1]. The term global health emergency has since evolved and most recently, the term "Public Health Emergency of International Concern" (as defined by the International Health Regulations in 2005) was applied to the Ebola epidemic in West Africa, which has caused over 11 000 deaths [2]. Ebola control efforts are now focussed on getting to zero cases. Yet, while huge public interest has focussed on Ebola, TB is bereft of public attention despite causing 1.5 million deaths since the Ebola epidemic began a year ago. International TB control efforts can learn valuable lessons from the recent Ebola outbreak <http://ow.ly/OaoKP>
Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy
Authors: E Shapiro, W Krivit, L Lockman, I Jambaqué, C Peters, M Cowan, R Harris, S Blanche, P Bordigoni, D Loes, R Ziegler, M Crittenden, D Ris, B Berg, C Cox, H Moser, A Fischer, P Aubourg
Journal: The Lancet (2000)
Association between <i>CCND1</i> G/A870 Polymorphism, Allele-Specific Amplification, Cyclin D1 Expression, and Survival in Esophageal and Lung Carcinoma
Authors: Vanita K. Gupta, Andrew Feber, Liqiang Xi, Arjun Pennathur, Maoxin Wu, James D. Luketich, Tony E. Godfrey
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cyclin D1 is found on 11q13, which is a region frequently amplified in several tumor types. The CCND1 locus gives rise to at least two protein isoforms of D1 (D1a and D1b). A common G/A polymorphism (G/A870) is thought to influence the expression levels of D1a and D1b. D1b has been suggested to be increased in the presence of the A allele and more oncogenic than D1a. Furthermore, the A allele has been reported to correlate with increased risk of carcinoma in several tumor types, suggesting that this polymorphism and D1b are important in tumor progression. However, contradictory data about the polymorphism, D1 variant expression, and correlation with survival have been reported. We explored the relationship between gene amplification, G/A870 genotype, D1a and D1b expression, and overall survival in esophageal adenocarcinoma and non–small cell lung cancer. Experimental Design: DNA and RNA were isolated from 54 esophageal adenocarcinoma samples and 89 non–small cell lung cancer samples and were analyzed for gene amplification, genotype at the polymorphism, gene expression, and association with overall survival. Results: The D1 variant expression did not correlate with amplification, genotype, or overall survival in either tumor type. The total D1 expression correlated with decreased patient survival. Several other genes on 11q13 also seem to be overexpressed and correlated with decreased survival. Conclusions: We report that the G/A870 polymorphism does not correlate with patient survival, or with D1a or D1b expression. However, the total D1 expression and the expression of several other genes on 11q13 seem to be associated with esophageal adenocarcinoma patient survival.
Choice of endogenous control for gene expression in nonsmall cell lung cancer
Authors: D. W. Liu, S. T. Chen, H. P. Liu
Journal: European Respiratory Journal (2005)

This study attempts to identify a suitable endogenous control gene for real-time RT-PCR in nonsmall cell lung cancer (NSCLC) tissues. Expression of seven common endogenous control genes (glyceraldehyde-3-phosphate dehydrogenase (GAPDH), v-abl Abelson murine leukaemia viral oncogene homologue 1, beta-2-microglobulin, hypoxanthin phosphoribosyltransferase 1 (HPRT1), phosphoglycerate kinase 1, peptidylprolyl isomerase A, and ribosomal protein, large, P0) in 18 heterogenous NSCLC tumour specimens, 10 normal lung tissues and six NSCLC cell lines were analysed by quantitative RT-PCR. The variances and correlation coefficients of cycle threshold (Ct) value of each control gene in three tissue groups and subgroups were compared. The difference and correlation coefficients between the Ct value for each control gene and the mean Ct value of the remaining control genes were calculated. The GAPDH gene transcript showed the least variance and linear regression analysis demonstrated that GAPDH and HPRT had the strongest correlation in pooled tumour and normal lung tissues. Furthermore, GAPDH expression value showed stringent correlation and had the lowest difference with the mean expression value of the remaining endogenous control genes. Among the seven common endogenous control genes, glyceraldehyde-3-phosphate dehydrogenase is the most suitable for quantitative RT-PCR reaction in nonsmall cell lung cancer tissue samples.
Extended Work Shifts and the Risk of Motor Vehicle Crashes among Interns
Authors: Laura K. Barger, Brian E. Cade, Najib T. Ayas, John W. Cronin, Bernard Rosner, Frank E. Speizer, Charles A. Czeisler
Journal: New England Journal of Medicine (2005)

Long work hours and work shifts of an extended duration (> or =24 hours) remain a hallmark of medical education in the United States. Yet their effect on health and safety has not been evaluated with the use of validated measures.We conducted a prospective nationwide, Web-based survey in which 2737 residents in their first postgraduate year (interns) completed 17,003 monthly reports that provided detailed information about work hours, work shifts of an extended duration, documented motor vehicle crashes, near-miss incidents, and incidents involving involuntary sleeping.The odds ratios for reporting a motor vehicle crash and for reporting a near-miss incident after an extended work shift, as compared with a shift that was not of extended duration, were 2.3 (95 percent confidence interval, 1.6 to 3.3) and 5.9 (95 percent confidence interval, 5.4 to 6.3), respectively. In a prospective analysis, every extended work shift that was scheduled in a month increased the monthly risk of a motor vehicle crash by 9.1 percent (95 percent confidence interval, 3.4 to 14.7 percent) and increased the monthly risk of a crash during the commute from work by 16.2 percent (95 percent confidence interval, 7.8 to 24.7 percent). In months in which interns worked five or more extended shifts, the risk that they would fall asleep while driving or while stopped in traffic was significantly increased (odds ratios, 2.39 [95 percent confidence interval, 2.31 to 2.46] and 3.69 [95 percent confidence interval, 3.60 to 3.77], respectively).Extended-duration work shifts, which are currently sanctioned by the Accreditation Council for Graduate Medical Education, pose safety hazards for interns. These results have implications for medical residency programs, which routinely schedule physicians to work more than 24 consecutive hours.
Carvedilol, a new vasodilating adrenoceptor blocker antihypertensive drug, protects endothelial cells from damage initiated by xanthine-xanthine oxidase and neutrophils
Authors: T.-L. Yue, P. J McKenna, J.-L. Gu, H.-Y. Cheng, R. E Ruffolo, G. Z Feuerstein
Journal: Cardiovascular Research (1994)

Oxygen radical mediated endothelial injury plays an important role in cardiovascular disease. Carvedilol, a new beta blocker and antihypertensive agent, has been shown to have antioxidant activity. The aim of this study was to determine whether carvedilol protects oxygen radical induced endothelial injury.Cultured bovine pulmonary artery (BPAEC) and human umbilical vein endothelial cells (HUVEC) were used and oxygen radicals were generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA) activated human neutrophils. Cell injury was assessed by lactate dehydrogenase (LDH) release and cell death, or 51 Cr release from prelabelled BPAEC. The electron paramagnetic resonance (EPR) spin trapping technique was used to detect the amount of radical spin adducts formed in cell lipids.Carvedilol dose dependently inhibited xanthine-xanthine oxidase induced LDH release from BPAEC and HUVEC, with IC50 values of 3.8 microM and 2.6 microM, respectively, and significantly reduced cell death by xanthine-xanthine oxidase. Other beta blockers tested (propranolol, labetalol, pindolol, and celiprolol) showed a mild effect or no effect at all. Increasing the time of pretreatment with carvedilol enhanced its cell protective effect against oxidative stress. Carvedilol also protected BPAEC dose dependently from PMA activated, neutrophil induced cell injury. Carvedilol had no effect on xanthine oxidase activity. EPR study confirmed that xanthine-xanthine oxidase induced the formation of lipid derived radicals in cell lipids and carvedilol scavenged free radicals, as indicated by the decreased EPR signal.Carvedilol protects endothelial cells against oxygen radical mediated cell injury and death by scavenging free radicals. The prevention of oxidative injury to endothelial cells might potentially contribute to the clinical beneficial effects of carvedilol as an antihypertensive agent.
Acidic Drinking Water and Risk of Childhood-Onset Type 1 Diabetes
Authors: Lars C. Stene, Dag Hongve, Per Magnus, Kjersti S. Rønningen, Geir Joner
Journal: Diabetes Care (2002)

OBJECTIVE—To estimate the associations of acidity and concentration of selected minerals in household tap water with the risk of type 1 diabetes. RESEARCH DESIGN AND METHODS—We designed a population-based case-control study with 64 cases of type 1 diabetes and 250 randomly selected control subjects. Acidity, color, and mineral content were measured in tap water from each participant’s household. RESULTS—Tap water pH 6.2–6.9 was associated with a fourfold higher risk of type 1 diabetes compared with pH ≥7.7 (OR 3.73, 95% CI 1.52–9.15). This result was similar after exclusion of individuals with the highly protective HLA-DQB1*0602 allele, but adjustment for maternal education, urban/rural residence, sex, and age tended to strengthen the estimated association. Higher tap water concentration of zinc was associated with lower risk of type 1 diabetes after adjustment for pH and other possible confounders, but the overall association was strictly not significant. CONCLUSIONS—These results suggest the possibility that quality of drinking water influences the risk of type 1 diabetes. The possible mechanisms by which water acidity or mineral content may be involved in the etiology of type 1 diabetes remain unknown, but the mechanisms are most likely indirect and may involve an influence on survival of microorganisms in the water.
Anti-<i>Saccharomyces cerevisiae</i> mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role
Authors: J-F Quinton, B Sendid, D Reumaux, P Duthilleul, A Cortot, B Grandbastien, G Charrier, S R Targan, J-F Colombel, D Poulain
Journal: Gut (1998)

Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease.To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease.Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively.The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement.ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.
Enhancement of the intensity, persistence, and passive transfer of delayed-type hypersensitivity lesions by pertussigen in mice.
Authors: W A Sewell, J J Munoz, M A Vadas
Journal: The Journal of Experimental Medicine (1983)

Pertussigen, a purified protein from Bordetella pertussis, was shown to increase delayed-type hypersensitivity (DTH) to protein antigens in mice. First, it caused an approximately twofold enhancement of the magnitude of 24-h DTH reactions. Second, the peak magnitude of DTH was delayed to 4-7 d after challenge, at which time it was five times more intense than in mice not receiving pertussigen. This reaction was antigen specific, and histologically was characterized by a dense mononuclear infiltrate. Third, pertussigen prolonged DTH so that it was still detectable 3-6 wk after challenge. The effect of pertussigen was seen only in antigen-driven reactions and was time and dose dependent, with 400 ng given 3 d after immunization resulting in the most prolonged reaction. The administration of pertussigen to the recipients of sensitized lymph node cells resulted in DTH that was more intense and prolonged than the reactions in control mice. Administration of pertussigen provides a model of prolonged and enhanced T cell-dependent inflammatory responses.
Risk of Thromboembolic Events After Percutaneous Left Atrial Radiofrequency Ablation of Atrial Fibrillation
Authors: Hakan Oral, Aman Chugh, Mehmet Özaydın, Eric Good, Jackie Fortino, Sundar Sankaran, Scott Reich, Petar Igic, Darryl Elmouchi, David Tschopp, Alan Wimmer, Sujoya Dey, Thomas Crawford, Frank Pelosi, Krit Jongnarangsin, Frank Bogun, Fred Morady
Journal: Circulation (2006)

In patients with atrial fibrillation (AF), the risk of thromboembolic events (TEs) is variable and is influenced by the presence and number of comorbid conditions. The effect of percutaneous left atrial radiofrequency ablation (LARFA) of AF on the risk of TEs is unclear.LARFA was performed in 755 consecutive patients with paroxysmal (n = 490) or chronic (n = 265) AF. Four hundred eleven patients (56%) had > or = 1 risk factor for stroke. All patients were anticoagulated with warfarin for > or = 3 months after LARFA. A TE occurred in 7 patients (0.9%) within 2 weeks of LARFA. A late TE occurred 6 to 10 months after ablation in 2 patients (0.2%), 1 of whom still had AF, despite therapeutic anticoagulation in both. Among 522 patients who remained in sinus rhythm after LARFA, warfarin was discontinued in 79% of 256 patients without risk factors and in 68% of 266 patients with > or = 1 risk factor. Patients older than 65 years or with a history of stroke were more likely to remain anticoagulated despite a successful outcome from LARFA. None of the patients in whom anticoagulation was discontinued had a TE during 25 +/- 8 months of follow-up.The risk of a TE after LARFA is 1.1%, with most events occurring within 2 weeks after the procedure. Discontinuation of anticoagulant therapy appears to be safe after successful LARFA, both in patients without risk factors for stroke and in patients with risk factors other than age > 65 years and history of stroke. Sufficient safety data are as yet unavailable to support discontinuation of anticoagulation in patients older than 65 years or with a history of stroke.
Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels
Authors: Laurence E. Ring, Lori M. Zeltser
Journal: Journal of Clinical Investigation (2010)

Distinct populations of leptin-sensing neurons in the hypothalamus, midbrain, and brainstem contribute to the regulation of energy homeostasis. To assess the requirement for leptin signaling in the hypothalamus, we crossed mice with a floxed leptin receptor allele (Leprfl) to mice transgenic for Nkx2.1-Cre, which drives Cre expression in the hypothalamus and not in more caudal brain regions, generating LeprNkx2.1KO mice. From weaning, LeprNkx2.1KO mice exhibited phenotypes similar to those observed in mice with global loss of leptin signaling (Leprdb/db mice), including increased weight gain and adiposity, hyperphagia, cold intolerance, and insulin resistance. However, after 8 weeks of age, LeprNkx2.1KO mice maintained stable adiposity levels, whereas the body fat percentage of Leprdb/db animals continued to escalate. The divergence in the adiposity phenotypes of Leprdb/db and LeprNkx2.1KO mice with age was concomitant with increased rates of linear growth and energy expenditure in LeprNkx2.1KO mice. These data suggest that remaining leptin signals in LeprNkx2.1KO mice mediate physiological adaptations that prevent the escalation of the adiposity phenotype in adult mice. The persistence of severe adiposity in LeprNkx2.1KO mice, however, suggests that compensatory actions of circuits regulating growth and energy expenditure are not sufficient to reverse obesity established at an early age.
Clinical and ultrasonographic remission determines different chances of relapse in early and long standing rheumatoid arthritis
Authors: G. Peluso, A. Michelutti, S. Bosello, E. Gremese, B. Tolusso, G. Ferraccioli
Journal: Annals of the Rheumatic Diseases (2010)

Treatment of rheumatoid arthritis (RA) should aim at full remission. The aims of this study were to define: (1) how many patients reached ultrasound power Doppler (US-PD) remission in a cohort of patients with early RA (ERA) compared with longstanding RA (LSRA); (2) possible predictors of US-PD remission; and (3) how many patients with and without US-PD remission relapsed after 1 year of follow-up in ERA and LSRA.48 patients with ERA and 46 with LSRA with disease activity score <1.6 underwent US assessment. Six hand and wrist joints were studied for active synovitis. 56.2% of patients with ERA and 50.0% of those with LSRA fulfilled American College of Rheumatology (ACR) remission criteria.43.7% of patients with ERA and 17.4% of those with LSRA had no evidence of synovitis at US evaluation. Using a stricter clinical definition of remission (ie, ACR criteria), US evaluation confirmed clinical remission in 66.7% of patients with ERA and 26.1% of those with LSRA. Early disease was predictive of clinical US remission. 20.0% of patients with RA who had a negative PD signal at the US evaluation had a flare during the 12-month follow-up period compared with 47.1% of patients who had a positive PD signal.US-PD remission occurs in half of patients with ERA and in a minority of patients with LSRA in clinical remission. Early disease seems to be the major determinant of full remission.
ATM and the Molecular Pathogenesis of Ataxia Telangiectasia
Authors: Peter J. McKinnon
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Ataxia telangiectasia (A-T) results from inactivation of the ATM protein kinase. DNA-damage signaling is a prime function of this kinase, although other roles have been ascribed to ATM. Identifying the primary ATM function(s) for tissue homeostasis is key to understanding how these functions contribute to the prevention of A-T-related pathology. In this regard, because A-T is primarily a neurodegenerative disease, it is essential to understand how ATM loss results in degenerative effects on the nervous system. In addition to delineating the biochemistry and cell biology of ATM, important insights into the molecular basis for neurodegeneration in A-T come from a spectrum of phenotypically related neurodegenerative diseases that directly result from DNA-repair deficiency. Together with A-T, these syndromes indicate that neurodegeneration can be caused by the failure to appropriately respond to DNA damage. This review focuses on defective DNA-damage signaling as the underlying cause of A-T.