tbuckley/cabot-search huggingface dataset:
Burden and Rates of Treatment and Control of Cardiovascular Disease Risk Factors in Obesity
Authors: Esther A. Molenaar, Shih-Jen Hwang, Ramachandran S. Vasan, Diederick E. Grobbee, James B. Meigs, Ralph B. D'Agostino, Daniel Levy, Caroline S. Fox
Journal: Diabetes Care (2008)

Obesity is associated with an increased risk for cardiovascular disease (CVD). We sought to determine rates of treatment and control of CVD risk factors among normal weight, overweight, and obese individuals in a community-based cohort.Participants free of CVD (n = 6,801; mean age 49 years; 54% women) from the Framingham Offspring and Third Generation cohorts who attended the seventh Offspring examination (1998-2001) or first Third Generation (2002-2005) examination were studied.Obese participants with hypertension were more likely to receive antihypertensive treatment (62.3%) than normal weight (58.7%) or overweight (59.0%) individuals (P = 0.002), but no differences in hypertension control across BMI subgroups among participants with hypertension were observed (36.7% [normal weight], 37.3% [overweight], and 39.4% [obese]; P = 0.48). Rates of lipid-lowering treatment were higher among obese participants with elevated LDL cholesterol (39.5%) compared with normal weight (34.2%) or overweight (36.4%) participants (P = 0.02), but control rates among those with elevated LDL cholesterol did not differ across BMI categories (26.7% [normal weight], 26.0% [overweight], and 29.2% [obese]; P = 0.11). There were no differences in diabetes treatment among participants with diabetes across BMI groups (69.2% [normal weight], 50.0% [overweight], 55.0% [obese]; P = 0.54), but obese participants with diabetes were less likely to have fasting blood glucose <126 mg/dl (15.7%) compared with normal weight (30.4%) or overweight (20.7%) participants (P = 0.02).These findings emphasize the suboptimal rates of treatment and control of CVD risk factors among overweight and obese individuals.
Sex differences in physiological progression of idiopathic pulmonary fibrosis
Authors: M. K. Han, S. Murray, C. D. Fell, K. R. Flaherty, G. B. Toews, J. Myers, T. V. Colby, W. D. Travis, E. A. Kazerooni, B. H. Gross, F. J. Martinez
Journal: European Respiratory Journal (2008)

In idiopathic pulmonary fibrosis, incidence is higher in males, and females may have better survival. The aim of the present study was to determine whether the rate of increase in desaturation during serial 6-min walk testing would be greater, and survival worse, for males versus females. Serial changes in the percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed models in 215 patients. DA was defined as the total area above the curve created using desaturation percentage values observed during each minute of the 6-min walk test. Multivariate Cox regression assessed survival differences. Adjusting for baseline DA, 6-min walk distance, change in 6-min walk distance over time and smoking history, the percentage of maximum DA increased by an average of 2.83 and 1.37% per month for males and females, respectively. Females demonstrated better survival overall, which was more pronounced in patients who did not desaturate below 88% on ambulation at baseline and after additionally adjusting for 6-month relative changes in DA and forced vital capacity. These data suggest that differences in disease progression contribute to, but do not completely explain, better survival of females with idiopathic pulmonary fibrosis.
Concentrations of methacholine for bronchial responsiveness according to symptoms, smoking and immunoglobulin E in a population-based study in Spain. Spanish Group of the European Asthma Study.
Authors: J Sunyer, A Muñoz
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To assess the simultaneous effects of symptoms related to asthma, smoking, and Immunoglobulin E (IgE) on the concentrations of methacholine at which different individuals fall below 80% the FEV1 values obtained with saline, we used parametric survival methods that fit the dose-response nature of bronchial responsiveness (BR). A general population-based sample of 1,615 adults (aged 20 to 44 yr) from five cities in Spain participating in the European Community Respiratory Health Survey was studied. The total number of subjects whose FEV1 values dropped below 80% was 237 (14.7%). We found that individuals with symptoms related to asthma, whether they were smokers or nonsmokers, responded at lower concentrations of methacholine than individuals without symptoms. The greatest decrease in the concentrations of methacholine at which different percentages of individuals responded was due to symptoms among the nonsmokers (relative percentiles ranging from 0.53 to 0.76, and a 90% confidence band not containing a value one). Among individuals without symptoms, smokers responded at moderately but significantly lower concentrations than nonsmokers, whereas an apparent protective effect of smoking was seen in symptomatic individuals, owing in part to a self-selection bias. The higher the concentration of IgE, the lower were the concentrations of methacholine needed to obtain a given level of BR. Moreover, the magnitude of the decrease in methacholine concentrations leading to a response was constant over all percentages of individuals responding. The analytical methods used in the study permit the incorporation of complexities in the relationships between BR and symptoms, smoking, and IgE, and are generally applicable to situations in which a dose-response relationship occurs.
Design of Agonistic Altered Peptides for the Robust Induction of CTL Directed towards H-2Db in Complex with the Melanoma-Associated Epitope gp100
Authors: Marianne J.B. van Stipdonk, Daniel Badia-Martinez, Marjolein Sluijter, Rienk Offringa, Thorbald van Hall, Adnane Achour
Journal: Cancer Research (2009)

Abstract Immunogenicity of tumor-associated antigens (TAA) is often weak because many TAA are autoantigens for which the T-cell repertoire is sculpted by tolerance mechanisms. Substitutions at main anchor positions to increase the complementarity between the peptide and the MHC class I (MHC-I) binding cleft constitute a common procedure to improve binding capacity and immunogenicity of TAA. However, such alterations are tailored for each MHC-I allele and may recruit different CTL specificities through conformational changes in the targeted peptides. Comparative analysis of substituted melanoma-differentiation antigen gp100 in complex with H-2Db revealed that combined introduction of glycine and proline residues at the nonanchor positions 2 and 3, respectively, resulted in an agonistic altered peptide with dramatically enhanced binding affinity, stability, and immunogenicity of this TAA. Peptide vaccination using the p2Gp3P-altered peptide version of gp100 induced high frequencies of melanoma-specific CTL in the endogenous CD8+ repertoire. Crystal structure analysis of MHC/peptide complexes revealed that the conformation of the modified p2Gp3P-peptide was similar to the wild-type peptide, and indicated that this mimotope was stabilized through interactions between peptide residue p3P and the tyrosine residue Y159 that is conserved among most known MHC-I molecules throughout mammalian species. Our results may provide an alternative approach to enhance MHC stabilization capacity and immunogenicity of low-affinity peptides for induction of robust tumor-specific CTL. [Cancer Res 2009;69(19):7784–92]
Calcium handling and cell contraction in rat cardiomyocytes depleted of intracellular magnesium
Authors: E Griffiths
Journal: Cardiovascular Research (2000)

Objectives: Depressed levels of cardiac Mg have been found in patients with ischaemic heart disease or heart failure, but it is not known whether low intracellular free [Mg2+] ([Mg2+]i) is a causal factor in such myocardial dysfunction. The aims for the present study were to develop a method of lowering [Mg2+]i in myocytes isolated from normal rat hearts, and so to determine whether a low [Mg2+]i itself would cause abnormalities of intracellular Ca2+ ([Ca2+]i) homeostasis or myocyte contractile function in absence of any cardiac disease. Methods: Rat ventricular myocytes were loaded with mag-indo-1/AM or indo-1/AM for determination of total [Mg2+]i and [Ca2+]i, respectively. Mitochondrial [Ca2+] was determined by selective loading of indo-1/AM into the mitochondria. Cell contraction was measured using an edge-tracking device. Myocytes were depleted of [Mg2+]i by incubation in absence of external Mg2+. This resulted in a decrease in [Mg2+]i from about 1.3 to 0.3 mM. In subsequent experiments, 1.2 mM MgCl2 was again present in the superfusate. Results: Under basal conditions (low rate of stimulation, 0.2 Hz, and 1 mM external [Ca2+]), the Mg-depleted cells showed very similar changes in [Ca2+] to control cells, despite an increase in the amplitude of cell contraction. But in presence of high external [Ca2+] (4 mM) and 5 Hz stimulation rate, the Mg-depleted cells showed defects in systolic Ca2+ handling and in cell contraction; in particular, they were unable to increase systolic [Ca2+] in response to the stimulus, unlike control cells. Despite these alterations in total [Ca2+]i, mitochondrial Ca2+ uptake was unchanged in the Mg-depleted cells. Conclusions: A low [Mg2+]i can itself cause significant cardiomyocyte dysfunction in absence of any contributing disease state.
Correlation between tests of small airway function
Authors: G. M. Cochrane, S. R. Benatar, J. Davis, J. V. Collins, T. J. H. Clark
Journal: Thorax (1974)

MicroRNAs are endogenous, noncoding, small RNAs that regulate expression and function of genes, but little is known about regulation of microRNA in the kidneys under normal or pathologic states. Here, we generated a mouse model in which the proximal tubular cells lack Dicer, a key enzyme for microRNA production. These mice had normal renal function and histology under control conditions despite a global downregulation of microRNAs in the renal cortex; however, these animals were remarkably resistant to renal ischemia-reperfusion injury (IRI), showing significantly better renal function, less tissue damage, lower tubular apoptosis, and improved survival compared with their wild-type littermates. Microarray analysis showed altered expression of specific microRNAs during renal IRI. Taken together, these results demonstrate evidence for a pathogenic role of Dicer and associated microRNAs in renal IRI.
Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: A randomized trial
Authors: John S. Strauss, Alice B. Gottlieb, Terry Jones, John Y.M. Koo, James J. Leyden, Anne Lucky, Anastasios A. Pappas, John McLane, Eileen E. Leach
Journal: Journal of the American Academy of Dermatology (2000)
Comment on: Rizzo et al. Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes: Role of Dipeptidyl Peptidase-IV Inhibition. Diabetes Care 2012;35:2076–2082
Authors: J. Hans DeVries
Journal: Diabetes Care (2012)

Rizzo et al. (1) report some remarkable differences in mean absolute glucose excursions (MAGE), markers of oxidative stress, and markers of inflammation in a randomized, open-label trial of sitagliptin 100 mg once daily versus vildagliptin 50 mg twice daily. MAGE is a measure of large glycemic swings, taking into account only …
Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice
Authors: Scott P. Heximer, Russell H. Knutsen, Xiaoguang Sun, Kevin M. Kaltenbronn, Man-Hee Rhee, Ning Peng, Antonio Oliveira-dos-Santos, Josef M. Penninger, Anthony J. Muslin, Thomas H. Steinberg, J. Michael Wyss, Robert P. Mecham, Kendall J. Blumer
Journal: Journal of Clinical Investigation (2003)

Signaling by hormones and neurotransmitters that activate G protein–coupled receptors (GPCRs) maintains blood pressure within the normal range despite large changes in cardiac output that can occur within seconds. This implies that blood pressure regulation requires precise kinetic control of GPCR signaling. To test this hypothesis, we analyzed mice deficient in RGS2, a GTPase-activating protein that greatly accelerates the deactivation rate of heterotrimeric G proteins in vitro. Both rgs2+/– and rgs2–/– mice exhibited a strong hypertensive phenotype, renovascular abnormalities, persistent constriction of the resistance vasculature, and prolonged response of the vasculature to vasoconstrictors in vivo. Analysis of P2Y receptor–mediated Ca2+ signaling in vascular smooth muscle cells in vitro indicated that loss of RGS2 increased agonist potency and efficacy and slowed the kinetics of signal termination. These results establish that abnormally prolonged signaling by G protein–coupled vasoconstrictor receptors can contribute to the onset of hypertension, and they suggest that genetic defects affecting the function or expression of RGS2 may be novel risk factors for development of hypertension in humans.
HER2 and Choice of Adjuvant Chemotherapy for Invasive Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15
Authors: S. Paik
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Recent retrospective analyses have suggested that breast cancer patients whose tumors overexpress HER2 derive preferential benefit from treatment with anthracyclines such as doxorubicin. This has led some clinicians to propose that HER2 should be used as a predictive marker in choosing between anthracycline-based regimens and combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). We evaluated this recommendation in a retrospective study of National Surgical Adjuvant Breast and Bowel Project Protocol B-15, in which patients received a combination of doxorubicin and cyclophosphamide (AC), CMF, or AC followed by CMF. We hypothesized that AC would be superior to CMF only in the HER2-positive patients. Methods: Immunohistochemical detection of HER2 was performed on tumor sections from 2034 of 2295 eligible patients. We used statistical analysis to evaluate the interaction between the efficacy of the assigned treatments and HER2 overexpression. All statistical tests were two-sided. Results: Tumor sections from 599 patients (29%) stained positive for HER2. AC was superior to CMF in HER2-positive patients only, although differences in outcomes did not reach statistical significance. In the HER2-positive cohort, relative risks of failure (i.e., after AC treatment as compared with CMF treatment) were 0.84 for disease-free survival (DFS) (95% confidence interval [CI] = 0.65–1.07; P = .15), 0.82 for survival (95% CI = 0.63–1.06; P = .14), and 0.80 for recurrence-free survival (RFS) (95% CI = 0.62–1.04; P = .10). Tests for interaction between treatment and HER2 status were suggestive but not statistically significant (P = .19 for DFS, P = .11 for survival, and P = .08 for RFS). Conclusions: These results, together with overview results indicating minor overall superiority for anthracycline-based regimens relative to CMF, indicate a preference for the AC regimen in patients with HER2-positive tumors. Both AC and CMF regimens may be considered for patients with HER2-negative tumors.
Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus
Authors: M Nikpour, A A Dempsey, M B Urowitz, D D Gladman, D A Barnes
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To determine whether peripheral blood gene expression of patients with systemic lupus erythaematosus (SLE) correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). <h3>Methods:</h3> RNA was isolated from peripheral blood of 269 patients with SLE and profiled on a custom microarray. Hierarchical clustering and a heat map were used to categorise samples into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics such as SLEDAI-2K score, of the major sample clusters were compared using multivariate regression models. <h3>Results:</h3> A set of 31 interferon (IFN)-regulated genes were seen to be driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature (n = 150) and the other by a relatively low IFN-regulated gene signature (n = 119). Disease activity measured using the SLEDAI-2K was significantly correlated with the high IFN gene signature. In multivariate regression analysis the immunological component of the SLEDAI-2K was a significant correlate of the high IFN gene signature as was presence of antibodies to U1RNP. There were no discernable correlates of the 156 non-IFN regulated genes profiled on the custom array. <h3>Conclusion:</h3> Peripheral blood gene expression profiling (GEP) in SLE allows patients to be categorised into two groups based on a high or low IFN gene signature. Disease activity measured using the SLEDAI-2K is correlated with the high IFN gene signature, indicating that GEP may be a useful biomarker of disease activity in SLE.
Interaction between isoprenaline and aminophylline in asthma
Authors: I. A. Campbell, W. G. Middleton, G. J. R. McHardy, M. V. Shotter, R. McKenzie, A. B. Kay
Journal: Thorax (1977)

<b>Campbell, I. A., Middleton, W. G., McHardy, G. J. R., Shotter, Margaret V., McKenzie, R., and Kay, A. B. (1977).</b><i>Thorax</i>, <b>32,</b> 424-428. <b>Interaction between isoprenaline and aminophylline in asthma.</b> Using a factorially designed study, 38 patients with bronchial asthma received a single dose of either isoprenaline by inhalation (9), aminophylline intravenously (10), isoprenaline and aminophylline (11), or placebo (8). The maximum expiratory flow (V max), the maximum expiratory flow at 50% of vital capacity (V max<sub>50</sub>), and the concentrations of plasma cyclic AMP were measured at time intervals up to two hours. The combination of isoprenaline and aminophylline acted synergistically in terms of the percent increase in V max<sub>50</sub>. However, this was statistically significant only at 20 minutes. Plasma cyclic AMP concentration rose with a similar time course of response to the changes in small airways. The elevations in plasma cyclic AMP observed with the drug combination were higher than those for the individual drugs at 10, 20, 30, and 60 minutes but these differences were not statistically significant. These observations support the concept that changes in bronchial smooth muscle tone are mediated by concentrations of cyclic nucleotides and that combinations of isoprenaline and aminophylline, rather than the administration of each drug separately, may have therapeutic advantages in the treatment of bronchial asthma.
Molecular Genetics of Human Thyroid Neoplasms
Authors: James A. Fagin
Journal: Annual Review of Medicine (1994)

Cancers are thought to develop as a result of sequential mutations of genes important in the control of cellular growth. Recently investigators identified a number of genetic defects that affect oncogenes and tumor-suppressor genes and that provide insight into the biology of benign and malignant thyroid neoplasms. Future implications for thyroid tumor diagnosis and prognosis are considered in this chapter.
Preventing injuries in public playgrounds through partnership between health services and local authority: community intervention study
Authors: J R Sibert, A. Mott, K. Rolfe, R. James, R. Evans, A. Kemp, F D J Dunstan
Journal: BMJ (1999)

Public playgrounds are important for children's play and development.Safety is a prime concern not only to prevent injuries but also because families need the assurance that it is safe for their children to play. 1 One way of improving safety is for health services and local authorities to form a partnership in the surveillance of injuries and the making of improvements.We report the results of such a partnership in Cardiff. 2 3
Serum Clara cell protein (CC16), a marker of the integrity of the air-blood barrier in sarcoidosis
Authors: C. Hermans, M. Petrek, V. Kolek, B. Weynand, T. Pieters, M. Lambert, A. Bernard
Journal: European Respiratory Journal (2001)

To test the hypothesis that sarcoidosis is associated with an intravascular leakage of lung epithelium secretory proteins, the occurrence and determinants in serum of sarcoid patients of CC16, a small size and readily diffusible lung-specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated. CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients with established sarcoidosis and of 117 healthy subjects matched for age, sex and smoking status. Stepwise regression analysis was used to identify extrapulmonary variables of CC16 changes in serum. These changes were then compared with biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as well as with the number of CC16 immunostaining cells on bronchial or pulmonary biopsy samples. CC16 concentration in serum of sarcoid patients was significantly increased, compared to their matched controls (25.9±16.2 versus 13.9±5.2 µg·L −1 ). In nonsmoking patients without significant renal impairment, CC16 in serum increased with the severity of the chest radiograph and computed tomography changes, and was on average 50–100% higher when parenchymal involvement was present. Sarcoid patients had, however, normal levels of CC16 in BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples, suggesting that an increased secretion of CC16 in the sarcoid lung is very unlikely, and that the elevation of CC16 in sarcoidosis results from an increased intravascular leakage of the protein across the air-blood barrier. The present study suggests that CC16 in serum might provide a useful tool to noninvasively evaluate the damage and increased permeability to proteins of the air-blood barrier associated with sarcoidosis.
IN-SITU HYBRIDISATION OF THE β-AMYLOID PROTEIN PROBE TO CHROMOSOME 9 IN PATIENTS WITH FAMILIAL ALZHEIMER'S DISEASE
Authors: EdmundC. Jenkins, EvelynA. Devine-Gage, Xiu-Lan Yao, GeorgeE. Houck, W.Ted Brown, HenrykM. Wisniewski, NikolaosK. Robakis
Journal: The Lancet (1987)