tbuckley/cabot-search huggingface dataset:
Infants' Dermatitis Quality of Life Index: a decade of experience of validation and clinical application
Authors: M.K.A. Basra, V. Gada, S. Ungaro, A.Y. Finlay, S.M. Salek
Journal: British Journal of Dermatology (2013)

The Infants' Dermatitis Quality of Life Index (IDQoL) is a questionnaire completed by parents to assess the impact of atopic dermatitis on the quality of life of infants aged 0-3 years. The aim was to review all clinical and psychometric data on the use of the IDQoL from its inception in 2001 until November 2012, to serve as a single reference source. A literature search was carried out using Medline, PubMed, EBSCOhost, Science Direct and Google Scholar. Articles and abstracts that described the clinical use of the IDQoL and those that investigated its psychometric properties were included. Articles not in English were excluded. Fifty-one publications were identified, of which 46 fulfilled the inclusion criteria. IDQoL data relating to psychometric, descriptive and clinical practice research, drug trials and therapeutic interventions were extracted. The IDQoL has been translated into 21 languages and used in 18 countries, including two multinational studies. Thirty-one studies demonstrated its psychometric properties, such as test-retest reliability, internal consistency, validity, responsiveness to change and interpretability. No studies investigated dimensionality, carried out factor analysis or described the minimal clinically important difference of the tool. Eight studies used the IDQoL to assess the effectiveness of therapeutic interventions such as education programmes, consultations and wet-wrap therapy, while seven studies described the use of IDQoL in topical interventions. When deciding whether to use the IDQoL, researchers and clinicians should consider the validation data, the relevant comparative clinical data available and the potential burden on the respondents.
Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study
Authors: Ida K Haugen, Vasan S Ramachandran, Devyani Misra, Tuhina Neogi, Jingbo Niu, Tianzhong Yang, Yuqing Zhang, David T Felson
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed. Methods We examined whether symptomatic (≥1 joint(s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity. Results We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity. Conclusions Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation.
Relation between bone turnover, oestradiol, and energy balance in women distance runners.
Authors: C L Zanker, I L Swaine
Journal: British Journal of Sports Medicine (1998)

OBJECTIVE: To explore relations between biochemical markers of bone turnover, indices of nutritional status, and serum oestradiol concentration in women distance runners. METHODS: Thirty three women distance runners of mean age (SD) 27.2 (1.8) years participated. Eighteen were defined as eumenorrhoeic, nine as amenorrhoeic, and six as oligomenorrhoeic. Mean (SD) running distance was 47.6 (22.4) km/week. Using bivariate correlation and regression analysis, serum levels of osteocalcin and bone alkaline phosphatase (BAP) and also urine deoxypyridinoline/creatinine (Dpyr/Cr) were correlated with mean daily energy balance, body mass index (BMI; kg/m2), and serum levels of total 3,5,3'-triiodothyronine and oestradiol within each group by menstrual status. RESULTS: All the amenorrhoeic women were in negative energy balance; they had a lower BMI, lower serum levels of oestradiol, triiodothyronine, osteocalcin and BAP and a lower urine Dpyr/Cr than any of the oligomenorrhoeic or eumenorrhoeic women. These variables were also lower in oligomenorrhoeic than in eumenorrhoeic women. Positive correlations were observed between serum levels of osteocalcin or BAP and both BMI and serum oestradiol concentration in amenorrhoeic, but not in oligomenorrhoeic or eumenorrhoeic women. Urine Dpyr/Cr did not correlate with any other variable within any group. Serum oestradiol concentration correlated positively with BMI in amenorrhoeic and oligomenorrhoeic, but not eumenorrhoeic women. CONCLUSIONS: Positive correlations between serum levels of bone formation markers, BMI and serum oestradiol concentration in our amenorrhoeic runners suggested that their reduced bone formation was linked to a low BMI and an oestrogen deficiency. Reduced bone turnover in amenorrhoeic distance runners has not previously been shown. These findings emphasise the importance of body mass and its possible link with a chronic energy deficit and hypothalamic dysfunction on bone remodelling balance in amenorrhoeic runners.
Tumor Suppressor von Hippel-Lindau (VHL) Stabilization of Jade-1 Protein Occurs through Plant Homeodomains and Is VHL Mutation Dependent
Authors: Mina I. Zhou, Hongmei Wang, Rebecca L. Foy, Jonathan J. Ross, Herbert T. Cohen
Journal: Cancer Research (2004)

Abstract The von Hippel-Lindau (VHL) gene is the major renal cancer gene in adults. The mechanism of renal tumor suppression by VHL protein is only partly elucidated. VHL loss increases expression of the hypoxia-inducible factor α transcription factors. However, clinical and biochemical data indicate that the hypoxia-inducible factors are necessary but not sufficient for renal tumorigenesis, which suggests other VHL effector pathways are involved. Jade-1 protein interacts strongly with VHL and is most highly expressed in renal proximal tubules, precursor cells of renal cancer. Short-lived Jade-1 protein contains plant homeodomain (PHD) and candidate PEST degradation motifs and is substantially stabilized by VHL. The effect of VHL on Jade-1 protein abundance and relative protein stability was further examined in immunoblots and metabolic labeling experiments using two time points. VHL-Jade-1 binding was tested in coimmunoprecipitations. In cotransfection studies with wild-type VHL, the Jade-1 PHD-extended PHD module, not the candidate PEST domain, was required for full VHL-mediated stabilization. This module is also found in leukemia transcription factors AF10 and AF17, as well as closely related Jade-like proteins, which suggests all might be VHL regulated. Intriguingly, naturally occurring truncations and mutations of VHL affected wild-type Jade-1 binding and stabilization. Although the VHL β domain was sufficient for Jade-1 binding, both the α and β domains were required for Jade-1 stabilization. Thus, truncating VHL mutations, which are severe and associated with renal cancer development, prevented Jade-1 stabilization. Moreover, well-controlled cotransfection and metabolic labeling experiments revealed that VHL missense mutations that cause VHL disease without renal cancer, such as Tyr98His and Tyr112His, stabilized Jade-1 fully. In contrast, like the VHL truncations, VHL missense mutations commonly associated with renal cancer, such as Leu118Pro or Arg167Trp, did not stabilize Jade-1 fully. Therefore, loss of Jade-1 stability may correlate with renal cancer risk. Endogenous Jade-1 in stable renal cancer lines also exhibited VHL mutation-dependent regulation. As in the cotransfections, VHL truncations did not increase endogenous Jade-1 abundance, whereas the VHL missense mutations tested partially increased Jade-1 expression. Additional studies with non-PHD proteins indicated that Jade-1 stabilization by VHL is highly specific. Fibronectin was not stabilized like Jade-1 by VHL, nor were candidate VHL interactors from a yeast screen. Thus, protein stabilization likely reflects the biological activity of largely intact VHL protein on the PHD-extended PHD module of Jade-1. Dysregulation of the VHL protein stabilization pathway or of Jade-1 itself may therefore contribute to VHL renal disease and renal cancer pathogenesis.
Generic Scan Using AFLP Markers as a Means to Assess the Role of Directional Selection in the Divergence of Sympatric Whitefish Ecotypes
Authors: D. Campbell
Journal: Molecular Biology and Evolution (2004)

Under the ecological theory of adaptive radiation, adaptation and reproductive isolation are thought to evolve as a result of divergent natural selection. Accordingly, elucidating the genetic basis of these processes is essential toward understanding the role of selection in shaping biological diversity. In this respect, the number of genes that evolved by selection remains contentious. To address this issue, the pattern of genetic differentiation obtained using 440 AFLP loci was compared with that expected under neutrality in four sympatric pairs of lake whitefish ecotypes that evolved adaptive phenotypic differences associated with the exploitation of distinct ecological niches. On average, 14 loci showed restricted gene flow relative to neutral expectation, suggesting a role of directional selection on their divergence. Among all loci that are most likely under directional selection, six exhibited parallel patterns of divergence, which provided further support for the role of selection in driving their divergence. Overall, these results indicate that only a small proportion of scored AFLP loci (between 1.4% and 3.2%) might be linked to genes implicated in the adaptive radiation of lake whitefish.
Sodium and Potassium Shifts Associated with Peripheral Resistance Changes in the Dog
Authors: JAMES D. JAMIESON, Sydney M. FRIEDMAN
Journal: Circulation Research (1961)

The relation of changes in peripheral vascular resistance to blood sodium and potassium activity was studied in the dog hind limb. Arterial inflow was controlled by a constant output pump in the femoral artery line. Cations were monitored with glass-to-silver cannula electrodes in the venous outflow. Vasoactive drugs were administered intra-arterially in amounts sufficient only to affect the limb vasculature. Vasoconstrietion induced by norepinephrine or epinephrine was associated with a fall in blood (Na + ) and often with a rise of (K + ). Larger doses tended to produce a biphasic response in (Na + ), a transient initial rise preceding the fall. Vasoconstrietion induced by serotonin or angio-tensin was associated with a fall in blood (Na + ) unaccompanied by any consistent change in (K + ). Vasoconstrietion induced by small amounts of pitressin (small series) produced a larger fall in (Na + ) and rise in (K + ) than with other agents producing an equal degree of vasoconstrietion. Vasodilatation induced by isoproterenol, acetylcholine, or histamine was accompanied by a rise in blood (Na + ) without any consistent change in (K + ).
Systemic Oxidative Stress Is Associated With Lower Aerobic Capacity and Impaired Skeletal Muscle Energy Metabolism in Patients With Metabolic Syndrome
Authors: Takashi Yokota, Shintaro Kinugawa, Mayumi Yamato, Kagami Hirabayashi, Tadashi Suga, Shingo Takada, Kuniaki Harada, Noriteru Morita, Noriko Oyama-Manabe, Yasuka Kikuchi, Koichi Okita, Hiroyuki Tsutsui
Journal: Diabetes Care (2013)

Systemic oxidative stress is associated with insulin resistance and obesity. We tested the hypothesis that systemic oxidative stress is linked to lower aerobic capacity and skeletal muscle dysfunction in metabolic syndrome (MetS).The incremental exercise testing with cycle ergometer was performed in 14 male patients with MetS and 13 age-, sex-, and activity-matched healthy subjects. Systemic lipid peroxidation was assessed by serum thiobarbituric acid reactive substances (TBARS), and systemic antioxidant defense capacity was assessed by serum total thiols and enzymatic activity of superoxide dismutase (SOD). To assess skeletal muscle energy metabolism, we measured high-energy phosphates in the calf muscle during plantar flexion exercise and intramyocellular lipid (IMCL) in the resting leg muscle, using (31)P- and (1)proton-magnetic resonance spectroscopy, respectively.Serum TBARS were elevated (12.4 ± 7.1 vs. 3.7 ± 1.1 μmol/L; P < 0.01), and serum total thiols and SOD activity were decreased (290.8 ± 51.2 vs. 398.7 ± 105.2 μmol/L, P < 0.01; and 22.2 ± 8.4 vs. 31.5 ± 8.5 units/L, P < 0.05, respectively) in patients with MetS compared with healthy subjects. Peak VO2 and anaerobic threshold normalized to body weight were significantly lower in MetS patients by 25 and 31%, respectively, and inversely correlated with serum TBARS (r = -0.49 and r = -0.50, respectively). Moreover, muscle phosphocreatine loss during exercise was 1.4-fold greater in patients with MetS (P < 0.05), and IMCL content was 2.9-fold higher in patients with MetS (P < 0.01), indicating impaired skeletal muscle energy metabolism, and these indices positively correlated with serum TBARS (r = 0.45 and r = 0.63, respectively).Systemic oxidative stress was associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in patients with MetS.
Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine—a pooled analysis of over 500 000 subjects in the Asia Cohort Consortium
Authors: P. Boffetta, W.D. Hazelton, Y. Chen, R. Sinha, M. Inoue, Y.T. Gao, W.P. Koh, X.O. Shu, E.J. Grant, I. Tsuji, Y. Nishino, S.L. You, K.Y. Yoo, J.M. Yuan, J. Kim, S. Tsugane, G. Yang, R. Wang, Y.B. Xiang, K. Ozasa, M. Nagai, M. Kakizaki, C.J. Chen, S.K. Park, A. Shin, H. Ahsan, C.X. Qu, J.E. Lee, M. Thornquist, B. Rolland, Z. Feng, W. Zheng, J.D. Potter
Journal: Annals of Oncology (2011)
Ventilatory-control Abnormalities in Familial Sleep Apnea
Authors: SUSAN REDLINE, JANICE LEITNER, JEAN ARNOLD, PETER V. TISHLER, MURRAY D. ALTOSE
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The role of ventilatory-control abnormalities in predisposing to familial sleep-disordered breathing (SDB) was assessed in 31 subjects 28 ± 10 yr of age (mean ± SD). Subjects with (n = 10) and without SDB (n = 12) were recruited from 13 families having two or more members with SDB. Nine age- and gender-matched controls were recruited from families having no member with SDB. Respiratory responses to eucapnic hypoxia, and ventilatory and occlusion pressure responses to hyperoxic hypercapnia with and without added resistive loads (6.5 cm H2O/L/s), were assessed through rebreathing. Age, FEV1, and FVC did not differ among the groups. Hypoxic responses ( Δ Ve/ Δ SaO2 ) were significantly lower among the first-degree relatives of SDB families than among controls ( − 0.76 ± 0.47 L/min/% SaO2 , and − 1.32 ± 0.92 L/min/% SaO2 , respectively, p < 0.05). Respiratory responses to hypercapnia during unloaded conditions were similar among the groups. With resistive loading, inspiratory impedance, as measured through the relationship of mouth occlusion pressure (P100) to inspiratory flow (Vt/Ti), increased with increasing hypercapnia to a greater extent in members of SDB families than in controls (0.169 ± 0.054 cm H2O/L/min versus 0.122 ± 0.051, respectively, p < 0.05). These data suggest that familial SDB may be based partly on a familial abnormality in ventilatory control associated with blunting of the hypoxic ventilatory response. The greater increase in impedance during inspiratory loading in members of affected families also suggests a propensity for dynamic airway narrowing.
Noninvasive Saliva-based <i>EGFR</i> Gene Mutation Detection in Patients with Lung Cancer
Authors: Fang Wei, Chien-Chung Lin, Aron Joon, Ziding Feng, Gabriel Troche, Maruja E. Lira, David Chia, Mao Mao, Chung-Liang Ho, Wu-Chou Su, David T. W. Wong
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Constitutive activation of the epidermal growth factor receptor (EGFR) is prevalent in epithelial cancers, particularly in non-small cell lung carcinoma (NSCLC). Mutations identified in EGFR predict the sensitivity to EGFR-targeted therapy. Detection of these mutations is mainly based on tissue biopsy, which is invasive, expensive, and time consuming.Noninvasive, real-time, inexpensive detection and monitoring of EGFR mutations in patients with NSCLC is highly desirable.We developed a novel core technology, electric field-induced release and measurement (EFIRM), which relies on a multiplexible electrochemical sensor that can detect EGFR mutations directly in bodily fluids.We established EFIRM for the detection of the EGFR mutations in vitro and correlated the results with tumor size from xenografted mice. In clinical application, we demonstrated that EFIRM could detect EGFR mutations in the saliva and plasma of 22 patients with NSCLC. Finally, a blinded test was performed on saliva samples from 40 patients with NSCLC. The receiver operating characteristic analysis indicated that EFIRM detected the exon 19 deletion with an area under the curve of 0.94 and the L858R mutation with an area under the curve of 0.96.Our data indicate that EFIRM is effective, accurate, rapid, user-friendly, and cost effective for the detection of EGFR mutations in the saliva of patients with NSCLC. We termed this saliva-based EGFR mutation detection (SABER).
Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study
Authors: Rachel Knevel, Gerður Gröndal, Tom W J Huizinga, A Willemien Visser, Helgi Jónsson, Arnór Víkingsson, Árni Jón Geirsson, Kristján Steinsson, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2012)

Background The susceptibility to rheumatoid arthritis (RA) is partly heritable, but whether the severity of RA is also influenced by genetics has not been determined. The evaluation of the heritability of the severity of RA is basic to further studies on genetic factors. A study was undertaken to determine whether joint destruction is heritable. Methods Iceland has an unique comprehensive genealogy database covering today's population and stretching back to ≥1000 years ago, as well as genome-wide single nucleotide polymorphism data for a large part of the population. Hand and feet x-rays of 325 Icelandic patients with RA were scored according to the Sharp-van der Heijde method. The degree of relatedness between patients was estimated in two ways: (1) kinship coefficients (KC) on the genealogical data were expressed; and (2) the identical-by-descent (IBD) was estimated applying long-range phasing of the genetic profile of the patients. The degree of relatedness was tested against the similarity in joint destruction rates by linear regression analysis and the heritability of joint destruction was calculated. Results Significant associations between degree of relatedness and similarity in joint destruction rates were observed for both methods of determining relatedness (p KC =0.018, p IBD =0.003). The estimated heritability was 45% using KC and 58% using the estimated IBD data. Conclusions The severity of joint destruction in RA is influenced by genetic factors.
Changes in rectal sensitivity after hypnotherapy in patients with irritable bowel syndrome.
Authors: A Prior, S M Colgan, P J Whorwell
Journal: Gut (1990)

Fifteen patients with the irritable bowel syndrome were studied to assess the effect of hypnotherapy on anorectal physiology. In comparison with a control group of 15 patients who received no hypnotherapy significant changes in rectal sensitivity were found in patients with diarrhoea-predominant irritable bowel syndrome both after a course of hypnotherapy and during a session of hypnosis (p less than 0.05). Although patient numbers were small, a trend towards normalisation of rectal sensitivity was also observed in patients with constipation-predominant irritable bowel syndrome. No changes in rectal compliance or distension-induced motor activity occurred in either subgroup nor were any changes in somatic pain thresholds observed. The results suggest that symptomatic improvement in irritable bowel syndrome after hypnotherapy may in part be due to changes in visceral sensitivity.
Stem Cell Research: A Target Article Collection Part II - What's in a Name: Embryos, Clones, and Stem Cells
Authors: Jane Maienschein
Journal: The American Journal of Bioethics (2002)

In 2001, the U.S. House of Representatives passed the "Human Cloning Prohibition Act" and President Bush announced his decision to allow only limited research on existing stem cell lines but not on "embryos." In contrast, the U.K. has explicitly authorized "therapeutic cloning." Much more will be said about bioethical, legal, and social implications, but subtleties of the science and careful definitions of terms have received much less consideration. Legislators and reporters struggle to discuss "cloning," "pluripotency," "stem cells," and "embryos," and whether "adult" are preferable to "embryonic" stem cells as research subjects. They profess to abhor "copying humans" or "killing embryos." Do they know what they are talking about? Do we? This paper explores the historical, philosophical, and scientific contexts that inform this heated discussion.
Experimental Membranous Glomerulonephritis in Rats
Authors: David J. Salant, Christine Darby, William G. Couser
Journal: Journal of Clinical Investigation (1980)

Quantitation of immune deposit formation in glomeruli and correlation with immunohistologic and functional changes has been accomplished only in models of anti-glomerular basement membrane antibody-induced nephritis, or indirectly in immune complex disease by measuring radiolabeled antigen deposition. The kinetics of subepithelial immune deposit formation and the relationship between the quantity of antibody deposited and proteinuria are defined here for the first time in an established model of membranous immune complex nephritis (passive Heymann nephritis) induced by a single intravenous injection of 125I-labeled sheep immunoglobulin (Ig)G antibody to rat tubular brush border antigen (Fx1A). Measurement of antibody deposition in glomeruli (GAb) isolated from rats injected with 10 mg of anti-Fx1A demonstrated a mean of 12 μg GAb in 4 h, which increased linearly to 48 μg in 5 d. GAb represented only 20 and 44% of total kidney antibody binding at these times. Proteinuria occurred only after 4-5 d of antibody deposition in rats with total kidney antibody binding exceeding ∼200 μg/2 kidneys. Steroid treatment and vasoactive amine blockade did not significantly alter the quantity or localization of immune deposits. It was also demonstrated that isolated rat glomeruli specifically bound nephritogenic quantities of anti-Fx1A in vitro within hours. Analysis of the quantitative aspects of glomerular antibody deposition in vivo and glomerular antibody binding in vitro provides additional evidence that subepithelial immune deposits in passive Heymann nephritis may form in situ by reaction of free antibody with antigenic constitutents of the normal rat glomerulus. The observed kinetics of deposit formation differ markedly from those in anti-glomerular basement membrane disease and suggest a role for factors in addition to antigen-antibody interaction in determining this unique pattern of glomerular immune deposit formation.