tbuckley/cabot-search huggingface dataset:
Interventions for Hirsutism
Authors: Esther J. van Zuuren, Zbys Fedorowicz
Journal: JAMA (2015)

What medical therapies are associated with greatest efficacy and fewest adverse events for treating hirsutism?Oral contraceptive pills (OCPs) have been associated with improvement for mild hirsutism, as has flutamide (250 mg) twice daily and spironolactone for more severe cases. Finasteride and gonadotropin-releasing analogues are associated with inconsistent results and metformin is not associated with benefit.
Immunoglobulin class-switched B cells form an active immune axis between CNS and periphery in multiple sclerosis
Authors: Arumugam Palanichamy, Leonard Apeltsin, Tracy C. Kuo, Marina Sirota, Shengzhi Wang, Steven J. Pitts, Purnima D. Sundar, Dilduz Telman, Lora Z. Zhao, Mia Derstine, Aya Abounasr, Stephen L. Hauser, H.-Christian von Büdingen
Journal: Science Translational Medicine (2014)

Ig class-switched B cells connect the periphery and CNS and support peripheral antigen-driven B cell activation in CNS autoimmunity.
Correlates of left ventricular mass in a population sample aged 36 to 37 years. Focus on lifestyle and salt intake.
Authors: M Kupari, P Koskinen, J Virolainen
Journal: Circulation (1994)

BACKGROUND Echocardiographically determined left ventricular (LV) mass predicts adverse cardiovascular events in the general population. We have assessed the correlates of LV mass in a population-based study focusing on lifestyle and salt intake. METHODS AND RESULTS A random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. The subjects' physical activity and alcohol, tobacco, and coffee consumption were quantified by 2-month dairy follow-up, and sodium intake was quantified by 7-day food records. Blood pressure was averaged for casual cuff measurements made 2 months apart. LV mass was determined by M-mode echocardiography, and stroke volume was determined by Doppler. Hematocrit and serum insulin were measured. In multiple linear regression analysis, LV mass was related positively and independently (P &lt; .05) to body weight, systolic blood pressure, stroke volume, sodium intake, hematocrit, and energy expenditure in leisure-time physical activity. Additional analyses showed that the relation of LV mass to daily sodium intake depended on blood pressure (P &lt; .001 for the interaction); the multiple regression coefficient (+/- SE) was 0.41 +/- 0.11 g.mEq-1 x d-1 (P = .001) in subjects with systolic blood pressure above the population median but statistically nonsignificant (-0.15 +/- 0.10 g.mEq-1 x d-1) in those with lower blood pressure. LV mass was clearly elevated only in persons with both blood pressure and sodium intake above the population medians. CONCLUSIONS Body weight, blood pressure, stroke volume, sodium intake, physical activity, and hematocrit are independent predictors of LV mass among unselected persons aged 36 to 37 years. The synergistic interaction of dietary salt with blood pressure suggests that high sodium intake may sensitize the heart to the hypertrophic stimulus of pressure load. Prospective studies are needed to confirm these cross-sectional associations.
CD14 expression and soluble CD14 after segmental allergen provocation in atopic asthma
Authors: None Virchow JC, P Julius, H Matthys, C Kroegel, W Luttmann
Journal: European Respiratory Journal (1998)

Allergic asthma is associated with the recruitment of activated inflammatory cells after allergen challenge. Surface expression of CD14 has been proposed as a marker of cell activation and differentiation. We therefore measured CD14 expression on activated macrophages and granulocytes as well as soluble CD14 (sCD14) concentrations in peripheral blood and bronchoalveolar lavage (BAL) following segmental allergen provocation (SAP) with individually standardized doses of allergen in eight patients with allergic asthma. Two segments of the right lung were challenged with allergen. Two segments of the left lung, into which saline was instilled, served as controls. CD14 expression on macrophages and granulocytes was determined by flow-cytometry and concentrations of interleukins and sCD14 were analysed by enzyme-linked immunosorbent assay (ELISA) 10 min and 18 h after challenge. Soluble CD14 concentrations remained unchanged in BAL fluid after saline challenge and 10 min after SAP, but increased significantly 18 h after SAP. Although macrophage numbers increased 18h after SAP, CD14 expression on these cells did not change. Unlike macrophages, granulocyte numbers correlated with sCD14 levels 18 h after SAP while their CD14 expression decreased significantly. Furthermore, sCD14 correlated with interleukin (IL)-13 concentrations 18 h after SAP. An increase in soluble CD14 can be observed 18 h but not 10 min after segmental allergen provocation suggesting local release of this surface antigen. Our findings imply that CD14-mediated cell activation following segmental allergen provocation could play a role in asthmatic inflammation.
How Do Control-Based Approaches Enter into Biology?
Authors: Philip R LeDuc, William C. Messner, John P. Wikswo
Journal: Annual Review of Biomedical Engineering (2011)

Control is intrinsic to biological organisms, whose cells are in a constant state of sensing and response to numerous external and self-generated stimuli. Diverse means are used to study the complexity through control-based approaches in these cellular systems, including through chemical and genetic manipulations, input-output methodologies, feedback approaches, and feed-forward approaches. We first discuss what happens in control-based approaches when we are not actively examining or manipulating cells. We then present potential methods to determine what the cell is doing during these times and to reverse-engineer the cellular system. Finally, we discuss how we can control the cell's extracellular and intracellular environments, both to probe the response of the cells using defined experimental engineering-based technologies and to anticipate what might be achieved by applying control-based approaches to affect cellular processes. Much work remains to apply simplified control models and develop new technologies to aid researchers in studying and utilizing cellular and molecular processes.
NAD(P)H Oxidase–Derived Superoxide Mediates Hypercholesterolemia-Induced Leukocyte–Endothelial Cell Adhesion
Authors: Karen Y. Stokes, E. Chris Clanton, Janice M. Russell, Chris R. Ross, D. Neil Granger
Journal: Circulation Research (2001)

Abstract —Experimental animals placed on a high-cholesterol diet for 2 or more weeks exhibit an inflammatory response in postcapillary venules. The aims of this study were to determine (1) whether superoxide mediates the hypercholesterolemia-induced inflammatory response and (2) whether leukocyte and/or vessel wall NAD(P)H oxidase contributes to this response. Intravital videomicroscopy was used to quantify leukocyte–endothelial cell adhesion in cremasteric postcapillary venules of wild-type (WT) mice, CuZn-superoxide dismutase transgenic (SOD TgN) mice, and mice heterozygous (p47 phox +/−) or homozygous (p47 phox −/−) for NAD(P)H oxidase placed on either a normal diet or high-cholesterol diet (HCD) for 2 weeks. The number of adherent and emigrated leukocytes in postcapillary venules of WT HCD mice was significantly higher than that detected in venules of their normal-diet counterparts. However, the HCD-induced recruitment of adherent and emigrated leukocytes was not observed in SOD TgN mice. Whereas hypercholesterolemic p47 phox +/− and WT mice exhibited similar inflammatory responses, p47 phox −/− mice did not. Bone marrow chimeras were developed to selectively delete p47 phox from either the vessel wall or circulating leukocytes. Whereas WT marrow transplanted into WT mice produced a normal inflammatory response of venules to HCD, chimeric mice with p47 phox deficiency in either the vessel wall or leukocytes exhibited an attenuated inflammatory response to HCD that was comparable with that observed in p47 phox −/− HCD mice. Our findings indicate that enhanced superoxide production is a critical event that initiates the leukocyte–endothelial cell adhesion in postcapillary venules of HCD mice. NAD(P)H oxidase appears to be an important source of this superoxide.
Role of integrins, including ?8, for neointima formation after vascular injury
Authors: N UESUGI, N SAKATA
Journal: Cardiovascular Research (2005)

See article by Z. Zangham and G. Thibault  [15]  (pages 813–822) in this issue .

Restenosis secondary to intimal hyperplasia is a serious complication of percutaneous transluminal coronary angioplasty, which is caused by smooth muscle cell (SMC) migration and proliferation within the neointima of coronary arteries. The principle function of vascular SMCs (VMSCs) is to maintain vascular tone and resistance. Differentiated SMCs exhibit a contractile phenotype that is characterized by smooth muscle (SM)-specific contractile and cytoskeletal proteins [1]. The other important function of SMCs is related to the response to the repair of the blood vessel wall after vascular injury [1,2]. These responses require modulation of the SM phenotype and synthetic and migratory activities of SMCs, which necessitate an alteration of adhesion receptors that anchor cells to the extracellular matrix (ECM) during cell contraction [2]. Integrins are the principle receptors for the ECM and serve as a transmembrane linkage between the ECM and the actin cytoskeleton. Integrins are composed of α and β subunits. Each αβ combination has its own ligand binding specificity [3] and signalling properties [4]. Most integrins recognize several ECM proteins [5]. Conversely, individual matrix proteins, such as fibronectin, laminin, collagens, osteopontin, and vitronectin, bind to several integrins [5].

Normal VSMCs exhibit predominantly activated β1 integrin [6], and α1, α3, α5 … 

*Corresponding author. Tel.: +81 92 801 1011x3285; fax: +81 92 863 8383. Email address: nysakata{at}fukuoka-u.ac.jp
Prevalence and classification of rhinitis in preschool children in <scp>P</scp>ortugal: a nationwide study
Authors: M. Morais‐Almeida, N. Santos, A. M. Pereira, M. Branco‐Ferreira, C. Nunes, J. Bousquet, J. A. Fonseca
Journal: Allergy (2013)

Abstract Background Information on rhinitis epidemiology in preschool children is scarce. Objectives To estimate, in children with 3–5 years of age, current rhinitis prevalence, to describe rhinitis symptoms and associated sociodemographic characteristics, and to report allergic rhinitis and its impact on asthma ( ARIA ) classification. Methods Cross‐sectional, nationwide, population‐based study including children aged 3–5 years. A multistep selection strategy was used to obtain a representative sample. Data were collected at kindergartens and parish centers by face‐to‐face interview to caregivers, using an adapted ISAAC questionnaire. ‘Current rhinitis’ ( CR ) was defined as the presence of ≥1 rhinitis symptom (repeated sneezing and/or itchy nose, blocked nose for &gt;1 h, or runny nose without having a cold/flu) in the last year. Rhinitis lasting ≥4 days/week and ≥4 consecutive weeks was classified as persistent. Moderate–severe disease interfered ‘a moderate amount’ or ‘a lot’ in daily activities. Results Five thousand and eighteen children were included. CR prevalence was 43.4% [95% CI (42.0–44.8%); n = 2179] and that of physician‐diagnosed rhinitis was 11.7% [95% CI (10.8–12.6%); n = 588]. Of children with CR , 67% reported blocked nose, 48% rhinorrhea, and 46% sneezing/itchy nose. Considering ARIA classification, 30% of the population had mild intermittent, 3% mild persistent, 7% moderate–severe intermittent, and 3% moderate–severe persistent rhinitis. Children with CR had more current wheezing, physician‐diagnosed asthma, self‐reported food allergy, and family history of allergic disease. These characteristics were also associated with persistent and moderate–severe rhinitis. Conclusions This is the first nationwide population‐based study reporting rhinitis prevalence and ARIA classification in preschool children. In this age‐group, rhinitis is frequent and underdiagnosed. About 25% children with rhinitis presented moderate–severe disease.
Calcitonin and bone formation: a knockout full of surprises
Authors: Mone Zaidi, Baljit S. Moonga, Etsuko Abe
Journal: Journal of Clinical Investigation (2002)

See the related article beginning on page 1849.



Conflict of interest: Mone Zaidi is a speaker for Proctor and Gamble, Merck, Eli Lilly, and Novartis. Work in the laboratory is also supported by Proctor and Gamble.



Nonstandard abbreviations used: calcitonin (CT); calcitonin gene–related peptide (CGRP); parathyroid hormone (PTH).
Factors influencing asthma remission: a longitudinal study from childhood to middle age
Authors: J. A. Burgess, M. C. Matheson, L. C. Gurrin, G. B. Byrnes, K. S. Adams, C. L. Wharton, G. G. Giles, M. A. Jenkins, J. L. Hopper, M. J. Abramson, E. H. Walters, S. C. Dharmage
Journal: Thorax (2011)

<h3>Objective</h3> To examine asthma remission from childhood to middle age. <h3>Methods</h3> This was a population-based cohort study. In 1968 the Tasmanian Longitudinal Health Study enrolled 8583 7-year-old Tasmanian schoolchildren who were re-surveyed in 2004. Those reporting ever having asthma when last surveyed completed another questionnaire in 2007 ascertaining age at last asthma attack and asthma medication use. The main outcome measure was asthma remission, defined as no asthma attack for 2 years and no current asthma medication use, or no self-reported asthma in adult life but with parent-reported childhood asthma. <h3>Results</h3> Of 5729 respondents to the 2004 survey, 1238 self-reported asthma. A further 573 denied asthma, but had parent-reported childhood asthma, giving a study sample of 1811. Asthma had remitted in 1177 (65.0%) of whom 649 (55.1%) were male. Childhood (OR 0.38, 95% CI 0.25 to 0.58) and later-onset allergic rhinitis (0.42, 0.29 to 0.63), childhood (0.66, 0.47 to 0.94) and later-onset eczema (0.66, 0.47 to 0.92), maternal asthma (0.66, 0.47 to 0.92) and childhood chronic bronchitis (0.56, 0.41 to 0.76) were negatively associated with remission. There was weaker evidence for a negative association between passive smoking (0.75, 0.54 to 1.04) and lower socio-economic status (p-trend 0.09) and remission. Childhood-onset asthma (3.76, 2.58 to 5.49) was more likely to remit than adult-onset asthma. Adult smoking was positively associated with remission in childhood-onset asthma (1.49, 1.06 to 2.09). Sex did not influence remission. <h3>Conclusion</h3> While inherited factors cannot be changed, the effect of allergic rhinitis or eczema on asthma remission might be altered by early, aggressive treatment. Every effort should be made to lessen passive exposure to tobacco smoke.
Eczema-like lesions and disruption of therapy in patients treated with interferon-alfa and ribavirin for chronic hepatitis C: the value of an interdisciplinary assessment
Authors: F. Vazquez-Lopez, J.A. Manjon-Haces, R. Perez-Alvarez, N. Perez-Oliva
Journal: British Journal of Dermatology (2004)

Sir, ‘I would urge upon you in your own practice, to care more particularly for the individual patient than for the special features of the disease’ (William Osler). We read with interest the controversy in the BJD1, 2 regarding the premature withdrawal from therapy with interferon‐alfa and ribavirin in patients treated for chronic hepatitis C (CHC), due to eczema‐like lesions. In the study of Dereure et al.1 this combined treatment had to be interrupted in half of their patients presenting with diffuse eczema‐like lesions (10 of 20). On the other hand, Kerl et al.2 followed 52 patients undergoing combination treatment with peginterferon alfa and ribavirin, of whom 12 (23%) developed eczema‐like lesions but, in contrast to Dereure et al. none had to interrupt the antiviral treatment, as the lesions were well controlled with topical corticosteroids and emollients. We consider it to be of interest to add our experience to this controversy.3 We evaluated 210 patients with CHC undergoing a 1‐year treatment with recombinant interferon‐alfa 2b and ribavirin, between June 1998 and September 2000. Not taking into account local reactions to injections, we observed de novo skin lesions in 27 patients (13%). Among patients with skin lesions, 16 patients (59%) presented eczema‐like lesions, mostly localized on the legs, arms or trunk. Only two of them had generalized eczematous lesions with very severe pruritus. We also observed disseminated prurigo‐like lesions (four patients, 2%); lichenoid eruptions (two patients, 1%); seborrhoeic dermatitis (two patients, 1%); maculopapular exanthema (two patients, 1%) and herpes zoster (one patient, 0·5%).
Anticardiolipin antibodies: isotype distribution and phospholipid specificity.
Authors: A E Gharavi, E N Harris, R A Asherson, G R Hughes
Journal: Annals of the Rheumatic Diseases (1987)

Quantitative isotype specific enzyme linked immunosorbent assay (ELISA) was used to determine the distribution of immunoglobulin isotypes and phospholipid specificities of anticardiolipin (anti-CL) antibodies in 40 patients with one or more of the following 9antiphospholipid (anti-PL) antibody associated clinical complications9--namely, thrombosis, fetal loss, thrombocytopenia. Twelve of 40 patients had IgG, IgM, and IgA anti-CL antibodies. Ten patients had IgG and IgM, five patients had IgG and IgA, and three patients had IgM and IgA anti-CL antibodies. There was no statistical association between any single isotype or any group of isotypes with thrombosis, fetal loss, or thrombocytopenia. The presence of IgG anti-CL antibodies in 36 of the 40 patients suggests that this isotype may be most important in determining clinical complications, but there were four patients without IgG anti-CL antibodies who also appeared susceptible to thrombosis, fetal loss, and thrombocytopenia. IgG, IgM, and IgA anti-CL antibodies bound the negatively charged phospholipids, phosphatidylserine and phosphatidylinositol, but not the zwitterionic phospholipid, phosphatidylcholine. There was no significant difference between binding to cardiolipin and binding to other negatively charged phospholipids, suggesting that the specificity of these antibodies is for negatively charged phospholipids in general rather than for cardiolipin in particular.
Lack of Association Between Parental Alcohol or Drug Addiction and Behavioral Inhibition in Children
Authors: Joseph Biederman, Dina R. Hirshfeld-Becker, Jerrold F. Rosenbaum, Sarah G. Perenick, Julia Wood, Stephen V. Faraone
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2–6 years)—offspring of parents with panic and depressive disorders—who had been assessed for behavioral inhibition through laboratory-based observations. METHOD: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. RESULTS: Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. CONCLUSIONS: These results are not consistent with the hypothesis linking behavioral inhibition to addictions.
DNA Methylation and Environmental Exposures in Human Hepatocellular Carcinoma
Authors: L. Shen
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Hypermethylation of a CpG-rich promoter (CpG island) blocks expression of the corresponding gene. The CpG island methylator phenotype (CIMP), defined as a variable pattern of hypermethylation of CpG islands in tumor suppressor genes, may be associated with carcinogenesis. To determine whether CIMP is associated with the development of hepatocellular carcinoma (HCC) and with exposure to environmental agents, we examined the methylation status of CpG islands in HCCs from countries with various HCC risks. Methods: We examined the methylation status of 12 CpG islands (eight for known genes) in 85 HCC tumors from various geographic locations by use of bisulfite–polymerase chain reaction methylation assays and analyzed results with univariate and multivariable methods. All statistical tests were two-sided. Results: Eight CpG islands were hypermethylated. The frequency of hypermethylation in the 85 tumors was 62% for the estrogen receptor (ER), 42% for p16, 18% for cyclooxygenase-2, 21% for the T-type calcium channel gene, 38% for MINT31, 28% for MINT1, 15% for MINT27, and 11% for MINT2 (the latter four CpG islands are not yet associated with genes). Methylation levels of the eight frequently methylated CpG islands were positively correlated (from R = .2 [P = .05] to R = .6 [P<.001]), supporting the presence of CIMP. p16 methylation had statistically significant geographic variation (34.4% in tumors from China and Egypt versus 12.2% in tumors from the United States and Europe, difference = 22.2%; 95% confidence interval [CI] = 11.2% to 33.2%; P<.001). Similar geographic variations were observed for ER methylation and CIMP. This observation was partly related to higher methylation in tumors from patients with cirrhosis (33.6% for patients with cirrhosis versus 11.7% for those without it; difference = 21.9%; 95% CI = 10.9% to 32.8%; P<.001) or hepatitis (34.2% for patients with hepatitis versus 6.2% for those without it; difference = 28%; 95% CI = 18.3% to 37.6%; P<.001). Conclusion: Geographic variations in the methylation status of various CpG islands indicate that environmental factors may influence the frequent and concordant degree of hypermethylation in multiple genes in HCC tumors.
PROTEASES IN PARASITIC DISEASES
Authors: James H. McKerrow, Conor Caffrey, Ben Kelly, P'ng Loke, Mohammed Sajid
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Parasitic diseases represent major global health problems of immense proportion. Schistosomiasis, malaria, leishmaniasis, Chagas disease, and African sleeping sickness affect hundreds of millions of people worldwide, cause millions of deaths annually, and present an immense social and economic burden. Recent advances in genomic analysis of several of the major global parasites have revealed key factors involved in the pathogenesis of parasite diseases. Among the major virulence factors identified are parasite-derived proteases. This review focuses on the direct role of proteases in disease pathogenesis. Well-characterized examples of the roles proteases play in pathogenesis include their involvement in invasion of the host by parasite migration through tissue barriers, degradation of hemoglobin and other blood proteins, immune evasion, and activation of inflammation.