tbuckley/cabot-search huggingface dataset:
Influence of the ACE Gene Insertion/Deletion Polymorphism on Insulin Sensitivity and Impaired Glucose Tolerance in Healthy Subjects
Authors: Fabrice Bonnet, Sheila Patel, Martine Laville, Beverley Balkau, Angela Favuzzi, Lucilla D. Monti, Nebojsa Lalic, Mark Walker
Journal: Diabetes Care (2008)

Recent studies suggested that the blockade of the renin-angiotensin system (RAS) may be associated with metabolic benefits. However, data about the potential influence of the ACE insertion/deletion (I/D) genotype on insulin resistance have been contradictory with studies of limited sample sizes. The purpose of this study was to investigate the relationship between the ACE gene I/D polymorphism and both insulin sensitivity and glucose intolerance in a large cohort of healthy subjects.A total of 1,286 participants in the Relationship Between Insulin Sensitivity and Cardiovascular Disease Risk Study had a 75-g oral glucose tolerance test and a hyperinsulinemic-euglycemic clamp to assess whole-body insulin sensitivity.Age, BMI, waist, fat-free mass (ffm), and physical activity did not differ by ACE genotype. Fasting glucose and insulin were similar among genotypes, but 2-h glucose levels were higher in DD than in ID and II subjects (DD: 5.9 +/- 1.7; ID: 5.7 +/- 1.5; II: 5.6 +/- 1.5 mmol/l) (P = 0.004). Participants with the DD genotype were more likely to have impaired glucose tolerance than those with the ID and II genotypes (13.1 vs. 8.7%; P = 0.02). Insulin sensitivity was lower in participants with the DD genotype than in those with the II genotype (136 +/- 63 vs. 147 +/- 65 micromol x min(-1)x kg ffm(-1) x mmol(-1) x l(-1); P = 0.02). The presence of the D allele was associated with a trend, albeit not significant, for reduced insulin secretion during the oral glucose tolerance test (P = 0.07).The ACE I/D polymorphism is associated with whole-body insulin sensitivity and with impaired glucose tolerance in our healthy population. These findings confirm potential interactions between the RAS and glucose metabolism.
Augmented arginine uptake, through modulation of cationic amino acid transporter-1, increases GFR in diabetic rats
Authors: Idit F. Schwartz, Adrian Iaina, Yishayahu Benedict, Yoram Wollman, Tamara Chernichovski, Eli Brasowski, Faina Misonzhnik, Amir Ben-Dor, Miriam Blum, Yoram Levo, Doron Schwartz
Journal: Kidney International (2004)
Impaired delayed hypersensitivity in juvenile rheumatoid arthritis.
Authors: H M Hoyeraal
Journal: Annals of the Rheumatic Diseases (1973)

Juvenile rheumatoid arthritis (JRA) is thought by many to be a different disease from rheumatoid arthritis in adults (RA), partly because of the infrequency of pathological serological phenomena (Calabro, 1966).Recent investigations have, however, shown that antigammaglobulin and antinuclear anti- bodies are often found in sera from patients with JRA (KAss and Munthe, 1969; Torrigiani, Ansell, Chown, and Roitt, 1969; Zutshi, Ansell, Bywaters, Epstein, Holborow, and Reading, 1969; Bianco, Panush, Stillman, and Schur, 1971).It is unknown whether these autoantibodies result from an abnormal antigen stimulation in a normal immunological apparatus or from a normal antigen stimulation in an abnormal immunological apparatus.Scant information is available regarding the possible alteration of cellular immune reactions in patients with JRA (Panush, Bianco, Schur, Rocklin, David, and Stillman, 1972).The purpose of this investigation was to study the immunological apparatus in patients with JRA.The present report describes the results of testing of delayed hypersensitivity in a group of patients, com- pared with the results obtained in age-and sex- matched controls. Materials and methods PATIENTS AND CONTROLSTesting was performed in 34 patients with JRA at the Oslo Sanitetsforening's Hospital for Rheumatic Diseases, Oslo, Norway, and in 34 age-and sex-matched healthy non-hospitalized children during the period September, 1971, to February, 1972.In both groups the mean age was 9 1 yrs (range 2 to 16).The age difference in each patient and matched control pair was less than 1 year.The ratio of the number of females to the number of males was 1 8.The diagnosis ofJRA was based on the criteria of Ansell and Bywaters (1969). 56per cent of the patients had the polyarticular, 29 per cent.monarticular, and 15 per cent.acute febrile disease type according to the criteria of Cala- bro and Marchesano (1968).22 patients were classified as active and twelve as inactive according to the criteria of Ansell and Bywaters (1959).The majority of the patients was classified as belonging to anatomical stage II and func- tional class II (Steinbrocker, Traeger, and Batterman,
Music to be born to, music to die to
Authors: J. Anderson, M. Baum, L. A Bero, I. Chalmers, S. Chapman, I. J Deary, S. Ebrahim, M. Evans, M. Farrell, D. Greaves, I. Higginson, J. Hippisley-Cox, B. James, H. McKenzie, A. C Macaulay, M. Rabow, R. L Smyth, G. Stores, L. Wolpert
Journal: BMJ (2000)

An outbreak of hepatitis-associated-antigen-(HB Ag)-positive hepatitis in a hospital unit for the care of male patients with pulmonary tuberculosis is described. Sixty-four patients were studied of whom 37 were HB Ag positive. Hepatitis developed in at least 20 and was icteric in 11. The illness was mild, without fatality due to hepatitis and persistent jaundice did not occur. A carrier state developed in 15 of 24 HB Ag-positive patients followed up for more than six months and was unrelated to the presence or absence of initial hepatitis. Spread of HB Ag to domestic and medical staff occurred and following the discharge of the patients, household contacts became positive. Five, all wives of patients, developed jaundice. Faeces and sputum were HB Ag negative in seropositive cases. The origin of the outbreak remains undetected. The probability of non-parenteral transmission of HB Ag in this outbreak is discussed. Closure of the unit, isolation of HB Ag-positive cases with separate toilet and kitchen facilities, and discharge of patients when their respiratory condition allowed, resulted in prevention of further spread and eventually all patients were discharged from the unit.
Functional Analysis of the Contribution of RhoA and RhoC GTPases to Invasive Breast Carcinoma
Authors: Kaylene J. Simpson, Aisling S. Dugan, Arthur M. Mercurio
Journal: Cancer Research (2004)

Abstract Although the RhoA and RhoC proteins comprise an important subset of the Rho GTPase family that have been implicated in invasive breast carcinomas, attributing specific functions to these individual members has been difficult. We have used a stable retroviral RNA interference approach to generate invasive breast carcinoma cells (SUM-159 cells) that lack either RhoA or RhoC expression. Analysis of these cells enabled us to deduce that RhoA impedes and RhoC stimulates invasion. Unexpectedly, this analysis also revealed a compensatory relationship between RhoA and RhoC at the level of both their expression and activation, and a reciprocal relationship between RhoA and Rac1 activation.
Participatory Surveillance of Hypoglycemia and Harms in an Online Social Network
Authors: Elissa R. Weitzman, Skyler Kelemen, Maryanne Quinn, Emma M. Eggleston, Kenneth D. Mandl
Journal: JAMA Internal Medicine (2013)

Surveillance systems for elucidating the burden of hypoglycemia are limited.To quantify experiences of hypoglycemia and related harms, members of an international online diabetes social network with insulin-dependent diabetes mellitus were polled through a software application ("app"). Aggregate results were returned to participants through network channels.The study period was from March 2011 through April 2012, during which time retrospective reports about experiences with hypoglycemia and related harms were collected from participants using the app.The study was undertaken within the TuDiabetes.org international online diabetes social network.Eligibility criteria included TuDiabetes membership, age 13 years or older, a self-reported diagnosis of diabetes mellitus, ability to read and write English, and Internet access. Of 2827 app users, 687 (response rate, 24.3%) opted in to the volunteer sample.Primary outcomes included the following: frequency of "going low" (having a low glucose value in the past 2 weeks) and episodes of severe hypoglycemia (in the past 12 months), and, for respondents reporting recent and/or severe hypoglycemia, lifetime experience of vehicle crashes or severe medical injury, daily debilitating worry, and withdrawal from driving, exercise, sex, and going outside of the home to avoid hypoglycemia and consequences. Secondary outcomes included measures of research engagement.Of 613 respondents (24.3% of app users), 49.1% reported more than 4 episodes of "going low" in the past 2 weeks and 29.2% reported 1 or more severe low in the past year; 16.6% reported both more than 4 recent low episodes and 1 or more severe event in the past year. Harms were common, including daily debilitating worry (45.8%), vehicle crash or injury (15.0%), and withdrawal from exercise, driving, leaving home, and having sex (54.0%, 37.4%, 24.8%, and 22.7%, respectively). Of all respondents, 54.2% reported multiple harms, the risks for which were highest (73.7%) among respondents with a past-year severe event (odds ratio, 2.39; 95% CI, 1.60-3.58; P < .001 controlling for frequent recent low episodes and demographic and disease factors). Engagement was high, with 96.6% of the sample permitting recontact for research and 31.7% posting personal study data on their app profile page; 40.5% of 2825 unique page views of research-related materials published on the community site involved views of returned research results.Participatory surveillance of hypoglycemia in an online diabetes social network enables characterization of patient-centered harms in a community sample and bidirectional communication with affected persons, augmenting traditional surveillance.
<i>LIN28B</i> Polymorphisms Influence Susceptibility to Epithelial Ovarian Cancer
Authors: Jennifer Permuth-Wey, Donghwa Kim, Ya-Yu Tsai, Hui-Yi Lin, Y. Ann Chen, Jill Barnholtz-Sloan, Michael J. Birrer, Gregory Bloom, Stephen J. Chanock, Zhihua Chen, Daniel W. Cramer, Julie M. Cunningham, Getachew Dagne, Judith Ebbert-Syfrett, David Fenstermacher, Brooke L. Fridley, Montserrat Garcia-Closas, Simon A. Gayther, William Ge, Aleksandra Gentry-Maharaj, Jesus Gonzalez-Bosquet, Ellen L. Goode, Edwin Iversen, Heather Jim, William Kong, John McLaughlin, Usha Menon, Alvaro N.A. Monteiro, Steven A. Narod, Paul D.P. Pharoah, Catherine M. Phelan, Xiaotao Qu, Susan J. Ramus, Harvey Risch, Joellen M. Schildkraut, Honglin Song, Heather Stockwell, Rebecca Sutphen, Kathryn L. Terry, Jonathan Tyrer, Robert A. Vierkant, Nicolas Wentzensen, Johnathan M. Lancaster, Jin Q. Cheng, Thomas A. Sellers
Journal: Cancer Research (2011)

Defective microRNA (miRNA) biogenesis contributes to the development and progression of epithelial ovarian cancer (EOC). In this study, we examined the hypothesis that single nucleotide polymorphisms (SNP) in miRNA biogenesis genes may influence EOC risk. In an initial investigation, 318 SNPs in 18 genes were evaluated among 1,815 EOC cases and 1,900 controls, followed up by a replicative joint meta-analysis of data from an additional 2,172 cases and 3,052 controls. Of 23 SNPs from 9 genes associated with risk (empirical P < 0.05) in the initial investigation, the meta-analysis replicated 6 SNPs from the DROSHA, FMR1, LIN28, and LIN28B genes, including rs12194974 (G>A), an SNP in a putative transcription factor binding site in the LIN28B promoter region (summary OR = 0.90, 95% CI: 0.82-0.98; P = 0.015) which has been recently implicated in age of menarche and other phenotypes. Consistent with reports that LIN28B overexpression in EOC contributes to tumorigenesis by repressing tumor suppressor let-7 expression, we provide data from luciferase reporter assays and quantitative RT-PCR to suggest that the inverse association among rs12194974 A allele carriers may be because of reduced LIN28B expression. Our findings suggest that variants in LIN28B and possibly other miRNA biogenesis genes may influence EOC susceptibility.
Plasma Epstein-Barr Virus (EBV) DNA Is a Biomarker for EBV-Positive Hodgkin's Lymphoma
Authors: Maher K. Gandhi, Eleanore Lambley, Jacqueline Burrows, Ujjwal Dua, Suzanne Elliott, Peter J. Shaw, H. Miles Prince, Max Wolf, Kerrie Clarke, Craig Underhill, Tony Mills, Peter Mollee, Devinder Gill, Paula Marlton, John F. Seymour, Rajiv Khanna
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity. Experimental Design: Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed. Results: EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated. Conclusions: We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.
Loss of epidermal integrity by T cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy-1+ epidermal cell numbers.
Authors: T Shiohara, N Moriya, C Gotoh, J Hayakawa, M Nagashima, K Saizawa, H Ishikawa
Journal: The Journal of Experimental Medicine (1990)

The cutaneous graft-versus-host disease (GVHD) lesions induced by intradermal injection of cloned autoreactive T cells have been shown to subside rapidly and the epidermis returns to normal 2 wk after injection. Those mice that had spontaneously recovered from the cutaneous GVHD became resistant to subsequent attempts to induce the cutaneous GVHD by the T cells while maintaining their activity to mount delayed-type hypersensitivity (DTH) responses and to induce the enlargement of the popliteal lymph nodes (PLN). The resistance appeared to be restricted to the epidermal structures of the injection sites, suggesting the involvement of locally acting suppression mechanisms. This local resistance was not specific for the clonotype used for the induction of the resistance. A loss of the epidermal integrity by an attack of T cells capable of producing cutaneous GVHD was a prerequisite for the induction of the resistance. By up to at least 8 mo after injection of the T cells, no mice became susceptible to the cutaneous GVHD again, provided that the T cells were injected into the same footpad sites that had initially received the T cells. This resistance correlated well with the great increase (20-30-fold) in Thy-1+ EC number. The great increase in the number of Thy-1+ EC following destruction of epidermal structures may be important in protecting the epidermal integrity from an additional attack by T cells.
Crocidolite as a Cause Of Mesothelioma
Authors: Robert T. P. de Treville
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Regarding our "Asbestos Bodies and Their Bioeffects" (<b>203</b>:1142, 1968) in which we said that types of asbestos other than crocidolite have been almost com-that crocidolite was almost completely ineffective as a cause of mesothelioma, further information qualifying the relative abilities of crocidolite and other forms of asbestos to produce mesotheliomas has come to hand. According to J. F. Knox (personal communication, March 1968) the Ministry of Labour in Great Britain uses a phrase which is considered preferable to our statement and is offered herewith: [while]... the Advisory Panel considers that the evidence to date on balance indicates a particular significance must be given to crocidolite as a cause of mesotheliomas... it cannot be concluded that only this type of fibre (crocidolite) is concerned with these tumours. In this regard also, Sluis-Cremer reports a high incidence of mesothelioma in one crocidolite mining area of South Africa (Cape
Barrier responses of human bronchial epithelial cells to grass pollen exposure
Authors: Cornelia Blume, Emily J. Swindle, Patrick Dennison, Nivenka P. Jayasekera, Sarah Dudley, Phillip Monk, Heidrun Behrendt, Carsten B. Schmidt-Weber, Stephen T. Holgate, Peter H. Howarth, Claudia Traidl-Hoffmann, Donna E. Davies
Journal: European Respiratory Journal (2012)

The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells. Following exposure to Timothy grass ( Phleum pratense ) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release via a post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3α, CCL22/monocyte-derived chemokine and tumour necrosis factor-α was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-γ-induced protein-10 were reduced in nonasthmatic cultures. The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma.
Re: Adaptive Therapy for Androgen-Independent Prostate Cancer: A Randomized Selection Trial of Four Regimens
Authors: A. J. Armstrong, E. L. Garrett-Mayer, M. Eisenberger
Journal: JNCI Journal of the National Cancer Institute (2008)

We commend Thall et al. ( 1 ) for their report on a four-arm crossover randomized phase II study of complex multiagent chemotherapy regimens in men with castration-resistant prostate cancer.The sequentially randomized design proposed by Thall et al. ( 1) is an attractive method that may enhance our ability to select a potentially active new regimen that deserves further testing.Indeed, they show that this design is feasible.This study was conducted before the US Food and Drug Administration approval of docetaxel and prednisone, which demonstrated improved overall survival and palliative ability in this population ( 2 ).Combination chemotherapy regimens in prostate cancer, which have been studied for many years, culminated in the Southwest Oncology 99-16 randomized phase III trial,
Early and specific antibody response to OspA in Lyme Disease.
Authors: S E Schutzer, P K Coyle, J J Dunn, B J Luft, M Brunner
Journal: Journal of Clinical Investigation (1994)

Borrelia burgdorferi (Bb), the cause of Lyme disease, has appeared not to evoke a detectable specific antibody response in humans until long after infection. This delayed response has been a biologic puzzle and has hampered early diagnosis. Antibody to the abundant organism-specific outer surface proteins, such as the 31-kD OspA, has rarely been detected less than 6 mo after infection. Antibody to a less organism-specific 41-kD flagellin protein, sharing common determinants with other bacteria and thus limiting its diagnostic potential, may appear after 4 to 6 wks. To investigate our hypothesis that specific antibody to OspA may actually be formed early but remain at low levels or bound in immune complexes, we analyzed serum samples from patients with concurrent erythema migrans (EM). This is the earliest sign of Lyme disease and occurs in 60-70% of patients, generally 4-14 d after infection. We used less conventional but more sensitive methods: biotin-avidin Western blots and immune complex dissociation techniques. Antibody specificity was confirmed with recombinant OspA. Specific complexed antibody to whole Bb and recombinant OspA was detected in 10 of 11 of the EM patients compared to 0 of 20 endemic area controls. IgM was the predominant isotype to OspA in these EM patients. Free IgM to OspA was found in half the EM cases. IgM to OspA was also detected in 10 of 10 European patients with EM who also had reactive T cells to recombinant OspA. In conclusion a specific antibody response to OspA occurs early in Lyme disease. This is likely to have diagnostic implications.
An FHL1-containing complex within the cardiomyocyte sarcomere mediates hypertrophic biomechanical stress responses in mice
Authors: Farah Sheikh, Anna Raskin, Pao-Hsien Chu, Stephan Lange, Andrea A. Domenighetti, Ming Zheng, Xingqun Liang, Tong Zhang, Toshitaka Yajima, Yusu Gu, Nancy D. Dalton, Sushil K. Mahata, Gerald W. Dorn, Joan Heller-Brown, Kirk L. Peterson, Jeffrey H. Omens, Andrew D. McCulloch, Ju Chen
Journal: Journal of Clinical Investigation (2008)

The response of cardiomyocytes to biomechanical stress can determine the pathophysiology of hypertrophic cardiac disease, and targeting the pathways regulating these responses is a therapeutic goal. However, little is known about how biomechanical stress is sensed by the cardiomyocyte sarcomere to transduce intracellular hypertrophic signals or how the dysfunction of these pathways may lead to disease. Here, we found that four-and-a-half LIM domains 1 (FHL1) is part of a complex within the cardiomyocyte sarcomere that senses the biomechanical stress–induced responses important for cardiac hypertrophy. Mice lacking Fhl1 displayed a blunted hypertrophic response and a beneficial functional response to pressure overload induced by transverse aortic constriction. A link to the Gαq (Gq) signaling pathway was also observed, as Fhl1 deficiency prevented the cardiomyopathy observed in Gq transgenic mice. Mechanistic studies demonstrated that FHL1 plays an important role in the mechanism of pathological hypertrophy by sensing biomechanical stress responses via the N2B stretch sensor domain of titin and initiating changes in the titin- and MAPK-mediated responses important for sarcomere extensibility and intracellular signaling. These studies shed light on the physiological regulation of the sarcomere in response to hypertrophic stress.