tbuckley/cabot-search huggingface dataset:
The first large population based twin study of coeliac disease
Authors: L Greco
Journal: Gut (2002)

Background and aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1–134), independent of the DQ at risk genotype. Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.
Randomized controlled trial of nettle sting for treatment of base-of-thumb pain
Authors: Colin Randall, Hester Randall, Frank Dobbs, Charles Hutton, Hilary Sanders
Journal: Journal of the Royal Society of Medicine (2000)

Summary There are numerous published references to use of nettle sting for arthritis pain but no randomized controlled trials have been reported. We conducted a randomized controlled double-blind crossover study in 27 patients with osteoarthritic pain at the base of the thumb or index finger. Patients applied stinging nettle leaf (Urtica dioica) daily for one week to the painful area. The effect of this treatment was compared with that of placebo, white deadnettle leaf (Lamium album), for one week after a five-week washout period. Observations of pain and disability were recorded for the twelve weeks of the study. After one week's treatment with nettle sting, score reductions on both visual analogue scale (pain) and health assessment questionnaire (disability) were significantly greater than with placebo (P=0.026 and P=0.0027).
Pharmacological manipulation of antituberculous therapies to improve treatment efficacy and compliance with ethionamide
Authors: N Stolagiewicz
Journal: Thorax (2009)

The global multidrug-resistant tuberculosis epidemic has prompted efforts to develop new antimycobacterial compounds and strategies to improve efficacy and compliance of drugs already in use. Several antituberculous compounds require in situ metabolic activation to become inhibitory to the mycobacterium. Ethionamide, a thiocarbamide-containing drug, is activated by the mycobacterial mono-oxygenase EthA. The production of EthA is inhibited …
A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24
Authors: Ellen L Goode, Georgia Chenevix-Trench, Honglin Song, Susan J Ramus, Maria Notaridou, Kate Lawrenson, Martin Widschwendter, Robert A Vierkant, Melissa C Larson, Susanne K Kjaer, Michael J Birrer, Andrew Berchuck, Joellen Schildkraut, Ian Tomlinson, Lambertus A Kiemeney, Linda S Cook, Jacek Gronwald, Montserrat Garcia-Closas, Martin E Gore, Ian Campbell, Alice S Whittemore, Rebecca Sutphen, Catherine Phelan, Hoda Anton-Culver, Celeste Leigh Pearce, Diether Lambrechts, Mary Anne Rossing, Jenny Chang-Claude, Kirsten B Moysich, Marc T Goodman, Thilo Dörk, Heli Nevanlinna, Roberta B Ness, Thorunn Rafnar, Claus Hogdall, Estrid Hogdall, Brooke L Fridley, Julie M Cunningham, Weiva Sieh, Valerie McGuire, Andrew K Godwin, Daniel W Cramer, Dena Hernandez, Douglas Levine, Karen Lu, Edwin S Iversen, Rachel T Palmieri, Richard Houlston, Anne M van Altena, Katja K H Aben, Leon F A G Massuger, Angela Brooks-Wilson, Linda E Kelemen, Nhu D Le, Anna Jakubowska, Jan Lubinski, Krzysztof Medrek, Anne Stafford, Douglas F Easton, Jonathan Tyrer, Kelly L Bolton, Patricia Harrington, Diana Eccles, Ann Chen, Ashley N Molina, Barbara N Davila, Hector Arango, Ya-Yu Tsai, Zhihua Chen, Harvey A Risch, John McLaughlin, Steven A Narod, Argyrios Ziogas, Wendy Brewster, Aleksandra Gentry-Maharaj, Usha Menon, Anna H Wu, Daniel O Stram, Malcolm C Pike, Jonathan Beesley, Penelope M Webb
Journal: Nature Genetics (2010)
Autophagy Proteins Promote Repair of Endosomal Membranes Damaged by the Salmonella Type Three Secretion System 1
Authors: Saskia Kreibich, Mario Emmenlauer, Jennifer Fredlund, Pauli Rämö, Christian Münz, Christoph Dehio, Jost Enninga, Wolf-Dietrich Hardt
Journal: Cell Host & Microbe (2015)

Salmonella Typhimurium (S.Tm) is an enteropathogen requiring multiple virulence factors, including two type three secretion systems (T1 and T2). T1 triggers epithelium invasion in which the bacteria are taken up into endosomes that mature into Salmonella-containing vacuoles (SCV) and trigger T2 induction upon acidification. Mechanisms controlling endosome membrane integrity or pathogen egress into the cytosol are incompletely understood. We screened for host factors affecting invasion and SCV maturation and identified a role for autophagy in sealing endosomal membranes damaged by T1 during host cell invasion. S.Tm-infected autophagy-deficient (atg5−/−) cells exhibit reduced SCV dye retention and lower T2 expression but no effects on steps preceding SCV maturation. However, in the absence of T1, autophagy is dispensable for T2 induction. These findings establish a role of autophagy at early stages of S.Tm infection and suggest that autophagy-mediated membrane repair might be generally important for invasive pathogens and endosomal membrane function.
Effects of Inhaled Nitric Oxide on Gas Exchange in Lungs with Shunt or Poorly Ventilated Areas
Authors: S. R. HOPKINS, E. C. JOHNSON, R. S. RICHARDSON, H. WAGNER, M. DE ROSA, P. D. WAGNER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator with beneficial effects on some lung diseases, yet conflicting results, particularly in chronic obstructive pulmonary disease, have been reported. We hypothesized that although inhaled NO would improve gas exchange in the presence of shunt (by increasing blood flow to normal areas), it could worsen gas exchange when areas of low ventilation-perfusion (V˙ a/Q˙) ratio were present since these areas could be preferentially vasodilated by NO. We examined how ∼ 80 ppm inhaled NO altered pulmonary gas exchange in anesthetized ventilated dogs with the following: (1) normal lungs (n = 8), (2) shunt (n = 9, 24.7% shunt) produced by complete obstruction of one lobar bronchus, and (3) V˙ a/Q˙ inequality (n = 8) created by partial obstruction of one lobar bronchus resulting in a bimodal V˙ a/Q˙ distribution with 13% perfusion of low V˙ a/Q˙ areas (0.005 < V˙ a/Q˙ < 0.1) without shunt. Inhaled No significantly reduced pulmonary arterial (p < 0.001) and wedge pressures (p < 0.01) and pulmonary vascular resistance (p < 0.01) without changing cardiac output in each group. In normal lungs, NO did not alter PaO2 or V˙ a/Q˙ inequality. However, with complete obstruction, shunt fell slightly (p < 0.001) with NO. In lungs with V˙ a/Q˙ inequality, NO variably affected V˙ a/Q˙ matching, which was improved in some dogs and worsened in others. In these lungs, changes in pulmonary vascular resistance of the abnormal area of the lung were negatively correlated with changes in V˙ a/Q˙ dispersion (logSDQ˙) (R = − 0.85, p < 0.01) and positively correlated with PaO2 (R = 0.79, p < 0.05). We conclude that NO has net effects on pulmonary gas exchange, depending on the underlying lung pathology consistent with competing vasodilatory effects on the normal and abnormal areas that receive the gas.
The protease inhibitor PI*S allele and COPD: a meta-analysis
Authors: M. Dahl, C. P. Hersh, N. P. Ly, C. S. Berkey, E. K. Silverman, B. G. Nordestgaard
Journal: European Respiratory Journal (2005)

In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24–8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02–1.38). However, PI MS genotype was not associated with COPD risk after correcting for smoking. Furthermore, mean forced expiratory volume in one second, a measure of airflow obstruction and a defining feature of COPD, did not differ between PI MS and PI MM individuals. There were not enough cases to summarise the risk of COPD in PI SS homozygotes. In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated.
Methodological Issues in Molecular Genetic Studies of Mental Disorders
Authors: Carrie E. Bearden, Anna J. Jasinska, Nelson B. Freimer
Journal: Annual Review of Clinical Psychology (2009)

The development of methodologies for assaying genetic variation at high resolution throughout the genome has revolutionized the search for susceptibility genes for common diseases. This search, however, has been less successful in psychiatry than in other areas of medicine. It is hypothesized that the imprecision and uncertain validity of psychiatric diagnoses are major factors in this disappointing progress. Here we discuss the methodologies employed for genetic investigation of mental disorders, including phenotyping strategies, approaches to genetic mapping, and use of animal models of psychopathology.
Endogenous factors involved in regulation of tone of arterial vasa vasorum: implications for conduit vessel physiology
Authors: R Scotland
Journal: Cardiovascular Research (2000)

The walls of conduit blood vessels are nourished by diffusion of oxygen from luminal blood and from the vasa vasorum. The vasa vasorum, or 'vessels of a vessel', form a network of microvessels that lie in the adventitia and penetrate the outer media of the host vessel wall. Although the importance of the vasa vasorum in providing nutritional support is not well defined, obstruction of blood flow through these vessels has been implicated in the pathogenesis of certain cardiovascular diseases including atherosclerosis. This review focuses on the mechanisms that regulate tone in the vasa vasorum of large arteries and the functional implications of changes in reactivity of vasa vasorum.
Control of breathing in children with mild sleep apnoea: a 6-year follow-up study
Authors: A. Rice, S. Costy-Bennett, J. L. Goodwin, S. F. Quan, R. F. Fregosi
Journal: European Respiratory Journal (2009)

We have previously shown that children (average age 9 yrs) with mildly elevated obstructive apnoea/hypopnoea indices (OAHI) retained CO 2 at rest. Here, we report the results of a 6-yr follow-up study on 14 children from that study. Minute ventilation ( V ′ E ) and end-tidal CO 2 partial pressure ( P ET,CO 2 ) were measured during hypercapnic challenge. OAHI decreased from 7.5±4.7 events·h −1 at age 9 yrs to 2.5±1.8 events·h −1 at age 15 yrs (p&lt;0.001), despite an increase in body mass index from 20±4.6 kg·m −2 to 26±5.7 kg·m −2 (p&lt;0.0001). Eupneic V ′ E increased from 4.1±0.31 L·min −1 ·m −2 to 5.9±0.4 L·min −1 ·m −2 (p&lt;0.01), while P ET,CO 2 fell from 44.1±0.8 to 33±1.0 mmHg (p&lt;0.001). The V ′ E – P ET,CO 2 obtained during hypercapnia was left shifted, such that V ′ E at a P ET,CO 2 of 50 mmHg increased from 24 L·min −1 at age 9 yrs to 36 L·min −1 at age 15 yrs. Central respiratory drive did not change. We hypothesise that somatic growth of the pharynx coupled with a regression of tonsillar tissue mass with age leads to enlargement of the upper airway lumen, a reduction in airway resistance and increased respiratory airflow at a given level of ventilatory drive.
P516Diastolic dysfunction in diabetic mice revealed by MRI
Authors: G Buonincontri, C-H Hu, SJ Sawiak, T Krieg
Journal: Cardiovascular Research (2014)

Purpose: Left ventricular diastolic dysfunction (LVDD) in diabetes is associated with high risk of heart failure [1]. New pharmaceutical strategies are being developed targeting LVDD in diabetes, but direct observation of their effect in mouse models is challenging [2]. In this study we used magnetic resonance imaging (MRI) to evaluate diastolic function in a streptozotocin-induced mouse model of diabetes. Methods: Diabetes was induced in five male mice (C57/Bl6) with 100 mg/kg i.p. streptozotocin daily for three successive days and five control mice were injected with saline. Confirmation of disease onset was made at four weeks with blood sugar measurements and mice had free access to food and water throughout. MRI was performed at four weeks and eight weeks from the start of the experiment using a Bruker BioSpec 47/40 system at 4.7T. For evaluation of systolic function, standard respiratory and ECG-gated acquisitions were performed on the whole heart in the short axis. To evaluate diastolic function, a single mid-ventricular short-axis slice was acquired with a flow-compensated gradient-echo sequence. We defined end-systolic and end-diastolic areas (ESA, EDA) as the smallest and largest areas of the slice respectively. The slice area measured at the time point occurring at 30% between end-systole and end-diastole (labelled d) was used to calculate a ‘diastolic index’ following [3]: (EDA-d)/(EDA-ESA). Results: Blood measurements confirmed the onset of diabetes in four out of five induced mice. Systolic function was preserved in all mice both at four and at eight weeks after induction (left ventricular ejection fraction LVEF > 57% in all tested subjects). The diastolic index was lower at four weeks in the diabetic animals (diabetic: 22 ± 6 %; controls: 51 ± 3 %) and this did not change at eight weeks (diabetic: 27 ± 7 %; controls 54 ± 3 %). Conclusions: We have shown that LVDD was present in mice four weeks after induction of diabetes and that it persisted at eight weeks, although systolic function was preserved. The data support the use of the LVDD MRI measurement for establishing diastolic dysfunction in mouse hearts.
Comprehensive Cardiac Magnetic Resonance Imaging and Spectroscopy Reveal a High Burden of Myocardial Disease in HIV Patients
Authors: Cameron J. Holloway, Ntobeko Ntusi, Joseph Suttie, Masliza Mahmod, Emma Wainwright, Genevieve Clutton, Gemma Hancock, Philip Beak, Abdelouahid Tajar, Stefan K. Piechnik, Jurgen E. Schneider, Brian Angus, Kieran Clarke, Lucy Dorrell, Stefan Neubauer
Journal: Circulation (2013)

Background— HIV infection continues to be endemic worldwide. Although treatments are successful, it remains controversial whether patients receiving optimal therapy have structural, functional, or biochemical cardiac abnormalities that may underlie their increased cardiac morbidity and mortality. The purpose of this study was to characterize myocardial abnormalities in a contemporary group of HIV-infected individuals undergoing combination antiretroviral therapy. Methods and Results— Volunteers with HIV who were undergoing combination antiretroviral therapy and age-matched control subjects without a history of cardiovascular disease underwent cardiac magnetic resonance imaging and spectroscopy for the determination of cardiac function, myocardial fibrosis, and myocardial lipid content. A total of 129 participants were included in this analysis. Compared with age-matched control subjects (n=39; 30.23%), HIV-infected subjects undergoing combination antiretroviral therapy (n=90; 69.77%) had 47% higher median myocardial lipid levels ( P &lt;0.003) and 74% higher median plasma triglyceride levels (both P &lt;0.001). Myocardial fibrosis, predominantly in the basal inferolateral wall of the left ventricle, was observed in 76% of HIV-infected subjects compared with 13% of control subjects ( P &lt;0.001). Peak myocardial systolic and diastolic longitudinal strain were also lower in HIV-infected individuals than in control subjects and remained statistically significant after adjustment for available confounders. Conclusions— Comprehensive cardiac imaging revealed cardiac steatosis, alterations in cardiac function, and a high prevalence of myocardial fibrosis in a contemporary group of asymptomatic HIV-infected subjects undergoing combination antiretroviral therapy. Cardiac steatosis and fibrosis may underlie cardiac dysfunction and increased cardiovascular morbidity and mortality in subjects with HIV.
Myocardial sulfhydryl pool alterations occur during reperfusion after brief and prolonged myocardial ischemia in vivo.
Authors: E J Lesnefsky, I M Dauber, L D Horwitz
Journal: Circulation Research (1991)

Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione (GSH), are both defenses against and potential markers of reactive oxygen metabolite injury during ischemia and reperfusion. We examined the alterations in GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed to brief (15 minutes, n = 7) or prolonged (90 minutes, n = 6) regional ischemia caused by occlusion of the left anterior descending artery. Ninety minutes of ischemia followed by 5 hours of reperfusion, which resulted in myocardial necrosis of 43.9 +/- 4.0% of the area at risk, caused a 22% reduction in total myocardial SH groups (p less than 0.01), a 57% decrease in nonprotein myocardial SH groups (p less than 0.01), a 56% decrease in GSH (p less than 0.01), and a 62% decrease in non-GSH, nonprotein SH groups (p less than 0.02). However, protein SH groups were not significantly reduced (12% decrease, p = NS). Also, myocardial release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent occurred during early reperfusion. In contrast, 15 minutes of ischemia, followed by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein SH groups, or GSH (9% decrease, p = NS); nor was there reperfusion release of GSH or GSSG. However, even with brief ischemia, nonprotein SH groups decreased 23% (p less than 0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool (p less than 0.05). These changes after brief ischemia occurred without alterations in myocardial GSSG or the GSH/GSSG ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Three-Tesla Magnetic Resonance–Guided Prostate Biopsy in Men With Increased Prostate-Specific Antigen and Repeated, Negative, Random, Systematic, Transrectal Ultrasound Biopsies: Detection of Clinically Significant Prostate Cancers
Authors: Caroline M.A. Hoeks, Martijn G. Schouten, Joyce G.R. Bomers, Stefan P. Hoogendoorn, Christina A. Hulsbergen-van de Kaa, Thomas Hambrock, Henk Vergunst, J.P. Michiel Sedelaar, Jurgen J. Fütterer, Jelle O. Barentsz
Journal: European Urology (2012)
One-stop-shop tumor imaging: buy hypoxia, get lactate free
Authors: Ashley A. Manzoor, Thies Schroeder, Mark W. Dewhirst
Journal: Journal of Clinical Investigation (2008)

The ability to noninvasively assess physiological changes in solid tumors is desired for its diagnostic and therapeutic potential. In this issue of JCI, Matsumoto and colleagues reveal their development and use of a novel imaging approach, combining pulsed electron paramagnetic resonance imaging (EPRI) with conventional MRI to image squamous cell carcinoma tumor-bearing mice (See the related article beginning on page 1965). This method provides coregistered images of oxygenation and blood volume/flow with the underlying anatomy and concentrations of metabolites such as lactate and choline. This technique, combining functional and anatomic imaging, shows immediate preclinical applicability in monitoring factors that control tumor hypoxia and metabolism and may have future clinical potential for monitoring tumor response to treatment.
ADHESION MOLECULES AND INHERITED DISEASES OF THE HUMAN NERVOUS SYSTEM
Authors: H. Kamiguchi, M. L. Hlavin, M. Yamasaki, V. Lemmon
Journal: Annual Review of Neuroscience (1998)

▪ Abstract Mutations in the human genes for the adhesion molecules Po, L1, and merosin cause severe abnormalities in nervous system development. Po and merosin are required for normal myelination in the nervous system, and L1 is essential for development of major axon pathways such as the corticospinal tract and corpus callosum. While mutations that lead to a loss of the adhesive function of these molecules produce severe phenotypes, mutations that disrupt intracellular signals or intracellular interactions are also deleterious. Geneticists have found that more than one clinical syndrome can be caused by mutations in each of these adhesion molecules, confirming that these proteins are multifunctional. This review focuses on identifying common mechanisms by which mutations in adhesion molecules alter neural development.
HALLUCINATION AND IMAGERY INDUCED BY MESCALINE
Authors: THOMAS THALE, BEVERLY WESCOTT GABRIO, KURT SALOMON
Journal: American Journal of Psychiatry (1950)

Mescaline produces altered visual experiences of several types, whose vividness and degree of distortion is proportionate to the size of the dose. There are no sharp boundaries dividing abnormal sensibility, illusions, and hallucinations. Subjects who gave fewer responses of the type "I see it" when asked to imagine situations were more likely to hallucinate than other patients. Visual responses declined still further after administration of mescaline in a degree more closely related to the amount of drug given than to the vividness of hallucinatory alterations, even in those experimental subjects who reported virtually no alteration in actual vision. The fall in reported visual imagery was not found in control subjects.
Characterization of an immunodominant Onchocerca volvulus antigen with patient sera and a monoclonal antibody.
Authors: R Lucius, H Schulz-Key, D W Büttner, A Kern, B Kaltmann, J Prod'hon, F Seeber, R D Walter, K C Saxena, H J Diesfeld
Journal: The Journal of Experimental Medicine (1988)

Adult Onchocerca voluvlus and infective larvae, but not microfilariae contain an immunodominant antigen (33,000 and 21,000 Mr in females, 39,000, 33,000, and 21,000 Mr in males, 133,000 Mr in infective larvae) which is recognized by an Onchocerca-specific mAb. The component is part of the reproductive organs and muscles. 96.2% of onchocerciasis sera contained antibodies detectable by immunoblotting against it. Antigen purified by immunoaffinity chromatography was specifically recognized in immunoblots by onchocerciasis sera, but not by sera from other filarial infections. The high immunogenicity, the specificity, and the occurrence in infective larvae of this antigen indicate an immunodiagnostic potential and a possible role in the immunobiology of the parasite.
The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores
Authors: Rafael A Irizarry, Christine Ladd-Acosta, Bo Wen, Zhijin Wu, Carolina Montano, Patrick Onyango, Hengmi Cui, Kevin Gabo, Michael Rongione, Maree Webster, Hong Ji, James B Potash, Sarven Sabunciyan, Andrew P Feinberg
Journal: Nature Genetics (2009)