tbuckley/cabot-search huggingface dataset:
Serum bilirubin levels on ICU admission are associated with ARDS development and mortality in sepsis
Authors: R Zhai, C C Sheu, L Su, M N Gong, P Tejera, F Chen, Z Wang, M P Convery, B T Thompson, D C Christiani
Journal: Thorax (2009)

Hyperbilirubinaemia is a common complication of sepsis. Elevated bilirubin may induce inflammation and apoptosis. It was hypothesised that increased serum bilirubin on Intensive Care Unit (ICU) admission contributes to sepsis-related acute respiratory distress syndrome (ARDS).Serum bilirubin on ICU admission was measured in 1006 patients with sepsis. Serial serum bilirubin was analysed prospectively in patients with sepsis who had ARDS for a period of 28 days. The effects of clinical factors and variants of the UGT1A1 gene on serum bilirubin levels were determined. Outcomes were ARDS risk and mortality.During 60-day follow-up, 326 patients with sepsis developed ARDS, of whom 144 died from ARDS. The hyperbilirubinaemia (>or=2.0 mg/dl) rate in patients with ARDS (22.4%) was higher than in those without ARDS (14.1%, p = 0.002). For each 1.0 mg/dl increase in admission bilirubin, ARDS risk and 28- and 60-day ARDS mortalities were increased by 7% (OR = 1.07; p = 0.003), 20% (OR = 1.20; p = 0.002) and 18% (OR = 1.18; p = 0.004), respectively. Compared with subjects with bilirubin levels <2.0 mg/dl, patients with hyperbilirubinaemia had higher risks of ARDS (OR = 2.12; p = 0.0007) and 28-day (OR = 2.24; p = 0.020) and 60-day ARDS mortalities (OR = 2.09; p = 0.020). In sepsis-related ARDS, serial bilirubin levels in non-survivors were consistently higher than in survivors (p<0.0001). Clinical variables explained 29.5% of the interindividual variation in bilirubin levels, whereas genetic variants of UGT1A1 contributed 7.5%.In sepsis, a higher serum bilirubin level on ICU admission is associated with subsequent ARDS development and mortality.
A Trial of Scheduled Deep Brain Stimulation for Tourette Syndrome
Authors: Michael S. Okun, Kelly D. Foote, Samuel S. Wu, Herbert E. Ward, Dawn Bowers, Ramon L. Rodriguez, Irene A. Malaty, Wayne K. Goodman, Donald M. Gilbert, Harrison C. Walker, Jonathan W. Mink, Stacy Merritt, Takashi Morishita, Justin C. Sanchez
Journal: JAMA Neurology (2012)

To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome.We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS.A university movement disorders center.Five patients with implanted DBS.A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness.This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches.clinicaltrials.gov Identifier: NCT01329198.
Silencing the major apple allergen Mal d 1 by using the RNA interference approach
Authors: Luud J.W.J. Gilissen, Suzanne T.H.P. Bolhaar, Catarina I. Matos, Gerard J.A. Rouwendal, Marjan J. Boone, Frans A. Krens, Laurian Zuidmeer, Astrid van Leeuwen, Jaap Akkerdaas, Karin Hoffmann-Sommergruber, André C. Knulst, Dirk Bosch, W. Eric van de Weg, Ronald van Ree
Journal: Journal of Allergy and Clinical Immunology (2005)
Identification of a Novel Genetic Locus for Familial Cardiac Myxomas and Carney Complex
Authors: Mairead Casey, Caroline Mah, Andrew D. Merliss, Lawrence S. Kirschner, Susan E. Taymans, Alfred E. Denio, Bruce Korf, Alan D. Irvine, Anne Hughes, J. Aidan Carney, Constantine A. Stratakis, Craig T. Basson
Journal: Circulation (1998)

Background —Intracardiac myxomas are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. In the autosomal dominant syndrome Carney complex, intracardiac myxomas arise in the setting of lentiginosis and other lesions associated with cutaneous hyperpigmentation, extracardiac myxomas, and nonmyxomatous tumors. Genetic factors that regulate cardiac tumor growth remain unknown. Methods and Results —We used the molecular genetic techniques of linkage analysis to study 4 kindreds affected by Carney complex to determine the genetic basis of this syndrome. Our investigation confirmed genetic heterogeneity of Carney complex. Moreover, genetic linkage analysis with polymorphic short tandem repeats on the long arm of chromosome 17 revealed maximal pairwise LOD scores of 5.9, 1.5, 1.8, and 2.9 for families YA, YB, YC01, and YC11, respectively. Haplotype analysis excluded a founder effect at this locus. These data identify a major 17 cM locus on chromosome 17q2 that contains the Carney complex disease gene. Conclusions —The ultimate identification and analysis of the Carney complex disease gene at this human chromosome 17q2 locus will facilitate diagnosis and treatment of cardiac myxomas and will foster new concepts in regulation of cardiac cell growth and differentiation.
Deterioration of the Metabolic Risk Profile in Women
Authors: Agnés Pascot, Jean-Pierre Després, Isabelle Lemieux, Natalie Alméras, Jean Bergeron, André Nadeau, Denis Prud’homme, Angelo Tremblay, Simone Lemieux
Journal: Diabetes Care (2001)

OBJECTIVE—To determine whether the impaired glucose tolerance (IGT) state contributes to the deterioration of the metabolic profile in women after taking into account the contribution of visceral adipose tissue (AT) accumulation, as measured by computed tomography. RESEARCH DESIGN AND METHODS—We studied 203 women with normal glucose tolerance (NGT) and 46 women with IGT, defined as a glycemia between 7.8 and 11.1 mmol/l measured 2 h after a 75-g oral glucose load. RESULTS—Women with IGT were characterized by a higher visceral AT accumulation and by higher concentrations of fasting plasma glucose, insulin, and C-peptide as well as by higher plasma concentrations of cholesterol, triglycerides, and apolipoprotein B (apoB) and by greater cholesterol–to–HDL-cholesterol ratio, reduced LDL peak particle size, lower HDL-cholesterol and HDL2-cholesterol concentrations, and higher blood pressure (P &amp;lt; 0.01) than women with NGT. When we matched 27 pairs of women for visceral AT and fat mass as well as for menopausal status, differences previously found in LDL-cholesterol, LDL peak particle size, HDL-cholesterol, and HDL2-cholesterol concentrations as well as in the cholesterol–to–HDL-cholesterol ratio and blood pressure were eliminated, whereas triglyceride concentrations remained significantly higher in women with IGT. CONCLUSIONS—A high visceral AT accumulation is a major factor involved in the deterioration of many metabolic variables in women with IGT, with the notable exception of triglyceride concentrations, which remained significantly different between women with NGT and women with IGT after adjustment for visceral fat.
Topically applied S-nitrosothiol-containing hydrogels as experimental and pharmacological nitric oxide donors in human skin
Authors: A.B. Seabra, A. Fitzpatrick, J. Paul, M.G. De Oliveira, R. Weller
Journal: British Journal of Dermatology (2004)

Journal Article Topically applied S‐nitrosothiol‐containing hydrogels as experimental and pharmacological nitric oxide donors in human skin Get access A.B. Seabra, A.B. Seabra Instituto de Química, Universidade Estadual de Campinas, CP 6154, CEP 13084‐971, Campinas, SP, Brazil *Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, U.K Search for other works by this author on: Oxford Academic Google Scholar A. Fitzpatrick, A. Fitzpatrick Instituto de Química, Universidade Estadual de Campinas, CP 6154, CEP 13084‐971, Campinas, SP, Brazil *Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, U.K Search for other works by this author on: Oxford Academic Google Scholar J. Paul, J. Paul Instituto de Química, Universidade Estadual de Campinas, CP 6154, CEP 13084‐971, Campinas, SP, Brazil *Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, U.K Search for other works by this author on: Oxford Academic Google Scholar M.G. De Oliveira, M.G. De Oliveira Instituto de Química, Universidade Estadual de Campinas, CP 6154, CEP 13084‐971, Campinas, SP, Brazil *Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, U.K Search for other works by this author on: Oxford Academic Google Scholar R. Weller R. Weller Instituto de Química, Universidade Estadual de Campinas, CP 6154, CEP 13084‐971, Campinas, SP, Brazil *Department of Dermatology, Lauriston Building, Lauriston Place, Edinburgh, EH3 9HA, U.K Dr Richard Weller. E‐mail: r.weller@ed.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 5, 1 November 2004, Pages 977–983, https://doi.org/10.1111/j.1365-2133.2004.06213.x Published: 01 November 2004 Article history Accepted: 05 March 2004 Published: 01 November 2004
Immunoregulation in Urinary Tract Inflammation—A Role of Tamm-Horsfall Glycoprotein
Authors: MD Sa[Combining Diaeresis]emann, T Weichhart, M Zeyda, G Staffler, M Schunn, KM Stuhlmeier, Y Sobanov, TM Stulnig, S Akira, A von Gabain, U von Ahsen, WH Horl, GJ Zlabinger
Journal: Journal of the American Society of Nephrology (2005)

The Tamm-Horsfall protein (THP), the most abundant protein in normal urine, was discovered five decades ago ([1][1]), or possibly even much earlier ([2][2]), but the role for the most abundant protein in normal urine had remained enigmatic for a long time. It is expressed in the thick ascending limb
Treatment of pancreatic fibrosis with siRNA against a collagen-specific chaperone in vitamin A-coupled liposomes
Authors: Hirotoshi Ishiwatari, Yasushi Sato, Kazuyuki Murase, Akihiro Yoneda, Ryosuke Fujita, Hiroki Nishita, Naoko Kubo Birukawa, Tsuyoshi Hayashi, Tsutomu Sato, Koji Miyanishi, Rishu Takimoto, Masayoshi Kobune, Shigenori Ota, Yasutoshi Kimura, Koichi Hirata, Junji Kato, Yoshiro Niitsu
Journal: Gut (2012)

Fibrosis associated with chronic pancreatitis is an irreversible lesion that can disrupt pancreatic exocrine and endocrine function. Currently, there are no approved treatments for this disease. We previously showed that siRNA against collagen-specific chaperone protein gp46, encapsulated in vitamin A-coupled liposomes (VA-lip-siRNAgp46), resolved fibrosis in a model of liver cirrhosis. This treatment was investigated for pancreatic fibrosis induced by dibutyltin dichloride (DBTC) and cerulein in rats.Specific uptake of VA-lip-siRNAgp46, conjugated with 6'-carboxyfluorescein (FAM) by activated pancreatic stellate cells (aPSCs), was analysed by fluorescence activated cell sorting (FACS). Intracellular distribution of VA-lip-siRNAgp46-FAM was examined by fluorescent microscopy. Suppression of gp46 expression by VA-lip-siRNAgp46 was assessed by immunoblotting. Collagen synthesis in aPSCs was assayed by dye-binding. Specific delivery of VA-lip-siRNAgp46 to aPSCs in DBTC rats was verified following intravenous VA-lip-siRNA-FAM and (3)H-VA-lip-siRNAgp46. The effect of VA-lip-siRNA on pancreatic histology in DBTC- and cerulein-treated rats was determined by Azan-Mallory staining and hydroxyproline content.FACS analysis revealed specific uptake of VA-lip-siRNAgp46-FAM through the retinol binding protein receptor by aPSCs in vitro. Immunoblotting and collagen assay verified knockdown of gp46 and suppression of collagen secretion, respectively, by aPSCs after transduction of VA-lip-siRNAgp46. Specific delivery of VA-lip-siRNAgp46 to aPSCs in fibrotic areas in DBTC rats was confirmed by fluorescence and radioactivity 24 h after the final injection. 10 systemic VA-lip-siRNAgp46 treatments resolved pancreatic fibrosis, and suppressed tissue hydroxyproline levels in DBTC- and cerulein-treated rats.These data suggest the therapeutic potential of the present approach for reversing pancreatic fibrosis.
Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis
Authors: April M. Adkison, Sofia Z. Raptis, Diane G. Kelley, Christine T.N. Pham
Journal: Journal of Clinical Investigation (2002)

Leukocyte recruitment in inflammation is critical for host defense, but excessive accumulation of inflammatory cells can lead to tissue damage. Neutrophil-derived serine proteases (cathepsin G [CG], neutrophil elastase [NE], and proteinase 3 [PR3]) are expressed specifically in mature neutrophils and are thought to play an important role in inflammation. To investigate the role of these proteases in inflammation, we generated a mouse deficient in dipeptidyl peptidase I (DPPI) and established that DPPI is required for the full activation of CG, NE, and PR3. Although DPPI–/– mice have normal in vitro neutrophil chemotaxis and in vivo neutrophil accumulation during sterile peritonitis, they are protected against acute arthritis induced by passive transfer of monoclonal antibodies against type II collagen. Specifically, there is no accumulation of neutrophils in the joints of DPPI–/– mice. This protective effect correlates with the inactivation of neutrophil-derived serine proteases, since NE–/– × CG–/– mice are equally resistant to arthritis induction by anti-collagen antibodies. In addition, protease-deficient mice have decreased response to zymosan- and immune complex–mediated inflammation in the subcutaneous air pouch. This defect is accompanied by a decrease in local production of TNF-α and IL-1β. These results implicate DPPI and polymorphonuclear neutrophil–derived serine proteases in the regulation of cytokine production at sites of inflammation.
Constitutive activation of integrin alpha 4 beta 1 defines a unique stage of human thymocyte development.
Authors: D R Salomon, C F Mojcik, A C Chang, S Wadsworth, D H Adams, J E Coligan, E M Shevach
Journal: The Journal of Experimental Medicine (1994)

Our understanding of thymocyte development and of the positive and negative selection events involved in shaping the repertoire of mature T lymphocytes has been greatly facilitated by the use of transgenic and gene knockout animals. Much less is known about the factors that control the homing and population of the thymus by T cell precursors and the subsequent migration of developing thymocytes through the thymic architecture. As the integrins represent a candidate group of cell surface receptors that may regulate thymocyte development, we have analyzed the expression and function of alpha 4 beta 1 and alpha 5 beta 1 on human thymocytes. A major portion of double positive (CD4+ CD8+) human thymocytes express alpha 4 beta 1 in a constitutively active form and adhere to fibronectin and vascular cell adhesion molecule 1. alpha 4 beta 1 expression is similar on adherent and nonadherent populations, thus, activity reflects the receptor state and not simple expression. The adherent cells are immature, expressing high levels of CD4/CD8 and low levels of CD3 and CD69. In contrast, nonadherent cells possess the phenotype of thymocytes after positive selection, expressing intermediate levels of CD4 and/or CD8 and high levels of CD3 and CD69. The adherent population fails to respond to activation with anti-CD3 and fibronectin, whereas nonadherents exhibit an alpha 5 beta 1-dependent proliferation. Differential regulation of alpha 4 beta 1 and alpha 5 beta 1 receptors may provide a mechanism controlling cellular traffic, differentiation, and positive selection of thymocytes.
P202 A survey of ILD expertise availability and High Resolution Computer Tomography (HRCT) protocols used in patients with Interstitial lung disease (ILD) across hospitals in England:
Authors: H Balata, A Ashish, I Aziz
Journal: Thorax (2013)

<h3>Introduction and aims</h3> ILD is increasingly being recognised as complex condition necessitating a multi-disciplinary approach to diagnosis and management requiring availability of a clinician and a radiologist with declared interest in ILD. HRCT is the imaging of choice used for assessment of ILD. The BTS ILD guidelines do recommend a “standard” HRCT protocol to be used in diagnosis of patients with ILD. It is however not known if there is a uniform availability of expertise within different centres in England and if “standard “HRCT protocol as recommended is being followed. <h3>Method</h3> A questionnaire was handed to radiologists with special interest in thoracic imaging working in different hospitals sites in England, at an ILD radiology conference. Questionnaires enquired about availability of ILD services and HRCT scanning technique used at their establishment. <h3>Results</h3> Of the 150 questionnaires, 100 were returned for analysis. There were responses from 39 teaching hospitals and 61 district general hospitals (DGH). Abstract P202 Table 1. Results of questionnaire given to thoracic radiologists across Hospitals in England. <h3>Conclusions</h3> Despite increasing focus on ILD as a sub-speciality, there is still a significant difference in the provision of expert care within district general hospitals in UK for patients with ILD. This may affect the quality of care provided with potential to variability of care standards. The “standard protocol” for HRCT techniques as specified by BTS is not being followed in England. Despite recommendations from BTS, aspects of HRCT scanning technique applied were variable and influenced by local preferences and expertise. This may lead to differences in scan interpretation, diagnosis and outcomes. This gap in provision of care and variability of techniques should be bridged to ensure uniformity of care and outcomes. <h3>References</h3> NICE guidelines, June 2013; CG163 2: <i>Thorax</i>; 63 (Suppl V); v1-v58
Pancreatic dysfunction and its association with fat malabsorption in HIV infected children
Authors: A Carroccio, M Fontana, M I Spagnuolo, G Zuin, G Montalto, R B Canani, F Verghi, D Di Martino, K Bastoni, F Buffardi, A Guarino
Journal: Gut (1998)

Background —Nutrient malabsorption frequently occurs in HIV infected children, but very few studies have investigated exocrine pancreatic digestive capacity in these cases. Aims —To investigate pancreatic function in HIV infected children and to determine whether faecal fat loss, a prominent feature of intestinal dysfunction, is associated with pancreatic dysfunction. Patients —Forty seven children with HIV infection without apparent pancreatic disease and 45 sex and age matched healthy controls. Methods —Pancreatic function was evaluated by measuring elastase 1 concentration and chymotrypsin activity in stools by ELISA and colorimetric methods, respectively. Intestinal function was evaluated by measuring fat and protein loss by the steatocrit method and by faecal α 1 antitrypsin concentration. Results —14 (30%) had abnormal pancreatic function tests: seven had isolated elastase activity deficiency, three isolated chymotrypsin deficiency, and four pancreatic deficiencies in both enzymes. Patient enzyme values were significantly lower than those of controls. Low faecal pancreatic enzymes were not associated with symptoms. Twelve children had steatorrhoea and four had increased α 1 antitrypsin. Steatorrhoea was significantly associated with reduced faecal pancreatic enzymes. There was a significant negative correlation between elastase 1 concentration and steatocrit. Children with pathological faecal elastase 1 or chymotrypsin values did not differ from the other HIV infected children with respect to nutritional and immunological status, stage of HIV disease, presence of opportunistic infections, or drug administration. Conclusions —Abnormal pancreatic function tests are a frequent feature of paediatric HIV infection; this condition is associated with steatorrhoea, which probably contributes to the disease.
Eczema and keratoconus.
Authors: P. W. Copeman
Journal: BMJ (1965)

no part in the genesis of this lactate, and infusion of A.C.D. bank blood had been stopped previously.The quantities of lactate and pyruvate circulating during the immediate post-operative period amount to 4 mEq/l.at maximum.No significant change occurs in hydrogen-ion concentrations as a result of these metabolites, and although the reason for their continued production is at present obscure they do not appear to be harmful per se. SummarySix cases have been studied during reconstructive surgery for aorto-iliac disease.Infrarenal aortic occlusion produces severe desaturation of blood in the lower limb, leading to anaerobic production of lactate.The change in hydrogen-ion concentration produced is small, transient, and not significant at normothermia.Alterations in hydrogen-ion concentration due to release of anoxic metabolites does not appear to be the cause of systemic hypotension after release of aortic clamps.We would like to express our thanks to Mr. G. Slaney and Mr. F. Ashton for allowing us to study patients under their care, and for their help and advice in the preparation of this paper.
Elevated placental growth factor concentrations at 11–14weeks of gestation to predict gestational diabetes mellitus
Authors: Makarios Eleftheriades, Ioannis Papastefanou, Irene Lambrinoudaki, Dimitra Kappou, Demetrios Lavranos, Athanasios Akalestos, Athena P. Souka, Panagiota Pervanidou, Demetrios Hassiakos, George P. Chrousos
Journal: Metabolism (2014)