tbuckley/cabot-search huggingface dataset:
Association of HLA Class I and II Alleles and Extended Haplotypes With Nasopharyngeal Carcinoma in Taiwan
Authors: A. Hildesheim
Journal: JNCI Journal of the National Cancer Institute (2002)

Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC.We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred.We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLA-B*4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4).The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.
Paediatric HERMES: update of the European Training Syllabus for Paediatric Respiratory Medicine
Authors: M. Gappa, J. Paton, E. Baraldi, A. Bush, K-H. Carlsen, J. C. de Jongste, E. Eber, B. Fauroux, S. McKenzie, J-L. Noël, P. Palange, P. Pohunek, K. Priftis, T. Séverin, J. H. Wildhaber, Z. Zivkovic, M. Zach
Journal: European Respiratory Journal (2009)

y providing free access for European medical specialists to the European job market via two relevant directives (issued in 1975 and 2005), the European Union (EU) has effected an automatic recognition of the diplomas and certificates of qualification in medicine in all member countries.This is only acceptable on the basis of harmonised training standards across the entire EU.Thus, it is mandatory to work towards such harmonised standards in all medical specialties.
What Is the Renal Replacement Method of First Choice for Intensive Care Patients?
Authors: RAYMOND VANHOLDER, WIM VAN BIESEN, NORBERT LAMEIRE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Renal replacement therapy for the patient with acute renal failure on the intensive care unit can be offered in several different formats: intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), and slow low-efficient daily dialysis (SLEDD). It is frequently claimed that CRRT offers several advantages over IHD, but most of these, such as correction of metabolic acidosis, better recovery of renal function, better clinical outcome due to application of biocompatible dialysis membranes, correction of malnutrition, and better removal of cytokines, are not corroborated by the results of controlled prospective studies. There is also no evidence that CRRT results in a better surival, compared with IHD. The only potential advantages of CRRT that stood the test of clinical evaluation (hemodynamic stability, correction of hypervolemia, better solute removal) can be offered as well by SLEDD. In addition, the latter strategy is less expensive because the same infrastructure is used as for IHD, while the patient is not immobilized continuously, which leaves time free for other activities such as nursing care and technical investigations. SLEDD is a relatively young technique, so thorough clinical studies are lacking. Nevertheless, the hypothesis is proposed that SLEDD offers a valuable alternative to the classical dialysis strategies, applied in the intensive care patient.
Myeloid Differentiation Factor-88 Plays a Crucial Role in the Pathogenesis of Coxsackievirus B3–Induced Myocarditis and Influences Type I Interferon Production
Authors: Koichi Fuse, Grace Chan, Youan Liu, Patrick Gudgeon, Mansoor Husain, Manyin Chen, Wen-Chen Yeh, Shizuo Akira, Peter P. Liu
Journal: Circulation (2005)

Myeloid differentiation factor (MyD)-88 is a key adaptor protein that plays a major role in the innate immune pathway. How MyD88 may regulate host response in inflammatory heart disease is unknown.We found that the cardiac protein level of MyD88 was significantly increased in the hearts of wild-type mice after exposure to Coxsackievirus B3 (CVB3). MyD88(-/-) mice showed a dramatic higher survival rate (86%) in contrast to the low survival (35%) in the MyD88(+/+) mice after CVB3 infection (P<0.0001). Pathological examination showed a significant decrease of cardiac and pancreatic inflammation in the MyD88(-/-) mice. Viral concentrations in the hearts were significantly decreased in the MyD88(-/-) mice. Cardiac mRNA levels for interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-18 were significantly decreased in the MyD88(-/-) mice. Similarly, serum levels of T-helper 1 cytokines were significantly decreased in the MyD88(-/-) mice. In contrast, cardiac protein levels of the activated interferon regulatory factor (IRF)-3 and IFN-beta were significantly increased in the MyD88(-/-) mice but not other usual upstream signals to IRF-3. The cardiac expression of coxsackie-adenoviral receptor and p56(lck) were also significantly decreased.MyD88 appears to be a key contributor to cardiac inflammation, mediating cytokine production and T-helper-1/2 cytokine balance, increasing coxsackie-adenoviral receptor and p56(lck) expression and viral titers after CVB3 exposure. Absence of MyD88 confers host protection possibly through novel direct activation of IRF-3 and IFN-beta.
Association Between Serum Bioavailable Testosterone Concentration and the Ratio of Glycated Albumin to Glycated Hemoglobin in Men With Type 2 Diabetes
Authors: Michiaki Fukui, Muhei Tanaka, Goji Hasegawa, Toshikazu Yoshikawa, Naoto Nakamura
Journal: Diabetes Care (2008)

Testosterone stimulates erythropoiesis and thus glycated hemoglobin (A1C) values may be relatively low in male diabetic patients with hypogonadism. We therefore investigated relationships between serum bioavailable testosterone concentration and the ratio of glycated albumin (GA) to A1C and between serum bioavailable testosterone and hemoglobin concentrations in men with type 2 diabetes.The above relationships were investigated in 222 consecutive men with type 2 diabetes. We also investigated how the ratio of GA to A1C is related to other variables such as age, BMI, and degree of diabetic microangiopathy.Mean ratio of GA to A1C was 2.94 +/- 0.38. Serum bioavailable testosterone concentration correlated positively with hemoglobin concentration (r = 0.368, P < 0.0001) and negatively with the ratio of GA to A1C (r = -0.278, P < 0.0001). Multiple regression analyses identified serum bioavailable testosterone concentration (beta = 0.187, P = 0.0062), age (beta = -0.204, P = 0.0075), BMI (beta = 0.151, P = 0.0302), systolic blood pressure (beta = 0.173, P = 0.0090), and plasma total cholesterol (beta = 0.155, P = 0.0141) as independent determinants of hemoglobin concentration; moreover, serum bioavailable testosterone concentration (beta = -0.155, P = 0.0381) and plasma total cholesterol (beta = -0.170, P = 0.0144) were identified as independent determinants of the ratio of GA to A1C.Serum bioavailable testosterone concentration correlated positively with hemoglobin concentration and negatively with the ratio of GA to A1C in men with type 2 diabetes, which may lead to underestimation of A1C in hypogonadal men with type 2 diabetes.
Menstrual and reproductive factors, and hormonal contraception use: associations with non-Hodgkin lymphoma in a pooled analysis of InterLymph case–control studies
Authors: E.V. Kane, E. Roman, N. Becker, L. Bernstein, P. Boffetta, P.M. Bracci, J.R. Cerhan, B. C. -H. Chiu, P. Cocco, L. Costas, L. Foretova, E.A. Holly, C. La Vecchia, K. Matsuo, M. Maynadie, S. Sanjose, J.J. Spinelli, A. Staines, R. Talamini, S.S. Wang, Y. Zhang, T. Zheng, A. Kricker
Journal: Annals of Oncology (2012)
End points in pulmonary arterial hypertension: the way forward
Authors: A. Peacock, R. Naeije, N. Galié, J.T. Reeves
Journal: European Respiratory Journal (2004)

Pulmonary arterial hypertension is a rare disease of poor prognosis. Despite its rarity >1,000 patients have been randomised in placebo-controlled trials using novel therapies, including prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase 5 inhibitors. Nearly all of these trials have used exercise capacity, measured by the unencouraged 6‐min walking distance, as the primary end point and a variety of other measurements as secondary end points. This approach has been productive, leading to the licensing of a number of effective treatments. Future clinical trials, however, will probably assess drug combinations, make comparisons between drugs and include less severely ill patients. It is, therefore, timely to examine the end points used. The authors discussed the various end points that have been used in the past and possible end points that might be used in the future. End points considered included measurements of: exercise capacity, haemodynamics, quality of life, imaging of the right heart and circulation, and chemical markers of pulmonary hypertension. Many of these show promise but will have to be used in parallel and compared with conventional end points such as the 6‐min walking distance before their value can be demonstrated convincingly to the regulatory authorities.
Sex Disparities in Treatment of Cardiac Risk Factors in Patients With Type 2 Diabetes
Authors: Deborah J. Wexler, Richard W. Grant, James B. Meigs, David M. Nathan, Enrico Cagliero
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetes eliminates the protective effect of female sex on the risk of coronary heart disease (CHD). We assessed sex differences in the treatment of CHD risk factors among patients with diabetes. RESEARCH DESIGN AND METHODS—A cross-sectional analysis included 3,849 patients with diabetes treated in five academic internal medicine practices from 2000 to 2003. Outcomes were stratified by the presence of CHD and included adjusted odds ratios (AORs) that women (relative to men) were treated with hypoglycemic, antihypertensive, lipid-lowering medications or aspirin (if indicated) and AORs of reaching target HbA1c, blood pressure, or lipid levels. RESULTS—Women were less likely than men to have HbA1c &amp;lt;7% (without CHD: AOR 0.84 [95% CI 0.75–0.95], P = 0.005; with CHD: 0.63 [0.53–0.75], P &amp;lt; 0.0001). Women without CHD were less likely than men to be treated with lipid-lowering medication (0.82 [0.71–0.96], P = 0.01) or, when treated, to have LDL cholesterol levels &amp;lt;100 mg/dl (0.75 [0.62–0.93], P = 0.004) and were less likely than men to be prescribed aspirin (0.63 [0.55–0.72], P &amp;lt; 0.0001). Women with diabetes and CHD were less likely than men to be prescribed aspirin (0.70 [0.60–0.83], P &amp;lt; 0.0001) or, when treated for hypertension or hyperlipidemia, were less likely to have blood pressure levels &amp;lt;130/80 mmHg (0.75 [0.69–0.82], P &amp;lt; 0.0001) or LDL cholesterol levels &amp;lt;100 mg/dl (0.80 [0.68–0.94], P = 0.006). CONCLUSIONS—Women with diabetes received less treatment for many modifiable CHD risk factors than diabetic men. More aggressive treatment of CHD risk factors in this population offers a specific target for improvement in diabetes care.
Extracellular matrix regulates human airway smooth muscle cell migration
Authors: K. Parameswaran, K. Radford, J. Zuo, L.J. Janssen, P.M. O'Byrne, P.G. Cox
Journal: European Respiratory Journal (2004)

Extracellular matrix proteins regulate the survival and proliferation of smooth muscle cells. Their effect on airway smooth muscle cell migration is not known. Their role in leukotriene-primed (0.1 µM leukotriene E 4 ) chemotaxis of cultured human airway smooth muscle cells towards platelet-derived growth factor BB (1 ng·mL −1 ) was investigated. Migration of cells was greater on membranes coated with collagens III and V and fibronectin compared to collagen I, elastin and laminin (all 10 µg·mL −1 ). Concentration-dependent promotion of migration was observed on collagen I (1,000&gt;10 µg·mL −1 ), which was associated with increased phosphorylation of Src kinase. This was not observed on laminin or elastin. The role of Src kinase was further confirmed by demonstrating that its inhibitor, PP1 analogue (1 µM), inhibited chemotaxis. Collagen I itself was not a chemoattractant; however, haptokinesis was observed when cells were primed with leukotriene E 4 , and haptotaxis when cells were primed with platelet-derived growth factor. The priming effect of leukotrienes on chemotaxis was not elicited by promoting adhesion, increasing surface expression of β 1 , α v and α 5 integrin, or Src kinase phosphorylation. These experiments demonstrate that the extracellular matrix, along with growth factors and cysteinyl leukotrienes, can regulate human airway smooth muscle cell migration. This may be relevant in the remodelling process in chronic airway diseases, such as asthma.
Effect of magnesium supplementation and depletion on the onset and course of acute experimental pancreatitis
Authors: Verena Schick, Jonas A Scheiber, Frank C Mooren, Stefan Turi, Güralp O Ceyhan, Jürgen Schnekenburger, Matthias Sendler, Theresa Schwaiger, Armin Omercevic, Cindy van den Brandt, Gabriele Fluhr, Wolfram Domschke, Burkhard Krüger, Julia Mayerle, Markus M Lerch
Journal: Gut (2013)

<h3>Background and objective</h3> High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis. <h3>Methods</h3> Pancreatic acini were incubated with up to 10 mM magnesium; [Ca<sup>2+</sup>]<sub>i</sub> (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (&lt;300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg<sup>2+</sup> 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated. <h3>Results</h3> Increasing extracellular Mg<sup>2+</sup> concentration significantly reduced [Ca<sup>2+</sup>]<sub>i</sub> peaks and frequency of [Ca<sup>2+</sup>]<sub>i</sub> oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow—even with low caerulein concentrations that normally cause no damage. <h3>Conclusions</h3> Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca<sup>2+</sup>]<sub>i</sub> signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis.
PREGNANCY AFTER TRANSFER OF SPERM UNDER ZONA
Authors: Soon-Chye Ng, Ariff Bongso, ShanS. Ratnam, Henry Sathananthan, ClementL.K. Chan, P.C. Wong, Leiff Hagglund, C. Anandakumar, Y.C. Wong, VictorH.H. Goh
Journal: The Lancet (1988)
Interactions Between Monoamines, Glutamate, and GABA in Schizophrenia: New Evidence
Authors: Arvid Carlsson, Nicholas Waters, Susanna Holm-Waters, Joakim Tedroff, Marie Nilsson, Maria L. Carlsson
Journal: The Annual Review of Pharmacology and Toxicology (2001)

In spite of its proven heuristic value, the dopamine hypothesis of schizophrenia is now yielding to a multifactorial view, in which the other monoamines as well as glutamate and GABA are included, with a focus on neurotransmitter interactions in complex neurocircuits. The primary lesion(s) in schizophrenia does not necessarily involve any of these neurotransmitters directly but could deal with a more general defect, such as a faulty connectivity of developmental origin. Nevertheless, a precise identification of neurotransmitter aberrations in schizophrenia will probably provide clues for a better understanding of the disease and for the development of new treatment and prevention strategies.
CD40 ligand induced cytotoxicity in carcinoma cells is enhanced by inhibition of metalloproteinase cleavage and delivery via a conditionally-replicating adenovirus
Authors: Taha Elmetwali, Peter F Searle, Iain McNeish, Lawrence S Young, Daniel H Palmer
Journal: Molecular Cancer (2010)

Abstract Background CD40 and its ligand (CD40L) play a critical role in co-ordinating immune responses. CD40 is also expressed in lymphoid malignancies and a number of carcinomas. In carcinoma cells the physiological outcome of CD40 ligation depends on the level of receptor engagement with low levels promoting cell survival and high levels inducing cell death. The most profound induction of cell death in carcinoma cells is induced by membrane-bound rather than recombinant soluble CD40L, but like other TNF family ligands, it is cleaved from the membrane by matrix metalloproteinases. Results We have generated a replication-deficient adenovirus expressing a mutant CD40L that is resistant to metalloproteinase cleavage such that ligand expression is retained at the cell membrane. Here we show that the mutated, cleavage-resistant form of CD40L is a more potent inducer of apoptosis than wild-type ligand in CD40-positive carcinoma cell lines. Since transgene expression via replication-deficient adenovirus vectors in vivo is low, we have also engineered a conditionally replicating E1A-CR2 deleted adenovirus to express mutant CD40L, resulting in significant amplification of ligand expression and consequent enhancement of its therapeutic effect. Conclusions Combined with numerous studies demonstrating its immunotherapeutic potential, these data provide a strong rationale for the exploitation of the CD40-CD40L pathway for the treatment of solid tumours.
A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud's phenomenon secondary to connective tissue diseases.
Authors: H I Torley, R Madhok, H A Capell, R M Brouwer, P J Maddison, C M Black, H Englert, J A Dormandy, H R Watson
Journal: Annals of the Rheumatic Diseases (1991)

<h3>Background:</h3> The purpose of this study was to determine the age-adjusted incidence of retinoblastoma in the USA over a 30-year period from 1975 to 2004 using a review of existing databases. <h3>Methods:</h3> Six hundred and fifty-eight patients with retinoblastoma (International Classification of Oncology (ICDO-3) codes C69.2 (retina) and C69.9 (eye, NOS)) were derived from the Surveillance, Epidemiology, and End Results (SEER) program database in the USA from 1975 to 2004. Nine historical SEER registries were utilised. The significance of trend in age-adjusted incidence rate was determined using the χ<sup>2</sup> test, and 95% CIs were calculated. The patients were stratified according to age at diagnosis, laterality, gender and race. <h3>Results:</h3> There were a total of 658 cases of retinoblastoma, representing 6.1% of all childhood cancers under age 5 years. The mean age-adjusted incidence of retinoblastoma in the USA was 11.8 per million children aged 0–4 years (95% CI 10.9 to 12.8). There was no significant trend in age-adjusted incidence for all races/genders, nor was there any significant variation of incidence between races or between genders. The proportion of bilateral cases (26.7%) versus unilateral cases (71.9%) remained stable over the 30-year period. <h3>Conclusions:</h3> The mean age-adjusted incidence rate of retinoblastoma of 11.8 cases per million children aged 0–4 years in the USA is similar to rates reported from European countries. The age-adjusted incidence rate of retinoblastoma in the USA has remained stable for the last 30 years.
Mobile phone base stations and early childhood cancers: case-control study
Authors: P. Elliott, M. B. Toledano, J. Bennett, L. Beale, K. de Hoogh, N. Best, D. J. Briggs
Journal: BMJ (2010)

<b>Objective</b> To investigate the risk of early childhood cancers associated with the mother's exposure to radiofrequency from and proximity to macrocell mobile phone base stations (masts) during pregnancy. <b>Design</b> Case-control study. <b>Setting</b> Cancer registry and national birth register data in Great Britain. <b>Participants</b> 1397 cases of cancer in children aged 0-4 from national cancer registry 1999-2001 and 5588 birth controls from national birth register, individually matched by sex and date of birth (four controls per case). <b>Main outcome measures</b> Incidence of cancers of the brain and central nervous system, leukaemia, and non-Hodgkin's lymphomas, and all cancers combined, adjusted for small area measures of education level, socioeconomic deprivation, population density, and population mixing. <b>Results</b> Mean distance of registered address at birth from a macrocell base station, based on a national database of 76 890 base station antennas in 1996-2001, was similar for cases and controls (1107 (SD 1131) m <i>v</i> 1073 (SD 1130) m, P=0.31), as was total power output of base stations within 700 m of the address (2.89 (SD 5.9) kW <i>v</i> 3.00 (SD 6.0) kW, P=0.54) and modelled power density (−30.3 (SD 21.7) dBm <i>v</i> −29.7 (SD 21.5) dBm, P=0.41). For modelled power density at the address at birth, compared with the lowest exposure category the adjusted odds ratios were 1.01 (95% confidence interval 0.87 to 1.18) in the intermediate and 1.02 (0.88 to 1.20) in the highest exposure category for all cancers (P=0.79 for trend), 0.97 (0.69 to 1.37) and 0.76 (0.51 to 1.12), respectively, for brain and central nervous system cancers (P=0.33 for trend), and 1.16 (0.90 to 1.48) and 1.03 (0.79 to 1.34) for leukaemia and non-Hodgkin's lymphoma (P=0.51 for trend). <b>Conclusions</b> There is no association between risk of early childhood cancers and estimates of the mother's exposure to mobile phone base stations during pregnancy.