tbuckley/cabot-search huggingface dataset:
The Rising Incidence of Type 1 Diabetes Is Accounted for by Cases With Lower-Risk Human Leukocyte Antigen Genotypes
Authors: Spiros Fourlanos, Michael D. Varney, Brian D. Tait, Grant Morahan, Margo C. Honeyman, Peter G. Colman, Leonard C. Harrison
Journal: Diabetes Care (2008)

OBJECTIVE—The rising incidence of type 1 diabetes has been attributed to environment, implying a lesser role for genetic susceptibility. However, the rise could be accounted for by either more cases with classic high-risk genes or by cases with other risk genes. Separately, for any degree of genetic susceptibility, age at presentation may decrease in a permissive environment. To examine these possibilities, human leukocyte antigen (HLA) class II DRB1 genes known to confer risk for type 1 diabetes were analyzed in relation to year of birth and age at diagnosis over the last five decades. RESEARCH DESIGN AND METHODS—Caucasoid subjects (n = 462) diagnosed with type 1 diabetes before age 18 between 1950 and 2005 were DRB1 genotyped. RESULTS—Mean ± SD age at diagnosis, 8.5 ± 4.5 years, did not differ across decades. Recent diagnosis was associated with a lower proportion but unchanged incidence of the highest-risk DRB1 genotype DR3,4 (2000–2005, 28% vs. 1950–1969, 79%; P &amp;lt; 0.0001) and a higher proportion of lower-risk genotypes DR4,X and DR3,X (2000–2005, 48% vs. 1950–1969, 20%; P = 0.0002). The frequency of the DRX,X genotype was low (≤3%) across decades. Recent birth was associated with a lower age at diagnosis for lower risk DR3,3 and DR4,4 (P &amp;lt; 0.0001) and DR4,X (P &amp;lt; 0.0001) and DR3,X (P = 0.015) genotypes but not for DR3,4. CONCLUSIONS—The rising incidence and decreasing age at diagnosis of type 1 diabetes is accounted for by the impact of environment on children with lower-risk HLA class II genes, who previously would not have developed type 1 diabetes in childhood.
Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures
Authors: Mattia Maroso, Silvia Balosso, Teresa Ravizza, Jaron Liu, Eleonora Aronica, Anand M Iyer, Carlo Rossetti, Monica Molteni, Maura Casalgrandi, Angelo A Manfredi, Marco E Bianchi, Annamaria Vezzani
Journal: Nature Medicine (2010)
Survival analysis can help determine which TLco prediction equations to use for patient data
Authors: Helen Ward, Robert Stockley, Martin Miller
Journal: European Respiratory Journal (2011)

Choosing which prediction equation to use for lung function data can be a problematic. In Europe the ECCS equations are commonly used but more recent ones are available and may be more applicable. To help decide which TLco prediction equations would be best for our data we extracted the earliest results for subjects from our lung function database who had a full set of all tests and determined their survival up to 29/1/2009. We calculated TLco results as standardised residuals (SR) using equations from ECCS (1993), RO Crapo (1981), A Miller (1983) and CM Roberts (1991) and used deciles of these results and of age and included sex to predict survival. There were full data for 5626 subjects (48% women) with mean (SD) age 59.3 yrs (14.7), mean survival 4.4 yrs (SD 2.6, range 0 to 24) with 2049 deaths. Using the ECCS equations the mean (range) of SR values for FEV 1  was -1.6 (-7.3 to +3.4), for FVC was -0.8 (-6.3 to +3.6) and for TLco was -1.5 (-6.5 to +6.2). The best Cox survival prediction model (highest Chi 2  value) was with the Miller equations as shown in the table of hazard ratios (95% CI) for death associated with oldest age decile, worst TLco decile and sex.  We conclude that for our UK data the Miller equations from the USA for TLco are best related to subsequent survival and so should be considered for determining if results are abnormal.
β7 integrins are required to give rise to intestinal mononuclear phagocytes with tolerogenic potential
Authors: Eduardo J Villablanca, Jaime De Calisto, Patricia Torregrosa Paredes, Barbara Cassani, Deanna D Nguyen, Susanne Gabrielsson, J Rodrigo Mora
Journal: Gut (2013)

<h3>Background and objective</h3> While pro-inflammatory monocyte trafficking to the intestine has been partially characterised, the molecules required for migration of tolerogenic mononuclear phagocytes (dendritic cells (DC) and macrophages) are unknown. We hypothesised that the gut-homing receptor integrin α4β7 is required for this process. <h3>Methods</h3> We used a T cell-mediated colitis model to study the role of α4β7 in the innate immune compartment. We then performed competitive bone marrow (BM) reconstitution experiments to assess the requirement of α4β7 in the generation of intestinal retinoic acid (RA)-producing CD11c<sup>hi</sup> DC (ALDE<sup>+</sup>DC) and CD64 macrophages. Using mixed BM chimeras we also asked whether α4β7 is required to give rise to tolerogenic mononuclear phagocytes. <h3>Results</h3> Lack of β7 integrins in the innate immune compartment (β7<sup>−/−</sup>RAG2<sup>−/−</sup> mice) markedly accelerated T cell-mediated colitis, which was correlated with lower numbers and frequencies of ALDE<sup>+</sup>DC in mesenteric lymph nodes. Consistent with a role of α4β7 in the generation of intestinal mononuclear phagocytes, BM cells from β7<sup>−/−</sup> mice poorly reconstituted small intestine ALDE<sup>+</sup>DC and Mφ when compared to their wild type counterparts. In addition, mice lacking β7 integrins in the CD11c<sup>hi</sup> compartment showed decreased ability to induce Foxp3<sup>+</sup> T<sub>REG</sub> and IL-10-producing T cells. <h3>Conclusions</h3> Mice lacking β7 integrins in the innate immune compartment are more susceptible to intestinal inflammation, which is correlated with a requirement of β7 integrins to reconstitute gut mononuclear phagocytes with tolerogenic potential.
ECG and morphologic adaptations in Arabic athletes: are the European Society of Cardiology's recommendations for the interpretation of the 12-lead ECG appropriate for this ethnicity?
Authors: Nathan R Riding, Othman Salah, Sanjay Sharma, François Carré, Keith P George, Abdulaziz Farooq, Bruce Hamilton, Hakim Chalabi, Gregory P Whyte, Mathew G Wilson
Journal: British Journal of Sports Medicine (2013)

To examine the cardiac structure and function of Arabic athletes and to establish if the European Society of Cardiology (ESC) guidelines for the interpretation of an athlete's ECG are applicable to this ethnicity.600 high-level Arabic, 415 Black African, 160 Caucasian male athletes (exercising ≥6 h/week) and 201 Arabic controls presented for ECG and echocardiographic screening.9 athletes (0.7%) were identified with a cardiac pathology associated with sudden cardiac death. Two Arabics (0.3%) and five Black Africans (1.2%) were diagnosed with hypertrophic cardiomyopathy; a prevalence four times greater in Black African compared to Arabic athletes. Arabic athletes had significantly greater (p<0.05) left ventricular (LV) end-diastolic diameters, maximal LV wall thicknesses and LV mass compared with controls; yet were significantly smaller than Black African and Caucasian athletes. The percentage of athletes demonstrating LV hypertrophy (≥12 mm) was comparable between Arabic, Black African and Caucasian populations (0.5%, 0.5% and 0.6%, respectively). There was no difference in the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian. However, Black Africans demonstrated a significantly greater prevalence than Arabic and Caucasian athletes (20% vs 8.4% and 6.9%, p<0.001); specifically more right/left atrial enlargement and T wave inversion.Arabic athletes present significantly smaller cardiac dimensions than Black African and Caucasian athletes. There was no significant difference between the frequency of an uncommon and training-unrelated ECG between Arabic and Caucasian athletes. Therefore, the use of ESC guidelines for the interpretation of an athlete's ECG is clinically relevant and acceptable for use within Arabic athletes.
Grb10 Promotes Lipolysis and Thermogenesis by Phosphorylation-Dependent Feedback Inhibition of mTORC1
Authors: Meilian Liu, Juli Bai, Sijia He, Ricardo Villarreal, Derong Hu, Chuntao Zhang, Xin Yang, Huiyun Liang, Thomas J. Slaga, Yonghao Yu, Zhiguang Zhou, John Blenis, Philipp E. Scherer, Lily Q. Dong, Feng Liu
Journal: Cell Metabolism (2014)
An individual patient-data comparison of combined modality therapy and ABVD alone for patients with limited-stage Hodgkin lymphoma
Authors: A.E. Hay, B. Klimm, B.E. Chen, H. Goergen, L.E. Shepherd, M. Fuchs, M.K. Gospodarowicz, P. Borchmann, J.M. Connors, J. Markova, M. Crump, A. Lohri, J.N. Winter, B. Dörken, R.G. Pearcey, V. Diehl, S.J. Horning, H.T. Eich, A. Engert, R.M. Meyer
Journal: Annals of Oncology (2013)
Molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA): think regionally but use globally uniform typing languages
Authors: A Jurke, R Köck, K Becker, S Thole, R Hendrix, J Rossen, I Daniels-Haardt, A W Friedrich
Journal: Eurosurveillance (2013)

Preview this article: Molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA): think regionally but use globally uniform typing languages, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/18/43/art20617-en-1.gif
Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis.
Authors: S Brul, A Westerveld, A Strijland, R J Wanders, A W Schram, H S Heymans, R B Schutgens, H van den Bosch, J M Tager
Journal: Journal of Clinical Investigation (1988)

We have used complementation analysis after somatic cell fusion to investigate the genetic relationships among various genetic diseases in humans in which there is a simultaneous impairment of several peroxisomal functions. The activity of acyl-coenzyme A:dihydroxyacetonephosphate acyltransferase, which is deficient in these diseases, was used as an index of complementation. In some of these diseases peroxisomes are deficient and catalase is present in the cytosol, so that the appearance of particle-bound catalase could be used as an index of complementation. The cell lines studied can be divided into at least five complementation groups. Group 1 is represented by a cell line from a patient with the rhizomelic form of chondrodysplasia punctata. Group 2 consists of cell lines from four patients with the Zellweger syndrome, a patient with the infantile form of Refsum disease and a patient with hyperpipecolic acidemia. Group 3 comprises one cel line from a patient with the Zellweger syndrome, group 4 one cell line from a patient with the neonatal form of adrenoleukodystrophy, and group 5 one cell line from a patient with the Zellweger syndrome. We conclude that at least five genes are required for the assembly of a functional peroxisome.
Fast acting nervous regulation of immunoglobulin A secretion from isolated perfused porcine ileum
Authors: P T Schmidt, L Eriksen, M Loftager, T N Rasmussen, J J Holst
Journal: Gut (1999)

<h3>BACKGROUND</h3> The intestinal mucosa harbours a large number of nerve fibres and also plasma cells, providing the anatomical basis for studies of neuroimmune interactions. <h3>AIMS</h3> To study the effect of different neurotransmitters and electrical stimulation of the extrinsic intestinal nerves on secretion of immunoglobulin A (IgA). <h3>METHODS</h3> IgA was measured, using a specific ELISA, in the luminal and venous effluent from isolated vascularly perfused porcine ileal segments with preserved extrinsic nerve supply. <h3>RESULTS</h3> Infusion of several neuropeptides stimulated IgA output. Somatostatin (10<sup>−8</sup>M) stimulated IgA secretion in the luminal effluent from 46.6 (14.3) to 79.3 (19.0) μg/5 min and increased the venous output to 148.3 (23.0)% (n=6) of basal output, whereas noradrenaline (10<sup>−6</sup> M) inhibited the secretion (to 49.2 (6.5)% of basal output, n=6). Electrical stimulation of the mixed extrinsic nerves supplying the intestinal segment had no effect by itself. However, electrical stimulation during infusion of α adrenergic blockers or coinfusion of both α adrenergic and muscarinic blockers resulted in an immediate and significant increase in IgA, an effect that was abolished by nicotinic blockade. <h3>CONCLUSION</h3> The extrinsic nerve supply to the intestine could be involved in fast acting regulation of mucosal immune functions.
Variations in the Care of HIV-Infected Adults in the United States
Authors: Martin F. Shapiro, Sally C. Morton, Daniel F. McCaffrey, J. Walton Senterfitt, John A. Fleishman, Judith F. Perlman, Leslie A. Athey, Joan W. Keesey, Dana P. Goldman, Sandra H. Berry, Samuel A. Bozzette, None Additional Authors From the HCSUS Consortium
Journal: JAMA (1999)

Studies of selected populations suggest that not all persons infected with human immunodeficiency virus (HIV) receive adequate care.
Comparison of<i>Tripterygium wilfordii</i>Hook F with methotrexate in the treatment of rheumatoid arthritis
Authors: Donald M Marcus
Journal: Annals of the Rheumatic Diseases (2014)

The study by Qian-wen Lv et al 1 found the efficacy of the herb Tripterygium wilfordii Hook F (TwHF) for treatment of rheumatoid arthritis to be non-inferior to that of methotrexate. The duration of that trial was 24 weeks, but rheumatoid arthritis is a chronic disease that requires years of therapy. The authors did not consider adequately the full range of the herb's potential adverse effects, especially for long-term treatment.

TwHF has direct effects on the male and female reproductive tracts of humans and laboratory animals.2–4 It causes irregular menses and amenorrhoea, which may be reversible, increased levels of follicle-stimulating and luteinising …
Expression of Neprilysin in Skeletal Muscle Reduces Amyloid Burden in a Transgenic Mouse Model of Alzheimer Disease
Authors: Yinxing Liu, Christa Studzinski, Tina Beckett, Hanjun Guan, Matthew A Hersh, M Paul Murphy, Ronald Klein, Louis B Hersh
Journal: Molecular Therapy (2009)

Neprilysin (NEP) is a zinc metallopeptidase that efficiently degrades the amyloid β (Aβ) peptides believed to be involved in the etiology of Alzheimer disease (AD). The focus of this study was to develop a new and tractable therapeutic approach for treating AD using NEP gene therapy. We have introduced adeno-associated virus (AAV) expressing the mouse NEP gene into the hindlimb muscle of 6-month-old human amyloid precursor protein (hAPP) (3X-Tg-AD) mice, an age which correlates with early stage AD. Overexpression of NEP in muscle decreased brain soluble Aβ peptide levels by ∼60% and decreased amyloid deposits by ∼50%, with no apparent adverse effects. Expression of NEP on muscle did not affect the levels of a number of other physiological peptides known to be in vitro substrates. These findings demonstrate that peripheral expression of NEP and likely other peptidases represents an alternative to direct administration into brain and illustrates the potential for using NEP expression in muscle for the prevention and treatment of AD.
Grave anaphylactic‐like reaction in the course of menstruation
Authors: Antonio Basomba, M. Guerrero, A. Campos, A. Peláz, I. G. Villalmanzo
Journal: Allergy (1987)

The case of a woman with a serious anaphylactic pattern during menstruation is described. The patient had a clinical picture of urticaria, angioedema and shock at each menstruation for a period of 2 years until hysterectomy was performed. The studies showed no hormonal or immunological change. The only relevant finding was the extraordinarily strong vasodilating action of the menstrual fluid in the patient, and not in the controls. The results of the study suggest the possibility of two mechanisms: 1) an IgE-mediated mechanism causing hypersensitivity to some metabolic substance in the menstrual fluid and 2) an excessive pharmacological vasodilatory action produced by the prostacyclin in the fluid itself.
Effect of IL-17A blockade with secukinumab in autoimmune diseases
Authors: Dhavalkumar D Patel, David M Lee, Frank Kolbinger, Christian Antoni
Journal: Annals of the Rheumatic Diseases (2012)

Genetic studies and correlative expression data in diseased tissues have pointed to the role of interleukin (IL)-17 and Th17 cells in the pathogenesis of autoimmune disorders such as psoriasis, inflammatory bowel disease and seronegative spondyloarthropathies. Th17 cells are known to produce the proinflammatory cytokine IL-17A as well as other effector cytokines, including IL-17F and IL-22. Recent research has demonstrated that IL-17A is also expressed by multiple lineages of the innate immune system, including mast cells, neutrophils, dendritic cells, γδ-T cells, macrophages and natural killer cells. It can thus be expected that the inhibition of IL-17A as a therapeutic target in autoimmune disease would exert different physiological effects than the suppression of Th17 cell activity. Early clinical data are now available on secukinumab (AIN457), a recombinant, highly selective, fully human monoclonal anti-IL-17A antibody of the IgG1/κ isotype, enabling a preliminary assessment of the effects of IL-17A inhibition in multiple autoimmune diseases. Rapid and sustained symptom reductions in psoriasis, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have been observed in secukinumab-treated patients, with no overt safety signals. In conjunction with studies using the humanised anti-IL-17A monoclonal antibody (mAb) ixekizumab (LY2439821) and the fully human anti-IL-17RA mAb brodalumab (AMG 827), the findings on secukinumab provide evidence for the role of IL-17A in the pathophysiology of autoimmune disease and suggest the potential value of targeting this cytokine.
Influence of long term silicone implantation on type II collagen induced arthritis in mice
Authors: C. J Schaefer, W D. Lawrence, P. H Wooley
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> The use of silicone implants in cosmetic and reconstructive surgery has been implicated in the development of autoimmune connective tissue diseases. Previous investigation of the influence of short-term silicone implantation using an experimental model of rheumatoid arthritis revealed no adverse influence upon disease despite the generation of autoantibodies against silicone bound proteins. This study was designed to examine the influence of long term implantation of different forms of silicone in collagen induced arthritis. <h3>METHODS</h3> DBA/1 mice were surgically implanted with silicone elastomers, gel or oil nine months before immunisation with type II collagen emulsified in Freund's incomplete adjuvant. The incidence and severity of arthritis, antibodies to type II collagen, and serum cytokines were assessed and compared with sham implanted mice. Silicone implants were recovered, and autoantibodies to silicone bound proteins evaluated in arthritic and non-arthritic mice. <h3>RESULTS</h3> Immunisation with CII/FIA resulted in a 30% arthritis incidence in sham implanted DBA/1 mice. Long term silicone implantation resulted in an increased incidence of arthritis, with a significant increase of 90% arthritis in animals implanted with silicone elastomers. Animals implanted with silicone elastomer also developed foreign body sarcomas during the study. Serum concentrations of interleukin 10 were increased in mice implanted with elastomers and immunised with CII/FIA, while interleukin 5 concentrations were significantly diminished in these mice. The production of autoantibodies to autologous silicone bound proteins, including anti-type I collagen antibody, was also attributed to the implantation of either silicone gel or silicone elastomer in type II collagen immunised animals. <h3>CONCLUSIONS</h3> These data suggest that long term silicone implantation results in both the production of autoantibodies to connective tissue antigens and increased susceptibility to an experimental model of autoimmune disease.
Microbiological surveillance in lung disease in ataxia telangiectasia
Authors: J. M. Bhatt, A. Bush
Journal: European Respiratory Journal (2014)

To the Editor: 

Ataxia telangiectasia is a progressive, neurodegenerative disease causing immunodeficiency, an increased risk of malignancy and respiratory disease, such as chronic sinopulmonary infection, aspiration, bronchiectasis and interstitial lung disease. The leading causes of premature death in ataxia telangiectasia are cancer and respiratory disease [1]. Published recommendations about management of pulmonary problems in ataxia telangiectasia are based on extrapolation from other conditions, which highlights the gaps in the understanding of this rare disease. Little is known about airway infections in ataxia telangiectasia [2]. Previous work has described retrospective data sets from single small clinics [3] or review of medical records in a large series of ataxia telangiectasia patients with chronic respiratory disease [4, 5]. The microbiology in these patients was found to be unlike that of any other primary immune deficiencies and had more similarities to that seen in patients with cystic fibrosis. In cystic fibrosis, it has been long recognised that the organisms infecting the lower airway will determine treatment, quality of life, prospects for transplantation and overall survival. The accurate and prompt identification of respiratory pathogens is essential for ensuring timely commencement of eradication treatment for early infection with bacterial pathogens, the use of appropriate long-term and rescue antibiotics for those with chronic bacterial infection, and the application of appropriate infection control measures [6]. Hence, microbiological surveillance is standard practice in cystic fibrosis clinics internationally. In patients with other primary immunodeficiencies, proactive treatment with immunoglobulin replacement therapy and broad-spectrum antibiotics prevents the development of bronchiectasis and alters the natural course of respiratory disease [7]. A state of the art document [2] recognises that future research in ataxia telangiectasia should address the identification of common organisms associated with sinopulmonary infections in ataxia telangiectasia …
Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with MLL gene rearrangement
Authors: K Nagai, H Fujiwara, T Ochi, S Okamoto, J Mineno, H Shiku, K Koh, K Sugita, E Ishii, M Yasukawa
Journal: Blood Cancer Journal (2011)

Feasibility of gene-immunotherapy using WT1-specific T-cell receptor gene transfer for infant acute lymphoblastic leukemia with  MLL  gene rearrangement