tbuckley/cabot-search huggingface dataset:
Does Helicobacter pylori protect against asthma and allergy?
Authors: M. J. Blaser, Y. Chen, J. Reibman
Journal: Gut (2008)

The microbes that persistently colonise their vertebrate hosts are not accidental.1 Although highly numerous and diverse, there is specificity by site and substantial conservation between individuals. The genus Helicobacter includes spiral, highly motile, urease-positive, Gram-negative bacteria that colonise the stomach in many mammals. Each mammal has one or more dominant Helicobacter species and they are highly, if not exclusively, host species-specific.2 Such observations are consistent with the hypothesis that when ancestral mammals diverged from reptiles about 150 million years ago, they contained ancestral helicobacters, which then diverged as their hosts changed. According to this hypothesis, helicobacters represent ancestral biota (flora) in the mammalian stomach. The human-adapted strain is H pylori ,3 which has not been reproducibly observed in any animals other than humans and other primates.3

Although we can not reliably estimate how long H pylori has been in the human stomach, its ancestors may have been present when our humanoid ancestors diverged from other primates about four million years ago. Consistent with this view are results from phylogeographic studies; strong and consistent evidence indicates that our ancestors already were carrying gastric H pylori when a group that ultimately populated much of the world last left Africa, more than 58 000 years ago.4 In any case, H pylori has been colonising the stomach of humans since at least Paleolithic times.

In this paper, we examine the evidence concerning the relationship of this ancient member of the human microbiota, and particularly its absence, with the recent and on-going epidemic of asthma and related allergic disorders. We discuss the possibility that gastric H pylori colonisation protects against these disorders and that its disappearance has fuelled their rise.

H pylori is acquired, and may be detected, in early childhood usually after the first year of life.5 Transmission is …
Differential Evolution of Voltage-Gated Sodium Channels in Tetrapods and Teleost Fishes
Authors: J. Widmark, G. Sundstrom, D. Ocampo Daza, D. Larhammar
Journal: Molecular Biology and Evolution (2010)

The voltage-gated sodium channel (SCN) alpha subunits are large proteins with central roles in the generation of action potentials. They consist of approximately 2,000 amino acids encoded by 24–27 exons. Previous evolutionary studies have been unable to reconcile the proposed gene duplication schemes with the species distribution and molecular phylogeny of the genes. We have carefully annotated the complete SCN gene sequences, correcting numerous database errors, for a broad range of vertebrate species and analyzed their phylogenetic relationships. We have also compared the chromosomal positions of the SCN genes relative to adjacent gene families. Our studies show that the ancestor of the vertebrates probably had a single sodium channel gene with two characteristic AT–AC introns, the second of which is unique to vertebrate SCN genes. This ancestral gene, located close to a HOX gene cluster, was quadrupled along with HOX in the two rounds of basal vertebrate tetraploidizations to generate the ancestors of the four channels SCN1A, SCN4A, SCN5A, and SCN8A. The third tetraploidization in the teleost fish ancestor doubled this set of genes and all eight are still present in at least three of four investigated teleost fish genomes. In tetrapods, the gene family expanded by local duplications before the radiation of amniotes, generating the cluster SCN5A, SCN10A, and SCN11A on one chromosome and the cluster SCN1A, SCN2A, SCN3A, and SCN9A on a different chromosome. In eutherian mammals, a tenth gene, SCN7A, arose in a local duplication in the SCN1A gene cluster. The SCN7A gene has undergone rapid evolution and has lost the ability to cause action potentials—instead, it functions as a sodium sensor. The three genes in the SCN5A cluster were translocated from the HOX-bearing chromosome in a mammalian ancestor along with several adjacent genes. This evolutionary scenario is supported by the adjacent TGF-β receptor superfamily (comprised of five distinct families) and the cysteine-serine–rich nuclear protein gene family as well as the HOX clusters. The independent expansions of the SCN repertoires in tetrapods and teleosts suggest that the functional diversification may differ between the two lineages.
Inflammation Among Women With a History of Gestational Diabetes Mellitus and Diagnosed Diabetes in the Third National Health and Nutrition Examination Survey
Authors: Catherine Kim, Yiling J. Cheng, Gloria L. Beckles
Journal: Diabetes Care (2008)

We compared inflammatory markers among women with a history of gestational diabetes mellitus (hGDM), women with diagnosed diabetes, and unaffected women in a population-based sample.We conducted cross-sectional analyses of 6,346 nonpregnant women in the Third National Health and Nutrition Examination Survey (1988-1994). Women were classified as having hGDM (n = 87), diagnosed diabetes (n = 244), or neither condition (n = 6,015). Inflammatory markers included ferritin, leukocyte count, and C-reactive protein levels.After adjustment, women with diagnosed diabetes had the most marked differences in inflammatory markers compared with unaffected women. Differences between unaffected women and women with hGDM were minimal.Women with diagnosed diabetes have less favorable inflammation profiles than unaffected women and greater ferritin levels than women with hGDM. After adjustment, women with hGDM who have not developed diagnosed diabetes have inflammation profiles similar to those of unaffected women.
Race and Differences in Breast Cancer Survival in a Managed Care Population
Authors: M. U. Yood, C. C. Johnson, A. Blount, J. Abrams, E. Wolman, B. D. McCarthy, U. Raju, D. S. Nathanson, M. Worsham, S. R. Wolman
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: African-American women with breast cancer have poorer survival than European-American women. After adjustment for socioeconomic variables, survival differences diminish but do not disappear, possibly because of residual differences in health care access, biology, or behavior. This study compared breast cancer survival in African-American and European-American women with similar health care access. METHODS: We measured survival in women with breast cancer who are served by a large medical group and a metropolitan Detroit health maintenance organization where screening, diagnosis, treatment, and follow-up are based on standard practices and mammography is a covered benefit. We abstracted data on African-American and European-American women who had been diagnosed with breast cancer from January 1986 through April 1996 (n = 886) and followed these women for survival through April 1997 (137 deaths). RESULTS: African-American women were diagnosed at a later stage than were European-American women. Median follow-up was 50 months. Five-year survival was 77% for African-American and 84% for European-American women. The crude hazard ratio for African-American women relative to European-American women was 1.6 (95% confidence interval [CI] = 1.1-2.2). Adjusting only for stage, the hazard ratio was 1.3 (95% CI = 0.9-1.9). Adjusting only for sociodemographic factors (age, marital status, and income), the hazard ratio was 1.2 (95% CI = 0.8-1.9). After adjusting for age, marital status, income, and stage, the hazard ratio was 1.0 (95% CI = 0.7-1.5). CONCLUSION: Among women with similar medical care access since before their diagnoses, we found ethnic differences in stage of breast cancer at diagnosis. Adjustment for this difference and for income, age, and marital status resulted in a negligible effect of race on survival.
Influence of beta blockade and chemical sympathectomy on myocardial function and arrhythmias in acute ischaemia
Authors: V. SETHI, B. HAIDER, S. S. AHMED, H. A. OLDEWURTEL, T. J. REGAN
Journal: Cardiovascular Research (1973)

Journal Article Influence of beta blockade and chemical sympathectomy on myocardial function and arrhythmias in acute ischaemia Get access VIRENDER SETHI, VIRENDER SETHI From the Department of Medicine, College of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar BUNYAD HAIDER, BUNYAD HAIDER From the Department of Medicine, College of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar S. SULTAN AHMED, S. SULTAN AHMED From the Department of Medicine, College of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar HENRY A. OLDEWURTEL, HENRY A. OLDEWURTEL From the Department of Medicine, College of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar TIMOTHY J. REGAN TIMOTHY J. REGAN 2 From the Department of Medicine, College of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey 07103, USA 2 Address for correspondence: Dr. Timothy J. Regan. New Jersey Medical School, 100 Bergen Street, Newark, New Jersey 07103, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 6, November 1973, Pages 740–747, https://doi.org/10.1093/cvr/7.6.740 Published: 01 November 1973
Molecular composition of an antigen-specific, Ly-1 T suppressor inducer factor. One molecule binds antigen and is I-J-; another is I-J+, does not bind antigen, and imparts an Igh-variable region-linked restriction.
Authors: K Yamauchi, N Chao, D B Murphy, R K Gershon
Journal: The Journal of Experimental Medicine (1982)

Immunized Ly-1+2-T cells (Ly-1 cells) make an antigen-specific soluble suppressor product (Lyl-1 TsiF) that will induce Ly-2+ cells to express suppressive activity but only if the Ly-2+ and the Ly-1 producer cell share genetic polymorphisms that are linked to the Igh locus and in particular that part where the Igh-V (or VH) is encoded. Ly-1 TsiF can be separated into entities, one binds antigen and does not express I-J determinants, and the other is I-J+ and does not bind antigen. Neither of these "subfactors" has biological activity, but a 50:50 mixture of them reconstitutes biological activity that expresses the antigen specificity of the antigen-binding molecule. Any of the three heterologous erythrocytes (antigens) studied can be used for immunization to produce the I-J+ nonantigen-binding factor, i.e., the I-J+ moiety makes no contribution to the factor's specificity. It does, however, determine the intact factor's Igh-V linked restriction. Thus, the antigen combining site of the factor is irrelevant to the factor's Igh-V restriction but crucial for its specificity. The I-J+ molecule does not bind antigen nor influence the factor's antigen specificity but expresses the Igh-V polymorphism (or anti-Igh-V polymorphism) that is required for the transmission of an inductive signal to the factor's Ly-2+ acceptor cell.
Network for Activation of Human Endothelial Cells by Oxidized Phospholipids
Authors: Casey E. Romanoski, Nam Che, Fen Yin, Nguyen Mai, Delila Pouldar, Mete Civelek, Calvin Pan, Sangderk Lee, Ladan Vakili, Wen-Pin Yang, Paul Kayne, Imran N. Mungrue, Jesus A. Araujo, Judith A. Berliner, Aldons J. Lusis
Journal: Circulation Research (2011)

Oxidized palmitoyl arachidonyl phosphatidylcholine (Ox-PAPC) accumulates in atherosclerotic lesions, is proatherogenic, and influences the expression of more than 1000 genes in endothelial cells.To elucidate the major pathways involved in Ox-PAPC action, we conducted a systems analysis of endothelial cell gene expression after exposure to Ox-PAPC.We used the variable responses of primary endothelial cells from 149 individuals exposed to Ox-PAPC to construct a network that consisted of 11 groups of genes, or modules. Modules were enriched for a broad range of Gene Ontology pathways, some of which have not been identified previously as major Ox-PAPC targets. Further validating our method of network construction, modules were consistent with relationships established by cell biology studies of Ox-PAPC effects on endothelial cells. This network provides novel hypotheses about molecular interactions, as well as candidate molecular regulators of inflammation and atherosclerosis. We validated several hypotheses based on network connections and genomic association. Our network analysis predicted that the hub gene CHAC1 (cation transport regulator homolog 1) was regulated by the ATF4 (activating transcription factor 4) arm of the unfolded protein response pathway, and here we showed that ATF4 directly activates an element in the CHAC1 promoter. We showed that variation in basal levels of heme oxygenase 1 (HMOX1) contribute to the response to Ox-PAPC, consistent with its position as a hub in our network. We also identified G-protein-coupled receptor 39 (GPR39) as a regulator of HMOX1 levels and showed that it modulates the promoter activity of HMOX1. We further showed that OKL38/OSGN1 (oxidative stress-induced growth inhibitor), the hub gene in the blue module, is a key regulator of both inflammatory and antiinflammatory molecules.Our systems genetics approach has provided a broad view of the pathways involved in the response of endothelial cells to Ox-PAPC and also identified novel regulatory mechanisms.
Skin test reactivity to natural and recombinant <i>Blomia</i> and <i>Dermatophagoides</i> spp. allergens among mite allergic patients in the UK
Authors: A. Simpson, R. Green, A. Custovic, A. Woodcock, L. K. Arruda, M. D. Chapman
Journal: Allergy (2003)

Many asthmatics in tropical and subtropical areas have positive skin prick tests to both Dermatophagoides spp. and to the mite Blomia tropicalis. This may be due to recognition by IgE of cross-reactive allergens between the different mite species or because of sensitization to species-specific allergens. A 14-kDa Blomia tropicalis allergen, Blo t 5, has been cloned and shows 40% sequence homology with Der p 5. The aim of this study was to investigate reactivity to B. tropicalis in patients known to be sensitized to D. pteronyssinus and to assess allergenic activity and cross-reactivity of recombinant (r) Group 5 allergens amongst these patients, who live in the UK and who are not exposed to B. tropicalis in their homes.Patients (n = 19) with asthma and/or rhinitis were selected based on clinical history and a positive skin prick test to D. pteronyssinus extract and were compared with non-allergic skin test negative controls (n = 10). IgE antibody responses to Blomia tropicalis, Dermatophagoides pteronyssinus, rDer p 5 and rBlo t 5 were compared by quantitative intradermal skin testing using serial 10-fold dilutions of each allergen. End point titre was the highest dilution giving an 8 x 8 mm wheal at 15 min. IgE antibodies to Blomia tropicalis, Dermatophagoides pteronyssinus, rDer p 5 and rBlo t 5 were measured using RAST, CAP and RIA, respectively.All 19 patients had positive skin tests to D. pteronyssinus at concentrations of 0.001 to 1 AU/ml and 10 were skin test positive to rDer p 5 at concentrations of 10-4 to 5 micro g/ml. Positive intradermal tests to Blomia tropicalis were seen in 12/19 patients at concentrations of 0.002 to 2 micro g/ml. However none of the patients had positive skin tests to rBlo t 5. Non-allergic controls were all skin test negative at the highest concentration of each allergen tested. All subjects had quantifiable specific IgE to D. pteronyssinus, but only two had IgE to B. tropicalis. IgE to Der p 5 was found in six patients, but no patients had IgE to Blo t 5.This study of patients naturally exposed to D. pteronyssinus but not to Blomia tropicalis, provides evidence for IgE mediated cross-reactivity between allergens produced by both mite species. The results suggest that the Group 5 allergens of D. pteronyssinus and B. tropicalis are species-specific.
Apoptosis of peripheral blood lymphocytes in patients with juvenile idiopathic arthritis
Authors: E Smolewska
Journal: Annals of the Rheumatic Diseases (2003)

Recent data suggested that abnormalities in mechanisms regulating apoptosis may have a role in the development of the rheumatoid process.To evaluate different aspects of apoptosis in children with juvenile idiopathic arthritis (JIA).The frequency of TUNEL positive peripheral blood (PB) lymphocytes (apoptotic index (AI)), as well as serum CD95 (APO1/Fas) antigen expression and serum levels of sFas and interleukin 15 (IL15), were examined in 44 cases of JIA. Results were correlated with type of onset, activity of JIA, and acute phase indicators.The AI of lymphocytes was significantly higher in patients with JIA than in controls (p=0.020). The mean AI of lymphocytes was increased in JIA with systemic type of onset and high activity (p=0.001). Moreover, IL15 levels in systemic disease were higher than in controls (p=0.012). An increased AI correlated with raised IL15 (p=0.046), erythrocyte sedimentation rate (p=0.005) and C reactive protein (CRP; p=0.017). Additionally, correlation was found between IL15 and CRP levels (p=0.039). CD95 and sFas levels were unchanged compared with controls.PB lymphocytes of children with JIA have an increased tendency to undergo apoptosis. The degree of apoptosis depends on the type of onset and activity of JIA and correlates with serum levels of IL15. Further studies are needed to explain whether this is an epiphenomenon of the disease activity or is related to the pathogenesis of JIA.
The Role of Inflammation and Infection in Coronary Artery Disease
Authors: Anton E. Becker, Onno J. de Boer, Allard C. van der Wal
Journal: Annual Review of Medicine (2001)

▪ Abstract New insights into atherosclerosis, the most common disease affecting coronary arteries, may change therapeutic strategies from largely symptomatic to causal. Atherosclerotic plaques contain a lipid-related, immune-mediated inflammation, with release of secretory products capable of changing plaque morphology. Plaques prone to complications contain large numbers of inflammatory cells; stable plaques contain little inflammation. Similarly, atherectomy specimens from patients with coronary syndromes revealed more inflammatory cells in unstable than in stable patients. These observations, and the fact that acute coronary syndromes are associated with increased blood levels of inflammatory markers, have renewed interest in the possible relationship between infection and atherogenesis. Of all potential candidate antigens, Chlamydia pneumoniae presently is considered the most likely because a substantial number of patients with unstable syndromes contain C. pneumoniae–reactive T cells, both in blood and within the atherosclerotic plaque, suggesting enhancement of intraplaque inflammation.
Eosinophils best marker of steroid response
Authors: N. Martin, C. E. Brightling, I. D. Pavord
Journal: Thorax (2010)

There are important aspects of the study design that cast doubt on the claim of Cowan et al that ‘modified responses’ to corticosteroids occur in patients with non-eosinophilic asthma.1

First, the population recruited was more likely to include patients who experienced loss of control of their asthma after steroid withdrawal than those who remained stable …
Roles of Myofibroblasts in Prostaglandin E2–Stimulated Intestinal Epithelial Proliferation and Angiogenesis
Authors: Jinyi Shao, George G. Sheng, Randy C. Mifflin, Don W. Powell, Hongmiao Sheng
Journal: Cancer Research (2006)

Prostaglandins (PG) are produced throughout the gastrointestinal tract and are critical mediators for a complex array of physiologic and pathophysiologic processes in the intestine. Intestinal myofibroblasts, which express cyclooxygenase (COX) and generate PGE(2), play important roles in intestinal epithelial proliferation, differentiation, inflammation, and neoplasia through secreting growth factors and cytokines. Here, we show that PGE(2) activated human intestinal subepithelial myofibroblasts (18Co) through Gs protein-coupled E-prostanoid receptors and the cyclic AMP/protein kinase A pathway. 18Co cells and primary colonic myofibroblast isolates expressed a number of growth factors; several of them were dramatically regulated by PGE(2). An epidermal growth factor-like growth factor, amphiregulin (AR), which was not expressed by untreated cells, was strongly induced by PGE(2). Expression of vascular endothelial growth factor A (VEGFA) was rapidly increased by PGE(2) exposure. Hepatocyte growth factor (HGF) was elevated in PGE(2)-treated myofibroblasts at both mRNA and protein levels. Thus, PGE(2)-activated myofibroblasts promoted the proliferation and migration of intestinal epithelial cells, which were attenuated by neutralizing antibodies to AR and HGF, respectively. Moreover, in the presence of PGE(2), myofibroblasts strongly stimulated the migration and tubular formation of vascular endothelial cells. Neutralizing antibody to VEGFA inhibited the observed stimulation of migration. These results suggest that myofibroblast-generated growth factors are important mediators for PGE(2)-induced intestinal epithelial proliferation and angiogenesis, which play critical roles in intestinal homeostasis, inflammation, and neoplasia.
Diagnostic classification of shoulder disorders: interobserver agreement and determinants of disagreement
Authors: A. F de Winter, M. P Jans, R. J P M Scholten, W. Deville, D. van Schaardenburg, L. M Bouter
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> To assess the interobserver agreement on the diagnostic classification of shoulder disorders, based on history taking and physical examination, and to identify the determinants of diagnostic disagreement. <h3>METHODS</h3> Consecutive eligible patients with shoulder pain were recruited in various health care settings in the Netherlands. After history taking, two physiotherapists independently performed a physical examination and subsequently the shoulder complaints were classified into one of six diagnostic categories: capsular syndrome (for example, capsulitis, arthritis), acute bursitis, acromioclavicular syndrome, subacromial syndrome (for example, tendinitis, chronic bursitis), rest group (for example, unclear clinical picture, extrinsic causes) and mixed clinical picture. To quantify the interobserver agreement Cohen's κ was calculated. Multivariate logistic regression analysis was applied to determine which clinical characteristics were determinants of diagnostic disagreement. <h3>RESULTS</h3> The study population consisted of 201 patients with varying severity and duration of complaints. The κ for the classification of shoulder disorders was 0.45 (95% confidence intervals (CI) 0.37, 0.54). Diagnostic disagreement was associated with bilateral involvement (odds ratio (OR) 1.9; 95% CI 1.0, 3.7), chronic complaints (OR 2.0; 95% CI 1.1, 3.7), and severe pain (OR 2.7; 95% CI 1.3, 5.3). <h3>CONCLUSIONS</h3> Only moderate agreement was found on the classification of shoulder disorders, which implies that differentiation between the various categories of shoulder disorders is complicated. Especially patients with high pain severity, chronic complaints and bilateral involvement represent a diagnostic challenge for clinicians. As diagnostic classification is a guide for treatment decisions, unsatisfactory reproducibility might affect treatment outcome. To improve the reproducibility, more insight into the reproducibility of clinical findings and the value of additional diagnostic procedures is needed.