tbuckley/cabot-search huggingface dataset:
Bronchial reactivity and dietary antioxidants
Authors: A. Soutar, A. Seaton, K. Brown
Journal: Thorax (1997)

It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants.The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity.Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity.This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.
CD26 Regulates p38 Mitogen-Activated Protein Kinase–Dependent Phosphorylation of Integrin β1, Adhesion to Extracellular Matrix, and Tumorigenicity of T-Anaplastic Large Cell Lymphoma Karpas 299
Authors: Tsutomu Sato, Tadanori Yamochi, Toshiko Yamochi, Ugur Aytac, Kei Ohnuma, Kathryn S. McKee, Chikao Morimoto, Nam H. Dang
Journal: Cancer Research (2005)

CD26 is an antigen with key role in T-cell biology and is expressed on selected subsets of aggressive T-cell malignancies. To elucidate the role of CD26 in tumor behavior, we examine the effect of CD26 depletion by small interfering RNA transfection of T-anaplastic large cell lymphoma Karpas 299. We show that the resultant CD26-depleted clones lose the ability to adhere to fibronectin and collagen I. Because anti-integrin beta1 blocking antibodies also prevent binding of Karpas 299 to fibronectin and collagen I, we then evaluate the CD26-integrin beta1 association. CD26 depletion does not decrease integrin beta1 expression but leads to dephosphorylation of both integrin beta1 and p38 mitogen-activated protein kinase (MAPK). Moreover, our data showing that the p38MAPK inhibitor SB203580 dephosphorylates integrin beta1 and that binding of the anti-CD26 antibody 202.36 dephosphorylates both p38MAPK and integrin beta1 on Karpas 299, leading to loss of cell adhesion to the extracellular matrix, indicate that CD26 mediates cell adhesion through p38MAPK-dependent phosphorylation of integrin beta1. Finally, in vivo experiments show that depletion of CD26 is associated with loss of tumorigenicity and greater survival. Our findings hence suggest that CD26 plays an important role in tumor development and may be a novel therapeutic target for selected neoplasms.
Cystic fibrosis and bone disease: are we missing a genetic link?
Authors: R. M. Aris
Journal: European Respiratory Journal (2005)

The manuscript by King et al. 1 in this issue of the European Respiratory Journal raises the possibility that mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) may be responsible, at least in part, for low bone density in CF cohorts. More than 100 publications from around the globe, the majority in the last decade, have described low bone density in CF adult and, to a lesser extent, paediatric populations. The pathogenesis, epidemiology, clinical manifestations, and preventative and therapeutic options have all been discussed previously 2. While the primary clinical correlates of low bone density in CF have previously been measures of lung function, body mass index and corticosteroid use 2, the good work of King et al. 1 has, for the first time, reported a direct link with ΔF508 (the major disease-causing mutation of the CFTR consisting of deletion of phenylalanine 508). While others have looked for this association in the past without success 3–5, the work of King et al. 1 does raise some very interesting possibilities.

The fundamental question is: do mutations in CFTR cause low bone density and, if so, what are the mechanisms ( via direct channel functions, interaction with other ion channels or other means). This editorial will concentrate almost exclusively on this topic, since other aspects of CF bone disease have been explored in detail elsewhere. The most likely, albeit not the only, link between bone health and CFTR may be found in the gut, kidney, parathyroid glands or bone. A discussion about the well-known effects of pancreatic insufficiency on fat-soluble vitamin absorption and their role in bone mineralisation is excluded here. The most important issue is whether chloride channels, which are numerous in type and expressed almost ubiquitously in all tissues types, are linked to a …
Amelioration of human lupus-like phenotypes in MRL/lpr mice by overexpression of interleukin 27 receptor (WSX-1)
Authors: N Sugiyama, H Nakashima, T Yoshimura, A Sadanaga, S Shimizu, K Masutani, T Igawa, M Akahoshi, K Miyake, A Takeda, A Yoshimura, S Hamano, H Yoshida
Journal: Annals of the Rheumatic Diseases (2007)

In the present work, we investigate the role of interleukin (IL)27/IL27 receptor alpha (Ralpha) (WSX-1) in the development of autoimmune disorders in the MRL/lpr mouse, which is considered as an experimental model of systemic lupus erythaematosus (SLE) in humans.We generated two strains of WSX-1 transgenic mice in the MRL/lpr background with different expression levels of WSX-1, and investigated the effect of WSX-1 overexpression on survival, glomerulonephritis and immunological properties.In comparison with wild type (WT) MRL/lpr and transgenic (Tg) low (TgL) mice, Tg high (TgH) mice exhibited a prolonged lifespan and no apparent development of autoimmune nephritis. Production of anti-dsDNA antibody and total IgG and IgG2a were significantly lower in TgH mice than those of TgL and WT mice. The expressed amounts of interferon (IFN)gamma and IL4 mRNA by CD4+ T cells from Tg mice decreased in a dose-dependent fashion. CD4+ splenic lymphocytes in TgH mice were more subject to the IL27-mediated suppression of cytokine production. In vitro stimulation of CD4+ T cells by IL27 resulted in over phosphorylation of STAT3 in TgH cells than in WT cells.WSX-1 overexpression in the MRL/lpr background rendered the autoimmune prone mice protected from the development of autoimmune diseases. Our results suggest that IL27 signalling may be a therapeutic target against autoimmune diseases, including human SLE.
Abstract 1187: The Metabolic Syndrome is Associated with Impaired Inhibition of Platelet Function by Low-Dose Aspirin
Authors: Dhananjay Vaidya, Lisa R Yanek, Nauder Faraday, Taryn F Moy, Lewis C Becker, Diane M Becker
Journal: Circulation (2008)

Aspirin (ASA) prophylaxis for coronary artery disease (CAD) is recommended for persons with the metabolic syndrome (MetS). We determined the extent to which persons with MetS who also have increase...
Erratum: Corrigendum: Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages
Authors: Sushil Kumar Pathak, Sanchita Basu, Kunal Kumar Basu, Anirban Banerjee, Shresh Pathak, Asima Bhattacharyya, Tsuneyasu Kaisho, Manikuntala Kundu, Joyoti Basu
Journal: Nature Immunology (2015)
Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis
Authors: Janos Sumegi, Michael G. Barnes, Shawnagay V. Nestheide, Susan Molleran-Lee, Joyce Villanueva, Kejian Zhang, Kimberly A. Risma, Alexei A. Grom, Alexandra H. Filipovich
Journal: Blood (2011)
Anxiety and Rehabilitation after Myocardial Infarction
Authors: Kazimierz Wrzesniewski
Journal: Psychotherapy and Psychosomatics (1976)

General and specific anxiety, connected with the fact of myocardial infarction (MI), were investigated in 105 patients before and at the end of posthospitalization rehabilitation. Results as regards general anxiety were compared with data of 63 employed men free of coronary disease and with 34 comparable rheumatic patients. The patients with MI, before the comprehensive rehabilitation, compared with both control groups, have had higher levels of general anxiety in a statistically significant way. At the end of rehabilitation there were no significant differences. There was a significant positive correlation between general and specific anxiety, connected with the fact of MI. During the organized comprehensive posthospitalization rehabilitation, we see that there is a statisticallysignificant decrease of general and specific anxiety.
Actin Gene Family Evolution and the Phylogeny of Coleoid Cephalopods (Mollusca: Cephalopoda)
Authors: D B Carlini, K S Reece, J E Graves
Journal: Molecular Biology and Evolution (2000)

Phylogenetic analysis conducted on a 784-bp fragment of 82 actin gene sequences of 44 coleoid cephalopod taxa, along with results obtained from genomic Southern blot analysis, confirmed the presence of at least three distinct actin loci in coleoids. Actin isoforms were characteri zed through phylogenetic analysis of representative cephalopod sequences from each of the three isoforms, along with translated actin cDNA sequences from a diverse array of metazoan taxa downloaded from GenBank. One of the three isoforms found in cephalopods was closely related to actin sequences expressed in the muscular tissues of other molluscs. A second isoform was most similar to cytoplasmic-specific actin amino acid sequences. The muscle type actins of molluscs were found to be distinct from those of arthropods, suggesting at least two independent derivations of muscle actins in the protostome lineage, although statistical support for this conclusion was lacking. Parsimony and maximum-likelihood analyses of two of the isoforms from which >30 orthologous coleoid sequences had been obtained (one of the cytoplasmic actins and the muscle actin) supported the monophyly of several higher-level coleoid taxa. These included the superorders Octopodiformes and Decapodiformes, the order Octopoda, the octopod suborder Incirrata, and the teuthoid suborder Myopsida. The monophyly of several taxonomic groups within the Decapodiformes was not supported, including the orders Teuthoidea and Sepioidea and the teuthoid suborder Oegopsida. Parametric bootstrap analysis conducted on the simulated cytoplasmic actin data set provided statistical support to reject the monophyly of the Sepioidea. Although parametric bootstrap analysis of the muscle actin isoform did not reject sepioid monophyly at the 5% level, the results (rejection at P = 0.068) were certainly suggestive of sepioid nonmonophyly.
CLINICAL OBSERVATIONS ON THE USE OF PROMETHAZINE HYDROCHLORIDE IN PSYCHIATRIC DISORDERS
Authors: H. J. ERWIN
Journal: American Journal of Psychiatry (1957)

Thirty-nine psychiatric patients were treated with promethazine hydrochloride. The severity of mental disturbances varied considerably from patient to patient. All were in need of psychiatric help, but hospitalization was not recommended. Promethazine hydrochloride was administered orally and intramuscularly. Dosage and method of administration were adjusted according to the needs of the patient. The total daily dosage ranged from 37.5 mg. orally, to combined oral and parenteral administration of 350 mg. Each patient showed some degree of improvement on the individualized regimen prescribed. Of the 39 patients, 11 recovered completely; 18 showed pronounced improvement, and 10 showed moderate improvement. The only side-effect noted was an occasional complaint of pain at the site of injection. None of the serious side-effects reported following use of chlorpromazine and reserpine was observed in this series. Of the 16 patients who have been followed the longest, 6 have maintained improvement on psychotherapy alone, without continued medication; in 8 improvement has been maintained on reduced dosage, and in 2 (psychotic patients) continuation of the original maintenance dose has been required.
Molecular Evidence for Multifocal Papillary Serous Carcinoma of the Peritoneum in Patients With Germline BRCA1 Mutations
Authors: J O Schorge, M G Muto, W R Welch, C A Bandera, S C Rubin, D A Bell, R S Berkowitz, S C Mok
Journal: JNCI Journal of the National Cancer Institute (1998)

Papillary serous carcinoma of the peritoneum (PSCP) diffusely involves peritoneal surfaces, while it spares or only superficially involves the ovaries. PSCP is histologically indistinguishable from serous epithelial ovarian carcinoma, and it may develop years after oophorectomy. The molecular pathogenesis of PSCP remains unresolved, although preliminary data suggest a multifocal origin in some cases. Patients with germline BRCA1 mutations may develop PSCP in addition to breast and ovarian carcinomas. The purpose of this study was to utilize the androgen receptor (AR) gene locus to test the hypothesis that some cases of PSCP have a multifocal origin and to determine if patients with germline BRCA1 mutations develop multifocal PSCP.Specimens of normal and tumor tissues from 22 women with PSCP were obtained, and DNA was extracted. The AR gene locus was evaluated for patterns of loss of heterozygosity (LOH) and X-chromosome inactivation. The methylation-sensitive Hpa II restriction enzyme was used to differentiate the active and inactive X chromosomes. Germline BRCA1 mutation status of the patients was determined previously.Genetic analysis of tumor specimens indicated that five (23%) of 22 case subjects had patterns of selective LOH at the AR locus, consistent with multifocal, polyclonal disease origin. Two patients with selective LOH also had alternating X-chromosome inactivation patterns. Patients with germline BRCA1 mutations were more likely to have evidence of multifocal disease (two-sided Fisher's exact test, P = .01).Our results show that PSCP has a multifocal origin in at least some cases. Furthermore, patients with germline BRCA1 mutations are more likely to develop multifocal PSCP than are patients without BRCA1 mutations.
T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila.
Authors: J A MacLean, R Ownbey, A D Luster
Journal: The Journal of Experimental Medicine (1996)

T lymphocytes have been implicated in controlling the recruitment of eosinophils into the lung in murine models of allergic asthma. The mechanism by which T cells assist in the recruitment of eosinophils to the lung in these models is not completely understood. We hypothesized that eosinophil-active chemokines might be regulated by antigen (Ag)-induced T cell activation in vivo and thereby mediate T cell-dependent eosinophil recruitment. To test this hypothesis, we examined the effect of an anti-CD3 mAb on Ag-induced pulmonary eosinophilia and correlated this with the expression of three eosinophil-active chemokines: eotaxin, macrophage inflammatory protein (MIP)-1 alpha, and RANTES. We found that Ag-induced pulmonary eosinophilia was associated with the induction of eotaxin and MIP-1 alpha, but not RANTES mRNA. Prechallenge treatment with anti-CD3 mAb inhibited eotaxin, but not MIP-1 alpha and RANTES mRNA induction, and significantly reduced eosinophil accumulation in the lung. In addition, Ag-specific antibody responses and mast cell degranulation after Ag challenge in sensitized mice were not affected by T cell elimination, and were not sufficient to induce the expression of eotaxin and cause pulmonary eosinophilia. These findings suggest that eotaxin is one of the molecular links between Ag-specific T cell activation and the recruitment of eosinophils into the airways.
Folate Is Associated with the Natural History of High-Risk Human Papillomaviruses
Authors: Chandrika J. Piyathilake, Olga L. Henao, Maurizio Macaluso, Phillip E. Cornwell, Sreelatha Meleth, Douglas C. Heimburger, Edward E. Partridge
Journal: Cancer Research (2004)

Several micronutrients have been implicated in cervical carcinogenesis. However, their mode of action is still a matter of speculation. In particular, it is unclear whether certain nutrients reduce the probability of acquiring high-risk human papillomavirus (HPV) or whether they facilitate the clearance of high-risk HPV. We conducted a 24-month prospective follow-up study to test the hypothesis that systemic concentrations of folate are associated with the occurrence and duration of high-risk HPV infections after controlling for other micronutrients (vitamins B(12), A, E, and C, total carotene) and known risk factors for high-risk HPV infections and cervical cancer. Circulating concentrations of these micronutrients and risk factors for cervical cancer were determined in a cohort of 345 women who were at risk of developing cervical intraepithelial neoplasia. Using the hybrid capture 2 (HC-2) assay, high-risk HPV status was evaluated at 6-month intervals up to 24 months. All women had at least three consecutive visit high-risk HPV test results. Higher folate status was inversely associated with becoming HC-2 test-positive [odds ratio (OR): 0.27; 95% confidence interval (CI), 0.08-0.91; P = 0.04]. Women with higher folate status were significantly less likely to be repeatedly HC-2 test-positive (OR: 0.33; 95% CI, 0.13-0.86; P = 0.02) and more likely to become test-negative during the study (OR: 2.50; 95% CI, 1.18-5.30; P = 0.02). To our knowledge, this is the first long-term prospective follow-up study reporting an independent protective role of higher folate status on several aspects of the natural history of high-risk HPV after controlling for known risk factors and other micronutrients. Improving folate status in subjects at risk of getting infected or already infected with high-risk HPV may have a beneficial impact in the prevention of cervical cancer.
A Single Nucleotide Polymorphism Associates With the Response of Muscle ATP Synthesis to Long-Term Exercise Training in Relatives of Type 2 Diabetic Humans
Authors: Gertrud Kacerovsky-Bielesz, Michaela Kacerovsky, Marek Chmelik, Michaela Farukuoye, Charlotte Ling, Rochus Pokan, Harald Tschan, Julia Szendroedi, Albrecht Ingo Schmid, Stephan Gruber, Christian Herder, Michael Wolzt, Ewald Moser, Giovanni Pacini, Gerhard Smekal, Leif Groop, Michael Roden
Journal: Diabetes Care (2011)

Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort.A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (VO(2)) during incremental tests and from maximal torque of knee flexors (MaxT(flex)) and extensors (MaxT(ext)) using isokinetic dynamometry. fATP and ectopic lipids were measured with (1)H/(31)P magnetic resonance spectroscopy.Endurance training increased power output and VO(2) by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxT(ext) and MaxT(flex) by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL · min(-1) · m(-2)) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 μmol · mL(-1) · m(-1) (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I.Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity.
Attenuation of virus-induced airway dysfunction in rats treated with imiquimod
Authors: None Stokes, RL Sorkness, MR Kaplan, WL Castleman, MA Tomai, RL Miller, None Lemanske RF
Journal: European Respiratory Journal (1998)

Viral respiratory infections cause acute airway abnormalities consisting of inflammation and physiological dysfunction in both animals and humans. It is likely that inflammatory cell products, such as cytokines, contribute substantially to viral-induced airway dysfunction. We hypothesized that imiquimod, an immune response enhancing agent that induces interferon-alpha, would attenuate the development of airway dysfunction during acute viral illness in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with either imiquimod or water. Respiratory system resistance (Rrs), arterial oxygen tension (Pa,O2), lung viral titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in anaesthetized, paralysed, ventilated rats. Virus-infected, water-treated rats had a significant decrease in Pa,O2 and had significant increases in leucocyte count and Rrs when compared to both the virus-infected, imiquimod-treated, (Pa,O2, p = 0.03; leucocyte count, p = 0.02; and Rrs, p = 0.009) and noninfected, water-treated rats (Pa,O2, p = 0.007; leucocyte count, p = 0.001; and Rrs, p = 0.01). In addition, imiquimod suppressed BAL eosinophils in both virus-infected (p = 0.02) and noninfected (p = 0.001) groups, and lowered overall virus titres (p = 0.03). Thus, both virus-induced airway inflammation and physiological dysfunction were attenuated significantly by imiquimod treatment in this animal model. By further delineating mechanisms by which infections induce airway dysfunction in animal models, more specific pharmacological interventions can be developed for the treatment of virus-induced asthma.
Cancer Chemoprevention Using Natural Vitamin D and Synthetic Analogs
Authors: Kathryn Z Guyton, Thomas W Kensler, Gary H Posner
Journal: The Annual Review of Pharmacology and Toxicology (2001)

Substantial epidemiologic data support a role for vitamin D in cancer prevention. However, dose-limiting hypercalcemic effects have proved a major obstacle to the development of natural vitamin D as a cancer chemopreventive. Structure-activity studies have sought to disassociate the toxicities and chemopreventive activities of vitamin D, and a number of synthetic deltanoids (vitamin D analogs) have shown considerable promise in this regard. Several such compounds have chemopreventive efficacy in preclinical studies, as does natural vitamin D. Data supporting further development of agents of this class include in vitro and in vivo evidence of antiproliferative, proapoptotic, prodifferentiating and antiangiogenic activities. Ongoing studies are aimed at further defining the molecular mechanisms through which vitamin D and synthetic deltanoids affect gene expression and cellular fate. Additional efforts are focused on establishing the chemopreventive index (efficacy vs toxicity) of each synthetic deltanoid.