tbuckley/cabot-search huggingface dataset:
Clara Cell 10-kD Protein Suppresses Chitinase 3-Like 1 Expression Associated with Eosinophilic Chronic Rhinosinusitis
Authors: Heng Wang, Xiao-Bo Long, Ping-Ping Cao, Nan Wang, Yang Liu, Yong-Hua Cui, Shau-Ku Huang, Zheng Liu
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS).To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model.Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line.Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1beta, tumor necrosis factor-alpha, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation.These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.
Topical methotrexate alters solute and water transport in the rat jejunum in vivo and rabbit ileum in vitro.
Authors: C R Pinkerton, I W Booth, P J Milla
Journal: Gut (1985)

The topical effect of methotrexate (MTX) on small intestinal hexose and ion transport has been studied using an in vivo steady state jejunal perfusion technique in the rat, and short circuited rabbit terminal ileum in Ussing chambers in vitro. In rat jejunum, perfusion with MTX (1 mumol/l) caused significant reductions in water, sodium, and glucose absorption within 110 minutes of exposure. Fructose absorption was, however, unimpaired. The same concentration of MTX, when added to the mucosal side of distal rabbit ileum caused significant increases in transmucosal potential difference, short circuit current and the unidirectional flux of chloride from serosa to mucosa. In the presence of a subphysiological magnesium concentration (0.3 mmol/l), MTX resulted in the abolition of net sodium absorption and the conversion of net chloride absorption to secretion. We conclude that MTX has a topical effect on small intestinal transport which is independent of its effect on crypt cell kinetics.
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials
Authors: Naveed Sattar, David Preiss, Heather M Murray, Paul Welsh, Brendan M Buckley, Anton JM de Craen, Sreenivasa Rao Kondapally Seshasai, John J McMurray, Dilys J Freeman, J Wouter Jukema, Peter W Macfarlane, Chris J Packard, David J Stott, Rudi G Westendorp, James Shepherd, Barry R Davis, Sara L Pressel, Roberto Marchioli, Rosa Maria Marfisi, Aldo P Maggioni, Luigi Tavazzi, Gianni Tognoni, John Kjekshus, Terje R Pedersen, Thomas J Cook, Antonio M Gotto, Michael B Clearfield, John R Downs, Haruo Nakamura, Yasuo Ohashi, Kyoichi Mizuno, Kausik K Ray, Ian Ford
Journal: The Lancet (2010)
Blinded, Randomized, Multicenter Study to Evaluate Single Administration Pegfilgrastim Once per Cycle Versus Daily Filgrastim as an Adjunct to Chemotherapy in Patients With High-Risk Stage II or Stage III/IV Breast Cancer
Authors: F.A. Holmes, J.A. O’Shaughnessy, S. Vukelja, S.E. Jones, J. Shogan, M. Savin, J. Glaspy, M. Moore, L. Meza, I. Wiznitzer, T.A. Neumann, L.R. Hill, B.C. Liang
Journal: Journal of Clinical Oncology (2002)

PURPOSE: This multicenter, randomized, double-blind, active-control study was designed to determine whether a single subcutaneous injection of pegfilgrastim (SD/01, sustained-duration filgrastim; 100 μg/kg) is as safe and effective as daily filgrastim (5 μg/kg/d) for reducing neutropenia in patients who received four cycles of myelosuppressive chemotherapy. PATIENTS AND METHODS: Sixty-two centers enrolled 310 patients who received chemotherapy with docetaxel 75 mg/m 2 and doxorubicin 60 mg/m 2 on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 2 either a single subcutaneous injection of pegfilgrastim 100 μg/kg per chemotherapy cycle (154 patients) or daily subcutaneous injections of filgrastim 5 μg/kg/d (156 patients). Absolute neutrophil count (ANC), duration of grade 4 neutropenia, and safety parameters were monitored. RESULTS: One dose of pegfilgrastim per chemotherapy cycle was comparable to daily subcutaneous injections of filgrastim with regard to all efficacy end points, including the duration of severe neutropenia and the depth of ANC nadir in all cycles. Febrile neutropenia across all cycles occurred less often in patients who received pegfilgrastim. The difference in the mean duration of severe neutropenia between the pegfilgrastim and filgrastim treatment groups was less than 1 day. Pegfilgrastim was safe and well tolerated, and it was similar to filgrastim. Adverse event profiles in the pegfilgrastim and filgrastim groups were similar. CONCLUSION: A single injection of pegfilgrastim 100 μg/kg per cycle was as safe and effective as daily injections of filgrastim 5 μg/kg/d in reducing neutropenia and its complications in patients who received four cycles of doxorubicin 60 mg/m 2 and docetaxel 75 mg/m 2 .
Phylogenetic Analysis of Population-Based and Deep Sequencing Data to Identify Coevolving Sites in the nef Gene of HIV-1
Authors: A. F.Y. Poon, L. C. Swenson, W. W.Y. Dong, W. Deng, S. L. Kosakovsky Pond, Z. L. Brumme, J. I. Mullins, D. D. Richman, P. R. Harrigan, S. D.W. Frost
Journal: Molecular Biology and Evolution (2009)

Rapidly evolving viruses such as HIV-1 display extensive sequence variation in response to host-specific selection, while simultaneously maintaining functions that are critical to replication and infectivity. This apparent conflict between diversifying and purifying selection may be resolved by an abundance of epistatic interactions such that the same functional requirements can be met by highly divergent sequences. We investigate this hypothesis by conducting an extensive characterization of sequence variation in the HIV-1 nef gene that encodes a highly variable multifunctional protein. Population-based sequences were obtained from 686 patients enrolled in the HOMER cohort in British Columbia, Canada, from which the distribution of nonsynonymous substitutions in the phylogeny was reconstructed by maximum likelihood. We used a phylogenetic comparative method on these data to identify putative epistatic interactions between residues. Two interactions (Y120/Q125 and N157/S169) were chosen to further investigate within-host evolution using HIV-1 RNA extractions from plasma samples from eight patients. Clonal sequencing confirmed strong linkage between polymorphisms at these sites in every case. We used massively parallel pyrosequencing (MPP) to reconstruct within-host evolution in these patients. Experimental error associated with MPP was quantified by performing replicates at two different stages of the protocol, which were pooled prior to analysis to reduce this source of variation. Phylogenetic reconstruction from these data revealed correlated substitutions at Y120/Q125 or N157/S169 repeated across multiple lineages in every host, indicating convergent within-host evolution shaped by epistatic interactions.
Midlife Body Mass Index and Hospitalization and Mortality in Older Age
Authors: Lijing L. Yan
Journal: JAMA (2006)

Abundant evidence links overweight and obesity with impaired health. However, controversies persist as to whether overweight and obesity have additional impact on cardiovascular outcomes independent of their strong associations with established coronary risk factors, eg, high blood pressure and high cholesterol level.To assess the relation of midlife body mass index with morbidity and mortality outcomes in older age among individuals without and with other major risk factors at baseline.Chicago Heart Association Detection Project in Industry study, a prospective study with baseline (1967-1973) cardiovascular risk classified as low risk (blood pressure < or =120/< or =80 mm Hg, serum total cholesterol level <200 mg/dL [5.2 mmol/L], and not currently smoking); moderate risk (nonsmoking and systolic blood pressure 121-139 mm Hg, diastolic blood pressure 81-89 mm Hg, and/or total cholesterol level 200-239 mg/dL [5.2-6.2 mmol/L]); or having any 1, any 2, or all 3 of the following risk factors: blood pressure > or =140/90 mm Hg, total cholesterol level > or =240 mg/dL (6.2 mmol/L), and current cigarette smoking. Body mass index was classified as normal weight (18.5-24.9), overweight (25.0-29.9), or obese (> or =30). Mean follow-up was 32 years.Participants were 17,643 men and women aged 31 through 64 years, recruited from Chicago-area companies or organizations and free of coronary heart disease (CHD), diabetes, or major electrocardiographic abnormalities at baseline.Hospitalization and mortality from CHD, cardiovascular disease, or diabetes, beginning at age 65 years.In multivariable analyses that included adjustment for systolic blood pressure and total cholesterol level, the odds ratio (95% confidence interval) for CHD death for obese participants compared with those of normal weight in the same risk category was 1.43 (0.33-6.25) for low risk and 2.07 (1.29-3.31) for moderate risk; for CHD hospitalization, the corresponding results were 4.25 (1.57-11.5) for low risk and 2.04 (1.29-3.24) for moderate risk. Results were similar for other risk groups and for cardiovascular disease, but stronger for diabetes (eg, low risk: 11.0 [2.21-54.5] for mortality and 7.84 [3.95-15.6] for hospitalization).For individuals with no cardiovascular risk factors as well as for those with 1 or more risk factors, those who are obese in middle age have a higher risk of hospitalization and mortality from CHD, cardiovascular disease, and diabetes in older age than those who are normal weight.
Wheeze and Mycoplasma pneumoniae
Authors: C D Shee
Journal: Journal of the Royal Society of Medicine (2002)

There is increasing interest in whether the atypical organisms Mycoplasma pneumoniae and Chlamydia pneumoniae can cause exacerbations of asthma1,2. I describe four previously fit non-asthmatic patients who developed severe wheeze and airways obstruction in association with M. pneumoniae and who made a full recovery. When atypical asthma is associated with systemic symptoms the differential diagnosis should include M. pneumoniae infection.
Lipoproteins and the inhibitory effect of human endothelial cells on platelet function.
Authors: A Nordøy, B Svensson, D Wiebe, J C Hoak
Journal: Circulation Research (1978)

We investigated the effect of plasma low density lipoproteins (LDL), very low density lipoproteins (VLDL), and high density lipoproteins (HDL) on the platelet inhibitory effect of primary cultures of human endothelial cell monolayers (ECM). ECM incubated with lipoprotein-deficient plasma (LDP) for 2 hours at 37 degrees C had an inhibitory effect on ADP- and collagen-induced platelet aggregation and prostaglandin production in platelet-rich plasma similar to that observed when ECM were preincubated with growth medium or plasma. Concentrations of LDL in LDP up to protein concentration of 1600 microgram/ml had an inhibitory effect on the endothelial cells' ability to modulate these platelet reactions. VLDL at the highest concentration (1600 microgram/ml) had a slightly inhibitory effect, whereas HDL showed no such effect. The inhibitory effect of LDL was not observed during the first hour of incubation. When HDL in concentrations similar to or higher than LDL were combined with LDL, the inhibitory effect of LDL was partially reduced. VLDL combined with LDL or HDL did not interfere with the effects of the later fractions. The inhibitory effect of LDL was significantly reduced when LDL were diluted in whole plasma. Prostacyclin which is synthesized and released from the endothelial cells and contributes to the inhibitory effect upon platelets did not change its effect on platelet reactivity by preincubation with the various lipoprotein fractions. The current studies may indicate that LDL have a direct effect on the endothelial cells and that this effect may be partially counteracted by HDL. This effect of LDL on the endothelial cells reduces the endothelium's ability to inhibit platelet aggregation and thus could favor the tendency to thrombus formation.
Antiendothelial cell antibodies in vasculitis and connective tissue disease
Authors: C Belizna, A Duijvestijn, M Hamidou, J W Cohen Tervaert
Journal: Annals of the Rheumatic Diseases (2006)

Antiendothelial cell antibodies (AECA) are a heterogeneous family of antibodies reacting with endothelial cell antigens. These antibodies are found in various diseases and recognise several antigen determinants. Different pathophysiological effects have been observed in in vitro experiments, which include direct or indirect cytotoxicity and endothelial cell apoptosis. Furthermore, some AECA activate endothelial cells, resulting in increased leucocyte adhesiveness, activation of coagulation and vascular thrombosis. In animal models, it has been shown that AECA could promote vascular damage. Neither the endothelial cell antigens nor their precise role in the pathogenecity of different diseases in which AECA are found is well characterised. Nowadays, it is not known whether AECA are an epiphenomenon accompanying vascular injury or whether they are pathogenic. It is controversial whether fluctuations in AECA titres are associated with disease activity during follow-up studies. This review summarises the present knowledge about AECA, AECA antigens and their potential role in the pathogenecity of vasculitis and connective tissue diseases.
Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection or sodium butyrate.
Authors: B Blazar, M Patarroyo, E Klein, G Klein
Journal: The Journal of Experimental Medicine (1980)

Superinfection of latently Epstein-Barr virus (EBV)-carrying Raji cells with the P3HR-1 substrain EBV, known to induce the entry of a substantial fraction of cells into an abortively lytic cycle, increased the susceptibility of the cells to natural killer (NK) effect of human blood lymphocytes. Reciprocal cold-target competition tests with known NK-cell sensitive and -resistant lymphoid cell ines showed that the increased susceptibility is a result of the appearance of an NK-sensitive target, rather than to a general increase in membrane fragility. Lymphocytes of EBV-seropositive and -negative donors were equally effective killers against P3HR-1 virus-superinfected targets. EBV-induced NK sensitivity increased with time. It was a result of some event associated with the intracellular viral cycle, and not to the adherence of viral particles to the cell surface. Induction of EBV-carrying P3HR-1 cells to entry into the viral cycle with n-butyrate also increased their NK sensitivity. A transforming, noncytopathic prototype strain of EBV, B95-8, failed to increase the susceptibility of theRaji cells to NK-lysis, although it had some effect on the Daudi line. Because NK cells can kill virus-producing cells at an early stage of the cycle, before the virus particles are assembled, they may restrict, in vivo, the spread of the virus from latently infected cells.
Onset and Remission of Allergic Rhinitis and Asthma and the Relationship with Atopic Sensitization and Smoking
Authors: PETER P. PLASCHKE, CHRISTER JANSON, EVA NORRMAN, EYTHOR BJÖRNSSON, SUSANNE ELLBJÄR, BENGT JÄRVHOLM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The aim of this study was to assess the influence of some risk factors for onset and remission of allergic rhinitis and asthma in Swedish adults. A random sample of 1,370 subjects, age 20 to 44 yr was investigated by means of postal questionnaires in 1990 and 1993. Skin prick tests were conducted in 1991-1992. The association between risk factors and onset or remission of allergic rhinitis and asthma was estimated using multivariate logistic regression analysis. Onset of allergic rhinitis was associated with sensitization to birch (odds ratio [OR] = 6.5), Parietaria (OR = 7.4); and pets (OR = 3.0) and with female sex (OR = 1.9). Onset of asthma was associated with allergic rhinitis (OR = 4.9), sensitization to pets (OR = 2.4); and with smoking (OR = 3.0). Onset of asthma was strongly associated with allergic rhinitis among atopics (OR = 5.7), but onset of asthma and rhinitis also tended to be related among nonatopics (OR = 3.5). A strong association between smoking and onset of asthma was found among nonatopics (OR = 5.7). In conclusion, sensitization to pollens and pets were risk factors for onset of allergic rhinitis, whereas allergic rhinitis, sensitization to pets, and smoking were risk factors for onset of asthma.
Symptomatic dermographism (factitious urticaria)—passive transfer experiments from human to monkey
Authors: G.M. MURPHY, P.E. ZOLLMAN, M.W. GREAVES, R.K. WINKELMANN
Journal: British Journal of Dermatology (1987)

Passive transfer experiments were carried out on three species of monkey, Macaca mulatta, Macaca nemestrina and Macaca fascicularis, using human serum from patients affected with severe symptomatic dermographism (factitious urticaria), cholinergic urticaria, chronic idiopathic urticaria and normal subjects. The monkeys were tested for dermographism by means of a calibrated dermographometer 24 h after intradermal injection of the serum, using Evans blue as a marker. Positive responses were seen initially in the M. nemestrina. Four sites injected with serum from patients with severe symptomatic dermographism gave positive responses, one site injected with serum from a normal subject produced a faint response. One of the four responses was reproduced one month later in M. fascicularis. These results indicate that passive transfer of dermographism is possible from human to monkey.
Palliative Cancer Care a Decade Later: Accomplishments, the Need, Next Steps—From the American Society of Clinical Oncology
Authors: Frank D. Ferris, Eduardo Bruera, Nathan Cherny, Charmaine Cummings, David Currow, Deborah Dudgeon, Nora JanJan, Florian Strasser, Charles F. von Gunten, Jamie H. Von Roenn
Journal: Journal of Clinical Oncology (2009)

In 1998, the American Society of Clinical Oncology (ASCO) published a special article regarding palliative care and companion recommendations. Herein we summarize the major accomplishments of ASCO regarding palliative cancer and highlight current needs and make recommendations to realize the Society's vision of comprehensive cancer care by 2020.ASCO convened a task force of palliative care experts to assess the state of palliative cancer care in the Society's programs. We reviewed accomplishments, assessed current needs, and developed a definition of palliative cancer. Senior ASCO members and the Board of Directors reviewed and endorsed this article for submission to Journal of Clinical Oncology.Palliative cancer care is the integration into cancer care of therapies that address the multiple issues that cause suffering for patients and their families and impact their life quality. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all patient settings, including outpatient clinics, acute and long-term care facilities, and private homes. Changes in current policy, drug availability, and education are necessary for the integration of palliative care throughout the experience of cancer, for the achievement of quality improvement initiatives, and for effective palliative cancer care research.The need for palliative cancer care is greater than ever notwithstanding the strides made over the last decade. Further efforts are needed to realize the integration of palliative care in the model and vision of comprehensive cancer care by 2020.
Cysteinyl leukotriene receptor 1 gene variation and risk of asthma
Authors: X. Hong, H. Zhou, H-J. Tsai, X. Wang, X. Liu, B. Wang, X. Xu, X. Xu
Journal: European Respiratory Journal (2008)

Although it has been recognised that genetics plays an important role in the development of asthma, important causal loci remain to be identified. The aim of the present study was to examine the association of known and novel candidate genes with asthma. Two independent samples, including 170 asthmatic cases and 347 controls in the initial sample, and 202 asthmatic cases and 332 controls in the confirmation sample, were recruited from the same region of China. Functional single nucleotide polymorphisms (SNPs; n = 129) from 105 genes were genotyped using MassARRAY technology, and 119 SNPs were used for the subsequent analysis. In the initial sample, three SNPs, rs320995 in the cysteinyl leukotriene receptor 1 gene, rs1047266 in the tumour necrosis factor receptor superfamily, member 10b, gene and rs40401 in the interleukin-3 gene, were associated with risk of asthma. Notably, under the recessive genetic model, subjects without the thymidine allele in SNP rs320995 had a 3.1 times higher risk of asthma, which remained significant after accounting for multiple testing. This association was replicated in the confirmation sample and validated by meta-analysis. Further, sex-specific analysis was performed, but no sex difference was found. The present study provided coherent evidence that cysteinyl leukotriene receptor 1 gene variation is associated with risk of asthma.
Increased Mortality in Bulimia Nervosa and Other Eating Disorders
Authors: Scott J. Crow, Carol B. Peterson, Sonja A. Swanson, Nancy C. Raymond, Sheila Specker, Elke D. Eckert, James E. Mitchell
Journal: American Journal of Psychiatry (2009)

Objective: Anorexia nervosa has been consistently associated with increased mortality, but whether this is true for other types of eating disorders is unclear. The goal of this study was to determine whether anorexia nervosa, bulimia nervosa, and eating disorder not otherwise specified are associated with increased all-cause mortality or suicide mortality. Method: Using computerized record linkage to the National Death Index, the authors conducted a longitudinal assessment of mortality over 8 to 25 years in 1,885 individuals with anorexia nervosa (N=177), bulimia nervosa (N=906), or eating disorder not otherwise specified (N=802) who presented for treatment at a specialized eating disorders clinic in an academic medical center. Results: Crude mortality rates were 4.0% for anorexia nervosa, 3.9% for bulimia nervosa, and 5.2% for eating disorder not otherwise specified. All-cause standardized mortality ratios were significantly elevated for bulimia nervosa and eating disorder not otherwise specified; suicide standardized mortality ratios were elevated for bulimia nervosa and eating disorder not otherwise specified. Conclusions: Individuals with eating disorder not otherwise specified, which is sometimes viewed as a “less severe” eating disorder, had elevated mortality risks, similar to those found in anorexia nervosa. This study also demonstrated an increased risk of suicide across eating disorder diagnoses.