tbuckley/cabot-search huggingface dataset:
Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis
Authors: Wen Hao Wu, Chang Ook Park, Sang Ho Oh, Hee Jung Kim, Yeon Sook Kwon, Byung Gi Bae, Ji Yeon Noh, Kwang Hoon Lee
Journal: Journal of Allergy and Clinical Immunology (2010)
Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy
Authors: Daniele Marras, Leslie A. Bruggeman, Feng Gao, Nozomu Tanji, Mahesh M. Mansukhani, Andrea Cara, Michael D. Ross, G Luca Gusella, Gary Benson, Vivette D. D'Agati, Beatrice H. Hahn, Mary E. Klotman, Paul E. Klotman
Journal: Nature Medicine (2002)
Mechanism of Gender-Specific Differences in Aortic Stiffness With Aging in Nonhuman Primates
Authors: Hongyu Qiu, Christophe Depre, Kaushik Ghosh, Ranillo G. Resuello, Filipinas F. Natividad, Franco Rossi, Athanasios Peppas, You-Tang Shen, Dorothy E. Vatner, Stephen F. Vatner
Journal: Circulation (2007)

Background— Our hypothesis was that the changes in vascular properties responsible for aortic stiffness with aging would be greater in old male monkeys than old female monkeys. Methods and Results— We analyzed the effects of gender differences in aging on in vivo measurements of aortic pressure and diameter and on extracellular matrix of the thoracic aorta in young adult (age, 6.6±0.5 years) versus old adult (age, 21.2±0.2 years) monkeys ( Macaca fascicularis ). Aortic stiffness, as represented by the pressure strain elastic modulus (Ep), increased more in old male monkeys (5.08±0.81; P &lt;0.01) than in old females (3.06±0.52). In both genders, collagen density was maintained, collagen-bound glycation end products increased, and collagen type 1 decreased. However, elastin density decreased significantly (from 22±1.5% to 15±1.2%) with aging ( P &lt;0.05) only in males. Furthermore, only old males were characterized by a decrease ( P &lt;0.05) in collagen type 3 (an isoform that promotes elasticity) and an increase in collagen type 8 (an isoform that promotes the neointimal migration of vascular smooth muscle cells). In contrast to the data in monkeys, collagen types 1 and 3 both increased significantly in aging rats. Conclusions— There are major species differences in the effects of aging on aortic collagen types 1 and 3. Furthermore, because alterations in collagen density, collagen content, hydroxyproline, and collagen advanced glycation end products were similar in both old male and female monkeys, these factors cannot be responsible for the greater increase in stiffness in old males. However, changes in collagen isoforms and the decrease in elastin observed only in old males likely account for the greater increase in aortic stiffness.
Upregulated IL-19 in Breast Cancer Promotes Tumor Progression and Affects Clinical Outcome
Authors: Chung-Hsi Hsing, Hung-Chi Cheng, Yu-Hsiang Hsu, Chien-Hui Chan, Ching-Hua Yeh, Chien-Feng Li, Ming-Shi Chang
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome. Experimental Design: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19–overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured. Results: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19–overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung. Conclusions: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer. Clin Cancer Res; 18(3); 713–25. ©2011 AACR.
Electrophysiological Maturation and Integration of Murine Fetal Cardiomyocytes After Transplantation
Authors: Marcel Halbach, Kurt Pfannkuche, Frank Pillekamp, Agnieszka Ziomka, Tobias Hannes, Michael Reppel, Juergen Hescheler, Jochen Müller-Ehmsen
Journal: Circulation Research (2007)

In the present study, we investigated the electrophysiological maturation and integration of immature cardiomyocytes after transplantation; maturation and integration are essential to achieve the cardiac regeneration. Murine fetal cardiomyocytes (FCMs) (d12.5-d15.5) expressing enhanced green fluorescent protein under the control of the alpha-actin promoter were injected into cryoinjured areas and adjacent myocardium of cryoinjured mouse ventricles. Viable short axis tissue slices (thickness, 150 microm) of the ventricles were prepared 5 to 6 days after transplantation. Glass microelectrodes were used for measurements of action potentials in transplanted FCMs and host cardiomyocytes within the slices. Stimulation at frequencies of up to 10 Hz was performed via a unipolar electrode placed in viable host tissue. Transplanted FCMs could be distinguished clearly from host tissue by their green fluorescence and their electrophysiological properties: maximal upstroke velocity (V(max)) was significantly lower and action potential duration at 50% repolarization (APD(50)) was significantly longer compared with values of adult cardiomyocytes. Transplanted FCMs surrounded by cryoinjured tissue showed spontaneous electrical and contractile activity, which was in no case synchronous with host tissue. V(max) and APD(50) of these nonintegrated cells matched values of cultivated dissociated FCMs. In contrast, 82% of transplanted FCMs surrounded by viable host tissue were electrically integrated; ie, electrical and contractile activity was synchronous with host tissue and these cells had more mature action potential parameters (significantly higher V(max) and shorter APD(50)) compared with nonintegrated FCMs. In conclusion, electrophysiological maturation and integration of transplanted FCMs depend on an embedment in viable host myocardium. FCMs surrounded by cryoinjured tissue maintain physiological but immature AP properties.
Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial
Authors: Wenying Yang, Jie Liu, Zhongyan Shan, Haoming Tian, Zhiguang Zhou, Qiuhe Ji, Jianping Weng, Weiping Jia, Juming Lu, Jing Liu, Yuan Xu, Zhaojun Yang, Wei Chen
Journal: The Lancet Diabetes & Endocrinology (2013)
Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib
Authors: Chan Y. Cheah, Kate Burbury, Jane F. Apperley, Francoise Huguet, Vincenzo Pitini, Martine Gardembas, David M. Ross, Donna Forrest, Philippe Genet, Philippe Rousselot, Nigel Patton, Graeme Smith, Cynthia E. Dunbar, Sawa Ito, Ricardo C. T. Aguiar, Olatoyosi Odenike, Alla Gimelfarb, Nicholas C. P. Cross, John F. Seymour
Journal: Blood (2014)
Prognostic Model Predicting Metastatic Castration-Resistant Prostate Cancer Survival in Men Treated With Second-Line Chemotherapy
Authors: S. Halabi, C.-Y. Lin, E. J. Small, A. J. Armstrong, E. B. Kaplan, D. Petrylak, C. N. Sternberg, L. Shen, S. Oudard, J. de Bono, O. Sartor
Journal: JNCI Journal of the National Cancer Institute (2013)

Several prognostic models for overall survival (OS) have been developed and validated in men with metastatic castration-resistant prostate cancer (mCRPC) who receive first-line chemotherapy. We sought to develop and validate a prognostic model to predict OS in men who had progressed after first-line chemotherapy and were selected to receive second-line chemotherapy. Data from a phase III trial in men with mCRPC who had developed progressive disease after first-line chemotherapy (TROPIC trial) were used. The TROPIC was randomly split into training (n = 507) and testing (n = 248) sets. Another dataset consisting of 488 men previously treated with docetaxel (SPARC trial) was used for external validation. Adaptive least absolute shrinkage and selection operator selected nine prognostic factors of OS. A prognostic score was computed from the regression coefficients. The model was assessed on the testing and validation sets for its predictive accuracy using the time-dependent area under the curve (tAUC). The nine prognostic variables in the final model were Eastern Cooperative Oncology Group performance status, time since last docetaxel use, measurable disease, presence of visceral disease, pain, duration of hormonal use, hemoglobin, prostate specific antigen, and alkaline phosphatase. The tAUCs for this model were 0.73 (95% confidence interval [CI] = 0.72 to 0.74) and 0.70 (95% CI = 0.68 to 0.72) for the testing and validation sets, respectively. A prognostic model of OS in the postdocetaxel, second-line chemotherapy, mCRPC setting was developed and externally validated. This model incorporates novel prognostic factors and can be used to provide predicted probabilities for individual patients and to select patients to participate in clinical trials on the basis of their prognosis. Prospective validation is needed.
Effect of chronic theophylline therapy on brain blood flow and function in adult asthmatics.
Authors: D L Bowton, D A Stump, R Anderson
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The impact of theophylline therapy on neuropsychological (NP) function in adult asthmatics is unclear. Additionally, whether the previously demonstrated acute reduction in cerebral blood flow (CBF) persists with continued administration of theophylline, or whether accommodation develops, has not been previously reported. We examined the effects of chronic theophylline administration on CBF and NP function in adults with mild to moderate asthma. Sixty adult patients with mild to moderate asthma were entered into this double-blind, placebo-controlled, crossover, random sequence study. Subjects received theophylline or placebo for 6 wk interposed with a 2-wk washout period. At the conclusion of Week 1 and Week 6 of each drug phase, patients received NP testing, and CBF was determined using the 133Xenon washout method. Forty-three patients completed the study. Theophylline administration was associated with small (6%), but statistically significant, reductions in CBF after both 1 and 6 wk of treatment. No differences consequent to theophylline administration were observed in any of the tests of NP function after 1 or 6 wk of therapy. While CBF was decreased after theophylline, the changes were small compared with previously reported decrements in CBF immediately after theophylline administration.
A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma
Authors: Eva Hoster, Martin Dreyling, Wolfram Klapper, Christian Gisselbrecht, Achiel van Hoof, Hanneke C. Kluin-Nelemans, Michael Pfreundschuh, Marcel Reiser, Bernd Metzner, Hermann Einsele, Norma Peter, Wolfram Jung, Bernhard Wörmann, Wolf-Dieter Ludwig, Ulrich Dührsen, Hartmut Eimermacher, Hannes Wandt, Joerg Hasford, Wolfgang Hiddemann, Michael Unterhalt
Journal: Blood (2007)
Mutational Bias and Gene Conversion Affect the Intraspecific Nitrogen Stoichiometry of the Arabidopsis thaliana Transcriptome
Authors: Torsten Günther, Christian Lampei, Karl J. Schmid
Journal: Molecular Biology and Evolution (2012)

The transcriptome and proteome of Arabidopsis thaliana are reduced in nitrogen content when compared with other taxa, which may result from ecological nitrogen limitation. We hypothesized that if the A. thaliana transcriptome is selected for a low nitrogen content, nitrogen-reducing derived alleles of single nucleotide polymorphisms (SNPs) should segregate at higher frequencies than nitrogen-increasing alleles. This pattern should be stronger in populations with a larger effective population size (Ne) if natural selection is more efficient in large than in small populations. We analyzed variation in the nitrogen content in the transcriptome of 80 natural accessions of A. thaliana. In contrast to our expectations, derived alleles increase the nitrogen content in all accessions, and there is a positive correlation between nitrogen difference and derived allele frequency, which is strongest with nonsynonymous SNPs (nsSNPs). Also, there is a positive correlation between nitrogen difference and Ne that was mainly caused by nsSNPs. These observations led us to reject the hypothesis that the transcriptome of A. thaliana is currently under selection to reduce nitrogen content. Instead, we show that a change in nitrogen content is a side effect of interacting evolutionary factors that influence base composition and include mutational bias, purifying selection of functionally deleterious alleles, and GC-biased gene conversion. We provide strong evidence that GC-biased gene conversion may play an important role for base composition in the highly selfing plant A. thaliana.
Airway obstruction and rheumatoid arthritis
Authors: A Vergnenegre, N Pugnere, MT Antonini, M Arnaud, B Melloni, R Treves, F Bonnaud
Journal: European Respiratory Journal (1997)

The aim of this study was to assess the percentage of respiratory disorders and airway obstruction in patients with rheumatoid arthritis by comparing lung function test results between patients with rheumatoid arthritis and control subjects with other rheumatological conditions. A prospective case-control study of respiratory symptoms and lung function abnormalities was performed in a series of 100 patients with rheumatoid arthritis. Eighty eight patients with other rheumatological diseases served as controls. Diagnosis of respiratory disorders was based on clinical, radiological and spirometric findings. Airway obstruction was determined from predicted values. The results were compared using Student's t-test and Chi-squared tests. An explanatory analysis was carried out by linear regression. The number of symptoms, respiratory disorders (including bronchiectasis) and lung function abnormalities was higher in patients with rheumatoid arthritis than in controls. After exclusion of smokers, the proportion of airway obstruction in patients with rheumatoid arthritis was 16% (versus 0% in controls), although the patients with rheumatoid arthritis still had more symptoms and respiratory disorders. The Chi-squared test did not identify any relationship between airway obstruction, duration of rheumatoid arthritis and type of treatment and occurrence of Sjogren's syndrome. In the nonsmokers, different explanatory models for the patients with and without a history of cardiac and respiratory disease emerged from multivariate analysis of indices of obstruction. These models included variables characterizing the severity and course of the rheumatoid arthritis. Respiratory disorders (including bronchiectasis) and airway obstruction are more frequent among patients with rheumatoid arthritis than in rheumatological controls. Although the exact pathophysiology of the link between bronchial obstruction and rheumatoid arthritis is still a matter of debate, explanatory factors for obstruction included variables characterizing the rheumatoid arthritis.
Regulation of Endothelial Nitric Oxide Synthase Expression by Albumin-Derived Advanced Glycosylation End Products
Authors: Armando Rojas, Sheyla Romay, Deyarina González, Beatriz Herrera, Rene Delgado, Karel Otero
Journal: Circulation Research (2000)

We examined whether albumin-derived advanced glycosylation end products (AGEs) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic endothelial cells were observed when exposed to different concentrations of albumin-derived AGEs. Western and Northern blot analyses showed significant decreases at the protein and transcript levels. Both reductions became evident after 24 hours of exposure. Nuclear run-on assays showed that AGE-BSA did not modify the transcription rate of the NOS III gene; however, AGE-BSA treatment markedly reduced the half-life of NOS III mRNA. In addition, AGE-treated endothelial cells displayed significant reduction on their antiplatelet properties. These results indicate that NOS expression is reduced by AGEs by increasing the rate of mRNA degradation and may be relevant to the impairment of some endothelial functions observed in diabetes and aging. The full text of this article is available at http://www.circresaha.org.
The Basel Institute for Immunology
Authors: Fritz Melchers
Journal: Annual Review of Immunology (2012)

At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it one of the ten cradles of creativity. The journal Nature likened its ideals to those of the French revolution--Liberté, Egalité, Fraternité--and called it a paradise devoted to the science of immune systems: the Basel Institute for Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in 2000, it was home to almost 450 scientific members, over 1,000 scientific visitors, and nearly 100 scientific advisors from more than 30 countries who worked in complete academic freedom and without commercial motives on over 3,500 projects, publishing more than 3,200 scientific papers, almost all of them on the structure and functions of immune systems of different species. This review contains a first collection of historical facts and dates that describe the background of the exceptionally successful performance and the strong scientific impact of the institute on the field of immunology.
Predicting Time to Nursing Home Care and Death in Individuals With Alzheimer Disease
Authors: Yaakov Stern, Min Xing Tang, Marilyn S. Albert, Jason Brandt, Diane M. Jacobs, Karen Bell, Karen Marder, Mary Sano, Devangere Devanand, Steven M. Albert, Frederick Bylsma, Wei Yann Tsai
Journal: JAMA (1997)

<h3>Objective.</h3> —To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. <h3>Design.</h3> —Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. <h3>Setting.</h3> —Three AD research centers. <h3>Patients.</h3> —All patients met National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. <h3>Intervention.</h3> —Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. <h3>Main Outcome Measures.</h3> —(1) Requiring the equivalent of nursing home placement and (2) death. <h3>Results.</h3> —Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted.Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients.When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. <h3>Conclusions.</h3> —The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.
Effect of Iron Fortification on Malaria Incidence in Infants and Young Children in Ghana
Authors: Stanley Zlotkin, Samuel Newton, Ashley M. Aimone, Irene Azindow, Seeba Amenga-Etego, Kofi Tchum, Emmanuel Mahama, Kevin E. Thorpe, Seth Owusu-Agyei
Journal: JAMA (2013)

In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies. In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas.To determine the effect of providing a micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area.Double-blind, cluster randomized trial of children aged 6 to 35 months (n = 1958 living in 1552 clusters) conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia (hemoglobin level <7 g/dL), or severe wasting (weight-for-length z score <-3).Children were randomized by cluster to receive a MNP with iron (iron group; 12.5 mg/d of iron) or without iron (no iron group). The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated.Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period.In intention-to-treat analyses, malaria incidence overall was significantly lower in the iron group compared with the no iron group (76.1 and 86.1 episodes/100 child-years, respectively; risk ratio (RR), 0.87 [95% CI, 0.79-0.97]), and during the intervention period (79.4 and 90.7 episodes/100 child-years, respectively; RR, 0.87 [95% CI, 0.78-0.96]). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (adjusted RR, 0.87; 95% CI, 0.75-1.01) and during the intervention period (adjusted RR, 0.86; 95% CI, 0.74-1.00).In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available, daily use of a MNP with iron did not result in an increased incidence of malaria among young children.clinicaltrials.gov Identifier: NCT01001871.
Signal transduction and oxidative processes in sinonasal polyposis
Authors: Steven B. Cannady, Pete S. Batra, Rachel Leahy, Martin J. Citardi, Allison Janocha, Kristin Ricci, Suzy A.A. Comhair, Melanie Bodine, Zeneng Wang, Stanley L. Hazen, Serpil C. Erzurum
Journal: Journal of Allergy and Clinical Immunology (2007)