tbuckley/cabot-search huggingface dataset:
Lung and blood mononuclear cell responses of tuberculosis patients to mycobacterial proteins
Authors: S. B. Sable, D. Goyal, I. Verma, D. Behera, G. K. Khuller
Journal: European Respiratory Journal (2006)

The differences in specificity of human lung and peripheral lymphocytes for mycobacterial antigens (Ag) need to be evaluated in order to identify vaccine candidates against pulmonary tuberculosis (TB). Therefore, the present study examined the response to low molecular weight secretory proteins of Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMCs) from minimal pulmonary TB and non-TB patients. Ag85A, Ag85B, culture filtrate protein (CFP)-31, CFP-22.5, CFP-21, M. tuberculosis protein-64 and an as yet uncharacterised 19 kDa protein were found to be predominantly recognised by BAL cells of TB patients on the basis of lymphocyte proliferation and significant interferon-γ release. However, recognition of CFP-8, 6-kDa early secreted antigenic target, CFP-10, CFP-14.5, M. tuberculosis secretory protein-17 and five other as yet uncharacterised low molecular weight polypeptides was found to be high on the basis of lymphocyte proliferation at the level of PBMCs. Furthermore, BAL macrophages, and not blood monocytes, were found to produce nitric oxide (NO) in response to mycobacterial Ags. Among polypeptides predominantly recognised by BAL lymphocytes, only Ag85A and Ag85B were found to induce both NO and interleukin-12 (p40) by alveolar macrophages. In conclusion, the present results indicate heterogeneity in antigen recognition by bronchoalveolar lavage cells and peripheral mononuclear blood cells of minimal tuberculosis patients, and also suggest the utility of antigen 85 complex polypeptides for the development of a future mucosal antituberculous vaccine.
Training head start family services coordinators (FSCs) to provide case management services to children with asthma
Authors: B. Calabrese, B. Adams, M. Kowzan, K. Riekert, K. Huss, A. Butz, M.L. Winkelstein, P.A. Eggleston, C.S. Rand
Journal: Journal of Allergy and Clinical Immunology (2003)
Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes.
Authors: P M Guyre, P M Morganelli, R Miller
Journal: Journal of Clinical Investigation (1983)

Although recent studies suggest that interferons can increase the number of IgG Fc receptor (FcR gamma) sites on mouse macrophages, direct assessment of similar effects on human mononuclear phagocytes is lacking. We therefore measured the specific binding of 125I- and fluorescein-labeled IgG1 to human monocytes and leukemic cell lines after culture in vitro with highly purified human interferons. We report that natural and recombinant human gamma-interferon causes a dramatic (nearly 10-fold) increase in the number of FcR gamma on normal human monocytes and on the human cell lines HL-60 and U-937. Alpha and beta-interferons cause a modest but significant increase in these receptors. This report demonstrates that gamma-interferon acts directly on human mononuclear phagocytes to increase FcR gamma sites, it identifies a qualitative difference in the physiologic actions of human type I and type II interferons, and it suggests that HL-60 and U-937 cells will be important models for further study of the molecular mechanisms of interferon action. The results reported here could also be the basis for a bioassay to assess the pharmacokinetics and variability of gamma-interferon action on monocytes of individual patients during treatment in vitro and in vivo.
Evolution of the Actin Gene Family in Testate Lobose Amoebae (Arcellinida) is Characterized by Two Distinct Clades of Paralogs and Recent Independent Expansions
Authors: D. J. G. Lahr, T. B. Nguyen, E. Barbero, L. A. Katz
Journal: Molecular Biology and Evolution (2010)

The evolution of actin gene families is characterized by independent expansions and contractions across the eukaryotic tree of life. Here, we assess diversity of actin gene sequences within three lineages of the genus Arcella, a free-living testate (shelled) amoeba in the Arcellinida. We established four clonal lines of two morphospecies, Arcella hemisphaerica and A. vulgaris, and assessed their phylogenetic relationship within the "Amoebozoa" using small subunit ribosomal DNA (SSU-rDNA) genealogy. We determined that the two lines of A. hemisphaerica are identical in SSU-rDNA, while the two A. vulgaris are independent genetic lineages. Furthermore, we characterized multiple actin gene copies from all lineages. Analyses of the resulting sequences reveal numerous diverse actin genes, which differ mostly by synonymous substitutions. We estimate that the actin gene family contains 40–50 paralogous members in each lineage. None of the three independent lineages share the same paralog with another, and divergence between actins reaches 29% in contrast to just 2% in SSU-rDNA. Analyses of effective number of codons (ENC), compositional bias, recombination signatures, and genetic diversity in the context of a gene tree indicate that there are two groups of actins evolving with distinct patterns of molecular evolution. Within these groups, there have been multiple independent expansions of actin genes within each lineage. Together, these data suggest that the two groups are located in different regions of the Arcella genome. Furthermore, we compare the Arcella actin gene family with the relatively well-described gene family in the slime mold Dictyostelium discoideum and other members of the Amoebozoa clade. Overall patterns of molecular evolution are similar in Arcella and Dictyostelium. However, the separation of genes in two distinct groups coupled with recent expansion is characteristic of Arcella and might reflect an unusual pattern of gene family evolution in the lobose testate amoebae. We provide a model to account for both the existence of two distinct groups and the pattern of recent independent expansion leading to a large number of actins in each lineage.
Gene Expression Profiles during<i>In Vivo</i>Human Rhinovirus Infection
Authors: David Proud, Ronald B. Turner, Birgit Winther, Shahina Wiehler, Jay P. Tiesman, Tim D. Reichling, Kenton D. Juhlin, Andy W. Fulmer, Begonia Y. Ho, Amy A. Walanski, Cathy L. Poore, Haruko Mizoguchi, Lynn Jump, Marsha L. Moore, Claudine K. Zukowski, Jeffrey W. Clymer
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases.To define changes in gene expression profiles during in vivo rhinovirus infections.Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections.Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells.Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
Novel Indenoisoquinolines NSC 725776 and NSC 724998 Produce Persistent Topoisomerase I Cleavage Complexes and Overcome Multidrug Resistance
Authors: Smitha Antony, Keli K. Agama, Ze-Hong Miao, Kazutaka Takagi, Mollie H. Wright, Ana I. Robles, Lyuba Varticovski, Muthukaman Nagarajan, Andrew Morrell, Mark Cushman, Yves Pommier
Journal: Cancer Research (2007)

Abstract Camptothecin (CPT) derivatives are effective anticancer drugs, especially against solid tumors. As CPTs are chemically unstable and have clinical limitations, we have synthesized indenoisoquinolines as novel topoisomerase I (Top1) inhibitors. We presently report two indenoisoquinoline derivatives, NSC 725776 and NSC 724998, which have been selected for therapeutic development. Both are potent Top1 inhibitors and induce Top1 cleavage at unique genomic positions compared with CPT. Consistent with Top1 poisoning, protein-linked DNA breaks were detected in cells treated with NSC 725776 and NSC 724998 at nanomolar concentrations. Those drug-induced protein-linked DNA breaks persisted longer after drug removal than those produced by CPT. Studies in human cells in culture show that NSC 725776 and NSC 724998 exert antiproliferative activity at submicromolar concentrations. Furthermore, NSC 725776 and NSC 724998 show cross-resistance in cells deficient or silenced for Top1, which is consistent with their selective Top1 targeting. Similar to other known Top1 inhibitors, NSC 725776–treated and NSC 724998–treated cells show an arrest of cell cycle progression in both S and G2-M and a dependence on functional p53 for their cytotoxicity. Dose-dependent γ-H2AX foci formation was readily observed in cells treated with NSC 725776 and NSC 724998. These γ-H2AX foci were detectable at pharmacologically relevant doses for up to 24 h and thus could be used as biomarkers for clinical trials (phase 0). [Cancer Res 2007;67(21):10397–405]
Inhibition of the Peptidyl-Prolyl-Isomerase Pin1 Enhances the Responses of Acute Myeloid Leukemia Cells to Retinoic Acid via Stabilization of RARα and PML-RARα
Authors: Maurizio Gianni', Andrea Boldetti, Valeria Guarnaccia, Alessandro Rambaldi, Edoardo Parrella, Ivan Raska, Cecile Rochette-Egly, Giannino Del Sal, Alessandra Rustighi, Mineko Terao, Enrico Garattini
Journal: Cancer Research (2009)

The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic activity of the protein. Mutants of Pin1 catalytically inactive or defective for client-protein-binding activity are incapable of inhibiting ligand-dependent RARalpha transcriptional activity. Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with degradation of the nuclear receptors via the proteasome-dependent pathway. In the acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased sensitivity to the cytodifferentiating and antiproliferative activities of all-trans retinoic acid. Treatment of the two cell lines and freshly isolated acute myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of Pin1 causes similar effects. Our results add a further layer of complexity to the regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an important target for strategies aimed at increasing the therapeutic index of retinoids.
Increased accumulation of advanced glycation endproducts in patients with Wegener's granulomatosis
Authors: Karina de Leeuw, Hans Nienhuis, Andries Smit, Coen Stegeman, Cees Kallenberg, Marc Bijl
Journal: Annals of the Rheumatic Diseases (2009)

Wegener's granulomatosis (WG) is a systemic autoimmune disease characterised by an increased risk for cardiovascular disease owing to accelerated atherosclerosis which cannot be fully explained by traditional risk factors.1 Non-traditional risk factors are therefore probably involved. Among these, accumulation of advanced glycation endproducts (AGEs) might be important. AGEs are implicated in vascular pathology2 and are independent predictors of cardiovascular mortality in patients with diabetes and those receiving haemodialysis.3 4

In this study, AGE accumulation, atherosclerosis and levels of the receptor for AGEs (sRAGE) were measured in 24 consecutive patients with WG who fulfilled the American College of Rheumatology criteria5 with inactive disease and 21 controls (table 1). AGE accumulation was assessed as previously described6 and intima media thickness (IMT) in both carotid …
Effect of Complete Revascularization on 10-Year Survival of Patients With Stable Multivessel Coronary Artery Disease
Authors: Ricardo D'Oliveira Vieira, Whady Hueb, Bernard J. Gersh, Eduardo Gomes Lima, Alexandre Costa Pereira, Paulo Cury Rezende, Cibele Larrosa Garzillo, Alexandre Ciappina Hueb, Desiderio Favarato, Paulo Rogério Soares, José Antonio Franchini Ramires, Roberto Kalil Filho
Journal: Circulation (2012)

The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P=0.001). The IR group had more prior myocardial infarction than the CR group (56.2% × 39.2%, P=0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P=0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P=0.05).Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI.URL: http://www.controlled-trials.com.ISRCTN66068876.
The Dead Sea lives! Someone's rockin' my dreamboat
Authors: K. T Weber
Journal: Cardiovascular Research (1995)

Journal Article The Dead Sea lives! Someone's rockin' my dreamboat Get access Karl T Weber Karl T Weber University of Missouri-Columbia, Division of Cardiology, Room MA432 Medical Sciences Building, Columbia, MO 65212, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 5, May 1995, Pages 604–610, https://doi.org/10.1016/S0008-6363(96)88628-7 Published: 01 May 1995 Article history Received: 18 October 1994 Accepted: 06 January 1995 Published: 01 May 1995
Transcription Factors T-bet and GATA-3 Regulate Development of Airway Remodeling
Authors: Takumi Kiwamoto, Yukio Ishii, Yuko Morishima, Keigyou Yoh, Atsuko Maeda, Kazusa Ishizaki, Takashi Iizuka, Ahmed E. Hegab, Yosuke Matsuno, Shinsuke Homma, Akihiro Nomura, Tohru Sakamoto, Satoru Takahashi, Kiyohisa Sekizawa
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Airway remodeling is an important feature of chronic asthma that causes irreversible airflow obstruction. Although asthma is considered to be a Th2 disease, the role of T-bet and GATA-3, the key transcription factors for differentiation toward Th1 and Th2 cells, in the pathogenesis of airway remodeling is poorly understood.We therefore examined the effects of GATA-3 or T-bet induction of Th1/Th2 bias on the development of airway remodeling in mice.The development of airway remodeling after repeated allergen challenges was analyzed using transgenic mice overexpressing either GATA-3 or T-bet.The degrees of subepithelial fibrosis and airway smooth muscle hyperplasia after repeated allergen exposure were significantly enhanced in mice overexpressing GATA-3, compared with wild-type mice. Allergen-induced goblet cell hyperplasia and mucus hypersecretion were significantly lower in mice overexpressing T-bet than in wild-type mice. Eosinophilic airway inflammation increased in mice overexpressing GATA-3, but decreased in mice overexpressing T-bet after repeated allergen exposure. Cytokine analysis revealed that the Th1/Th2 cytokine balance shifted to Th2 in lung homogenates and lung T cells of mice overexpressing GATA-3, whereas this balance shifted to Th1 in those of mice overexpressing T-bet after allergen exposure. Lung transforming growth factor-beta and eotaxin levels were associated with the degree of subepithelial fibrosis and eosinophilic airway inflammation, respectively.Overall, the results indicate that development of airway remodeling is regulated by the lung Th1/Th2 bias induced by GATA-3 and T-bet.
High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran
Authors: M H Derakhshan
Journal: Gut (2004)

<b>Background:</b> In the West, the subsite incidence of gastric cancer has changed in recent decades, with cancer of the cardia increasing in incidence and that of the more distal stomach decreasing. NW Iran has a very high incidence of upper gastrointestinal cancer and we have examined the anatomical site specific incidence in this geographical region. <b>Method and materials:</b> Of 33 718 patients who visited our clinic from March 2000 to Jan 2003, 3119 (9.3%) with persistent upper gastrointestinal symptoms underwent upper gastrointestinal fibreoptic endoscopy. Exact tumour site, subsite, and axial view were determined. Demographic data including age, sex, and place of residence were assessed. Using matched data from the cancer registry and endoscopic survey, age standardised rates (ASR) for all subsites were calculated. <b>Results:</b> Upper gastrointestinal cancer was diagnosed histologically in 499 patients (16.0%). The most frequent site was the gastric cardia (126 (25.3%)) followed by the oesophageal body (90 (18.0%)), antrum (82 (16.4%)), corpus (74 (14.8%)), distal oesophagus (57 (11.4%)), gastro-oesophageal junction (47 (9.4%)), and proximal oesophagus (22 (4.4%)). From axial views of the cardia, 51.4% and 6.8% of tumours were found to originate from the lesser and greater curve, respectively. ASR for gastric cancer were 51.2 in males and 15.4 in females. Cardia cancer with ASR of 26.4 in males and 8.6 in females was the major component of gastric cancer. <b>Conclusion:</b> NW Iran is a geographical region with a very high incidence of cardia cancer and with the great majority originating from the right side of the cardia. This suggests a locally acting luminal carcinogen. Studying the aetiology of this cancer in NW Iran is likely to increase our understanding of the rising incidence of this cancer throughout the Western world.
Recent biochemical approaches to post-testicular, epididymal contraception
Authors: T. Cooper
Journal: Human Reproduction Update (1999)

Results from recent animal models with implications for putative human male contraceptives acting on the epididymis are reviewed. Inducing sterility by enhancing sperm transport through the epididymis has not been achieved. The induction of infertility in males of several species is easier to achieve by direct actions of drugs on sperm function (e.g. inhibition of sperm-specific isoenzymes of the glycolytic pathway by chloro-compounds) than by indirectly reducing amounts of epididymal secretions normally present in high concentration (e.g. α-glucosidase, L-carnitine). The former show promise for the clinic since human spermatozoa are susceptible to inhibition. On the other hand, the infertile male mice of the c-ros knock-out model demonstrate the influence of even a small region of the epididymis on fertility, so that targeting the as yet unknown epididymal factors presumably secreted in limiting amounts by this epididymal segment, is a new lead for a contraceptive. Targeting a specific sperm protein acquired in the testis, but depleted in the epididymis by toxicants that induce rapid infertility, may also lead to the discovery of new contraceptives, but these will require developing new means of organ-specific delivery of contraceptive drugs. Keywords: animal models/antifertility/contraception/epididymis/male infertility
Attention to principles of exercise training: a review of exercise studies for survivors of cancers other than breast
Authors: Kerri M Winters-Stone, Sarah E Neil, Kristin L Campbell
Journal: British Journal of Sports Medicine (2013)

Objectives Randomised controlled trials (RCTs) can evaluate how well a particular exercise programme reduces cancer treatment-related side effects. Adequate design and reporting of the exercise prescription employed in RCTs is central to interpreting study findings and translating effective interventions into practice. Our previous review on the quality and reporting of exercise prescriptions in RCTs in breast cancer survivors revealed several inadequacies. This review similarly evaluates exercise prescriptions used in RCTs in patients with cancers other than the breast. Methods The literature was searched for RCTs in persons diagnosed with a cancer other than breast. Data were extracted to evaluate the attention to the principles of exercise training in the study design and the reporting of and adherence to the exercise prescription used for the intervention. Results Of the 33 studies reviewed, none attended to all of the exercise training principles. Specificity was applied by 89%, progression by 26%, overload by 37%, initial values by 26%, diminishing returns by 9% and reversibility by 3%. Only 2 of 33 studies (6%) reported both the exercise prescription in full and adherence to each individual component of the prescription. Conclusions Application of the principles of training in exercise RCTs of non-breast cancer survivors was incomplete and inconsistent. Given these observations, interpretation of findings from the reviewed studies should consider potential shortcomings in intervention design. Though the prescribed exercise programme was often described, adherence to the entire prescription was rarely reported providing a less accurate picture of dose–response and challenges in translating programmes to community settings.