tbuckley/cabot-search huggingface dataset:
Chemokines in the Pathogenesis of Vascular Disease
Authors: Israel F. Charo, Mark B. Taubman
Journal: Circulation Research (2004)

Our increasing appreciation of the importance of inflammation in vascular disease has focused attention on the molecules that direct the migration of leukocytes from the blood stream to the vessel wall. In this review, we summarize roles of the chemokines, a family of small secreted proteins that selectively recruit monocytes, neutrophils, and lymphocytes to sites of vascular injury, inflammation, and developing atherosclerosis. Chemokines induce chemotaxis through the activation of G-protein-coupled receptors, and the receptors that a given leukocyte expresses determines the chemokines to which it will respond. Monocyte chemoattractant protein 1 (MCP-1), acting through its receptor CCR2, appears to play an early and important role in the recruitment of monocytes to atherosclerotic lesions and in the formation of intimal hyperplasia after arterial injury. Acute thrombosis is an often fatal complication of atherosclerotic plaque rupture, and recent evidence suggests that MCP-1 contributes to thrombin generation and thrombus formation by generating tissue factor. Because of their critical roles in monocyte recruitment in vascular and nonvascular diseases, MCP-1 and CCR2 have become important therapeutic targets, and efforts are underway to develop potent and specific antagonists of these and related chemokines.
Cre-loxP adenovirus-mediated foreign gene expression in skin-equivalent keratinocytes
Authors: Y. Hanakawa, Y. Shirakata, H. Nagai, Y. Yahata, S. Tokumaru, K. Yamasaki, M. Tohyama, K. Sayama, K. Hashimoto
Journal: British Journal of Dermatology (2005)

Journal Article Cre‐loxP adenovirus‐mediated foreign gene expression in skin‐equivalent keratinocytes Get access Y. Hanakawa, Y. Hanakawa Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Shirakata, Y. Shirakata Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Nagai, H. Nagai Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Y. Yahata, Y. Yahata Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Tokumaru, S. Tokumaru Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Yamasaki, K. Yamasaki Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Tohyama, M. Tohyama Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Sayama, K. Sayama Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar K. Hashimoto K. Hashimoto Department of Dermatology, Ehime University School of Medicine, Shitukawa, Toon City 791–0295, Japan E‐mail: hanakawa@m.ehime‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1391–1392, https://doi.org/10.1111/j.1365-2133.2005.06637.x Published: 01 June 2005
Polymorphisms Of Genes Encoding Interleukin-4 and Its Receptor Are Associated With Chronic Idiopathic Urticaria
Authors: Zahra Aryan, Marzieh Tavakol, Ali Akbar Amirzargar, Masoud Movahedi, Alireza Zare Bidoki, Mohammad Gharagozlou, Asghar Aghamohammadi, Mohammad Nabavi, Alireza Ahmadvand, Nasrin Behniafard, Kimia Heidari, Samaneh Soltani, Nima Rezaei
Journal: Journal of Allergy and Clinical Immunology (2014)
Telomere Length in Prospective and Retrospective Cancer Case-Control Studies
Authors: Karen A. Pooley, Manjinder S. Sandhu, Jonathan Tyrer, Mitul Shah, Kristy E. Driver, Robert N. Luben, Sheila A. Bingham, Bruce A.J. Ponder, Paul D.P. Pharoah, Kay-Tee Khaw, Douglas F. Easton, Alison M. Dunning
Journal: Cancer Research (2010)

Abstract Previous studies have reported that shorter mean telomere length in lymphocytes was associated with increased susceptibility to common diseases of aging, and may be predictive of cancer risk. However, most analyses have examined retrospectively collected case-control studies. Mean telomere length was measured using high-throughput quantitative real-time PCR. Blood for DNA extraction was collected after cancer diagnosis in the East Anglian SEARCH Breast (2,243 cases and 2,181 controls) and SEARCH Colorectal (2,249 cases and 2,161 controls) studies. Prospective case-control studies were conducted for breast cancer (199 cases) and colorectal cancer (185 cases), nested within the EPIC-Norfolk cohort. Blood was collected at least 6 months prior to diagnosis, and was matched to DNA from two cancer-free controls per case. In the retrospective SEARCH studies, the age-adjusted odds ratios for shortest (Q4) versus longest (Q1) quartile of mean telomere length was 15.5 [95% confidence intervals (CI), 11.6–20.8; p-het = 5.7 × 10−75], with a “per quartile” P-trend = 2.1 × 10−80 for breast cancer; and 2.14 (95% CI, 1.77–2.59; p-het = 7.3 × 10−15), with a per quartile P-trend = 1.8 × 10−13 for colorectal cancer. In the prospective EPIC study, the comparable odds ratios (Q4 versus Q1) were 1.58 (95% CI, 0.75–3.31; p-het = 0.23) for breast cancer and 1.13 (95% CI, 0.54–2.36; p-het = 0.75) for colorectal cancer risk. Mean telomere length was shorter in retrospectively collected cases than in controls but the equivalent association was markedly weaker in the prospective studies. This suggests that telomere shortening largely occurs after diagnosis, and therefore, might not be of value in cancer prediction. Cancer Res; 70(8); 3170–6. ©2010 AACR.
Investigating regional differences in short-term effects of air pollution on daily mortality in the APHEA project: a sensitivity analysis for controlling long-term trends and seasonality.
Authors: E Samoli, J Schwartz, B Wojtyniak, G Touloumi, C Spix, F Balducci, S Medina, G Rossi, J Sunyer, L Bacharova, H R Anderson, K Katsouyanni
Journal: Environmental Health Perspectives (2001)

Short-term effects of air pollution on daily mortality in eight western and five central-eastern European countries have been reported previously, as part of the APHEA project. One intriguing finding was that the effects were lower in central-eastern European cities. The analysis used sinusoidal terms for seasonal control and polynomial terms for meteorologic variables, but this is a more rigid approach than the currently accepted method, which uses generalized additive models (GAM). We therefore reanalyzed the original data to examine the sensitivity of the results to the statistical model. The data were identical to those used in the earlier analyses. The outcome was the daily total number of deaths, and the pollutants analyzed were black smoke (BS) and sulfur dioxide (SO(2)). The analyses were restricted to days with pollutant concentration < 200 microg/m(3) and < 150 microg/m(3) alternately. We used Poisson regression in a GAM model, and combined individual city regression coefficients using fixed and random-effect models. An increase in BS by 50 microg/m(3) was associated with a 2.2% and 3.1% increase in mortality when analysis was restricted to days < 200 microg/m(3) and < 150 microg/m(3), respectively. The corresponding figures were 5.0% and 5.6% for a similar increase in SO(2). These estimates are larger than the ones published previously: by 69% for BS and 55% for SO(2). The increase occurred only in central-eastern European cities. The ratio of western to central-eastern cities for estimates was reduced to 1.3 for BS (previously 4.8) and 2.6 for SO(2) (previously 4.4). We conclude that part of the heterogeneity in the estimates of air pollution effects between western and central-eastern cities reported in previous publications was caused by the statistical approach used and the inclusion of days with pollutant levels above 150 microg/m(3). However, these results must be investigated further.
Clinical, Biochemical, and Pharmacological Role of Zinc
Authors: A S Prasad
Journal: The Annual Review of Pharmacology and Toxicology (1979)

Although zinc had been known to be essential to the growth of microorgan­ isms for over one hundred years, it was not until 1934 that zinc was shown to be necessary for the growth and well-being of the rat (I, 2). Clinical manifestations in zinc-deficient animals include growth retardation, testicu­ lar atrophy, skin changes, and poor appetite. In 1961 , it was first suspected that zinc deficiency may occur in man (3); this was confirmed in 1963 (4-6). In studies from Iran (7, 8), it was clearly demonstrated that zinc is a principal limiting factor in the nutrition of children and adolescents and that this probably accounted for growth retar­ dation so commonly seen there. Recent reports indicate that marginal deficiency of zinc in man is proba­ bly widespread and common throughout the world including the USA (9, 10). It is also evident that not only nutritional deficiency but also condi­ tioned deficiency of zinc may complicate many diseased states. In recent years, many biochemical and physiological roles of zinc have been reported. The purpose of this paper is to elucidate the clinical, bio­ chemical, and pharmacological role of zinc in human subjects.
Since Chemotherapy Is Now the Standard in Node-Positive Lung Cancer, What Is the Role of Postoperative Radiotherapy?
Authors: Andrew Turrisi, Steven Keller
Journal: Journal of Clinical Oncology (2007)

cardiovascular effects, the final benchmark of success of the hypofractionation approach-overall survival-has not yet been reported for patients treated with hypofractionated regimens.For reliable estimates of the fractionation sensitivity of breast cancer, results of the United Kingdom Standardization of Radiotherapy (UK START) trial A of 2,236 patients (International Standard Randomized Controlled Trial No. 59368779) are eagerly awaited, which includes randomized comparisons of 41.6 Gy in 13 fractions of 3.2 Gy and 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks with a control schedule of 50 Gy in 25 fractions of 2.0 Gy.The results of the UK START Trial B, which randomly assigned 2,215 women to 40 Gy in 15 fractions over 3 weeks or to 50 Gy in 25 fractions over 5 weeks, will attempt to confirm the findings of the Toronto trial.The other current endeavors include the randomized United Kingdom FAST trial, which compares two doses (5.7 Gy and 6.0 Gy) in 5 fractions over 5 weeks with a control dose of 50 Gy in 25 fractions. 12o summarize, hypofractionation in breast cancer is an issue that can have widespread implications in breast cancer throughout the world.If found to have equivalent cosmesis, locoregional control, and survival to standard doses and schedules, it would be a revolutionary breakthrough for the future for breast cancer.Unfortunately, the demonstration of all of these would need follow-up data nearing 15 years.For now, the general acceptance of hypofractionation in breast cancer hangs in the balance.
Local and Circulating Microchimerism Is Associated with Hypersensitivity Pneumonitis
Authors: Martha L. Bustos, Sara Frías, Sandra Ramos, Andrea Estrada, José Luis Arreola, Felipe Mendoza, Miguel Gaxiola, Mauricio Salcedo, Annie Pardo, Moisés Selman
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Hypersensitivity pneumonitis (HP) is a lymphocytic alveolitis provoked by exposure to a variety of antigens. However, the disease occurs in only a subset of exposed individuals, suggesting that additional factors may be involved. Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age.Objectives: To evaluate the presence of circulating and local microchimeric cells in female patients with HP.Methods: Male microchimerism was examined in 103 patients with HP, 30 with idiopathic pulmonary fibrosis (IPF), and 43 healthy women. All of them had given birth to at least one son, with no twin siblings, blood transfusions, or transplants. Microchimerism was examined by dot blot hybridization (peripheral blood), and by fluorescence in situ hybridization in bronchoalveolar lavage cells and lungs.Measurements and Main Results: Blood microchimerism was found in 33% of the patients with HP in comparison with 10% in those with IPF (p = 0.019) and 16% in healthy women (p = 0.045). Patients with HP with microchimerism showed a significant reduction of diffusing capacity of carbon monoxide (DlCO; 53.5 ± 11.9% vs. 65.2 ± 19.7%; p = 0.02) compared with patients with HP without microchimerism. In bronchoalveolar lavage cells, microchimerism was detected in 9 of 14 patients with HP compared with 2 of 10 patients with IPF (p = 0.047). Cell sorting revealed that microchimeric cells were either macrophages or CD4+ or CD8+ T cells. Male microchimeric cells were also found in the five HP lungs examined by fluorescence in situ hybridization.Conclusions: Our findings (1) demonstrate that patients with HP exhibit increased frequency of fetal microchimerism, (2) confirm the multilineage capacity of microchimeric cells, and (3) suggest that microchimeric cells may increase the severity of the disease.
Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8+ T cells directly within the tumor microenvironment
Authors: Stefani Spranger, Holly K Koblish, Brendan Horton, Peggy A Scherle, Robert Newton, Thomas F Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2014)

<h3>Background</h3> Blockade of immune inhibitory pathways is emerging as an important therapeutic modality for the treatment of cancer. Single agent treatments have partial anti-tumor activity in preclinical models and in human cancer patients. Inasmuch as the tumor microenvironment shows evidence of multiple immune inhibitory mechanisms present concurrently, it has been reasoned that combination therapies may be required for optimal therapeutic effect. <h3>Methods</h3> To test this notion, we utilized permutations of anti-CTLA-4 mAb, anti-PD-L1 mAb, and/or the IDO inhibitor INCB23843 in the murine B16.SIY melanoma model. <h3>Results</h3> All three combinations showed markedly improved tumor control over single treatments, with many mice achieving complete tumor rejection. This effect was seen in the absence of vaccination or adoptive T cell therapy. The mechanism of synergy was investigated to examine the priming versus effector phase of the anti-tumor immune response. Only a minimal increase in priming of anti-tumor T cells was observed at early time points in the tumor-draining lymph nodes (TdLN). In contrast, as early as three days after therapy initiation, a marked increase in the capacity of tumor-infiltrating CD8<sup>+</sup> T cells to produce IL-2 and to proliferate was found in all groups treated with the effective combinations. Treatment of mice with FTY720 to block new T cell trafficking from secondary lymphoid structures still enabled restoration of IL-2 production and proliferation by intratumoral T cells, and also retained most of the tumor growth control. <h3>Conclusions</h3> Our data suggest that the therapeutic effect of these immunotherapies was mainly mediated through direct reactivation of T cells in situ. These three combinations are attractive to pursue clinically, and the ability of intratumoral CD8<sup>+</sup> T cells to produce IL-2 and to proliferate could be an important biomarker to integrate into clinical studies.
Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice
Authors: Mitsuteru Akahoshi, Chang Ho Song, Adrian M. Piliponsky, Martin Metz, Andrew Guzzetta, Magnus Åbrink, Susan M. Schlenner, Thorsten B. Feyerabend, Hans-Reimer Rodewald, Gunnar Pejler, Mindy Tsai, Stephen J. Galli
Journal: Journal of Clinical Investigation (2011)

Mast cell degranulation is important in the pathogenesis of anaphylaxis and allergic disorders. Many animal venoms contain components that can induce mast cell degranulation, and this has been thought to contribute to the pathology and mortality caused by envenomation. However, we recently reported evidence that mast cells can enhance the resistance of mice to the venoms of certain snakes and that mouse mast cell-derived carboxypeptidase A3 (CPA3) can contribute to this effect. Here, we investigated whether mast cells can enhance resistance to the venom of the Gila monster, a toxic component of that venom (helodermin), and the structurally similar mammalian peptide, vasoactive intestinal polypeptide (VIP). Using 2 types of mast cell-deficient mice, as well as mice selectively lacking CPA3 activity or the chymase mouse mast cell protease-4 (MCPT4), we found that mast cells and MCPT4, which can degrade helodermin, can enhance host resistance to the toxicity of Gila monster venom. Mast cells and MCPT4 also can limit the toxicity associated with high concentrations of VIP and can reduce the morbidity and mortality induced by venoms from 2 species of scorpions. Our findings support the notion that mast cells can enhance innate defense by degradation of diverse animal toxins and that release of MCPT4, in addition to CPA3, can contribute to this mast cell function.
Lack of Long-term Effects of In Utero Exposure to Zidovudine Among Uninfected Children Born to HIV-Infected Women
Authors: Mary Culnane, Mary Glenn Fowler, Sophia S. Lee, George McSherry, Michael Brady, Karen O'Donnell, Lynne Mofenson, Steven L. Gortmaker, David E. Shapiro, Gwendolyn Scott, Eleanor Jimenez, Ellen C. Moore, Clemente Diaz, Patricia M. Flynn, Bethann Cunningham, James Oleske
Journal: JAMA (1999)

THE SUCcessful perinatal human immunodeficiency virus (HIV) prevention trial, the Pediatric AIDS Clinical Trials Group Protocol 076 (PACTG 076), which included an intensive regimen of zidovudine, were reported in February 1994, use of zidovudine for prevention of mother-toinfant transmission of HIV has become widespread in the United States. 1,2However, the late effects of perinatal exposure to antiretroviral drugs on the subsequent health of uninfected children are unknown and can be determined only by the long-term follow-up of children exposed in utero.Zidovudine is a nucleoside analog reverse transcriptase inhibitor that has been extensively studied in adults and children infected with HIV and shown to--
Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare
Authors: Gunter J Sturm, Bettina Kranzelbinder, Christian Schuster, Eva M Sturm, Danijela Bokanovic, Jutta Vollmann, Karl Crailsheim, Wolfgang Hemmer, Werner Aberer
Journal: Journal of Allergy and Clinical Immunology (2013)
Functional Recovery in a Primate Model of Parkinson's Disease following Motor Cortex Stimulation
Authors: Xavier Drouot, Satoru Oshino, Bechir Jarraya, Laurent Besret, Haruhiko Kishima, Philippe Remy, Julien Dauguet, Jean Pascal Lefaucheur, Frédéric Dollé, Françoise Condé, Michel Bottlaender, Marc Peschanski, Yves Kéravel, Philippe Hantraye, Stéphane Palfi
Journal: Neuron (2004)
Kinase Domain Activation of FGFR2 Yields High-Grade Lung Adenocarcinoma Sensitive to a Pan-FGFR Inhibitor in a Mouse Model of NSCLC
Authors: Jeremy H. Tchaicha, Esra A. Akbay, Abigail Altabef, Oliver R. Mikse, Eiki Kikuchi, Kevin Rhee, Rachel G. Liao, Roderick T. Bronson, Lynette M. Sholl, Matthew Meyerson, Peter S. Hammerman, Kwok-Kin Wong
Journal: Cancer Research (2014)

Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although mouse models of FGFR-driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade 3/4 adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting.
Treatment of bile duct lesions after laparoscopic cholecystectomy.
Authors: J J Bergman, G R van den Brink, E A Rauws, L de Wit, H Obertop, K Huibregtse, G N Tytgat, D J Gouma
Journal: Gut (1996)

<h3>Introduction</h3> Early childhood is an important period for establishing behaviours that will affect weight gain and health across the life course. Early feeding choices, including breast and/or formula, timing of introduction of solids, physical activity and electronic media use among infants and young children are considered likely determinants of childhood obesity. Parents play a primary role in shaping these behaviours through parental modelling, feeding styles, and the food and physical activity environments provided. Children from low socio-economic backgrounds have higher rates of obesity, making early intervention particularly important. However, such families are often more difficult to reach and may be less likely to participate in traditional programs that support healthy behaviours. Parents across all socio-demographic groups frequently access primary health care (PHC) services, including nurses in community health services and general medical practices, providing unparalleled opportunity for engagement to influence family behaviours. One emerging and promising area that might maximise engagement at a low cost is the provision of support for healthy parenting through electronic media such as the Internet or smart phones. The Growing healthy study explores the feasibility of delivering such support via primary health care services. <h3>Methods</h3> This paper describes the Growing healthy study, a non-randomised quasi experimental study examining the feasibility of an intervention delivered via a smartphone app (or website) for parents living in socioeconomically disadvantaged areas, for promoting infant feeding and parenting behaviours that promote healthy rather than excessive weight gain. Participants will be recruited via their primary health care practitioner and followed until their infant is 9 months old. Data will be collected via web-based questionnaires and the data collected inherently by the app itself. <h3>Ethics and dissemination</h3> This study received approval from the University of Technology Sydney Ethics committee and will be disseminated via peer-reviewed publications and conference presentations.