tbuckley/cabot-search huggingface dataset:
Role of interleukin-5 and substance P in development of airway hyperreactivity to histamine in guinea-pigs
Authors: AJ Van Oosterhout, I van Ark, G Hofman, HJ Van Der Linde, D Fattah, FP Nijkamp
Journal: European Respiratory Journal (1996)

In this study, we examined the mechanism by which bronchoalveolar lavage (BAL) cells induced hyperreactivity of the trachea in vitro. As both interleukin-5 (IL-5) and substance P (SP) appeared to be involved, the effect of these mediators was examined in vivo. Tracheae were incubated with BAL cells from ovalbumin or saline challenged animals, and from naive animals, in the absence or presence of either IL-5, SP, or both. In addition, the effect of intra-airway application of IL-5, SP, both, or vehicle on tracheal hyperreactivity was examined. Incubation of tracheae with BAL cells from ovalbumin challenged animals induced an increase (30 +/- 10%) in the maximal response to histamine. The hyperreactivity could be completely inhibited by co-incubation with 5-lipoxygenase inhibitor, AA861. The hyperreactivity could be mimicked by incubation of tracheae with BAL cells from naive animals in the presence of IL-5 and SP. After in vivo administration of either IL-5 or SP, maximal responses to histamine were increased and amounted to 105 +/- 35 and 101 +/- 37%, respectively. Administration of IL-5 but not SP induced a significant increase in the number of eosinophils (67 +/- 22%) and eosinophil peroxidase (EPO) activity (94 +/- 33%) in BAL cells. The simultaneous administration of IL-5 and SP did not potentiate the hyperreactivity and eosinophilia observed with IL-5 alone. These data suggest that IL-5 is important in the recruitment of eosinophils, whereas both IL-5 and substance P are involved in the induction of airway hyperreactivity.
Oophorectomy and Tamoxifen Adjuvant Therapy in Premenopausal Vietnamese and Chinese Women With Operable Breast Cancer
Authors: Richard R. Love, Nguyen Ba Duc, D. Craig Allred, Nguyen Cong Binh, Nguyen Van Dinh, Nguyen Ngoc Kha, Tran Van Thuan, Syed K. Mohsin, Le Dinh Roanh, Hoang Xuan Khang, Trinh Luong Tran, Tran Tu Quy, Nguyen Van Thuy, Pham Nhu Thé, Ton That Cau, Nguyen Dinh Tung, Dang Thanh Huong, Le Minh Quang, Nguyen Ngoc Hien, Le Thuong, Tian-zhen Shen, Ye Xin, Qian Zhang, Thomas C. Havighurst, Yonghong Fred Yang, Bruce E. Hillner, David L. DeMets
Journal: Journal of Clinical Oncology (2002)

PURPOSE: In 1992, the Early Breast Cancer Trialists’ Collaborative Group reported that a meta-analysis of six randomized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation. Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer (652 from Vietnam, 47 from China) to a randomized clinical trial of adjuvant oophorectomy and tamoxifen (20 mg orally every day) for 5 years or observation and this combined hormonal treatment on recurrence. At later dates estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases (66%). RESULTS: Treatment arms were well balanced. With a median follow-up of 3.6 years, there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group, with 5-year disease-free survival rates of 75% and 58% (P = .0003 unadjusted; P = .0075 adjusted), and overall survival rates of 78% and 70% (P = .041 unadjusted) for the adjuvant and observation groups, respectively. Only patients with hormone receptor–positive tumors benefited from the adjuvant treatment. In Vietnam, for women unselected for hormone receptor status, a cost-effectiveness analysis suggests that this intervention costs $350 per year of life saved. CONCLUSION: Vietnamese and Chinese women with hormone receptor–positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.
Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.
Authors: J S Goodwin, A D Bankhurst, R P Messner
Journal: The Journal of Experimental Medicine (1977)

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.
Abstract A33: Combination immunotherapy with anti-CD40 mAb and MPL results in T cell-independent antitumor effects against B16 melanoma in mice.
Authors: Tyler Van De Voort, Paul Sondel, Mildred Felder, Richard Young, Nicholas Kalogriopoulos, Alexander Rakhmilevich
Journal: Cancer Research (2013)

Abstract Combination immunotherapies are promising candidates for clinical testing. In this study, monophosphoryl lipid A (MPL), a nontoxic derivative of LPS and agonist of Toll-like receptor (TLR) 4, was tested in combination with an agonistic anti-CD40 monoclonal antibody (anti-CD40) to assess the antitumor synergy between the two agents. We show that anti-CD40 is capable of priming mouse macrophages for subsequent ex vivo activation by MPL to an extent comparable to a TLR9 agonist, CpG. When given intratumorally (i.t.) to C57BL/6 mice bearing subcutaneous B16 melanoma, anti-CD40 and MPL induced synergistic antitumor effects. When administered i.t. into a primary tumor, anti-CD40 and MPL also slowed the growth of a secondary tumor growing simultaneously at a distant site in both immunocompetent mice and mice depleted of T cells. Taken together, our results show that the antitumor effects of anti-CD40 are enhanced by subsequent treatment with MPL, even in T cell-deficient hosts. These data suggest that anti-CD40+MPL could be a clinically promising immunotherapy for immunosuppressed cancer patients. Citation Format: Tyler Van De Voort, Paul Sondel, Mildred Felder, Richard Young, Nicholas Kalogriopoulos, Alexander Rakhmilevich. Combination immunotherapy with anti-CD40 mAb and MPL results in T cell-independent antitumor effects against B16 melanoma in mice. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A33.
Primary Intravitreal Bevacizumab (Avastin) for Diabetic Macular Edema
Authors: J. Fernando Arevalo, Jans Fromow-Guerra, Hugo Quiroz-Mercado, Juan G. Sanchez, Lihteh Wu, Mauricio Maia, Maria H. Berrocal, Adriana Solis-Vivanco, Michel E. Farah
Journal: Ophthalmology (2007)
Ovulation induction in perspective
Authors: Roy Homburg, Vaclav Insler
Journal: Human Reproduction Update (2002)

It has been suggested recently that, in some quarters, IVF be offered as first-line therapy to all infertile couples, regardless of the type of infertility. Hence, the time was thought right to scrutinise the results and complications of ovulation induction for anovulatory infertile couples. In addition to examining the outcome of conventional treatment with gonadotrophins and clomiphene citrate, special attention has been paid to the suggested improvement of results by taking into account the influence of obesity and the use of a low-dose gonadotrophin protocol. The possible contribution of more recent additions to the armamentarium such as insulin sensitizers and aromatase inhibitors, although still at an infant stage, are promising. Attention has been given to the prevention and treatment of ovarian hyperstimulation syndrome. The use of intra-uterine insemination (IUI) as an adjuvant to induction of ovulation and controlled ovarian hyperstimulation (COH) is examined. The very firm conclusion has been reached that, taking into account efficiency, complication rate and cost of treatment, at this stage, women with hypogonadotrophic hypogonadism or polycystic ovary syndrome should be offered accepted methods of ovulation induction and that couples with 'unexplained' or 'multifactorial subfertility' should still be exposed to COH with IUI and only after the failure of these therapies, be offered IVF.
Organization of the genes encoding complement receptors type 1 and 2, decay-accelerating factor, and C4-binding protein in the RCA locus on human chromosome 1.
Authors: M C Carroll, E M Alicot, P J Katzman, L B Klickstein, J A Smith, D T Fearon
Journal: The Journal of Experimental Medicine (1988)

The organization and physical linkage of four members of a major complement locus, the RCA locus, have been determined using the technique of pulsed field gradient gel electrophoresis in conjunction with Southern blotting. The genes encoding CR1, CR2, DAF, and C4bp were aligned in that order within a region of 750 kb. In addition, the 5' to 3' orientation of the CR1 gene (5' proximal to CR2) was determined using 5'- and 3'-specific DNA probes. The proximity of these genes may be related to structural and functional homologies of the protein products. Overall, a restriction map including 1,500 kb of DNA was prepared, and this map will be important for positioning of additional coding sequences within this region on the long arm of chromosome 1.
Gemtuzumab ozogamicin (Mylotarg®) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups
Authors: S Amadori, S Suciu, R Stasi, R Willemze, F Mandelli, D Selleslag, C Denzlinger, P Muus, R Stauder, Z Berneman, J Pruijt, F Nobile, V Cassibba, J-P Marie, F Beeldens, L Baila, M Vignetti, T de Witte
Journal: Leukemia (2005)
MT<sub>1</sub> and MT<sub>2</sub> Melatonin Receptors: A Therapeutic Perspective
Authors: Jiabei Liu, Shannon J. Clough, Anthony J. Hutchinson, Ekue B. Adamah-Biassi, Marina Popovska-Gorevski, Margarita L. Dubocovich
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Melatonin, or 5-methoxy-N-acetyltryptamine, is synthesized and released by the pineal gland and locally in the retina following a circadian rhythm, with low levels during the day and elevated levels at night. Melatonin activates two high-affinity G protein-coupled receptors, termed MT1 and MT2, to exert beneficial actions in sleep and circadian abnormality, mood disorders, learning and memory, neuroprotection, drug abuse, and cancer. Progress in understanding the role of melatonin receptors in the modulation of sleep and circadian rhythms has led to the discovery of a novel class of melatonin agonists for treating insomnia, circadian rhythms, mood disorders, and cancer. This review describes the pharmacological properties of a slow-release melatonin preparation (i.e., Circadin®) and synthetic ligands (i.e., agomelatine, ramelteon, tasimelteon), with emphasis on identifying specific therapeutic effects mediated through MT1 and MT2 receptor activation. Discovery of selective ligands targeting the MT1 or the MT2 melatonin receptors may promote the development of novel and more efficacious therapeutic agents.
Microfluidics and Coagulation Biology
Authors: Thomas V. Colace, Garth W. Tormoen, Owen J.T. McCarty, Scott L. Diamond
Journal: Annual Review of Biomedical Engineering (2013)

The study of blood ex vivo can occur in closed or open systems, with or without flow. Microfluidic devices, which constrain fluids to a small (typically submillimeter) scale, facilitate analysis of platelet function, coagulation biology, cellular biorheology, adhesion dynamics, and pharmacology and, as a result, can be an invaluable tool for clinical diagnostics. An experimental session can accommodate hundreds to thousands of unique clotting, or thrombotic, events. Using microfluidics, thrombotic events can be studied on defined surfaces of biopolymers, matrix proteins, and tissue factor, under constant flow rate or constant pressure drop conditions. Distinct shear rates can be generated on a device using a single perfusion pump. Microfluidics facilitated both the determination of intraluminal thrombus permeability and the discovery that platelet contractility can be activated by a sudden decrease in flow. Microfluidic devices are ideal for multicolor imaging of platelets, fibrin, and phosphatidylserine and provide a human blood analog to mouse injury models. Overall, microfluidic advances offer many opportunities for research, drug testing under relevant hemodynamic conditions, and clinical diagnostics.
Inhibition of a TREK-like K+ channel current by noradrenaline requires both β1- and β2-adrenoceptors in rat atrial myocytes
Authors: Richard C. Bond, Stéphanie C.M. Choisy, Simon M. Bryant, Jules C. Hancox, Andrew F. James
Journal: Cardiovascular Research (2014)

Noradrenaline plays an important role in the modulation of atrial electrophysiology. However, the identity of the modulated channels, their mechanisms of modulation, and their role in the action potential remain unclear. This study aimed to investigate the noradrenergic modulation of an atrial steady-state outward current (IKss).Rat atrial myocyte whole-cell currents were recorded at 36°C. Noradrenaline potently inhibited IKss (IC50 = 0.90 nM, 42.1 ± 4.3% at 1 µM, n = 7) and potentiated the L-type Ca(2+) current (ICaL, EC50 = 136 nM, 205 ± 40% at 1 µM, n = 6). Noradrenaline-sensitive IKss was weakly voltage-dependent, time-independent, and potentiated by the arachidonic acid analogue, 5,8,11,14-eicosatetraynoic acid (EYTA; 10 µM), or by osmotically induced membrane stretch. Noise analysis revealed a unitary conductance of 8.4 ± 0.42 pS (n = 8). The biophysical/pharmacological properties of IKss indicate a TREK-like K(+) channel. The effect of noradrenaline on IKss was abolished by combined β1-/β2-adrenoceptor antagonism (1 µM propranolol or 10 µM β1-selective atenolol and 100 nM β2-selective ICI-118,551 in combination), but not by β1- or β2-antagonist alone. The action of noradrenaline could be mimicked by β2-agonists (zinterol and fenoterol) in the presence of β1-antagonist. The action of noradrenaline on IKss, but not on ICaL, was abolished by pertussis toxin (PTX) treatment. The action of noradrenaline on ICaL was mediated by β1-adrenoceptors via a PTX-insensitive pathway. Noradrenaline prolonged APD30 by 52 ± 19% (n = 5; P < 0.05), and this effect was abolished by combined β1-/β2-antagonism, but not by atenolol alone.Noradrenaline inhibits a rat atrial TREK-like K(+) channel current via a PTX-sensitive mechanism involving co-operativity of β1-/β2-adrenoceptors that contributes to atrial APD prolongation.
Risk of all-cause and cardiovascular mortality in patients with chronic liver disease
Authors: G. Targher, G. Zoppini, C. P. Day
Journal: Gut (2010)

We read with interest the article by Stepanova et al in a recent issue of Gut . These authors used death certificate data from the third National Health and Nutrition Examination survey (NHANES-III 1988–1994) in order to assess the impact of metabolic syndrome components on all-cause and cause-specific mortality in patients with chronic liver disease (CLD).1 They concluded that components of the metabolic syndrome are independently associated with overall and liver-related mortality in patients with CLD (principally among those with viral hepatitis C, alcohol-related liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD)).1

Overall, the article is well written and the authors have discussed their results cautiously and in a balanced way, given the well-recognised limitations of using the NHANES-III dataset …
Association of fine particulate matter from different sources with daily mortality in six U.S. cities.
Authors: F Laden, L M Neas, D W Dockery, J Schwartz
Journal: Environmental Health Perspectives (2000)

Previously we reported that fine particle mass (particulate matter [less than and equal to] 2.5 microm; PM(2.5)), which is primarily from combustion sources, but not coarse particle mass, which is primarily from crustal sources, was associated with daily mortality in six eastern U.S. cities (1). In this study, we used the elemental composition of size-fractionated particles to identify several distinct source-related fractions of fine particles and examined the association of these fractions with daily mortality in each of the six cities. Using specific rotation factor analysis for each city, we identified a silicon factor classified as soil and crustal material, a lead factor classified as motor vehicle exhaust, a selenium factor representing coal combustion, and up to two additional factors. We extracted daily counts of deaths from National Center for Health Statistics records and estimated city-specific associations of mortality with each source factor by Poisson regression, adjusting for time trends, weather, and the other source factors. Combined effect estimates were calculated as the inverse variance weighted mean of the city-specific estimates. In the combined analysis, a 10 microg/m(3) increase in PM(2.5) from mobile sources accounted for a 3.4% increase in daily mortality [95% confidence interval (CI), 1.7-5.2%], and the equivalent increase in fine particles from coal combustion sources accounted for a 1.1% increase [CI, 0.3-2.0%). PM(2.5) crustal particles were not associated with daily mortality. These results indicate that combustion particles in the fine fraction from mobile and coal combustion sources, but not fine crustal particles, are associated with increased mortality.
Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and lamina propria lymphocytes.
Authors: J Ruthlein, G Heinze, I O Auer
Journal: Gut (1992)

The effector function of immunocompetent cells in the gut mucosa has not yet been defined. The cytotoxic function of these cells might be important in the normal immune response and could be relevant to the mucosal damage seen in inflammatory conditions. The cytotoxic function of isolated intraepithelial and lamina propria mononuclear cells in six and 18 hour assays after the addition of various stimuli that interact with the human leukocyte antigens CD2 and CD3 on the mucosal effector cells was investigated. T cell phenotypes were determined using CD4, CD8, and HML1 to characterise cells of the appropriate compartments. Anti-CD3 and phytohaemagglutinin can induce toxic activity of lamina propria lymphocytes in most individuals after six hours and in all individuals after 18 hours. Anti-CD2, anti-CD3, and phytohaemagglutinin are similarly effective at triggering lamina propria lymphocytes. Intraepithelial lymphocytes contain predominantly CD8 and HML1 positive T cells, differentiating phenotypically intraepithelial lymphocytes from lamina propria lymphocytes. Intraepithelial lymphocytes are not cytotoxic at six hours, but have a toxic function comparable with lamina propria lymphocytes after 18 hours with all three triggers. Intraepithelial lymphocytes from inflamed mucosa (Crohn9s disease and diverticulitis) mediate significantly reduced cytotoxicity in vitro compared with normal mucosa, whereas lamina propria lymphocyte toxicity is not different. Reduced numbers of cytotoxic cells and reduced reactivity to the trigger substances used after in vivo activation or cold target inhibition could explain the observed differences between intraepithelial lymphocytes from inflamed and uninflamed mucosa. Changes in cell mediated cytotoxicity of intraepithelial lymphocytes and lamina propria lymphocytes may be involved in the mucosal damage in these inflammatory conditions.
Survival Effect of Lung Transplantation Among Patients With Cystic Fibrosis
Authors: Theodore G. Liou
Journal: JAMA (2001)

Patients with cystic fibrosis (CF) are the second largest group of lung transplant recipients in the United States. The survival effect of transplantation on a general CF population has not previously been measured.To determine the impact of bilateral lung transplantation on survival in patients with CF.Retrospective observational cohort study of 11 630 CF patients who did not undergo lung transplantation (controls) and 468 transplant recipients with CF from 115 CF centers in the United States, 1992-1998. Patients were stratified into 5 groups based on a 5-year survival prediction model (survival group 1: <30%; survival group 2: 30 to <50%; survival groups 3-5: 50 to <100%.)Five-year survival from date of transplantation in 1992-1997 in the transplant group and from January 1, 1993, in the control group.Lung transplantation increased 5-year survival of CF patients in survival group 1. Survival group 2 had equivocal survival effects, and groups 3-5 had negative survival effects from transplantation. From 1994-1997, there was a mean annual prevalence of 238 patients in survival group 1 and mean annual incidence of 154 patients entering the group, approximately 1.5 times the number of lung transplantations performed each year in CF patients (mean, 104). Use of the criterion of forced expiratory volume in 1 second of less than 30% resulted in an equivocal survival benefit and identified 1458 potential candidates for transplantation in 1993.Cystic fibrosis patients in group 1 have improved 5-year survival after lung transplantation. The majority of patients with CF have equivocal or negative survival effects from the procedure. Selection of patients with CF for transplantation based on group 1 survival predictions maximizes survival benefits to individuals and may reduce the demand for scarce donor organs.
The Immune Microenvironment Confers Resistance to MAPK Pathway Inhibitors through Macrophage-Derived TNFα
Authors: Michael P. Smith, Berta Sanchez-Laorden, Kate O'Brien, Holly Brunton, Jennifer Ferguson, Helen Young, Nathalie Dhomen, Keith T. Flaherty, Dennie T. Frederick, Zachary A. Cooper, Jennifer A. Wargo, Richard Marais, Claudia Wellbrock
Journal: Cancer Discovery (2014)

Recently, the rationale for combining targeted therapy with immunotherapy has come to light, but our understanding of the immune response during MAPK pathway inhibitor treatment is limited. We discovered that the immune microenvironment can act as a source of resistance to MAPK pathway-targeted therapy, and moreover during treatment this source becomes reinforced. In particular, we identified macrophage-derived TNFα as a crucial melanoma growth factor that provides resistance to MAPK pathway inhibitors through the lineage transcription factor MITF (microphthalmia transcription factor). Most strikingly, in BRAF-mutant melanomas of patients and BRAF(V600E) melanoma allografts, MAPK pathway inhibitors increased the number of tumor-associated macrophages, and TNFα and MITF expression. Inhibiting TNFα signaling with IκB kinase inhibitors profoundly enhanced the efficacy of MAPK pathway inhibitors by targeting not only the melanoma cells but also the microenvironment. In summary, we identify the immune microenvironment as a novel source of resistance and reveal a new strategy to improve the efficacy of targeted therapy in melanoma.
Practical Management of Oesophageal Disease
Authors: R C HEADING
Journal: Gut (2001)

Practical Management of Oesophageal Disease . Edited by A Adam, R Mason, W Owen (£69.95). UK: Isis Medical Media Ltd, 2000. ISBN 1-899066-94-2.

The choice of title for a book can make or break its sales. Despite any caution or maturity of judgement we may claim, it seems we are all at risk of being seduced by books with titles such as “ Improve your golf”, or “Make the stock market work for you”. Read the book and find the success/wealth/glamorous lifestyle or whatever that has eluded you up to now. Practical management of oesophageal disease is in this mould—the title hints not at …