tbuckley/cabot-search huggingface dataset:
Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles
Authors: Edward W. Lee, Mieczyslaw Michalkiewicz, Joanna Kitlinska, Ivana Kalezic, Hanna Switalska, Peter Yoo, Amarin Sangkharat, Hong Ji, Lijun Li, Teresa Michalkiewicz, Milos Ljubisavljevic, Hakan Johansson, Derrick S. Grant, Zofia Zukowska
Journal: Journal of Clinical Investigation (2003)

Previously we showed that neuropeptide Y (NPY), a sympathetic vasoconstrictor neurotransmitter, stimulates endothelial cell migration, proliferation, and differentiation in vitro. Here, we report on NPY's actions, receptors, and mediators in ischemic angiogenesis. In rats, hindlimb ischemia stimulates sympathetic NPY release (attenuated by lumbar sympathectomy) and upregulates NPY-Y2 (Y2) receptor and a peptidase forming Y2/Y5-selective agonist. Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance. NPY-mediated ischemic angiogenesis is not prevented by a selective Y1 receptor antagonist but is reduced in Y2–/– mice. Nonischemic muscle vascularity is also lower in Y2–/– mice, whereas it is increased in NPY-overexpressing rats compared with their WT controls. Ex vivo, NPY-induced aortic sprouting is markedly reduced in Y2–/– aortas and spontaneous sprouting is severely impaired in NPY–/– mice. NPY-mediated aortic sprouting, but not cell migration/proliferation, is blocked by an antifetal liver kinase 1 antibody and abolished in mice null for eNOS. Thus, NPY mediates neurogenic ischemic angiogenesis at physiological concentrations by activating Y2/Y5 receptors and eNOS, in part due to release of VEGF. NPY's effectiveness in revascularization and restoring function of ischemic tissue suggests its therapeutic potential in ischemic conditions.
Gastrointestinal manifestations in mastocytosis: A study of 83 patients
Authors: Harry Sokol, Sophie Georgin-Lavialle, Danielle Canioni, Stéphane Barete, Gandhi Damaj, Erinn Soucie, Julie Bruneau, Marie-Olivia Chandesris, Felipe Suarez, Jean-Marie Launay, Achille Aouba, Catherine Grandpeix-Guyodo, Fanny Lanternier, Bernard Grosbois, Christian de Gennes, Pascal Cathébras, Olivier Fain, Nadia Hoyeau-Idrissi, Patrice Dubreuil, Olivier Lortholary, Laurent Beaugerie, Brigitte Ranque, Olivier Hermine
Journal: Journal of Allergy and Clinical Immunology (2013)
Catechol<i>O</i>-Methyltransferase Genetic Polymorphism in Panic Disorder
Authors: Jong-Min Woo, Kyung-Sik Yoon, Bum-Hee Yu
Journal: American Journal of Psychiatry (2002)

The authors examined the distribution of catechol O-methyltransferase (COMT) genotypes in patients with panic disorder as well as the relationship between a COMT polymorphism and the clinical characteristics of these patients.Fifty-one patients with panic disorder and 45 healthy comparison subjects were tested for a genetic polymorphism of COMT. Clinical variables were assessed for the patients with panic disorder.The frequency of the L/L genotype was significantly higher in the patients with panic disorder than in the healthy subjects (19.6% versus 2.2%). Panic disorder was significantly associated with the L allele and L/L genotype. Patients with panic disorder who had the L/L genotype showed poorer treatment response than those with other genotypes.These results suggest that the L/L genotype of the COMT gene may be related to the development and treatment outcome of panic disorder in some patients.
Isosorbide‐5‐mononitrate in the treatment of pulmonary hypertension associated with portal hypertension
Authors: J. Ribas, J. Angrill, J.a Barberà, J.c García-Pagán, J. Roca, J. Bosch, R. Rodriguez-Roisin
Journal: European Respiratory Journal (1999)

Pulmonary hypertension is uncommonly associated with portal hypertension. The current approach for the management of pulmonary hypertension involves the use of vasodilators in patients who show vascular responsiveness during an acute challenge. Since the association of portal hypertension with pulmonary hypertension is very seldomly presented, its optimal therapy has not been defined. Moreover, calcium-channel blockers, which are usually used in pulmonary hypertension treatment, may exert a deleterious effect on portal hypertension. Therefore, the search for drugs that may be active under both conditions has important clinical implications. This report presents the case of a patient with portal hypertension-associated pulmonary artery hypertension that was effectively treated with isosorbide-5-mononitrate (Is-5-Mn). The patient had severe portal hypertension (hepatic venous pressure gradient=14.5 mmHg) and pulmonary hypertension (mean pulmonary artery pressure (PAP)=50 mmHg). Acute administration of prostacyclin and nitric oxide elicited a significant reduction in both PAP and pulmonary vascular resistance (PVR), an effect that was also achieved with Is-5-Mn. The patient was treated with 40 mg Is-5-Mn twice daily and a haemodynamic study performed 6 months later showed that the reduction in both PAP and PVR persisted.
The 70-Gene Profile (MammaPrintTM) Is an Independent Predictor of Breast Cancer Specific Survival for Women 65 Years of Age or Older.
Authors: P. Bedard, P. Bedard, S. Mook, S. Mook, M. Knauer, M. Knauer, V. Durbecq, C. Bernard-Marty, A. Glas, F. Cardoso, F. Cardoso, L. van 't Veer, L. van 't Veer
Journal: Cancer Research (2009)

Abstract Background: One-half of all new breast cancer diagnoses occur in women age 65 years or older. In this age group, the use of adjuvant chemotherapy is largely influenced by co-morbidity and little is known about the applicability of prognostic multi-gene assays. The 70-gene profile (MammaPrint) is an independent prognostic indicator in early breast cancer, however, its performance in women with breast cancer 65 years or older has not been systematically studied.Methods: Women 65 years or older who were diagnosed at the Jules Bordet Institute and the Netherlands Cancer Institute between 1987 and 2003 with primary breast cancer with 0-3 involved lymph nodes who received either no adjuvant systemic therapy or adjuvant hormonal therapy alone were selected. MammaPrint test results were compared with clinical-pathological risk assessment using Adjuvant!Online.Results: Of 204 women aged 65 years or older (median age 70 years), 129 (63.2%) were classified as genomic low risk and 75 (36.8%) as genomic high risk. After a median follow-up of 8.6 years (range 0.3-17.9), the 5- and 10-year breast cancer specific survival (BCSS) for the genomic low risk group was 96% (SE 2%) and 86% (SE 4%) versus 82% (SE 4%) and 66% (SE 6%) for the genomic high risk group (log-rank p=0.001). In univariate analysis, MammaPrint was prognostic for 5-year BCSS (HR=5.0, 95%CI 1.8-14.1, p=0.002) and 10-year BCSS (HR=3.1, 95%CI 1.6-6.0, p=0.001). In a multivariate model adjusted for 10-year risk predicted by Adjuvant!Online, MammaPrint was independently prognostic for 5-year BCSS (HR=4.4, 95%CI 1.6-12.7, p=0.005) and 10-year BCSS (HR=2.5, 95%CI 1.3-5.0, p=0.009). As in prior validation series, the performance of MammaPrint was time dependent, with improved prognostication for early BCSS (≤5 years).Conclusion: Although a smaller proportion of breast cancers diagnosed in women 65 years or older are classified as high-risk by MammaPrint, it is an independent prognostic indicator that may be useful to select patients that can safely forego adjuvant chemotherapy. Additional data from patients over 70 years of age will be available at the time of the meeting. If these data are confirmatory, the ongoing prospective MINDACT trial will be amended to include older women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4049.
Characterization of Cbl tyrosine phosphorylation and a Cbl-Syk complex in RBL-2H3 cells.
Authors: Y Ota, L O Beitz, A M Scharenberg, J A Donovan, J P Kinet, L E Samelson
Journal: The Journal of Experimental Medicine (1996)

Tyrosine phosphorylation of the Cbl protooncogene has been shown to occur after engagement of a number of different receptors on hematopoietic cells. However, the mechanisms by which these receptors induce Cbl tyrosine phosphorylation are poorly understood. Here we demonstrate that engagement of the high affinity IgE receptor (Fc epsilon R1) leads to the tyrosine phosphorylation of Cbl and analyze how this occurs. We show that at least part of Fc epsilon R1-induced Cbl tyrosine phosphorylation is mediated by the Syk tyrosine kinase, and that the Syk-dependent tyrosine phosphorylation of Cbl occurs mainly distal to the Cbl proline-rich region within the COOH-terminal 250 amino acids. Furthermore, we show by coprecipitation that Cbl is present in a complex with Syk before receptor engagement, that the proline-rich region of Cbl and a region of Syk comprised of the two SH2 domains and intradomain linker are required for formation of the complex, and that little or no tyrosine-phosphorylated Cbl is detected in complex with Syk. Overexpression of truncation mutants of Cbl capable of binding Syk has the effect of blocking tyrosine phosphorylation of endogenous Cbl. These results define a potentially important intramolecular interaction in mast cells and suggest a complex function for Cbl in intracellular signaling pathways.
CELL TO CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: G. F. Mitchell, J. F. A. P. Miller
Journal: The Journal of Experimental Medicine (1968)

The number of discrete hemolytic foci and of hemolysin-forming cells arising in the spleens of heavily irradiated mice given sheep erythrocytes and either syngeneic thymus or bone marrow was not significantly greater than that detected in controls given antigen alone. Thoracic duct cells injected with sheep erythrocytes significantly increased the number of hemolytic foci and 10 million cells gave rise to over 1000 hemolysin-forming cells per spleen. A synergistic effect was observed when syngeneic thoracic duct cells were mixed with syngeneic marrow cells: the number of hemolysin-forming cells produced in this case was far greater than could be accounted for by summating the activities of either cell population given alone. The number of hemolytic foci produced by the mixed population was not however greater than that produced by an equivalent number of thoracic duct cells given without bone marrow. Thymus cells given together with syngeneic bone marrow enabled irradiated mice to produce hemolysin-forming cells but were much less effective than the same number of thoracic duct cells. Likewise syngeneic thymus cells were not as effective as thoracic duct cells in enabling thymectomized irradiated bone marrow-protected hosts to produce hemolysin-forming cells in response to sheep erythrocytes. Irradiated recipients of semiallogeneic thoracic duct cells produced hemolysin-forming cells of donor-type as shown by the use of anti-H2 sera. The identity of the hemolysin-forming cells in the spleens of irradiated mice receiving a mixed inoculum of semiallogeneic thoracic duct cells and syngeneic marrow was not determined because no synergistic effect was obtained in these recipients in contrast to the results in the syngeneic situation. Thymectomized irradiated mice protected with bone marrow for a period of 2 wk and injected with semiallogeneic thoracic duct cells together with sheep erythrocytes did however produce a far greater number of hemolysin-forming cells than irradiated mice receiving the same number of thoracic duct cells without bone marrow. Anti-H2 sera revealed that the antibody-forming cells arising in the spleens of these thymectomized irradiated hosts were derived, not from the injected thoracic duct cells, but from bone marrow. It is concluded that thoracic duct lymph contains a mixture of cell types: some are hemolysin-forming cell precursors and others are antigen-reactive cells which can interact with antigen and initiate the differentiation of hemolysin-forming cell precursors to antibody-forming cells. Bone marrow contains only precursors of hemolysin-forming cells and thymus contains only antigen-reactive cells but in a proportion that is far less than in thoracic duct lymph.
Molecular evolution of mammalian class I alcohol dehydrogenase.
Authors: S Yokoyama, R Yokoyama
Journal: Molecular Biology and Evolution (1987)

Phylogenetic relationship and the rates of evolution of mammalian alcohol dehydrogenases (ADHs) have been studied by using the amino acid sequences from the human (ADH alpha, ADH beta, and ADH gamma), rat, mouse, and horse (ADH E and ADH S). With the maize ADH1 and ADH2 used as references, the patterns of the amino acid replacements in the beta-sheets, alpha-helices, and random coils in each of the catalytic and coenzyme-binding domains were analyzed separately. The phylogenetic trees based on the different sets of amino acid substitutions consistently showed that (1) multiple ADHs in human and horse have arisen after mammalian radiation, (2) the common ancestor of human ADHs alpha and beta diverged from the ancestor of ADH gamma first and the former two ADHs diverged from each other more recently, and (3) the human ADHs are more closely related to the rodent ADHs than to the horse ADHs. Furthermore, the estimated branch lengths showed that the rodent ADHs are evolving faster than the other ADHs. This difference in evolutionary rate between the two groups of organisms is explainable either in terms of the difference in the number of cell generations per year or in terms of reduction of functional constraints.
Achievement of American Diabetes Association Clinical Practice Recommendations Among U.S. Adults With Diabetes, 1999–2002
Authors: Helaine E. Resnick, Gregory L. Foster, Joan Bardsley, Robert E. Ratner
Journal: Diabetes Care (2006)

To estimate the proportion of U.S. adults with diabetes who meet American Diabetes Association (ADA) clinical practice recommendations.Using data from the 1999-2002 National Health and Nutrition Examination Survey, 998 adults aged >/=18 years with self-reported diabetes were identified. The proportion of adults with diabetes meeting ADA recommendations for HbA(1c) (A1C), HDL cholesterol, LDL cholesterol, triglycerides, blood pressure, renal function, nutrient intake, smoking, pneumococcal vaccination, and physical activity was estimated.Among U.S. adults with diabetes in 1999-2002, 49.8% had A1C <7%; 27.4, 36.0, and 65.0% were classified as low risk for HDL cholesterol, LDL cholesterol, and triglycerides, respectively. Nearly 40% met blood pressure recommendations, 66% had normal renal function, and daily nutrient recommendations for protein, saturated fat, unsaturated fat, and fiber were met by 64.0, 48.3, 28.3, and 18.3%, respectively. Although >81% of the sample reported not smoking at the time of the exam, only 38.2% reported ever having had a pneumococcal immunization, and 28.2% reported getting the recommended level of physical activity. Race, age, duration of diabetes, and education affected achievement of ADA recommendations.Achievement of ADA clinical practice recommendations is far from adequate in U.S. adults with diabetes.
CC Chemokine Receptor Gene Polymorphisms in Czech Patients with Pulmonary Sarcoidosis
Authors: MARTIN PETŘEK, JIŘÍ DRÁBEK, VÍTĚZSLAV KOLEK, JAROSLAV ZLÁMAL, KENNETH I. WELSH, MICHAEL BUNCE, EVŽEN WEIGL, ROLAND du BOIS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Genes for the chemokine receptors CCR5 and CCR2 are characterized by polymorphisms resulting in a nonfunctional receptor expression. Ligands for CCR2 and CCR5 (chemokines monocyte chemotactic protein-1 [MCP-1] and RANTES) are implicated in the pathogenesis of sarcoidosis. We have, therefore, analyzed polymorphisms of CCR5 (32-bp deletion in CCR5 gene [ Δ 32]) and of CCR2 (replacement of valine by isoleucine in CCR2 gene [64I]) in 66 Czech patients with sarcoidosis in comparison with a representative sample of Czech normal population. The frequencies of CCR5 Δ 32 and CCR2-64I polymorphisms in patients with sarcoidosis were different from that in control subjects. CCR5 Δ 32 allelic frequency was significantly increased in patients. By contrast, the CCR2-64I allele was more frequent in control subjects; however, the difference did not attain significance. Interestingly, the CCR5 Δ 32 allele was associated with clinically more apparent disease: it was present in 39.1% of patients requiring corticosteroids but only in 16.7% patients who did not need therapeutic intervention (odds ratio [OR] = 2.9). When patients requiring corticosteroids were compared with control subjects, the differences in the CCR5 Δ 32 frequencies were enhanced (p < 0.01). In conclusion, the observed association of CCR5 Δ 32 and CCR2-64I with sarcoidosis implicates a role for these polymorphisms in disease susceptibility and protection.
Induction of anti-tobacco mosaic virus antibodies in mice by rabbit antiidiotypic antibodies.
Authors: M Francotte, J Urbain
Journal: The Journal of Experimental Medicine (1984)

Conventional rabbit antiidiotypic antibodies were raised against a private rabbit anti-tobacco mosaic virus (TMV) idiotype. These rabbit antiidiotypic antibodies were covalently coupled to lipopolysaccharide and then injected into BALB/c mice. As compared with controls, these mice, which have never seen the antigen, synthesized anti-TMV antibodies that are strongly idiotypically cross-reactive with the starting rabbit idiotype. Monoclonal anti-TMV antibodies were prepared from these mice. Furthermore, xenogeneic or syngeneic antiidiotypic antibodies, raised against these monoclonal anti-TMV antibodies, recognized specifically the rabbit idiotype. Rabbit antiidiotypic antibodies alone can induce the same effects, but the concentration of anti-TMV antibodies is lower.
Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement
Authors: Evanthia Diamanti-Kandarakis, Jean-Pierre Bourguignon, Linda C. Giudice, Russ Hauser, Gail S. Prins, Ana M. Soto, R. Thomas Zoeller, Andrea C. Gore
Journal: Endocrine Reviews (2009)

Abstract There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.
Airflow limitation and changes in pulmonary function among bleachery workers
Authors: A. J. Mehta, P. K. Henneberger, K. Torén, A-C. Olin
Journal: European Respiratory Journal (2005)

This study investigated whether chronic airflow limitation and rapid decline in pulmonary function were associated with peak exposures to ozone and other irritant gases in pulp mills. Bleachery workers potentially exposed to irritant gassings (n = 178) from three Swedish pulp mills, and a comparison group of workers not exposed to irritant gassings (n = 54) from two paper mills, were studied. Baseline surveys occurred in 1995–1996, with follow-up surveys in 1998–1999. Participants performed spirometry and answered questions regarding ozone, chlorine dioxide (ClO 2 ), and sulphur dioxide (SO 2 ) gassings. From regression models controlling for potential confounders, declines in both the forced expiratory volume in one second (FEV 1 ) (−24 mL·yr −1 ) and the forced vital capacity (FVC) (−19 mL·yr −1 ) were associated with ClO 2 /SO 2 gassings. At follow-up, the prevalence of chronic airflow limitation ( i.e. FEV 1 /FVC less than the lower limit of normal) was elevated for participants with only pre-baseline ozone gassings and with both pre-baseline and interval ozone gassings, after controlling for potential confounders. These findings suggest that obstructive effects among bleachery workers are associated with ozone gassings, and that adverse effects on spirometry might also accompany chlorine dioxide/sulphur dioxide gassings. Peak exposures to irritant gases in pulp mills should be prevented.
Perceived Impact of Diabetes Genetic Risk Testing Among Patients at High Phenotypic Risk for Type 2 Diabetes
Authors: Sarah M. Markowitz, Elyse R. Park, Linda M. Delahanty, Kelsey E. O’Brien, Richard W. Grant
Journal: Diabetes Care (2011)

Rapid advances in diabetes genetic epidemiology may lead to a new era of "personalized medicine" based on individual genetic risk assessment. There is minimal experience to guide how best to clinically implement such testing so that results (e.g., "higher" or "lower" relative genetic risk) improve rather than reduce patient motivation for behavior change.Between November 2009 and May 2010, we conducted in-depth interviews with 22 overweight participants at high phenotypic risk for type 2 diabetes to explore perceptions of diabetes genetic risk testing compared with currently available prediction using nongenetic risk factors (e.g., family history, abnormal fasting glucose, obesity). We used hypothetical scenarios to specifically investigate the impact of both "higher" and "lower" relative genetic risk results on participants' views about diabetes prevention.Many participants conferred a unique value on personal genetic risk information relative to nongenetic risk based on the perceived scientific certainty and durability of genetic results. In contrast, other participants considered their genetic risk within the overall context of their other measured risk factors. Reactions to diabetes genetic test results differed by current motivation levels. Whereas most subjects reported that "higher" risk results would motivate behavior change, subjects with lower current motivation often reported that "lower" genetic risk results would further reduce their motivation to engage in diabetes prevention behaviors.To be effective, future clinical implementation of type 2 diabetes genetic risk testing should be individualized based on each patient's risk perception and current level of motivation to prevent diabetes.