tbuckley/cabot-search huggingface dataset:
Angiotensin II Type 1 Receptor Blockade Prevents Lethal Malignant Hypertension
Authors: Karl F. Hilgers, Andrea Hartner, Markus Porst, Roland Veelken, Johannes F.E. Mann
Journal: Circulation (2001)

Background — Angiotensin II is elevated in malignant hypertension. We tested the hypothesis that angiotensin II type 1 receptor blockade can prevent the development of malignant hypertension even in the absence of a blood pressure-lowering effect. Methods and Results — Two-kidney, 1-clip rats were followed up for 28 days; blood pressure was measured by tail-cuff plethysmography and intra-arterially. After a 2-week run-in phase, rats received valsartan at a dose of 0.3 (n=14) or 3 (n=12) mg · kg −1 · d −1 or solvent (n=27). Only the higher dose of valsartan, but not the lower dose, decreased blood pressure. Both doses of valsartan prevented the development of lethal malignant hypertension. Twenty of 27 solvent-treated renovascular hypertensive rats died, but only 3 of 14 rats treated with the low dose and 1 of 12 rats treated with the high dose of valsartan died. Histological signs of malignant nephrosclerosis were found in all rats examined that had died throughout the study and in 6 of 7 surviving solvent-treated renovascular hypertensive animals. Increased expression of monocyte chemoattractant protein-1 and prominent interstitial influx of macrophages occurred in the nonclipped kidneys exposed to high pressure in solvent-treated rats. These alterations were prevented by valsartan at both doses, irrespective of blood pressure effects. Conclusions — Angiotensin II type 1 receptor blockade by valsartan prevents lethal malignant hypertension independently of blood pressure. The results suggest that reduction of angiotensin-induced inflammation in the kidney may contribute to the protective effects of valsartan.
Erectile Dysfunction and Premature Ejaculation are the Most Frequently Self-Reported Sexual Concerns: Profiles of 9,536 Men Calling A Helpline
Authors: Stamatis Papaharitou, Loukas Athanasiadis, Evangelia Nakopoulou, Paraskevi Kirana, Alexandra Portseli, Maria Iraklidou, Konstantinos Hatzimouratidis, Dimitrios Hatzichristou
Journal: European Urology (2005)
Modifiers of epigenetic reprogramming show paternal effects in the mouse
Authors: Suyinn Chong, Nicola Vickaryous, Alyson Ashe, Natasha Zamudio, Neil Youngson, Sarah Hemley, Tomas Stopka, Arthur Skoultchi, Jacqui Matthews, Hamish S Scott, David de Kretser, Moira O'Bryan, Marnie Blewitt, Emma Whitelaw
Journal: Nature Genetics (2007)
Low-Fat Diet Trial Set To Take Off
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Low-Fat Diet Trial Set To Take Off Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 22, 21 November 1990, Pages 1736–1737, https://doi.org/10.1093/jnci/82.22.1736 Published: 21 November 1990
Pulmonary and systemic inflammatory responses in rabbits with gram-negative pneumonia.
Authors: R Fox-Dewhurst, M K Alberts, O Kajikawa, E Caldwell, M C Johnson, S J Skerrett, R B Goodman, J T Ruzinski, V A Wong, E Y Chi, T R Martin
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The major goals of this study were to define the relationships between intrapulmonary and systemic inflammatory responses in animals with gram-negative pneumonia. We treated rabbits with intrapulmonary Escherichia coli (1 x 10(7) to 1 x 10(10) cfu/ml), and then measured physiologic, cellular, and molecular events in the lungs and systemic circulation for 24 h. The treatment protocols resulted in groups of animals that mimicked the stages of the septic inflammatory response in humans. Animals treated with low inocula had systemic changes consistent with systemic inflammatory response syndrome and cleared the bacteria and inflammatory products from the lungs. Animals treated with high inocula failed to clear bacteria from the lungs, had severe intrapulmonary inflammatory responses, and developed septic shock. Intrapulmonary leukocyte recruitment was directly related to the size of the bacterial inoculum, but lung protein accumulation was not. Tumor neurosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and GRO were detectable in lung lavage fluid at 4 h and declined by 24 h in animals that cleared intrapulmonary E. coli. In contrast, lavage TNF-alpha, IL-8, and GRO increased over 24 h in animals that failed to clear intrapulmonary bacteria. MCP-1 increased between 4 h and 24 h in the lungs of all of the animals as the histologic response evolved from neutrophilic to mononuclear cell predominance. Thus, the intensity of systemic inflammatory and physiologic responses to intrapulmonary gram-negative infection depends on the inoculum size and whether the bacteria are cleared from or proliferate in the lungs. The results provide experimental support for the recently proposed classification of septic responses in humans.
Tumor-Reactive CD8+ Early Effector T Cells Identified at Tumor Site in Primary and Metastatic Melanoma
Authors: Andrea Anichini, Alessandra Molla, Claudia Vegetti, Ilaria Bersani, Roberta Zappasodi, Flavio Arienti, Fernando Ravagnani, Andrea Maurichi, Roberto Patuzzo, Mario Santinami, Hanspeter Pircher, Massimo Di Nicola, Roberta Mortarini
Journal: Cancer Research (2010)

Abstract CD8+ T cells at the earliest stage of effector generation have not been identified at tumor site of melanoma patients. Such early effectors, if present, should be characterized by a specific phenotype, distinct from that expressed at later stages of the antigen-induced differentiation program, by short-lived effector cells, memory precursors, and terminal effectors. Here, we show that neoplastic tissues from primary and metastatic lesions of melanoma patients contain a subset of CD8+ T cells expressing FOXP3. CD8+ FOXP3+ CD25+ T lymphocytes were found in tumor-invaded lymph nodes (TILN), s.c. metastases, and advanced primary lesions. Their frequency was significantly higher in TILN compared with tumor-free lymph nodes or with peripheral blood and in primary tumors compared with TILN. CD8+ FOXP3+ T cells did not express markers of regulatory [CTLA-4, CCL4, interleukin-10 (IL-10), transforming growth factor-β1], exhausted (PD-1), or senescent (CD57) CD8+ T lymphocytes. Instead, this subset showed an antigen-experienced “EM1” phenotype (CCR7− CD45RA− CD28+ CD27+) and exhibited a CD127−, KLRG1−, HLA-DR+, CD38+, T-bet+, perforin+ “early effector” profile predicted by current models. CD8+ FOXP3+ T cells produced IFN-γ on short in vitro activation, recognized autologous tumor by CD107a mobilization, and expressed Ki-67 on ex vivo analysis. In response to autologous tumor plus IL-2/IL-15, the CD8+ FOXP3+ T cells proliferated promptly and showed competence for differentiation (downregulation of CD27 and upregulation of T-bet). These results suggest development of early phases of antitumor immunity even in advanced melanoma. Moreover, the CD8+ FOXP3+ “early effector” subset may be an invaluable tool for monitoring immunity at tumor site. Cancer Res; 70(21); 8378–87. ©2010 AACR.
Bornavirus Closely Associates and Segregates with Host Chromosomes to Ensure Persistent Intranuclear Infection
Authors: Yusuke Matsumoto, Yohei Hayashi, Hiroko Omori, Tomoyuki Honda, Takuji Daito, Masayuki Horie, Kazuyoshi Ikuta, Kan Fujino, Shoko Nakamura, Urs Schneider, Geoffrey Chase, Tamotsu Yoshimori, Martin Schwemmle, Keizo Tomonaga
Journal: Cell Host & Microbe (2012)
Inhibition of Angiogenesis and Invasion by 3,3′-Diindolylmethane Is Mediated by the Nuclear Factor–κB Downstream Target Genes <i>MMP-9</i> and <i>uPA</i> that Regulated Bioavailability of Vascular Endothelial Growth Factor in Prostate Cancer
Authors: Dejuan Kong, Yiwei Li, Zhiwei Wang, Sanjeev Banerjee, Fazlul H. Sarkar
Journal: Cancer Research (2007)

Progression of prostate cancer is believed to be dependent on angiogenesis induced by tumor cells. 3,3'-Diindolylmethane (DIM) has been shown to repress neovascularization in a Matrigel plug assay and inhibit cell proliferation, migration, invasion, and capillary tube formation of cultured human umbilical vein endothelial cells. However, the molecular mechanism, by which DIM inhibits angiogenesis and invasion, has not been fully elucidated. Therefore, we sought to explore the molecular mechanism by which DIM inhibits angiogenesis and invasion, specifically by investigating the role of angiogenic factors secreted by prostate cancer cells which control all steps of angiogenesis. We found that BioResponse DIM (B-DIM), a formulated DIM with higher bioavailability, inhibited angiogenesis and invasion by reducing the bioavailability of vascular endothelial growth factor (VEGF) via repressing extracellular matrix-degrading proteases, such as matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (uPA), in human prostate cancer cells and reduced vascularity (angiogenesis) in vivo using Matrigel plug assay. We also found that B-DIM treatment inhibited DNA binding activity of nuclear factor-kappaB (NF-kappaB), which is known to mediate the expression of many NF-kappaB downstream target genes, including VEGF, IL-8, uPA, and MMP-9, all of which are involved in angiogenesis, invasion, and metastasis. Our data suggest that inhibition of NF-kappaB DNA binding activity by B-DIM contributes to the regulated bioavailability of VEGF by MMP-9 and uPA and, in turn, inhibits invasion and angiogenesis, which could be mechanistically linked with the antitumor activity of B-DIM as observed previously by our laboratory in a prostate cancer animal model.
NICE is too generous in approving drugs, analysis says
Authors: N. Hawkes
Journal: BMJ (2015)

The method used by the National Institute for Health and Care Excellence to assess the value of new drugs in England has done more harm than good, concludes an analysis by the Centre for Health Economics at the University of York.1 And the Cancer Drugs Fund has done even greater harm, it found, saying that the money spent by the fund on expensive cancer drugs would have done five times as much good if spent elsewhere in the NHS.

Karl Claxton, lead author of the analysis, told a briefing at the Science Media Centre in London that NHS outcomes would be better if it refused to fund any drug that cost more than £13 000 (€17 500; $20 000) per quality adjusted life year …
Behavioural pharmacology: 40+ years of progress, with a focus on glutamate receptors and cognition
Authors: Trevor W. Robbins, Emily R. Murphy
Journal: Trends in Pharmacological Sciences (2006)

Behavioural pharmacology is an interdisciplinary field at the intersection of several research areas that ultimately lead to the development of drugs for clinical use and build understanding of how brain functions enable cognition and behaviour. In this article, the development of behavioural pharmacology in the UK is briefly surveyed, and the current status and success of the field is highlighted by the progress in our understanding of learning and memory that has resulted from discoveries in glutamate receptor pharmacology allied to theoretical and methodological advances in behavioural neuroscience. We describe the original breakthrough in terms of the role of NMDA receptors in hippocampal-mediated spatial learning and long-term potentiation, and review recent advances that demonstrate the involvement of glutamate receptor in working memory, recognition memory, stimulus-response learning and memory, and higher cognitive functions. We also discuss the unique functions of NMDA receptors and the fundamental role of AMPA receptors in processes that are common to some of these forms of memory, including encoding, consolidation and retrieval.
Association of Body Fat Distribution and Cardiovascular Risk Factors in Children and Adolescents
Authors: Stephen R. Daniels, John A. Morrison, Dennis L. Sprecher, Philip Khoury, Thomas R. Kimball
Journal: Circulation (1999)

Obesity is associated with increased risk of cardiovascular disease in adults and less favorable cardiovascular risk factor status in children and adolescents. In adults, fat distribution has been shown to be related to lipid and lipoprotein concentrations, blood pressure levels, and left ventricular mass. These relationships have not been extensively studied in young subjects.This was a cross-sectional study of 127 children and adolescents 9 to 17 years of age. Dual-energy x-ray absorptiometry was used to measure total and regional fat mass. The dependent variables were fasting lipid and lipoprotein concentrations, systolic and diastolic blood pressures, and left ventricular mass. There were significant (P<0.05) univariate correlations between fat distribution and log triglycerides (r=0.27), log HDL cholesterol (r=-0.23), systolic blood pressure (r=0.26), and left ventricular mass (r=0.37). Multiple regression analysis showed that the significant independent correlates for triglycerides and HDL cholesterol were age and fat distribution; for systolic blood pressure, height and fat distribution; and for left ventricular mass, height, race, sex, and fat distribution.These results demonstrate that fat distribution is a more important independent correlate of cardiovascular risk factors than percent body fat in children and adolescents. Greater deposition of central fat (an android fat pattern) is associated with less favorable plasma lipid and lipoprotein concentrations, blood pressure, and left ventricular mass.
Coronary calcifications in young patients with first, unheralded myocardial infarction: a risk factor matched analysis by electron beam tomography
Authors: Karsten Pohle, Dieter Ropers, Patricia Geitner, Theresa Menendez, Matthias Regenfus, Werner Moshage, Wemer G. Daniel, Stephan Achenbach
Journal: Journal of the American College of Cardiology (2002)
Effect of 60Co gamma-irradiation on the nonspecific cytotoxicity of alveolar macrophages in vitro.
Authors: Y Gong, L Hu, D Wu
Journal: Environmental Health Perspectives (1992)

This paper reports on the effect of radiation on the nonspecific cytotoxicity of rat alveolar macrophages (AM). AM (effector cells) of bacille Calmette-Guerin-activated Wistar rats were irradiated with 60Co gamma rays in vitro to give doses of 0, 100, 300, and 500 Gy. Three hours after irradiation, the AM were cultured with human lung adenocarcinoma AGZY83-a and HeLa target cells in 125I-deoxyuridine-containing media for 6 hr and the cytotoxicity indexes determined. The results indicated that the cytotoxicity indexes of AM against human lung adenocarcinoma cells and HeLa cells were 94.3 +/- 0.3% and 81.3 +/- 1.9%, respectively. The cytotoxicity indexes using an effector/target cell ratio (E/T) of 10 seemed to be greater than with ratios of 20 and 30. The cytotoxicity indexes of AM (7 rats), irradiated to give doses of 0, 100, 300, and 500 Gy, against adenocarcinoma cells at an E/T ratio of 10 were 87.9 +/- 8.4%, 65.4 +/- 14.1%, 47.5 +/- 17.5%, and 36.7 +/- 9.7%, respectively. The significance of the nonspecific cytotoxicity of AM in the immunological elimination of tumors and the inhibitory effect of radiation on AM cytotoxicity are discussed.
Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects.
Authors: G Joos, R Pauwels, M van der Straeten
Journal: Thorax (1987)

The neuropeptides substance P and neurokinin A are present in sensory airway nerves. Their effect on airway calibre was compared in six healthy non-smoking subjects and six asthmatic subjects. On separate days increasing concentrations (from 10(-9) to 10(-6) mol/ml) of each neuropeptide were administered by nebuliser and the airway response measured as change in specific airway conductance (sGaw). Substance P and neurokinin A caused no change in sGaw in the healthy subjects. Inhalation of substance P up to the highest concentration of 10(-6) mol/ml caused no change in sGaw in the asthmatic subjects. Neurokinin A, however, caused bronchoconstriction with a mean fall in sGaw of 48% (SEM 12%) after 5 x 10(-7) mol/ml. The onset of bronchoconstriction was rapid, but sGaw had returned to baseline values within one hour in all but one patient.
Mutagenic activity of concentrated drinking water samples.
Authors: P Wilcox, S Williamson
Journal: Environmental Health Perspectives (1986)

Concentrated drinking water extracts prepared by adsorption onto XAD-2 resin have been tested for their ability to induce chromosome damage in mammalian cells. Extracts prepared from drinking waters derived from upland and lowland sources have been found to induce chromosome aberrations in Chinese hamster ovary (CHO) cells and human lymphocytes in vitro. Although the identity of the compounds responsible for this activity is unknown, they are generated when the water is chlorinated and appear to bind readily to exogenous protein. When groups of mice were dosed orally with a concentrated water extract, however, no evidence of clastogenic activity in bone marrow cells was apparent. The absence of an in vivo effect may indicate that the mutagenic compounds failed to reach the bone marrow. The possibility that genetic damage could be induced in the cells first encountered in the body after ingestion (i.e., cells in the esophagus, stomach, and intestinal tract) is not precluded by this result. The relevance of these findings in evaluating the potential health hazard of mutagenic compounds in drinking water is discussed.
Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma.
Authors: V M Keatings, P D Collins, D M Scott, P J Barnes
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Asthma and chronic obstructive pulmonary disease are characterized by chronic airway inflammation. Studies using bronchoalveolar lavage (BAL) have shown an increased proportion of eosinophils in the BAL fluid from asthmatics compared with that from normal subjects, whereas studies of chronic obstructive pulmonary disease (COPD) have shown increased numbers of neutrophils. Induced sputum allows sampling of respiratory tract secretions from patients and control subjects, providing a noninvasive method of studying airway secretions and allowing characterization of cells and measurement of soluble markers. We investigated whether induced sputum was a useful method of studying airway fluid from patients with moderate to severe COPD and whether it could be used to compare inflammation in this condition with that in asthma. An initial reproducibility study was undertaken. Sputum was induced twice in 13 patients with severe COPD at a 14-d interval. Total and differential cell counts were carried out and were found to be reproducible over this period. Sputum was then induced in 14 patients with COPD, 23 patients with asthma, 12 healthy cigarette smokers, and 16 normal nonsmoking control subjects. We found a significant increase in neutrophils and increased concentrations of tumor necrosis factor-alpha (TNF alpha) and interleukin-8 (IL-8) in the patients with COPD compared with the smoking and nonsmoking control subjects. Interleukin-8, but not TNF alpha, was significantly higher in the COPD group than in the asthmatic group. We conclude that the cytokines TNF alpha and IL-8 may be involved in the inflammation in COPD.
Organochlorine Exposure and Colorectal Cancer Risk
Authors: Mike Howsam, Joan O. Grimalt, Elisabet Guinó, Matilde Navarro, Juan Martí-Ragué, Miguel A. Peinado, Gabriel Capellá, Victor Moreno
Journal: Environmental Health Perspectives (2004)

Organochlorine compounds have been linked to increased risk of several cancers. Despite reductions in their use and fugitive release, they remain one of the most important groups of persistent pollutants to which humans are exposed, primarily through dietary intake. We designed a case-control study to assess the risk of colorectal cancer with exposure to these chemicals, and their potential interactions with genetic alterations in the tumors. A subsample of cases (n = 132) and hospital controls (n = 76) was selected from a larger case-control study in Barcelona, Catalonia, Spain. We measured concentrations in serum of several organochlorines by gas chromatography. We assessed point mutations in K-ras and p53 genes in tissue samples by polymerase chain reaction/single-strand conformation polymorphism and assessed expression of p53 protein by immunohistochemical methods. An elevated risk of colorectal cancer was associated with higher serum concentrations of mono-ortho polychlorinated biphenyl (PCB) congeners 28 and 118. The odds ratio for these mono-ortho PCBs for middle and higher tertile were, respectively, 1.82 [95% confidence interval (CI), 0.90-3.70] and 2.94 (95% CI, 1.39-6.20). Alpha-hexachlorocyclohexane, hexachlorobenzene, and p,p'-DDE (4,4'-dichlorodiphenyltrichloroethene) showed nonsignificant increases in risk. Risk associated with mono-ortho PCBs was slightly higher for tumors with mutations in the p53 gene but was not modified by mutations in K-ras. Mono-ortho PCBs were further associated with transversion-type mutations in both genes. These results generate the hypothesis that exposure to mono-ortho PCBs contributes to human colorectal cancer development. The trend and magnitude of the association, as well as the observation of a molecular fingerprint in tumors, raise the possibility that this finding may be causal.
<i>Helicobacter pylori</i>— Not a Good Bug after All
Authors: James G. Fox, Timothy C. Wang
Journal: New England Journal of Medicine (2001)

Worldwide, gastric cancer is the second most frequent cancer and the second leading cause of death from cancer. Since the discovery of Helicobacter pylori in 1982 by Marshall and Warren, an association between the bacterium and gastric cancer has been suspected. Ten years ago, several case–control studies based on enzyme-linked immunosorbent assays (ELISAs) of stored serum found an association between H. pylori and cancer, but as defined by an odds ratio it was somewhat weak. These initial reports could attribute only 60 percent of cases of gastric cancer to H. pylori infection.1 Although the World Health Organization and the International . . .
INCREASED MORBIDITY AND MORTALITY AMONG ATRIAL FIBRILLATION PATIENTS WITH PROLONGED QRS: RESULTS FROM THE AFFIRM STUDY
Authors: Matthew Whitbeck, Richard Charnigo, Brandon Fornwalt, Gustavo Morales, Jignesh Shah, Milagros M. Zegarra, Alison Bailey, Paul Anaya, Tracy Macaulay, Charles Campbell, John Gurley, Khaled Ziada, Bai Rong, Luigi Di Biase, Andrea Natale, Susan Smyth, David Moliterno, Claude S. Elayi
Journal: Journal of the American College of Cardiology (2012)
Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial
Authors: Caroline Robert, Antoni Ribas, Jedd D Wolchok, F Stephen Hodi, Omid Hamid, Richard Kefford, Jeffrey S Weber, Anthony M Joshua, Wen-Jen Hwu, Tara C Gangadhar, Amita Patnaik, Roxana Dronca, Hassane Zarour, Richard W Joseph, Peter Boasberg, Bartosz Chmielowski, Christine Mateus, Michael A Postow, Kevin Gergich, Jeroen Elassaiss-Schaap, Xiaoyun Nicole Li, Robert Iannone, Scot W Ebbinghaus, S Peter Kang, Adil Daud
Journal: The Lancet (2014)
Bone Marrow Transplantation
Authors: E. Donnall Thomas
Journal: JAMA (1983)

<h3>How Is Bone Marrow Transplantation Performed?</h3><h3>JAMA:</h3> How is bone marrow transplantation performed? <b>Thomas</b>: We take the donor to the operating room, and, under sterile conditions, we carry out a series of aspirations of bone marrow from the anterior and posterior iliac crests. It takes about an hour in the operating room and involves more than 100 aspirations. The marrow is like a honeycomb, and one has to keep putting the point of the needle in different places to continue to get marrow. On the average, the volume of marrow aspirated is about 750 mL. We usually take a pint of the donor's blood in advance and reinfuse it during the procedure. As a procedure, it is not too formidable; in fact, I tease my surgical colleagues by saying that this is the one branch of transplantation where one can work without the complication of needing a surgeon. The marrow