tbuckley/cabot-search huggingface dataset:
Cardiac muscle function following chronic dietary potassium depletion in the rabbit
Authors: J. P T Ward
Journal: Cardiovascular Research (1990)

Study objective – The aim was to investigate a possible defect in cardiac muscle contractile performance following chronic K+ depletion. Design – Cardiac muscle force development, membrane potential, and action potential configuration were measured in isolated superfused right ventricular papillary muscles or trabeculae from control or K+ depleted NZW rabbits. The effects of adrenaline, strophanthidin, and changes in external [Ca2+] and [K+] were investigated. Experimental materials – Experiments were performed on 50 adult NZW rabbits, average weight 2.3 kg, which were fed either a control diet (n = 25), or a K+ deficient diet (n = 25) for 25 d. Measurements and main results – There was a significant reduction in contractile force in preparations from the K+ depleted group compared to those from control animals. This was associated with an increased positive inotropic response to low [K+], but an apparent reduction in response to adrenaline. There was no significant difference between groups as to the effect of strophanthidm. Conclusions – It is suggested that the reduction in response to adrenaline reflects a down regulation in β receptor density, due to an increased level of circulating catecholamines, and that the defect in myocardial function is a result of adaptive changes to Ca2+ handling mechanisms within the cell.
Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions
Authors: Michael K Skinner, Mohan Manikkam, Md M Haque, Bin Zhang, Marina I Savenkova
Journal: Genome biology (2012)

Abstract Background Environmentally induced epigenetic transgenerational inheritance of adult onset disease involvesa variety of phenotypic changes, suggesting a general alteration in genome activity. Results Investigation of different tissue transcriptomes in male and female F3 generation vinclozolinversus control lineage rats demonstrated all tissues examined had transgenerational transcriptomes.The microarrays from 11 different tissues were compared with a gene bionetwork analysis. Althougheach tissue transgenerational transcriptome was unique, common cellular pathways and processes wereidentified between the tissues. A cluster analysis identified gene modules with coordinated geneexpression and each had unique gene networks regulating tissue-specific gene expression andfunction. A large number of statistically significant over-represented clusters of genes wereidentified in the genome for both males and females. These gene clusters ranged from 2-5 megabasesin size, and a number of them corresponded to the epimutations previously identified in sperm thattransmit the epigenetic transgenerational inheritance of disease phenotypes. Conclusions Combined observations demonstrate that all tissues derived from the epigenetically altered germline develop transgenerational transcriptomes unique to the tissue, but common epigenetic controlregions in the genome may coordinately regulate these tissue-specific transcriptomes. This systemsbiology approach provides insight into the molecular mechanisms involved in the epigenetictransgenerational inheritance of a variety of adult onset disease phenotypes.
A Microbe-Dependent Viral Key to Crohn’s Box
Authors: Daniel A. Peterson, Peter J. Turnbaugh
Journal: Science Translational Medicine (2010)

Once Pandora unlocked her fateful box and liberated the evil forces within, it became impossible to put them back. Now, new work on Crohn's disease suggests the existence of a viral "key" that irreversibly renders a genetically susceptible mouse prone to pathogenesis. Indeed, dangerous liaisons among host genotype, viral infection, intestinal injury, and trillions of gut microbes may in part determine which individuals progress to a full-blown disease state. These findings suggest that viral and bacterial triggers may serve as therapeutic targets for Crohn's and prompt new hypotheses that relate inflammation, host immune status, microbial community structure, and human health.
Effects of Diet and Exercise in Preventing NIDDM in People With Impaired Glucose Tolerance: The Da Qing IGT and Diabetes Study
Authors: Xiao-Ren Pan, Guang-Wei Li, Ying-Hua Hu, Ji-Xing Wang, Wen-Ying Yang, Zuo-Xin An, Ze-Xi Hu, None Juan-Lin, Jina-Zhong Xiao, Hui-Bi Cao, Ping-An Liu, Xi-Gui Jiang, Ya-Yan Jiang, Jin-Ping Wang, Hui Zheng, Hui Zhang, Peter H Bennett, Barbara V Howard
Journal: Diabetes Care (1997)

OBJECTIVE Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8–75.2) in the control group compared with 43.8% (95% CI, 35.5–52.3) in the diet group, 41.1% (95% CI, 33.4–49.4) in the exercise group, and 46.0% (95% CI, 37.3–54.7) in the diet-plus-exercise group (P &amp;lt; 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P &amp;lt; 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI &amp;lt; or ≥ 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P &amp;lt; 0.03), 46% (P &amp;lt; 0.0005), and 42% (P &amp;lt; 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.
STUDIES ON NORMAL AND LEUKEMIC LEUKOCYTES. VI. THYMIDYLATE SYNTHETASE AND DEOXYCYTIDYLATE DEAMINASE*
Authors: Robert Silber, Beverly W. Gabrio, F. M. Huennekens
Journal: Journal of Clinical Investigation (1963)

cleic acid; RNA, ribonucleic acid; Tris, tris (hydroxymethyl)aminomethane; FUDR, fluorodeoxyuridine; FU- DRP, fluorodeoxyuridine-5'-phosphate; DEAE, diethyl- aminoethyl; C,, 1-carbon unit; AML and CML, acute and chronic myelocytic leukemia; ALL and CLL, acute and chronic lymphocytic leukemia.zyme in normal and leukemic leukocytes.Stud- ies are also presented on an ancillary enzyme, deoxycytidylate deaminase, which is responsible for the conversion of dCMP to dUMP via Equation 3.
Differences in rate of uptake of immunisation among ethnic groups.
Authors: M R Baker, R Bandaranayake, M S Schweiger
Journal: BMJ (1984)

In the Bradford health district ethnic origin is associated with appreciable differences in morbidity and mortality. In view of these differences a study was undertaken to determine whether there were differences among the ethnic groups in utilisation of the National Health Service, as reflected in the rate of uptake of immunisation, which is offered to all children. Significant differences were found between the British group and some other ethnic groups--notably Pakistani, Indian, and half Negro groups. The rate of uptake of immunisation was nearer the optimum in the Indian group than in the British group. The most unsatisfactory rate of uptake of immunisation overall was found in the half Negro group. No clear explanation of the differences has been shown, they are likely to be due to various factors in the National Health Service and in the community.
Failure to Prevent Progressive Dilation of Ascending Aorta by Aortic Valve Replacement in Patients With Bicuspid Aortic Valve: Comparison With Tricuspid Aortic Valve
Authors: Hisayo Yasuda, Satoshi Nakatani, Marie Stugaard, Yuko Tsujita-Kuroda, Ko Bando, Junjiro Kobayashi, Masakazu Yamagishi, Masafumi Kitakaze, Soichiro Kitamura, Kunio Miyatake
Journal: Circulation (2003)

Background— Patients with bicuspid aortic valve (BAV) have been frequently complicated with ascending aortic dilation possibly because of hemodynamic burdens by aortic stenosis (AS) or regurgitation (AR) or congenital fragility of the aortic wall. Methods and Results— To clarify if the aortic dilation could be prevented by aortic valve replacement (AVR) in BAV patients, we studied 13 BAV (8 AR dominant, 5 AS dominant) and 14 tricuspid aortic valve (TAV) patients (7 AR, 7 AS) by echocardiography before and after AVR (9.7±4.8 years). We also studied 18 BAV (11 AR, 7 AS) without AVR. Diameters of the sinuses of Valsalva, sinotubular junction and the proximal aorta were measured. The annual dilation rate was calculated by dividing changes of diameters during the follow-up period by the body surface area and the observation interval. We found that aortic dilation in BAV patients tended to be faster than that in TAV patients, although a significant difference was found only at the proximal aorta (0.18±0.08 versus −0.08±0.08 mm/(m 2 /year), P =0.03). BAV patients with and without AVR showed similar progressive dilation. AR dominant group showed tendency of more progressive dilation than AS dominant group in BAV, although it did not reach statistical significance. TAV patients did not show further aortic dilation after AVR. Conclusions— AVR could not prevent progressive aortic dilation in BAV. Since the aorta did not dilate in TAV, progressive aortic dilation in BAV seems mainly due to the fragility of the aortic wall rather than hemodynamic factors.
Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: Their prevalence and clinical relevance
Authors: Charles L. Mendenhall, Leonard Seeff, Anna Mae Diehl, Saad J. Ghosn, Samuel W. French, Peter S. Gartside, Susan D. Rouster, Zelma Buskell-Bales, Charles J. Grossman, Gary A. Roselle, Robert E. Weesner, Pedro Garcia-Pont, Stephen J. Goldberg, Thomas W. Kiernan, Carlo H. Tamburro, Rowen Zetterman, Antonio Chedid, Thomas Chen, Lionel Rabin
Journal: Hepatology (1991)

Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis B virus and hepatitis C virus antibodies to determine the prevalence of these antibodies and any clinical association in the progression and outcome of alcoholic liver disease. Antibodies to hepatitis B (anti-HBs and/or anti-HBc) were found in 29.2% of patients with alcoholic liver disease, in 26.1% of hospitalized alcoholic patients without liver disease and in 24.2% of hospitalized nonalcoholic patients without liver disease; frequencies were not significantly different from one another. HBsAg was not evaluated because HBsAg+ patients had been excluded from the original trial. The presence of these antibody markers correlated with ethnic origin of and immunoglobulin levels in the patients. In contrast, antibody to hepatitis C, as detected by enzyme immunoassay, was positive in 27.1%, 4.8% and 3.0% of the three groups, respectively, the first differing significantly from the other two. Antibody to hepatitis C virus positivity correlated significantly with clinical severity of the disease and with the presence of histological features that imply chronic viral infection (periportal inflammation, cirrhosis), despite the fact that the supplementary assay for antibody to hepatitis C virus, using recombinant immunoblot assay, reduced the positive rate by 79%. Although the presence of hepatitis B antibodies did not correlate with patient survival, some categories of patients with antibody to hepatitis C virus did; the survival of those with antibody to hepatitis C virus and recombinant immunoblot assay reactivity was 67%; for those with antibody to hepatitis C virus positivity but recombinant immunoblot assay negativity the survival was 29% (p &lt; 0.01). The reason for the poor prognosis for those with antibody to hepatitis C virus positivity and recombinant immunoblot assay negativity is not clear, although some theories are offered. (Hepatology 1991;14:581-589.)
Transcription and Translation are Coupled in Archaea
Authors: S. L. French, T. J. Santangelo, A. L. Beyer, J. N. Reeve
Journal: Molecular Biology and Evolution (2007)

Polysomes have been visualized by electron microscopy attached directly to dispersed strands of genomic DNA extruded from lysed cells of the hyperthermophilic archaeon Thermococcus kodakaraensis. These complexes are consistent with transcription and translation being coupled in this Archaeon, with translation of transcripts being initiated before the transcript is complete.
Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice.
Authors: J L Masferrer, B S Zweifel, K Seibert, P Needleman
Journal: Journal of Clinical Investigation (1990)

We have studied the effect of glucocorticoids administered in vivo on the activity and synthesis of the cyclooxygenase enzyme (COX) in mice treated with or without concurrent intravenous administration of LPS. Mouse peritoneal macrophages from LPS-treated animals showed a two to three fold increase in COX activity determined by the production of PGE2 and PGI2 after stimulation of the cells with exogenous arachidonate. Dexamethasone injected simultaneously with LPS, 12 h before killing of the animal and removal of the macrophages, completely blocked the LPS-induced increase COX activity in peritoneal macrophages. The regulation observed in COX activity by LPS and dexamethasone are due primarily to changes in COX mass as determined by immunoprecipitation of [35S]methionine endogenously labeled enzyme. In contrast, the COX present in the nonadherent cells and in renal medullary microsomes obtained from the same animals, showed no significant changes between treatments. These results indicate that LPS in vivo stimulates COX synthesis in the peritoneal macrophages but not in the kidney. The effect of dexamethasone to inhibit COX synthesis is selective to the LPS-induced enzyme.
Transient erythroblastopenia of childhood: Varied pathogenesis
Authors: Melvin H. Freedman, E. Fred Saunders
Journal: American Journal of Hematology (1983)

Abstract The mechanism of anemia in four patients with transient red cell aplasia of childhood (“erythroblastopenia”) was studied at the time of diagnosis by assessing the colony growth of marrow erythroid progenitors in methylcellulose tissue cultures. Marrow from Patient 1 yielded high normal numbers of BFU‐E colonies that were completely abolished on addition of autologous serum or IgG. Patient 2 had normal BFU‐E growth that markedly declined when autologous serum or IgM was added to the cultures, but growth remained unchanged with added autologous IgG or peripheral blood mononuclear cells (PBMC). Marrow from Patient 3 yielded low CFU‐E and BFU‐E numbers with standard plating techniques, but colonies strikingly increased when marrow fractions from an albumin density gradient were cultured. PBMC from Patient 3 suppressed control marrow CFU‐E and BFU‐E, but serum had no effect. Patient 4 had normal CFU‐E and BFU‐E that increased with autologous serum and remained unchanged with autologous PBMC. We conclude that the red cell aplasia in Patients 1, 2, and 3 was due to suppressed erythropoiesis via IgG, IgM, and cell‐mediated inhibition, respectively. In contrast, in Patient 4 no immune mechanism was demonstrated. Whereas transient red cell aplasia has a uniform clinical presentation, there are at least four pathogenetic mechanisms that can be detected in vitro.
Translating evidence into practice: a model for large scale knowledge translation
Authors: P. J Pronovost, S. M Berenholtz, D. M Needham
Journal: BMJ (2008)

Changes that can improve patients' health are often difficult to get into practice, even when backed by good evidence. <b>Peter Pronovost</b>, <b>Sean Berenholtz</b>, and <b>Dale Needham</b> describe a collaborative model that has been shown to work
Cytochrome P450 proteins and potential utilization in biodegradation.
Authors: F P Guengerich
Journal: Environmental Health Perspectives (1995)

The cytochrome P450 enzymes are major catalysts involved in the oxidations of xenobiotic chemicals in microorganisms as well as higher animals and plants. Because of their functional roles, they offer potential in biodegradation technology. A number of microbial P450s have already been characterized and offer advantages in terms of their high catalytic rates and facile expression in microorganisms. One approach to extending the catalytic selectivity to more compounds in the environment is rational design. In three cases, the three-dimensional structures of bacterial cytochrome P450 enzymes are available and can be further understood through studies with molecular dynamics. Many mammalian cytochrome P450 enzymes have been studied extensively and have potential for biodegradation because of their broad catalytic selectivities (e.g., P450 2E1). Several advances have been made in the heterologous expression of these proteins in microorganisms. Improvements under development include electron transfer from flavodoxin and the use of cytochrome P450:NADPH-cytochrome P450 reductase fusion proteins. Random mutagenesis offers the potential of improving the catalytic activities of some of these proteins. Future challenges include the use of cytochrome P450 expression vectors in microorganisms capable of thriving in the environment; recent success in expression of vectors in Salmonella genotoxicity tester strains may be encouraging in this regard.
Further Studies with Antifoaming Agents in Experimental Pulmonary Edema
Authors: ALDO A. LUISADA, LUIGI CARDI
Journal: Circulation Research (1955)

The effect of several antifoaming agents by inhalation in preventing paroxysmal pulmonary edema was tested in a series of rabbits. Three single agents (silicone aerosol, freon, and ethyl alcohol vapor) proved beneficial; their combination did not enhance the beneficial effect. A new agent (silicone aerosol) and a new combination (10 per cent ether in alcohol by aerosol) are now ready for clinical trial.
Plastics and Health Risks
Authors: Rolf U. Halden
Journal: Annual Review of Public Health (2010)

By 2010, the worldwide annual production of plastics will surpass 300 million tons. Plastics are indispensable materials in modern society, and many products manufactured from plastics are a boon to public health (e.g., disposable syringes, intravenous bags). However, plastics also pose health risks. Of principal concern are endocrine-disrupting properties, as triggered for example by bisphenol A and di-(2-ethylhexyl) phthalate (DEHP). Opinions on the safety of plastics vary widely, and despite more than five decades of research, scientific consensus on product safety is still elusive. This literature review summarizes information from more than 120 peer-reviewed publications on health effects of plastics and plasticizers in lab animals and humans. It examines problematic exposures of susceptible populations and also briefly summarizes adverse environmental impacts from plastic pollution. Ongoing efforts to steer human society toward resource conservation and sustainable consumption are discussed, including the concept of the 5 Rs—i.e., reduce, reuse, recycle, rethink, restrain—for minimizing pre- and postnatal exposures to potentially harmful components of plastics.
<i>ATM</i> Mutations in Patients with Hereditary Pancreatic Cancer
Authors: Nicholas J. Roberts, Yuchen Jiao, Jun Yu, Levy Kopelovich, Gloria M. Petersen, Melissa L. Bondy, Steven Gallinger, Ann G. Schwartz, Sapna Syngal, Michele L. Cote, Jennifer Axilbund, Richard Schulick, Syed Z. Ali, James R. Eshleman, Victor E. Velculescu, Michael Goggins, Bert Vogelstein, Nickolas Papadopoulos, Ralph H. Hruban, Kenneth W. Kinzler, Alison P. Klein
Journal: Cancer Discovery (2011)

Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition.