tbuckley/cabot-search huggingface dataset:
A Population-Based Study of Primary Human Herpesvirus 6 Infection
Authors: Danielle M. Zerr, Amalia S. Meier, Stacy S. Selke, Lisa M. Frenkel, Meei-Li Huang, Anna Wald, Margaret P. Rhoads, Long Nguy, Rena Bornemann, Rhoda Ashley Morrow, Lawrence Corey
Journal: New England Journal of Medicine (2005)

Serologic studies indicate that human herpesvirus 6 (HHV-6) infects 90 percent of children by two years of age. Little is known about the acquisition, virologic course, and clinical manifestations of HHV-6 infection.We prospectively studied a cohort of 277 children from birth through the first two years of life to define the pattern of acquisition of HHV-6. The children's saliva was tested weekly for HHV-6 DNA with the use of the polymerase chain reaction. Parents maintained a daily log of signs and symptoms of illness in their children.Primary HHV-6 infection occurred in 130 children, with cumulative percentages of 40 percent by the age of 12 months and 77 percent by the age of 24 months. The peak age of acquisition was between 9 and 21 months. The acquisition of HHV-6 was associated with female sex (adjusted hazard ratio, 1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9). Among 81 children with a well-defined time of acquisition of HHV-6, 93 percent had symptoms, and 38 percent were seen by a physician. None had seizures. As compared with children who had other illnesses, those with primary HHV-6 infection were more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash (P=0.003), and roseola (P=0.002) and were more likely to visit a physician (P=0.003).The acquisition of HHV-6 in infancy is usually symptomatic and often results in medical evaluation. Roseola occurs in a minority of patients, and febrile seizures are infrequently associated with primary HHV-6 infection. Older siblings appear to serve as a source of HHV-6 transmission.
Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD
Authors: D. C. Berton, P. B. Barbosa, L. S. Takara, G. R. Chiappa, A. C. B. Siqueira, D. M. Bravo, L. F. Ferreira, J. A. Neder
Journal: Thorax (2010)

<h3>Background</h3> Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O<sub>2</sub> delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung hyperinflation after the inhalation of bronchodilators would improve skeletal muscle oxygenation during exercise was tested. <h3>Methods</h3> Twelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV<sub>1</sub>)=38.5±12.9% predicted; Pao<sub>2</sub>&gt;60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70–80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de)oxygenation (∼fractional O<sub>2</sub> extraction) was determined in the vastus lateralis by changes (Δ) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from near-infrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. <h3>Results</h3> Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (454±131 s vs 321±140 s, respectively; p&lt;0.05). On-exercise kinetics of QT and pulmonary O<sub>2</sub> uptake <math xmlns="http://www.w3.org/1998/Math/MathML" id="m1"><mrow><mrow><mo>(</mo><mrow><msub><mrow><mover><mi mathvariant="normal">V</mi><mo>˙</mo></mover><mi mathvariant="normal">o</mi></mrow><mn>2</mn></msub></mrow><mo>)</mo></mrow></mrow></math> were accelerated with active treatment; Δ[HHb] dynamics, however, were delayed by ∼78% and the signal amplitude diminished by ∼21% (p&lt;0.01). Consequently, the ratio between <math xmlns="http://www.w3.org/1998/Math/MathML" id="m2"><mrow><mrow><mrow><msub><mrow><mover><mi mathvariant="normal">V</mi><mo>˙</mo></mover><mi mathvariant="normal">o</mi></mrow><mn>2</mn></msub></mrow></mrow></mrow></math> and Δ[HHb] dynamics decreased, suggesting improved microvascular O<sub>2</sub> delivery (τ-<math xmlns="http://www.w3.org/1998/Math/MathML" id="m3"><mrow><mrow><mrow><msub><mrow><mover><mi mathvariant="normal">V</mi><mo>˙</mo></mover><mi mathvariant="normal">o</mi></mrow><mn>2</mn></msub></mrow></mrow></mrow></math>/MRT-Δ[HHb]=4.48±1.57 s vs 2.08±1.15 s, p&lt;0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in τ-<math xmlns="http://www.w3.org/1998/Math/MathML" id="m4"><mrow><mrow><mrow><msub><mrow><mover><mi mathvariant="normal">V</mi><mo>˙</mo></mover><mi mathvariant="normal">o</mi></mrow><mn>2</mn></msub></mrow></mrow></mrow></math>/MRT-Δ[HHb] (p&lt;0.01). <h3>Conclusions</h3> Decreases in operating lung volumes after the inhalation of bronchodilators are associated with faster 'central' cardiovascular adjustments to high-intensity exercise with beneficial consequences on muscle oxygenation in patients with moderate to severe COPD.
Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis
Authors: Seung-Hoi Koo
Journal: Clinical and Molecular Hepatology (2013)

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD. Keywords: Free fatty acids; De novo lipogenesis; Fatty acid beta oxidation; TG secretion
Production of Mice Deficient in Genes for Interleukin (IL)-1α, IL-1β, IL-1α/β, and IL-1 Receptor Antagonist Shows that IL-1β Is Crucial in Turpentine-induced Fever Development and Glucocorticoid Secretion
Authors: Reiko Horai, Masahide Asano, Katsuko Sudo, Hirotaka Kanuka, Masatoshi Suzuki, Masugi Nishihara, Michio Takahashi, Yoichiro Iwakura
Journal: The Journal of Experimental Medicine (1998)

Interleukin (IL)-1 is a major mediator of inflammation and exerts pleiotropic effects on the neuro-immuno-endocrine system. To elucidate pathophysiological roles of IL-1, we have first produced IL-1α/β doubly deficient (KO) mice together with mice deficient in either the IL-1α, IL-1β, or IL-1 receptor antagonist (IL-1ra) genes. These mice were born healthy, and their growth was normal except for IL-1ra KO mice, which showed growth retardation after weaning. Fever development upon injection with turpentine was suppressed in IL-1β as well as IL-1α/β KO mice, but not in IL-1α KO mice, whereas IL-1ra KO mice showed an elevated response. At this time, expression of IL-1β mRNA in the diencephalon decreased 1.5-fold in IL-1α KO mice, whereas expression of IL-1α mRNA decreased &amp;gt;30-fold in IL-1β KO mice, suggesting mutual induction between IL-1α and IL-1β. This mutual induction was also suggested in peritoneal macrophages stimulated with lipopolysaccharide in vitro. In IL-1β KO mice treated with turpentine, the induction of cyclooxygenase-2 (EC 1.14.99.1) in the diencephalon was suppressed, whereas it was enhanced in IL-1ra KO mice. We also found that glucocorticoid induction 8 h after turpentine treatment was suppressed in IL-1β but not IL-1α KO mice. These observations suggest that IL-1β but not IL-1α is crucial in febrile and neuro-immuno-endocrine responses, and that this is because IL-1α expression in the brain is dependent on IL-1β. The importance of IL-1ra both in normal physiology and under stress is also suggested.
An official American Thoracic Society and European Respiratory Society policy statement: disparities in respiratory health
Authors: Dean E. Schraufnagel, Francesco Blasi, Monica Kraft, Mina Gaga, Patricia Finn, Klaus F. Rabe
Journal: European Respiratory Journal (2013)

Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality healthcare contributes to disparities. The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by their full executive committees and boards of directors of the societies. This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. The ERS and the ATS have strong international commitments and work with leaders from governments, academia, and other organisational bodies to address and reduce avoidable health inequalities. Their training initiatives improve the function of healthcare systems and health equality. Both the ATS and the ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organisations carry out most of their activities. The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to join in this commitment.
Bromodomain and Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype
Authors: Donna A. Santillan, Catherine M. Theisler, Amanda S. Ryan, Relja Popovic, Tara Stuart, Ming-Ming Zhou, Serhan Alkan, Nancy J. Zeleznik-Le
Journal: Cancer Research (2006)

Abstract A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein–binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAFII250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced proliferative capacity in vitro but lacked expression of myeloid cell surface markers normally seen with MLL-CBP. Mice reconstituted with domain-swapped hematopoietic progenitors developed different disease from those with MLL-CBP. This included development of lymphoid disease and lower frequency of the myelodysplastic phase in those mice developing AML. We conclude that both the CBP bromodomain and HAT domain play different but critical roles in determining the phenotype of MLL-CBP leukemia. Our results support an important role for MLL partner genes in determining the leukemia phenotype besides their necessity in leukemogenesis. Here, we find that subtleties in MLL fusion protein domain specificity direct cells toward a specific disease phenotype. (Cancer Res 2006; 66(20):10032-9)
Screening for HIV in Health Care Settings: A Guidance Statement From the American College of Physicians and HIV Medicine Association
Authors: Amir Qaseem
Journal: Annals of Internal Medicine (2009)

The American College of Physicians (ACP) developed this guidance statement to present the available evidence on screening for HIV in health care settings.This guidance statement is derived from an appraisal of available guidelines on screening for HIV. Authors searched the National Guideline Clearinghouse to identify guidelines on screening for HIV in the United States and used the AGREE (Appraisal of Guidelines Research and Evaluation) instrument to evaluate guidelines from the U.S. Preventive Services Task Force and the Centers for Disease Control and Prevention. GUIDANCE STATEMENT 1: ACP recommends that clinicians adopt routine screening for HIV and encourage patients to be tested. GUIDANCE STATEMENT 2: ACP recommends that clinicians determine the need for repeat screening on an individual basis.
Liverpool Care Pathway for patients with cancer in hospital: a cluster randomised trial
Authors: Massimo Costantini, Vittoria Romoli, Silvia Di Leo, Monica Beccaro, Laura Bono, Paola Pilastri, Guido Miccinesi, Danila Valenti, Carlo Peruselli, Francesco Bulli, Catia Franceschini, Sergio Grubich, Cinzia Brunelli, Cinzia Martini, Fabio Pellegrini, Irene J Higginson
Journal: The Lancet (2013)
Metformin, Sulfonylureas, or Other Antidiabetes Drugs and the Risk of Lactic Acidosis or Hypoglycemia
Authors: Michael Bodmer, Christian Meier, Stephan Krähenbühl, Susan S. Jick, Christoph R. Meier
Journal: Diabetes Care (2008)

OBJECTIVE—Lactic acidosis has been associated with use of metformin. Hypoglycemia is a major concern using sulfonylureas. The aim of this study was to compare the risk of lactic acidosis and hypoglycemia among patients with type 2 diabetes using oral antidiabetes drugs. RESEARCH DESIGN AND METHODS—This study is a nested case-control analysis using the U.K.-based General Practice Research Database to identify patients with type 2 diabetes who used oral antidiabetes drugs. Within the study population, all incident cases of lactic acidosis and hypoglycemia were identified, and hypoglycemia case subjects were matched to up to four control patients based on age, sex, practice, and calendar time. RESULTS—Among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use. CONCLUSIONS—Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity. Hypoglycemic episodes were substantially more common among sulfonylurea users than among users of metformin.
Activation of α1B-adrenoceptors alleviates ischemia/reperfusion injury by limitation of mitochondrial Ca2+ overload in cardiomyocytes
Authors: H GAO, L CHEN, H YANG
Journal: Cardiovascular Research (2007)

Activation of alpha(1)-adrenergic receptors (alpha(1)-ARs) mimics ischemic preconditioning (IP). However, the subtypes of alpha(1)-ARs involved and the protective mechanisms are not entirely clear. Here we tested the hypothesis that preservation of mitochondrial integrity, in particular, Ca(2+) homeostasis via the epsilon isoform of protein kinase C (PKCepsilon) and mitoK(ATP) channels, may underlie the basis of alpha(1B)-AR-triggered cardioprotection.Indo-1 fluorescence in adult rat cardiomyocytes was used as an index of cytosolic ([Ca(2+)](c)) or mitochondrial free Ca(2+) concentration ([Ca(2+)](m)), and cell shortening was measured simultaneously. Cells were subjected to 20 min of simulated ischemia followed by 30 min of reperfusion (I/R).Activation of a(1)-ARs by phenylephrine significantly decreased I/R-induced [Ca(2+)](c) and [Ca(2+)](m) overload, mitochondrial cytochrome c release and ATP reduction, and improved Ca(2+) transients and cell shortening. These protective effects were markedly inhibited by blockade of alpha(1B)-AR (chloroethylclonidine) but not alpha(1A)-AR (5'-methylurapidil) or alpha(1D)-AR (BMY 7378). Moreover, phenylephrine-afforded protection on the [Ca(2+)](m), [Ca(2+)](c), and cell shortening was lost when mitoK(ATP) channels were inhibited with 5-hydroxydecanoate and PKCepsilon with PKCepsilon V(1-2). However, PKCepsilon V(1-2) did not affect the mitoK(ATP) channel opener diazoxide-induced protection on these parameters.These findings indicate that phenylephrine-induced protection on [Ca(2+)](m) homeostasis is mediated by selective activation of alpha(1B)-AR via mitoK(ATP) channel opening and PKCepsilon activation. Mitochondrial function appears to be a determinant of [Ca(2+)](c) and contractile function during I/R injury.
Role of oxygen-dependent mechanisms in antibody-induced lysis of tumor cells by activated macrophages
Authors: C Nathan, Z Cohn
Journal: The Journal of Experimental Medicine (1980)

The alloantiserum-dependent lysis of TLX9 lymphoma cells by peritoneal cells from Bacille Calmette-Guerin (BCG)-treated mice was inhibited 62 percent by depletion of oxygen. This effect did not appear to be a result of interference with mitochondrial respiration because cyanide, azide, and dinitrophenol did not inhibit cytotoxicity. Preincubating the effector cells for 2 h without glucose, which markedly reduces their ability to release hydrogen peroxide, likewise suppressed antibody-dependent cytolysis by 62 percent. Lysis of sensitized lymphoma cells was virtually abolished by 6 mg/ml of thioglycollate broth, a concentration that also abrogated the detectable release of hydrogen peroxide and the lysis of lymphoma cells by BCG-activated macrophages in response to phorbol myristate acetate (PMA). This concentration of thioglycollate broth was not toxic to the effector cells, as judged by adherence to plastic, binding of opsonized erythrocytes, and phagocytosis of radiolabeled starch granules. Catalase, superoxide dismutase, horseradish peroxidase, mannitol, ethanol, benzoate, and diazabicyclooctane were without consistent effects. Cytochalasin B and dihydrocytochalasin B both markedly suppressed cytolysis, whether induced by antibody or by PMA (ID(50), 0.5 μg/ml). Cytoehalasin B was an equally potent suppressor of glucose uptake and PMA-induced hydrogen peroxide release by BCG-activated macrophages (ID(50), 0.5 μg/ml). However, dihydrocytochalasin B lacked these latter effects, which suggests that cytotoxicity required intact contractile elements. The extracellular lysis of antibody-coated lymphoma cells by BCG-activated macrophages appears to have a predominantly oxidative basis.
Compensatory Upregulation of Tyrosine Kinase Etk/BMX in Response to Androgen Deprivation Promotes Castration-Resistant Growth of Prostate Cancer Cells
Authors: Bojie Dai, Hege Chen, Shengjie Guo, Xi Yang, Douglas E. Linn, Feng Sun, Wei Li, Zhiyong Guo, Kexin Xu, Oekyung Kim, Xiangtian Kong, Jonathan Melamed, Shaopeng Qiu, Hegang Chen, Yun Qiu
Journal: Cancer Research (2010)

We previously showed that targeted expression of non-receptor tyrosine kinase Etk/BMX in mouse prostate induces prostate intraepithelial neoplasia, implying a possible causal role of Etk in prostate cancer development and progression. Here, we report that Etk is upregulated in both human and mouse prostates in response to androgen ablation. Etk expression seems to be differentially regulated by androgen and interleukin 6 (IL-6), which is possibly mediated by the androgen receptor (AR) in prostate cancer cells. Our immunohistochemical analysis of tissue microarrays containing 112 human prostate tumor samples revealed that Etk expression is elevated in hormone-resistant prostate cancer and positively correlated with tyrosine phosphorylation of AR (Pearson correlation coefficient rho = 0.71, P < 0.0001). AR tyrosine phosphorylation is increased in Etk-overexpressing cells, suggesting that Etk may be another tyrosine kinase, in addition to Src and Ack-1, which can phosphorylate AR. We also showed that Etk can directly interact with AR through its Src homology 2 domain, and such interaction may prevent the association of AR with Mdm2, leading to stabilization of AR under androgen-depleted conditions. Overexpression of Etk in androgen-sensitive LNCaP cells promotes tumor growth while knocking down Etk expression in hormone-insensitive prostate cancer cells by a specific shRNA that inhibits tumor growth under androgen-depleted conditions. Taken together, our data suggest that Etk may be a component of the adaptive compensatory mechanism activated by androgen ablation in prostate and may play a role in hormone resistance, at least in part, through direct modulation of the AR signaling pathway.
MEDICAL NEWS FROM CHINA
Authors: M. P. YOUNG
Journal: Annals of Internal Medicine (1941)

Editorial1 April 1941MEDICAL NEWS FROM CHINAM. P. YOUNG, M.D., F.A.C.P.M. P. YOUNG, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-10-1933 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe following brief account of medical findings in a busy Red Cross Clinic in China has been contributed by one of the Fellows of the American College of Physicians who is at work at Soochow in the province of Kiangsu. It is a revealing report which will be read with interest by our membership."The Red Cross Clinics in Soochow have been in operation for 29 months. During this time 300,000 people, in round numbers, have been treated. Sixty per cent were from the city and the remaining 40 per cent were refugees from the surrounding city and country districts.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1941Volume 14, Issue 10Page: 1933-1934 ePublished: 1 December 2008 Issue Published: 1 April 1941 PDF downloadLoading ...
Opioid peptides and the heart
Authors: B Barron
Journal: Cardiovascular Research (1999)

The heart is a complex neuroendocrine (opioids, NPY, VIP) or mechanoendocrine (ANP) organ. Opioid peptides and receptors are present in the heart and nerves such that they can easily modulate cardiac function. Cardiac opioids may have autocrine, paracrine and endocrine function. The challenge is to find the signal that turns them on and then what they do in the face of an overwhelmingly redundant system making knock-out technology hard to interpret. Determining the cardiac release of opioids in an intact system still requires a larger animal model.