tbuckley/cabot-search huggingface dataset:
Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1–dependent pathway
Authors: Refaat A.F. Hegazi, Kavitha N. Rao, Aqila Mayle, Antonia R. Sepulveda, Leo E. Otterbein, Scott E. Plevy
Journal: The Journal of Experimental Medicine (2005)

Heme oxygenase (HO)-1 and its metabolic product carbon monoxide (CO) play regulatory roles in acute inflammatory states. In this study, we demonstrate that CO administration is effective as a therapeutic modality in mice with established chronic colitis. CO administration ameliorates chronic intestinal inflammation in a T helper (Th)1-mediated model of murine colitis, interleukin (IL)-10–deficient (IL-10−/−) mice. In Th1-mediated inflammation, CO abrogates the synergistic effect of interferon (IFN)-γ on lipopolysaccharide-induced IL-12 p40 in murine macrophages and alters IFN-γ signaling by inhibiting a member of the IFN regulatory factor (IRF) family of transcription factors, IRF-8. A specific signaling pathway, not previously identified, is delineated that involves an obligatory role for HO-1 induction in the protection afforded by CO. Moreover, CO antagonizes the inhibitory effect of IFN-γ on HO-1 expression in macrophages. In macrophages and in Th1-mediated colitis, pharmacologic induction of HO-1 recapitulates the immunosuppressive effects of CO. In conclusion, this study begins to elucidate potential etiologic and therapeutic implications of CO and the HO-1 pathway in chronic inflammatory bowel diseases.
Does Asbestos Exposure Cause Airway Obstruction, in the Absence of Confirmed Asbestosis?
Authors: Jacques Ameille, Marc Letourneux, Christophe Paris, Patrick Brochard, Audrey Stoufflet, Evelyne Schorle, Antoine Gislard, François Laurent, Françoise Conso, Jean-Claude Pairon
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Whether occupational exposure to asbestos causes airway obstruction remains controversial.Objectives: This study evaluated lung function in relation to cumulative exposure to asbestos in a large cohort of retired or unemployed workers exposed to asbestos.Methods: The study population consisted of 3,660 volunteer subjects. An individual cumulative exposure index to asbestos was calculated for each subject, and information was obtained on smoking status. Pulmonary function tests were performed in all subjects; high-resolution chest computed tomography was also performed in 3,335 subjects.Measurements and Main Results: Values of FEV1/FVC and FEF25–75% did not differ between five classes (quintiles) of cumulative exposure to asbestos, and no significant correlation was observed between cumulative exposure to asbestos and pulmonary function parameters, after adjustment for sex, tobacco consumption, emphysema, and body mass index. Furthermore, the proportion of abnormal pulmonary function tests did not differ between the five classes of cumulative exposure to asbestos.Conclusions: The results do not support a causal relationship between asbestos exposure alone and airway obstruction. However, the study sample may not be representative of all people occupationally exposed to asbestos, because a fraction of subjects with previously diagnosed asbestosis probably did not participate in this screening program.
The importance of religious affiliation and culture on end-of-life decisions in European intensive care units
Authors: Charles L. Sprung, Paulo Maia, Hans-Henrik Bulow, Bara Ricou, Apostolos Armaganidis, Mario Baras, Elisabet Wennberg, Konrad Reinhart, Simon L. Cohen, Dietmar R. Fries, George Nakos, Lambertius G. Thijs
Journal: Intensive Care Medicine (2007)
Natriuretic Peptide Receptor-C Regulates Coronary Blood Flow and Prevents Myocardial Ischemia/Reperfusion Injury
Authors: Adrian Hobbs, Paul Foster, Craig Prescott, Ramona Scotland, Amrita Ahluwalia
Journal: Circulation (2004)

Ischemia/reperfusion (I/R) injury complicates myocardial infarction and stroke by exacerbating tissue damage and increasing risk of mortality. We have recently identified C-type natriuretic peptide (CNP) as an endothelium-derived hyperpolarizing factor in the mesenteric resistance vasculature and described a novel signaling pathway involving activation of natriuretic peptide receptor C (NPR-C), which plays a pivotal role in the regulation of local blood flow. We tested the hypothesis that CNP/NPR-C signaling is a novel regulatory pathway governing coronary blood flow and protecting against I/R injury.CNP and (Cys18)-atrial natriuretic factor (4-23) amide (cANF(4-23)) elicited dose-dependent decreases in coronary perfusion pressure (CPP) that were blocked by Ba(2+) and ouabain in the isolated Langendorff rat heart. The endothelium-dependent vasodilator acetylcholine elicited the release of CNP from the coronary endothelium. CNP and cANF(4-23) reduced infarct size after 25 minutes of global ischemia and 120 minutes of reperfusion, maintaining CPP and left ventricular pressure at preischemic values. The vasorelaxant and protective activity of CNP and cANF(4-23) were enhanced in the absence of endothelium-derived nitric oxide.Endothelium-derived CNP is involved in the regulation of the coronary circulation, and NPR-C activation underlies the vasorelaxant activity of this peptide. Moreover, this newly defined pathway represents a protective mechanism against I/R injury and a novel target for therapeutic intervention in ischemic cardiovascular disorders.
Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes
Authors: Yingnan Zhao, Claudia R. Campbell, Vivian Fonseca, Lizheng Shi
Journal: Diabetes Care (2012)

Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score-matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA(1c) of 10.69 ± 2.61%. The 1-year change in HbA(1c) was similar (hypoglycemia group -0.51 vs. control group -0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63-2.44]) and microvascular complications (1.76 [1.46-2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10-1.66]).Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.
Telmisartan Shows an Equivalent Effect of Vitamin C in Further Improving Endothelial Dysfunction After Glycemia Normalization in Type 1 Diabetes
Authors: Antonio Ceriello, Ludovica Piconi, Katherine Esposito, Dario Giugliano
Journal: Diabetes Care (2007)

Long-lasting hyperglycemia in type 1 diabetic patients induces permanent alterations of endothelial function by increased oxidative stress, even when glycemia is normalized.In this study, 36 type 1 diabetic patients and 12 control subjects were enrolled. The diabetic patients were divided into three groups. The first group was treated for 24 h with insulin, achieving a near normalization of glycemia. After 12 h of this treatment, vitamin C was added for the remaining 12 h. The second group was treated for 24 h with vitamin C. After 12 h of this treatment, insulin was started, achieving a near normalization of glycemia for the remaining 12 h. The third group was treated for 24 h with both vitamin C and insulin, achieving near normalization of glycemia. The same protocols were performed after 1 month of telmisartan or placebo.Neither normalization of glycemia nor vitamin C treatment alone was able to normalize endothelial dysfunction or oxidative stress. Combining insulin and vitamin C normalized endothelial dysfunction and decreased oxidative stress to normal levels. Telmisartan significantly improved basal endothelial function and decreased nitrotyrosine plasma levels. In patients treated with telmisartan, a near normalization of both flow-mediated vasodilation and oxidative stress was achieved when glycemia was normalized, whereas adding vitamin C infusion did not show further effect on endothelial function or nitrotyrosine plasma levels.These data indicate that combining the normalization of glycemia with an antioxidant can normalize endothelial function in type 1 diabetic patients and that telmisartan works as an antioxidant like vitamin C.
Small-Molecule Inhibitors of the Wnt Pathway Potently Promote Cardiomyocytes From Human Embryonic Stem Cell–Derived Mesoderm
Authors: Erik Willems, Sean Spiering, Herman Davidovics, Marion Lanier, Zebin Xia, Marcia Dawson, John Cashman, Mark Mercola
Journal: Circulation Research (2011)

Human embryonic stem cells can form cardiomyocytes when cultured under differentiation conditions. Although the initiating step of mesoderm formation is well characterized, the subsequent steps that promote for cardiac lineages are poorly understood and limit the yield of cardiomyocytes.Our aim was to develop a human embryonic stem cell-based high-content screening assay to discover small molecules that drive cardiogenic differentiation after mesoderm is established to improve our understanding of the biology involved. Screening of libraries of small-molecule pathway modulators was predicted to provide insight into the cellular proteins and signaling pathways that control stem cell cardiogenesis.Approximately 550 known pathway modulators were screened in a high-content screening assay, with hits being called out by the appearance of a red fluorescent protein driven by the promoter of the cardiac-specific MYH6 gene. One potent small molecule was identified that inhibits transduction of the canonical Wnt response within the cell, which demonstrated that Wnt inhibition alone was sufficient to generate cardiomyocytes from human embryonic stem cell-derived mesoderm cells. Transcriptional profiling of inhibitor-treated compared with vehicle-treated samples further indicated that inhibition of Wnt does not induce other mesoderm lineages. Notably, several other Wnt inhibitors were very efficient in inducing cardiogenesis, including a molecule that prevents Wnts from being secreted by the cell, which confirmed that Wnt inhibition was the relevant biological activity.Pharmacological inhibition of Wnt signaling is sufficient to drive human mesoderm cells to form cardiomyocytes; this could yield novel tools for the benefit of pharmaceutical and clinical applications.
Medical and Public Health Aspects of Boxing
Authors: Robert Glenn Morrison
Journal: JAMA (1986)

In recent years, an extensive medical literature has accumulated regarding the health hazards associated with boxing. As the evidence that boxing produces irreversible brain damage in boxers has become more compelling, physicians have begun to consider the larger issue of whether the sport is acceptable in its present form. This has resulted in a number of proclamations concerning boxing by various representatives of the medical community, which have both added information to and fueled the public debate over boxing. This article seeks to review the relevant medical literature concerning the health effects of boxing; to look at the contributions made in the last few years by the medical community to the public debate over boxing; and to suggest ways in which the objectives of the medical professional concerning boxing can best be achieved. (<i>JAMA</i>1986;255:2475-2480)
Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses
Authors: Roland Grenningloh, Bok Yun Kang, I-Cheng Ho
Journal: The Journal of Experimental Medicine (2005)

To mount an effective type 1 immune response, type 1 T helper (Th1) cells must produce inflammatory cytokines and simultaneously suppress the expression of antiinflammatory cytokines. How these two processes are coordinately regulated at the molecular level is still unclear. In this paper, we show that the proto-oncogene E26 transformation–specific-1 (Ets-1) is necessary for T-bet to promote interferon-γ production and that Ets-1 is essential for mounting effective Th1 inflammatory responses in vivo. In addition, Ets-1–deficient Th1 cells also produce a very high level of interleukin 10. Thus, Ets-1 plays a crucial and unique role in the reciprocal regulation of inflammatory and antiinflammatory Th responses.
Abnormal development of NG2+PDGFR-α+ neural progenitor cells leads to neonatal hydrocephalus in a ciliopathy mouse model
Authors: Calvin S Carter, Timothy W Vogel, Qihong Zhang, Seongjin Seo, Ruth E Swiderski, Thomas O Moninger, Martin D Cassell, Daniel R Thedens, Kim M Keppler-Noreuil, Peggy Nopoulos, Darryl Y Nishimura, Charles C Searby, Kevin Bugge, Val C Sheffield
Journal: Nature Medicine (2012)
Measurement of β<sub>2</sub>‐glycoprotein i (apolipoprotein h)‐independent anticardiolipin antibody in human immunodeficiency virus‐1‐positive and‐negative hemophiliacs
Authors: Juzo Matsuda, Noriko Saitoh, Miyo Tsukamoto, Kengo Gohchi, Katsuhisa Asami, Masakatsu Hashimoto
Journal: American Journal of Hematology (1993)

The authors studied whether or not anticardiolipin antibody (aCL), which is frequently detected in hemophiliacs with human immunodeficiency virus-1 (HIV-1) infection, is dependent on beta 2-glycoprotein I (GPI), a cofactor of cardiolipin (CL). GPI-independent aCL was positive in 27 of 36 hemophiliacs with HIV-1 antibody (75%) and in 23 of 29 patients without HIV-1 antibody (79%). However, only six HIV-1-positive and four HIV-1-negative patients were positive for GPI-dependent aCL. Thus the aCL in these hemophiliacs was GPI independent and therefore different from the aCL found in autoimmune diseases, such as systemic lupus erythematosus.
Doppler-Derived Myocardial Systolic Strain Rate Is a Strong Index of Left Ventricular Contractility
Authors: Neil L. Greenberg, Michael S. Firstenberg, Peter L. Castro, Michael Main, Agnese Travaglini, Jill A. Odabashian, Jeanne K. Drinko, L. Leonardo Rodriguez, James D. Thomas, Mario J. Garcia
Journal: Circulation (2002)

Background — Myocardial fiber strain is directly related to left ventricular (LV) contractility. Strain rate can be estimated as the spatial derivative of velocities (dV/ds) obtained by tissue Doppler echocardiography (TDE). The purposes of the study were (1) to determine whether TDE-derived strain rate may be used as a noninvasive, quantitative index of contractility and (2) to compare the relative accuracy of systolic strain rate against TDE velocities alone. Methods and Results — TDE color M-mode images of the interventricular septum were recorded from the apical 4-chamber view in 7 closed-chest anesthetized mongrel dogs during 5 different inotropic stages. Simultaneous LV volume and pressure were obtained with a combined conductance–high-fidelity pressure catheter. Peak elastance (E max ) was determined as the slope of end-systolic pressure-volume relationships during caval occlusion and was used as the gold standard of LV contractility. Peak systolic TDE myocardial velocities (S m ) and peak (ε′ p ) and mean (ε′ m ) strain rates obtained at the basal septum were compared against E max by linear regression. E max as well as TDE systolic indices increased during inotropic stimulation with dobutamine and decreased with the infusion of esmolol. A stronger association was found between E max and ε′ p ( r =0.94, P &lt;0.01, y =0.29 x +0.46) and ε′ m ( r =0.88, P &lt;0.01) than for S m ( r =0.75, P &lt;0.01). Conclusions — TDE-derived ε′ p and ε′ m are strong noninvasive indices of LV contractility. These indices appear to be more reliable than S m , perhaps by eliminating translational artifact.
Studies of Mouse Mammary Glands. II. Cytomorphology of Mammary Transplants in Inguinal Fat Pads, Nipple-Excised Host Glands, and Whole Mammary-Gland Transplants&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K. K. Sekhri, D. R. Pjtelka, K. B. DeOme
Journal: JNCI Journal of the National Cancer Institute (1967)

The cytology of mammary transplants in inguinal glandfree fat pads, nipple-excised host glands, and whole mammary-gland transplants of 136 C57BL/Crgl mice was investigated by light and electron microscopy. Among 31 successful whole-gland transplants, 6 were suckled by young; the fine structure of these suckled, whole-gland transplants and the glands in situ was similar. The unsuckled, whole-gland transplants, the nipple-excised host glands, and the inguinal glandfree transplants responded normally to the endogenous hormones of the hosts and were indistinguishable from the suckled glands up to the 1st day after parturition. Within the next 24 hours, however, all nippleless glands started deviating from the controls and exhibited degenerative changes reminiscent of normal postlactational involution. The events of cytolysis at the ultrastructural level were identical in all regressing glands, irrespective of the circumstances that led to regression. The process of involution proceeded at a demonstrable rate for about 1 week, after which it became imperceptibly slow. The alveoli persisting even after 3 weeks of lactation revealed intracellular accumulations of protein particles, hypotrophied Golgi apparatus, and breakdown of the endoplasmic reticulum. The results emphasize the importance of suckling coupled with the removal of secretion products for the maintenance of mammary gland in the functionally differentiated state.
BALB- and Harvey-murine sarcoma virus transformation of a novel lymphoid progenitor cell.
Authors: J H Pierce, S A Aaronson
Journal: The Journal of Experimental Medicine (1982)

BALB- and Harvey-murine sarcoma viruses (MSV) comprise a family of retroviruses whose mouse- and rat-derived onc genes are closely related. These viruses induce sarcomas and erythroleukemias in susceptible animals. An in vitro colony assay that detects transformation of lymphoid cells by Abelson-murine leukemia virus was used to demonstrate that BALB- and Harvey-MSV transform a novel hematopoietic cell both in culture and in vivo. Bone marrow colony formation was sarcoma virus dependent, followed single-hit kinetics, and required the presence of mercaptoethanol in the agar medium. BALB- and Harvey-MSV-induced colonies could be established in culture as continuous cell lines that demonstrated unrestricted self-renewal capacity and leukemogenicity in vivo. The cells had a blast cell morphology and lacked detectable markers of mature cells within the myeloid or erythroid series. They also lacked detectable immunoglobulin mu chain or Thy-1 antigen, markers normally associated with committed cells of the B and T lymphoid lineages, respectively. However, the transformants contained very high levels of terminal deoxynucleotidyl transferase (TdT), an enzyme believed to be specific to early stages within the lymphoid differentiation pathway. This phenotype distinguishes these BALB- and Harvey-MSV transformants from any previously reported hematopoietic targets of transforming retroviruses, including the pre-B lymphoid cell transformed by Abelson-MuLV under identical assay conditions. These newly identified lymphoid progenitor cell transformants may provide an important means of studying early stages of lymphoid ontogeny and the possible role of TdT in lymphoid development.
Impact on contraceptive practice of making emergency hormonal contraception available over the counter in Great Britain: repeated cross sectional surveys
Authors: Cicely Marston, Howard Meltzer, Azeem Majeed
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To examine the impact on contraceptive practice of making emergency hormonal contraception available over the counter. <b>Design</b> Analysis of data on contraceptive practice for women aged 16-49 years in the period 2000-2 from the Omnibus Survey, a multipurpose survey in which around 7600 adults living in private households are interviewed each year. <b>Setting</b> Private households in Great Britain. <b>Main outcome measures</b> Use of different types of contraception and rates of unprotected sex. <b>Results</b> After emergency hormonal contraception was made available over the counter, levels of use of different types of contraception by women aged 16-49 remained similar. No significant change occurred in the proportion of women using emergency hormonal contraception (8.4% in 2000, 7.9% in 2001, 7.2% in 2002) or having unprotected sex. A change did, however, occur in where women obtained emergency hormonal contraception; a smaller proportion of women obtained emergency hormonal contraception from physicians and a greater proportion bought it over the counter. No significant change occurred in the proportion of women using more reliable methods of contraception, such as the oral contraceptive pill, or in the proportion of women using emergency hormonal contraception more than once during a year. <b>Conclusions</b> Making emergency hormonal contraception available over the counter does not seem to have led to an increase in its use, to an increase in unprotected sex, or to a decrease in the use of more reliable methods of contraception.
<i>MUC1</i> Expression Is Regulated by DNA Methylation and Histone H3 Lysine 9 Modification in Cancer Cells
Authors: Norishige Yamada, Yukari Nishida, Hideaki Tsutsumida, Tomofumi Hamada, Masamichi Goto, Michiyo Higashi, Mitsuharu Nomoto, Suguru Yonezawa
Journal: Cancer Research (2008)

Abstract MUC1 is a transmembrane mucin that is highly expressed in various cancers and correlates with malignant potential. Important cancer-related genes such as p16 and E-cadherin are controlled epigenetically; however, MUC1 has been overlooked in epigenetics. Herein, we provide the first report that MUC1 gene expression is regulated by DNA methylation and histone H3 lysine 9 (H3-K9) modification of the MUC1 promoter. The recently developed MassARRAY assay was performed to investigate the DNA methylation status of 184 CpG sites from −2,753 to +263. Near the transcriptional start site, the DNA methylation level of MUC1-negative cancer cell lines (e.g., MDA-MB-453) was high, whereas that of MUC1-positive cell lines (e.g., MCF-7) was low. Histone H3-K9 modification status was also closely related to MUC1 gene expression. Furthermore, MUC1 mRNA expression in MUC1-negative cells was restored by treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Our results indicate that DNA methylation and histone H3-K9 modification in the 5′ flanking region play a critical role in MUC1 gene expression, and this study defines MUC1 as a new member of the class of epigenetically controlled genes. An understanding of the epigenetic changes of MUC1 may be of importance for diagnosis of carcinogenic risk and prediction of outcome for cancer patients. [Cancer Res 2008;68(8):2708–16]