tbuckley/cabot-search huggingface dataset:
Na,K-ATPase Overexpression Improves Alveolar Fluid Clearance in a Rat Model of Elevated Left Atrial Pressure
Authors: Zaher S. Azzam, Vidas Dumasius, Fernando J. Saldias, Yochai Adir, Jacob I. Sznajder, Phillip Factor
Journal: Circulation (2002)

Background — Acute elevation of left atrial pressure (LAP) increases extravascular water and impairs active Na + transport in rat lungs. We have reported that overexpression of Na,K-ATPase subunit genes in the alveolar epithelium increases alveolar fluid clearance (AFC) in normal and injured rat lungs with normal LAP. We reasoned that adenovirus-mediated transfer of an Na,K-ATPase β-subunit gene to the alveolar epithelium could improve AFC in rat lungs in the presence of acutely elevated LAP. Methods and Results — Normal rats were infected with 4×10 9 plaque-forming units of E1a − /E3 − recombinant adenoviruses that contained a cytomegalovirus promoter coupled to a rat Na,K-ATPase β 1 -subunit cDNA (adβ 1 ) or no cDNA (adNull) 7 days before study. Na,K-ATPase α 1 - and β 1 -subunit abundance in basolateral cell membranes isolated from the peripheral lung was significantly increased in adβ 1 -infected lungs compared with sham and adNull-infected controls. In all groups, elevation of LAP reduced membrane-bound Na,K-ATPase abundance; however, abundance in adβ 1 -infected lungs remained greater than in controls. AFC, measured with a fluid-filled isolated lung preparation in the presence of elevated LAP (15 cmH 2 O), in Na,K-ATPase β 1 -subunit-overexpressing lungs was up to 100% greater than in controls and was not different from rats studied at normal LAP (0 cmH 2 O). Conclusions — These data suggest that alveolar overexpression of an Na,K-ATPase β 1 -subunit can counteract downregulation of membrane-bound solute transporters owing to elevated pulmonary vascular pressures and can restore active Na + transport and AFC in this rat model of acute hydrostatic pulmonary edema.
Analysis of the DNA methylome and transcriptome in granulopoiesis reveals timed changes and dynamic enhancer methylation
Authors: Michelle Rönnerblad, Robin Andersson, Tor Olofsson, Iyadh Douagi, Mohsen Karimi, Sören Lehmann, Ilka Hoof, Michiel de Hoon, Masayoshi Itoh, Sayaka Nagao-Sato, Hideya Kawaji, Timo Lassmann, Piero Carninci, Yoshihide Hayashizaki, Alistair R. R. Forrest, Albin Sandelin, Karl Ekwall, Erik Arner, Andreas Lennartsson
Journal: Blood (2014)
Physician Recommendations and Patient Autonomy: Finding a Balance between Physician Power and Patient Choice
Authors: Timothy E. Quill
Journal: Annals of Internal Medicine (1996)

Medical care in the United States has rapidly moved away from a paternalistic approach to patients and toward an emphasis on patient autonomy.At one extreme end of this spectrum is the "independent choice" model of decision making, in which physicians objectively present patients with options and odds but withhold their own experience and recommendations to avoid overly influencing patients. This model confuses the concepts of independence and autonomy and assumes that the physician's exercise of power and influence inevitably diminishes the patient's ability to choose freely. It sacrifices competence for control, and it discourages active persuasion when differences of opinion exist between physician and patient. This paper proposes an "enhanced autonomy" model, which encourages patients and physicians to actively exchange ideas, explicitly negotiate differences, and share power and influence to serve the patient's best interests. Recommendations are offered that promote an intense collaboration between patient and physician so that patients can autonomously make choices that are informed by both the medical facts and the physician's experience.
Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading.
Authors: M C Haigney, E G Lakatta, M D Stern, H S Silverman
Journal: Circulation (1994)

BACKGROUND Studies have shown that the rise in intracellular ionized calcium, [Ca2+]i, in hypoxic myocardium is driven by an increase in sodium, [Na+]i, but the source of Na+ is not known. METHODS AND RESULTS Inhibitors of the voltage-gated Na+ channel were used to investigate the effect of Na+ channel blockade on hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated adult rat cardiac myocytes. Single electrically stimulated (0.2 Hz) cells were loaded with either SBFI (to index [Na+]i) or indo-1 (to index [Ca2+]i) and exposed to glucose-free hypoxia (PO2 &lt; 0.02 mm Hg). Both [Na+]i and [Ca2+]i increased during hypoxia when cells became inexcitable following ATP-depletion contracture. The hypoxic rise in [Na+]i and [Ca2+]i was significantly attenuated by 1 mumol/L R 56865. Tetrodotoxin (60 mumol/L), a selective Na(+)-channel blocker, also markedly reduced the rise in [Ca2+]i during hypoxia and reoxygenation. Reoxygenation-induced cellular hypercontracture was reduced from 83% (45 of 54 cells) under control conditions to 12% (4 of 32) in the presence of R 56865 (P &lt; .05). Lidocaine reduced hypercontracture dose dependently with 13% of cells hypercontracting in 100 mumol/L lidocaine, 42% in 50 mumol/L lidocaine, and 93% in 25 mumol/L lidocaine. The Na(+)-H+ exchange blocker, ethylisopropylamiloride (10 mumol/L) was also effective, limiting hypercontracture to 12%. R 56865, lidocaine, and ethylisopropylamiloride were also effective in preventing hypercontracture in normoxic myocytes induced by 75 mumol/L veratridine, an agent that impairs Na+ channel inactivation. Ethylisopropylamiloride prevented the veratridine-induced rise in [Ca2+]i without affecting Na(+)-Ca2+ exchange, suggesting that amiloride derivatives can reduce Ca2+ loading by blocking Na+ entry through Na+ channels, an action that may in part underlie their ability to prevent hypoxic Na+ and Ca2+ loading. CONCLUSIONS Na+ influx through the voltage-gated Na+ channel is an important route of hypoxic Na+ loading, Na(+)-dependent Ca2+ loading, and reoxygenation hypercontracture in isolated rat cardiac myocytes. Importantly, the Na+ channel appears to serve as a route for hypoxic Na+ influx after myocytes become inexcitable.
Variant lymphoproliferative disorder of granular lymphocytes (LDGL) following Hodgkin lymphoma
Authors: Brian Douglas Jenkins, Daniel Snower, Anwar Mohamed, Ayad Al‐Katib
Journal: American Journal of Hematology (2005)

Abstract A 41‐year‐old Caucasian female was diagnosed with a CD3 + CD4 + CD8 + variant of lymphoproliferative disorder of granular lymphocytes (LDGL) in the third year of remission following treatment of stage III‐B Hodgkin lymphoma (HL). The patient was asymptomatic at diagnosis, without clinical evidence of immune disorder or recurrence of HL. Diagnosis was made incidentally, secondary to lymphocytosis discovered on a routine follow‐up post HL therapy. Clonal chromosomal abnormalities were seen in 20% of peripheral blood lymphocytes with a karyotype 46, XX, t(2;6;2;11) (p13;q23;q24;q23). The breakpoint on 11q23 is distal to the MLL gene as shown by fluorescence in situ hybridization (FISH) analysis. To our knowledge, this is the first report of variant LDGL in association with HL treatment with documented clonal chromosomal abnormalities. Am. J. Hematol. 79:128–131, 2005. © 2005 Wiley‐Liss, Inc.
Relation of Hormone-Replacement Therapy to Measures of Plasma Fibrinolytic Activity
Authors: Eyal Shahar, Aaron R. Folsom, Veikko V. Salomaa, Valarie L. Stinson, Paul G. McGovern, Tomoko Shimakawa, Lloyd E. Chambless, Kenneth K. Wu
Journal: Circulation (1996)

Background The mechanisms by which replacement hormones may reduce the risk of coronary heart disease are not fully understood. Of specific interest is a potential effect of replacement hormones on plasma fibrinolytic activity, a putative determinant of thrombotic events. Methods and Results We investigated the relation of current use of replacement hormones to three measures of plasma fibrinolytic activity: tissue-type plasminogen activator (TPA) antigen, plasminogen activator inhibitor–1 (PAI-1) antigen, and d -dimer. The sample was composed of 288 women, free of clinical cardiovascular disease, who were selected for a case-control study of atherosclerosis: 142 women with ultrasonographic evidence of carotid intimal-medial thickening (cases) and 146 control subjects. Twenty percent (59 women) reported current use of replacement hormones. TPA antigen and PAI-1 antigen were highly correlated with each other ( r =.67), whereas d -dimer correlated only weakly with TPA or PAI-1. Compared with nonusers, current users of replacement hormones had lower mean levels of TPA and PAI-1 antigens, suggesting enhanced fibrinolytic potential. In the entire sample, the multivariate-adjusted geometric mean values of TPA antigen were 6.3 and 7.3 ng/mL among current users and nonusers, respectively ( P =.01); the corresponding values for PAI-1 antigen were 6.1 and 7.5 ng/mL ( P =.13). These results were generally consistent for both atherosclerosis cases and their control subjects. d -dimer levels were lower in current hormone users than in nonusers, but the difference was not statistically significant ( P &gt;.15) in any of the analyses. Conclusions The use of replacement hormones appears to be associated with enhancement of endogenous fibrinolytic potential. Enhanced plasma fibrinolytic activity among hormone users may explain, in part, the inverse association between hormone replacement therapy and coronary heart disease.
It's a great idea and workable
Authors: A. N. Turner, D. O'Donoghue, K. Simpson
Journal: BMJ (2010)

In the same population as Greenhalgh and colleagues report an unimpressive response to HealthSpace,1 more than 11 000 UK renal patients are active users of an online system Renal PatientView (www.renalpatientview.org; www.renal.org/rpv), which allows them to see live unscreened test results, with information about their diagnosis and …
Regulation of Connexin43 Protein Complexes by Intracellular Acidification
Authors: Heather S. Duffy, Anthony W. Ashton, Phyllis O’Donnell, Wanda Coombs, Steve M. Taffet, Mario Delmar, David C. Spray
Journal: Circulation Research (2003)

Ischemia-induced acidification of astrocytes or cardiac myocytes reduces intercellular communication by closing gap junction channels and subsequently internalizing gap junction proteins. To determine whether such coupling changes might be attributable to altered interactions between connexin43 (Cx43) and other proteins, we applied the nigericin/high K+ method to vary intracellular pH (pHi) in cultured cortical astrocytes. Intracellular acidification was accompanied by internalization of Cx43 with retention of Cx43 scaffolding protein Zonula Occludens-1 (ZO-1) at cell surfaces, suggesting that ZO-1 and Cx43 dissociate at low pHi. Coimmunoprecipitation studies revealed decreased binding of ZO-1 and increased binding of c-Src to Cx43 at low pHi. Resonant mirror spectroscopy was used to quantify binding of the SH3 domain of c-Src and the PDZ domains of ZO-1 to the carboxyl terminal domain of Cx43 (Cx43CT). Data indicate that the c-Src/Cx43CT interaction is highly pH dependent whereas the ZO-1/Cx43CT interaction is not. Moreover, binding of c-Src to Cx43CT prevented and reversed ZO-1/Cx43CT binding. We hypothesize that increased affinity of c-Src for Cx43 at low pHi aids in separation of Cx43 from ZO-1 and that this may facilitate internalization of Cx43. These data suggest that protracted acidification may remodel protein-protein interactions involving Cx43 and thus provide an important protective mechanism to limit lesion spread after ischemic injury.
Treatment of Depression in Patients With Alcohol or Other Drug Dependence
Authors: Edward V. Nunes, Frances R. Levin
Journal: JAMA (2004)

Depression and substance abuse are common and costly disorders that frequently co-occur, but controversy about effective treatment for patients with both disorders persists.To conduct a systematic review and meta-analysis to quantify the efficacy of antidepressant medications for treatment of combined depression and substance use disorders.PubMed, MEDLINE, and Cochrane database search (1970-2003), using the keywords antidepressant treatment or treatment depressed in conjunction with each of the following alcohol dependence, benzodiazepine dependence, opiate dependence, cocaine dependence, marijuana dependence, and methadone; a search of bibliographies; and consultation with experts in the field.Among inclusion criteria used for study selection were prospective, parallel group, double-blind, controlled clinical trials with random assignment to an antidepressant medication or placebo for which trial patients met standard diagnostic criteria for current alcohol or other drug use and a current unipolar depressive disorder. Of the more than 300 citations extracted, 44 were placebo-controlled clinical trials, 14 of which were selected for this analysis and included 848 patients: 5 studies of tricyclic antidepressants, 7 of selective serotonin re-uptake inhibitors, and 2 from other classesWe independently screened the titles and abstracts of each citation, identified placebo-controlled trials of patients with both substance dependence and depression, applied the inclusion criteria, and reached consensus. Data on study methods, sample characteristics, and depression and substance use outcomes were extracted. The principal measure of effect size was the standardized difference between means on the Hamilton Depression Scale (HDS).For the HDS score, the pooled effect size from the random-effects model was 0.38 (95% confidence interval, 0.18-0.58). Heterogeneity of effect on HDS across studies was significant (P <.02), and studies with low placebo response showed larger effects. Moderator analysis suggested that diagnostic methods and concurrent psychosocial interventions influenced outcome. Studies with larger depression effect sizes (>0.5) demonstrated favorable effects of medication on measures of quantity of substance use, but rates of sustained abstinence were low.Antidepressant medication exerts a modest beneficial effect for patients with combined depressive- and substance-use disorders. It is not a stand-alone treatment, and concurrent therapy directly targeting the addiction is also indicated. More research is needed to understand variations in the strength of the effect, but the data suggest that care be exercised in the diagnosis of depression-either by observing depression to persist during at least a brief period of abstinence or through efforts by clinical history to screen out substance-related depressive symptoms.
color categories in biological evolution: broadening the palette
Authors: wayne d. christensen, luca tommasi
Journal: Behavioral and Brain Sciences (2005)

the general structure of steels &amp; belpaeme's (s&amp;b's) central premise is appealing. theoretical stances that focus on one type of mechanism miss the fact that multiple mechanisms acting in concert can provide convergent constraints for a more robust capacity than any individual mechanism might achieve acting in isolation. however, highlighting the significance of complex constraint interactions raises the possibility that some of the relevant constraints may have been left out of s&amp;b's own models. although abstract modeling can help clarify issues, it also runs the risk of oversimplification and misframing. a more subtle implication of the significance of interacting constraints is that it calls for a close relationship between theoretical and empirical research.
Influence of exposure mode on the toxicity of NO2.
Authors: D E Gardner, F J Miller, E J Blommer, D L Coffin
Journal: Environmental Health Perspectives (1979)

Pollutant gases are subject to a variety of physical and chemical interactions within the atmosphere due to cyclic production and various meteorological influences. In consequence there is generally a diurnal concentration profile for NO2 which consists of peaks of short duration and irregular occurrence superimposed on a low background. Since this variation could play an important role in the toxic effect of NO2, the influences of various exposure modes was studied. Continuous and intermittent exposure studies were used to determine the relationship between biological response and length of exposure to various concentrations of NO2. As the concentration decreased, the slope of the regression line decreased. After adjusting for total differences in the product concentration x time, the response for the two exposure modes was essentially the same. When a constant concentration x time level was employed, a short-term exposure to a high concentration produced a greater effect than exposure to a lower concentration administered over a longer period. Using these curves, the relationship between level of effect, concentration, and time can be determined. Results of these studies indicated that the frequency and amplitude of short-term peaks are of significance even though the exposure is interrupted with periods of zero concentration of NO2.
Anthracycline Antibiotics and the Heart
Authors: Samuel Vaisrub
Journal: JAMA (1977)

Whenever we prescribe antimicrobial antibiotic, our attention is usually focused on the kidney more than any other organ because of its exposure to high concentrations of the drug by glomerular filtration and tubular reabsorption. Sometimes, as with antibiotics of the tetracycline group, we worry about the gastrointestinal tract, which may become vulnerable to injury by commensals. Frequently, we may be concerned with injury to the blood cells or the liver. Rarely, if ever, do we think of the heart as a target of antibiotic toxicity. With the advent of antitumor antibiotics of the anthracycline group, the heart lost its privileged position vis-à-vis other organs. It, too, became vulnerable. An increasing number of reports have attested to this vulnerability since Tan et al<sup>1</sup>reported lethal cardiotoxicity in seven children, and Ainger et al<sup>2</sup>described a similar fatal outcome in two adults, in whom electronmicroscopic study of the myocardium demonstrated
Judging Public Health Research: Epistemology, Public Health and the Law
Authors: Matthew K. Wynia
Journal: The American Journal of Bioethics (2005)

With this issue, we begin a regular feature on bioethics and public health. We welcome Matthew K. Wynia, M.D., M.P.H., Director of the Institute for Ethics of the American Medical Association as our new Contributing Editor. If you have comments or suggestions regarding this feature, please email us at manuscript@ bioethics.net.
Association of clathrin with microsomes isolated from canine myocardium.
Authors: D R Caprette, M L Entman, W B Van Winkle
Journal: Circulation Research (1986)

We and others have observed specialized regions of sarcoplasmic reticulum membranes that resemble coated vesicles, in the I-band region of myocardial cells. These structures have been named "corbular" sarcoplasmic reticulum, and are distinct in appearance from Golgi-associated coated vesicles, in that they are larger and contain a flocculent material that has been identified as calsequestrin. Whereas it has been suggested that these structures have a role in cardiac calcium metabolism, their function(s) and the molecular identity of the characteristic "bristle" coat remain unknown. Microsomes enriched in sarcoplasmic reticulum were prepared from canine ventricular muscle by Polytron homogenization in pH 6.5 buffer, followed by differential centrifugation. Protein was released by incubation in 50 mM Tris/HCl, pH 8, followed by centrifugation. We found these extracts to be enriched in a protein that was identical to brain clathrin in mobility on a Sepharose 4B gel filtration column, final position of the native protein following nondenaturing electrophoresis, relative mobility in denaturing (sodium dodecyl sulfate) electrophoresis on 6% and 7.5% gels, and antigenicity to anti-clathrin IgG. These findings confirmed the presence of clathrin triskelions in the cardiac microsome extract. On this basis, we suggest that clathrin may be a component of the electron dense "coat" of corbular sarcoplasmic reticulum.
Abstract 791: T cells in visceral adipose tissue: A potential source of inflammation to drive tumorigenesis
Authors: Joanne Lysaght, Emma H. Allott, Claire L. Donohoe, Julia M. Howard, Graham P. Pidgeon, John V. Reynolds
Journal: Cancer Research (2011)

Abstract Introduction: Visceral adipose tissue is believed to be fuelling a state of chronic inflammation in obese patients, establishing an environment favourable for tumor growth. However, the exact immunological mechanisms remain unclear. Recent animal studies have pointed to an important role for visceral adipose tissue CD8+ T cells in both the establishment of and maintenance of adipose tissue inflammation in obese models. This novel study aimed to phenotypically characterize both CD4+ and CD8+ T cells in the omentum of esophageal adenocarcinoma (EAC) patients, as EAC has one of the strongest association with obesity and arises in a background of inflammation. Methods: Peripheral blood and visceral adipose tissue from the greater omentum were taken from 30 EAC patients at the commencement of resectional surgery. Peripheral blood mononuclear cells were isolated using density centrifugation and the stromal vascular fraction of the adipose tissue was obtained following collagenase digestion. T cell activation status and cytokine production were assessed by both surface and intracellular flow cytometry and serum cytokines were determined by ELISA. Results: The omentum was found to be a rich source of both CD4+ and CD8+ T cells, which display an activated inflammatory phenotype, expressing significantly higher (p&amp;lt;0.0001) CD69, CD107a, CD45RO and IFN-γ than T cells in the blood. Omental CD8+ T cells also expressed significantly higher (p&amp;lt;0.0001) IFN-γ than CD4+ T cells, suggesting that CD8+ T cells are an important source of this inflammatory cytokine within visceral fat. The highest circulating levels of the IFN-γ were detected in the serum of viscerally obese cancer patients. Conclusions: This novel study demonstrates that omental T cells may be key players in driving adipose tissue inflammation, potentially mediated by IFN-γ. The highest serum levels of IFN-γ were detected in viscerally obese cancer patients, suggesting that visceral adipose tissue may be the source of this inflammatory cytokine, thus providing an immunotherapeutic target to attenuate chronic inflammation associated with visceral obesity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 791. doi:10.1158/1538-7445.AM2011-791
Wegener's and Lethal Midline Granulomatosis
Authors: Edith E. Sproul
Journal: JAMA (1961)

LITTLE has been added of late to the observed j phenomena constituting the disease patterns commonly designated as Wegener's granulomatosis and lethal midline disease. However, from the numerous precise detailed descriptions of clinical course, response to therapies, and necropsy findings there has emerged a recognizable natural history which is fairly constant and an aid to choice of therapy and prognostic evaluation. Patients differ in predictable ways, but, whatever course is assumed, the processes are aggressive and invariably fatal. <h3>Lethal Midline Granulomatosis</h3> There have been many pseudonyms affixed to lethal midline granulomatosis over the 65 years since Dr. McBride's presentation of a case in 1897.<sup>1</sup>In all of the patients reported (more than 100) it is indicated that it is an aggressive necrotizing inflammatory process leading to destruction of soft tissues and bones of the nose, the paranasal sinuses, soft palate, and pharynx. The cell response is heavy and