tbuckley/cabot-search huggingface dataset:
Activation of β <sub>2</sub> -Adrenergic Receptors Hastens Relaxation and Mediates Phosphorylation of Phospholamban, Troponin I, and C-Protein in Ventricular Myocardium From Patients With Terminal Heart Failure
Authors: Alberto Kaumann, Sabine Bartel, Peter Molenaar, Louise Sanders, Kylie Burrell, Donathe Vetter, Petra Hempel, Peter Karczewski, Ernst-Georg Krause
Journal: Circulation (1999)

Background —Catecholamines hasten cardiac relaxation through β-adrenergic receptors, presumably by phosphorylation of several proteins, but it is unknown which receptor subtypes are involved in human ventricle. We assessed the role of β 1 - and β 2 -adrenergic receptors in phosphorylating proteins implicated in ventricular relaxation. Methods and Results —Right ventricular trabeculae, obtained from freshly explanted hearts of patients with dilated cardiomyopathy (n=5) or ischemic cardiomyopathy (n=5), were paced at 60 bpm. After measurement of the contractile and relaxant effects of epinephrine (10 μmol/L) or zinterol (10 μmol/L), mediated through β 2 -adrenergic receptors, and of norepinephrine (10 μmol/L), mediated through β 1 -adrenergic receptors, tissues were freeze clamped. We assessed phosphorylation of phospholamban, troponin I, and C-protein, as well as specific phosphorylation of phospholamban at serine 16 and threonine 17. Data did not differ between the 2 disease groups and were therefore pooled. Epinephrine, zinterol, and norepinephrine increased contractile force to approximately the same extent, hastened the onset of relaxation by 15±3%, 5±2%, and 20±3%, respectively, and reduced the time to half-relaxation by 26±3%, 21±3%, and 37±3%. These effects of epinephrine, zinterol, and norepinephrine were associated with phosphorylation (pmol phosphate/mg protein) of phospholamban 14±3, 12±4, and 12±3; troponin I 40±7, 33±7, and 31±6; and C-protein 7.2±1.9, 9.3±1.4, and 7.5±2.0. Phosphorylation of phospholamban occurred at both Ser16 and Thr17 residues through both β 1 - and β 2 -adrenergic receptors. Conclusions —Norepinephrine and epinephrine hasten human ventricular relaxation and promote phosphorylation of implicated proteins through both β 1 - and β 2 -adrenergic receptors, thereby potentially improving diastolic function.
Evidence That Macrophages in Atherosclerotic Lesions Contain Angiotensin II
Authors: D. Dean Potter, Christopher G. Sobey, Pamela K. Tompkins, James D. Rossen, Donald D. Heistad
Journal: Circulation (1998)

Background —We have reported that human mononuclear leukocytes contain large amounts of angiotensin II (Ang II). The goal of the present study was to test the hypothesis that Ang II is present in monocyte/macrophages in atherosclerotic lesions. Methods and Results —Segments of thoracic aorta and left circumflex coronary artery were obtained from 3 groups of cynomolgus monkeys: normal, atherosclerotic, and regression. Samples of human coronary arterial atherosclerotic lesions were obtained from directional atherectomy. Sections were stained for Ang II with 3 different polyclonal rabbit anti–human Ang II antisera. In aorta and coronary arteries from normal monkeys, there was no or minimal anti–Ang II staining in endothelial cells. All sections from atherosclerotic monkeys displayed discrete, localized regions of staining for Ang II in intima-media. Macrophages were present throughout the atherosclerotic intima-media, and anti–Ang II staining appeared to colocalize with macrophages. All human coronary atherectomy samples stained positive for Ang II and macrophages. Staining for both Ang II and macrophages was observed in vascular lesions from all 5 monkeys after regression of atherosclerosis, but staining was less extensive than in atherosclerotic blood vessels from monkeys. Conclusions —These findings suggest that Ang II is present in atherosclerotic lesions in monkeys and humans, colocalizes with macrophages in intima-media of atherosclerotic vessels from monkeys, and decreases in lesions in monkeys with regression of atherosclerosis.
A Comparison between Two Strategies for Monitoring Hepatic Function during Antituberculous Therapy
Authors: Aran Singanayagam, Saranya Sridhar, Jaideep Dhariwal, Dalia Abdel-Aziz, Kerry Munro, David W. Connell, Peter M. George, Philip L. Molyneaux, Graham S. Cooke, Andrew K. Burroughs, Ajit Lalvani, Melissa Wickremasinghe, Onn Min Kon
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The optimum strategy for monitoring liver function during antituberculous therapy is unclear.Objectives: To assess the value of the American Thoracic Society risk-factor approach for predicting drug-induced liver injury and to compare with a uniform policy of liver function testing in all patients at 2 weeks.Methods: We conducted an observational study of adult patients undergoing therapy for active tuberculosis at a tertiary center. All patients had alanine transferase measurement at baseline and 2 weeks following commencement of therapy. Sensitivity, specificity, and positive and negative predictive values were used to assess strategies.Measurements and Main Results: There were 288 patients included, and 21 (7.3%) developed drug-induced liver injury (57.1% "early" at 2 wk and 42.9% "late," after 2 wk). There were increased rates of individuals with HIV infection in the early drug-induced liver injury group compared with no drug-induced liver injury and late drug-induced liver injury groups (33% vs. 7.1% vs. 0%; P = 0.004). The American Thoracic Society algorithm had a sensitivity and specificity of 66.7 and 65.6%, respectively, for prediction of early and 22.2% and 63.7% for late drug-induced liver injury. The uniform monitoring policy had poor sensitivity but better specificity (22.2 and 82.1%) for prediction of late drug-induced liver injury.Conclusions: In our urban, ethnically diverse population, a risk-factor approach is neither sensitive nor specific for prediction of drug-induced liver injury. A uniform policy of liver function testing at 2 weeks is useful for prompt identification of a subgroup who develop early drug-induced liver injury and may offer better specificity in ruling out late drug-induced liver injury.
Are Guidelines Following Guidelines?
Authors: Terrence M. Shaneyfelt, Michael F. Mayo-Smith, Johann Rothwangl
Journal: JAMA (1999)

Practice guidelines play an important role in medicine. Methodological principles have been formulated to guide their development.To determine whether practice guidelines in peer-reviewed medical literature adhered to established methodological standards for practice guidelines.Structured review of guidelines published from 1985 through June 1997 identified by a MEDLINE search.Mean number of standards met based on a 25-item instrument and frequency of adherence.We evaluated 279 guidelines, published from 1985 through June 1997, produced by 69 different developers. Mean overall adherence to standards by each guideline was 43.1% (10.77/25). Mean (SD) adherence to methodological standards on guideline development and format was 51.1% (25.3%); on identification and summary of evidence, 33.6% (29.9%); and on the formulation of recommendations, 46% (45%). Mean adherence to standards by each guideline improved from 36.9% (9.2/25) in 1985 to 50.4% (12.6/25) in 1997 (P<.001). However, there was little improvement over time in adherence to standards on identification and summary of evidence from 34.6% prior to 1990 to 36.1 % after 1995 (P = .11). There was no difference in the mean number of standards satisfied by guidelines produced by subspecialty medical societies, general medical societies, or government agencies (P = .55). Guideline length was positively correlated with adherence to methodological standards (P = .001).Guidelines published in the peer-reviewed medical literature during the past decade do not adhere well to established methodological standards. While all areas of guideline development need improvement, greatest improvement is needed in the identification, evaluation, and synthesis of the scientific evidence.
The Psychotherapy of Schizophrenia: An NIMH Program
Authors: RAYMOND J. FRIEDMAN, JOHN G. GUNDERSON, DAVID B. FEINSILVER
Journal: American Journal of Psychiatry (1973)

The authors discuss a current NIMH program whose purpose is to study the empirical knowledge of senior psychotherapists who treat schizophrenic patients and to translate this knowledge into potential research data. Such data, it is hoped, may add a new dimension to the treatment of the schizophrenic patient, which currently emphasizes the use of drugs. Thus far, the five groups of therapists who comprise the program have agreed upon a working definition of schizophrenia, the qualities of patients and therapists who do well in therapy, and the task of the initial treatment phase.
Visualization of stem cell features in human hepatocellular carcinoma reveals<i>in vivo</i>significance of tumor-host interaction and clinical course
Authors: Shunsuke Muramatsu, Shinji Tanaka, Kaoru Mogushi, Rama Adikrisna, Arihiro Aihara, Daisuke Ban, Takanori Ochiai, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Koh Nakayama, Hiroshi Tanaka, Shoji Yamaoka, Shigeki Arii
Journal: Hepatology (2013)

Abstract Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies because of recurrence and/or metastasis even after curative resection. Emerging evidence suggests that tumor metastasis and recurrence might be driven by a small subpopulation of stemness cells, so-called cancer stem cells (CSCs). Previous investigations have revealed that glioma and breast CSCs exhibit intrinsically low proteasome activity and that breast CSCs also reportedly contain a lower reactive oxygen species (ROS) level than corresponding nontumorigenic cells. Here we visualized two stem cell features, low proteasome activity and low intracellular ROS, in HCC cells using two-color fluorescence activated cell sorting to isolate cells with stem cell features. These cells were then analyzed for their division behavior in normoxia and hypoxia, expression of stem cell markers, tumorigenicity, metastatic potential, specific gene expression signatures, and their clinical implications. A visualized small subpopulation of HCC cells demonstrated asymmetric divisions. Their remarkable tumorigenicity in nonobese diabetic/severe combined immunodeficient mice suggested the cancer initiation potential of these HCC CSCs. Comprehensive gene expression analysis revealed that chemokine-related genes were up-regulated in the CSCs subpopulation. Our identified HCC CSCs facilitated the migration of macrophages in vitro and demonstrated metastatic potential by way of recruitment of macrophages in vivo . In patients who undergo curative operation for HCC, the CSC-specific gene signature in the liver microenvironment significantly correlates with recurrence. Conclusion : Based on these findings, the stem cell feature monitoring system proposed here is a promising tool to analyze the in vivo significance of CSC microenvironments in human HCCs. (HEPATOLOGY 2013;)
Alterations in Cyclic AMP Metabolism in Human Bronchial Asthma. III. LEUKOCYTE AND LYMPHOCYTE RESPONSES TO STEROIDS
Authors: Charles W. Parker, Mary G. Huber, Mary L. Baumann
Journal: Journal of Clinical Investigation (1973)

On the basis of serial studies the responsiveness of leukocytes and lymphocytes from asthmatic donors to catecholamines was increased during high dose corticosteroid therapy. Similar changes were observed in the cells of normal control subjects given 200 mg of hydrocortisone intravenously. The increase in responsiveness did not appear to be due to changes in lymphocyte subpopulations although this may be a contributing factor. In an effort to elucidate the basis for the improved response, in vitro effects of glucocorticoids on lymphocyte cyclic AMP concentrations were investigated. Glucocorticoids (prednisolone succinate, hydrocortisone, hydrocortisone phosphate, and hydrocortisone succinate) stimulated cyclic AMP accumulation in asthma and normal control lymphocytes, increases occurring within the first 2 min of incubation. In the absence of theophylline, responses were regularly obtained at 10 μM hydrocortisone and usually at 1 μM hydrocortisone but not at submicromolar steroid concentrations. Theophylline potentiated the cyclic AMP response to glucocorticoids and also increased the percentage of positive responses in the 0.01-1.0 μM corticosteroid range. Combinations of 1 μM hydrocortisone and 1 μM epinephrine were sometimes additive or synergistic but in many instances higher glucocorticoid concentrations were needed to obtain augmentation of the catecholamine response. The in vitro glucocorticoid effects may not fully explain their potentiating action in vivo.
NHS will soon have to specify what care is and what isn't freely available, GPs say
Authors: N. Hawkes
Journal: BMJ (2012)

The NHS needs to think carefully about what will and what won’t be funded as budgets contract, the Nuffield Trust concludes in a new report. It rules out producing a national list of treatments and procedures as too challenging a task and one that, even if successful, would inhibit local autonomy and be vulnerable to political lobbying.

But if a national list of NHS treatments is ruled out, how can an undefined offering be managed? Most (85%) of the GPs in England who responded to a survey carried out for the Nuffield Trust to coincide with the report agreed that the financial challenge will eventually force the NHS to set out more clearly what care is, or is not, freely available. Only half believe that the NHS will be able to achieve enough efficiency savings in the next five years to avoid having to cut back on services. A representative sample of 821 GPs in England was surveyed.

The Nuffield Trust’s answer to the problem relies heavily on evidence, …
Hemodynamic and humoral changes after liver transplantation in patients with cirrhosis
Authors: Miquel Navasa, Faust Feu, Joan Carles García-Pagan, Wladimiro Jiménez, Josep Llach, Antoni Rimola, Jaume Bosch, Joan Rodés
Journal: Hepatology (1993)

Splanchnic and systemic hemodynamics and plasma levels of aldosterone, glucagon and plasma renin were investigated in 12 patients with advanced cirrhosis before and 2 wk (14.6 +/- 2.8 days) and 2 mo (60.8 +/- 10.5 days) after orthotopic liver transplantation. Liver transplant was followed by significant (p < 0.01) changes in systemic hemodynamics at 2 wk, with a marked reduction in cardiac index (4.9 +/- 0.8 vs. 3.7 +/- 0.7 L/min.m2) and increases in mean arterial pressure (79 +/- 8 vs. 101 +/- 11 mm Hg) and peripheral vascular resistance (721 +/- 149 vs. 1,274 +/- 253 dyn.sec.cm-5). Two months after liver transplant, we saw further significant increases in peripheral vascular resistance (1,700 +/- 341 dyn.sec.cm-5; p < 0.05) without changes in cardiac index. Hepatic venous pressure gradient, very high before transplantation, was normal 2 wk after liver transplant (18.7 +/- 3.0 vs. 2.1 +/- 0.8 mm Hg; p < 0.01). Hepatic blood flow rose markedly from 1.03 +/- 0.46 to 2.25 +/- 0.79 L/min (p < 0.01) and was still elevated at 2 mo (1.84 +/- 0.74 L/min). Azygos blood flow had not changed after 2 wk with respect to pretransplant values (0.65 +/- 0.26 vs. 0.69 +/- 0.39 L/min) but had decreased significantly at 2 mo (0.39 +/- 0.16 L/min; p < 0.05). The elevated aldosterone, plasma renin and glucagon levels found in our cirrhotic patients before transplantation decreased to near-normal values 2 wk after the procedure. These results suggest that most of the hemodynamic and humoral abnormalities characteristic of advanced cirrhosis are reversed after liver transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
Structure of Cerebral Arterioles in Cystathionine β-Synthase-Deficient Mice
Authors: Gary L. Baumbach, Curt D. Sigmund, Teodoro Bottiglieri, Steven R. Lentz
Journal: Circulation Research (2002)

We examined effects of hyperhomocysteinemia on structure and mechanics of cerebral arterioles. We measured plasma total homocysteine (tHcy) and pressure, diameter, and cross-sectional area of the vessel wall in maximally dilated cerebral arterioles in heterozygous cystathionine beta-synthase-deficient (CBS(+/-)) mice and wild-type (CBS(+/+)) littermates that were provided with drinking water that was unsupplemented (control diet) or supplemented with 0.5% L-methionine (high-methionine diet). Plasma tHcy was 5.0+/-1.1 micro mol/L in CBS(+/+) mice and 8.3+/-0.9 micro mol/L in CBS(+/-) mice (P<0.05 versus CBS(+/+) mice) fed the control diet. Plasma tHcy was 17.2+/-4.6 micro mol/L in CBS(+/+) mice and 21.2+/-3.9 micro mol/L in CBS(+/-) mice (P<0.05) fed the high-methionine diet. Cross-sectional area of the vessel wall was significantly increased in CBS(+/-) (437+/-22 micro m(2)) mice fed control diet and CBS(+/+) (442+/-36 micro m(2)) and CBS(+/-) (471+/-46 micro m(2)) mice fed high-methionine diet relative to CBS(+/+) (324+/-18 micro m(2)) mice fed control diet (P<0.05). During maximal dilatation, the stress-strain curves in cerebral arterioles of CBS(+/-) mice on control diet and CBS(+/+) and CBS(+/-) mice on high-methionine diet were shifted to the right of the curve in cerebral arterioles of CBS(+/+) mice on control diet, an indication that distensibility of cerebral arterioles was increased in mice with elevated levels of plasma tHcy. Thus, hyperhomocysteinemia in mice was associated with hypertrophy and an increase in distensibility of cerebral arterioles. These findings suggest that hyperhomocysteinemia promotes cerebral vascular hypertrophy and altered cerebral vascular mechanics, both of which may contribute to the increased incidence of stroke associated with hyperhomocysteinemia.
Manchester Royal Infirmary
Authors: Wm. Roberts
Journal: BMJ (1858)

portion of sensation or thought, however minute, of which we are conscious.If so, we can perceive that, both as to the infinitely great and the infirnitely small, whether as regards space or timiie, our minds are necessarily and essentially un- fathomalble, i. c., that there is somethin-in them which can- not admiiit of the limitation either of space or of time.And, if this con-viction is thus duly impressed on our belief-at the same tinme that we lieep steadily in view what I have said of the arlitrary adlaptation of means to ends, in the forms adapted and the.powers granted to all living beings, and within a limited period of time, as made known by geology-it seems to me, as it did to those illustrious predecessors of mine in this university, as the most truly connecting link between Science and Religion-the very point to which it is desirable, with a view to the power of religion over the natural sciences, that tlhe -votarie-s of science-more numerous, as they are more intelligent, than in any former period of the earlth's history- should be led, by their inquiries,* where they may hope to lhave their alliance firmiily established with that Higher Power whlich has spoken on earth, not to them only, but to the hulman race.ItJJstratiorns
Assessment and follow-up of pediatric survivors of sudden cardiac death.
Authors: M J Silka, J Kron, C G Walance, J E Cutler, J H McAnulty
Journal: Circulation (1990)

In the young patient resuscitated from sudden cardiac arrest, the risks of recurrence are uncertain and so are the criteria defining therapeutic efficacy for the presumed cause of the initial event. In this study, we analyzed the outcome of 15 consecutive young patients, who were resuscitated from pulseless ventricular tachycardia or ventricular fibrillation and who were evaluated by comprehensive hemodynamic and electrophysiological testing. Patients were 11.2 +/- 2.7 (mean +/- SD) years old at the time of their event, and each was known to have some form of heart disease before sudden cardiac arrest. Ventricular tachycardia or fibrillation was inducible by programmed electrical stimulation in eight patients. Accessory atrioventricular connections, with antegrade effective refractory periods less than 220 msec, were identified in three patients. Sustained atrial flutter was the only arrhythmia inducible in two patients, and no arrhythmias were inducible in two other patients. Surgical or electrophysiological-guided medical therapy resulted in noninducibility of the ventricular arrhythmias in six patients. Surgical division of the accessory atrioventricular connections was performed in three patients, and arrhythmias were not inducible after operation. The four patients with atrial flutter or without defined arrhythmia were treated with an empiric therapy. During 37 +/- 14 months of follow-up, the nine patients with documented noninducibility of a defined cause of sudden cardiac arrest were free of recurrent events. In contrast, during 18 +/- 10 months of follow-up, two of the six patients with empiric therapy or persistent inducibility of ventricular tachycardia died suddenly, and three others had recurrence of ventricular tachycardia or fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)
THE LEGAL RESTRICTION OF MARRIAGE FOR THE PREVENTION OF PAUPERISM, CRIME AND MENTAL DISEASES.
Authors: DANIEL R. BROWER
Journal: JAMA (1900)

Pauperism, crime and insanity have in their etiology most important relations to heredity, that great fundamental law of Nature by which like must produce like, not in never-ending sameness, but in variety, tending on the one hand to improvement by environment, or by the same ever-powerful modification to destruction. The child comes into the world with life and certain gifts from parents, often loaded with encumbrances so burdensome that they prove a curse to their possessor, sometimes so free that the heir at law has nothing to fear in the race of life. How the minute cells, that by their union make conception, microscopic as they are, should contain within themselves all the possibility and all the minutiæ of a life of pauperism on the one hand or of exalted statesmanship on the other is a mystery that can not now be solved. The farmer recognizes the great law of
Woodchuck Hepatitis Virus: Experimental Infection and Natural Occurrence
Authors: Irving Millman, Lenore Southam, Theresa Halbherr, Heidi Simmons, Chong Myung Kang
Journal: Hepatology (1984)

Sera from 588 woodchucks were assayed for woodchuck hepatitis virus (WHV) markers using hepatitis B virus (HBV) reagents which have cross-reactivity with WHV markers. Twenty per cent of these woodchucks, trapped in Delaware, Maryland and Pennsylvania, had WHsAg; 50% of these had DNA polymerase. There are areas of high and low endemicity within these states. Female woodchucks may have a higher incidence of WHV markers than do males. Woodchuck hepatitis surface antigen (WHsAg) and anti-WHc often occur together but less commonly than HBsAg and anti-HBc do in human HBV infection. Experimental infection of woodchucks with WHV produced a prolonged infection (up to 40 weeks). WHsAg and DNA polymerase appeared to be more reliable indicators of infectivity than anti-WHc, woodchuck hepatitis e antigen (WHeAg) or anti-WHe. WHeAg was not detected throughout this period of infection, while anti-WHe appeared late in two of three experimentally infected animals. Four male and four female woodchucks which developed primary hepatocellular carcinoma in captivity were analyzed for WHV markers throughout their period of confinement. Seven were WHsAg and anti-WHc positive when captured. The animal that was free of WHV markers on capture converted to the WHsAg and anti-WHc positive state prior to the development of primary hepatocellular carcinoma. One primary hepatocellular carcinoma animal produced WHeAg and none anti-WHs or anti-WHe.