tbuckley/cabot-search huggingface dataset:
Myeloperoxidase Predicts Progression of Carotid Stenosis in States of Low High-Density Lipoprotein Cholesterol
Authors: Markus Exner, Erich Minar, Wolfgang Mlekusch, Schila Sabeti, Jasmin Amighi, Wolfgang Lalouschek, Gerald Maurer, Christian Bieglmayer, Heidi Kieweg, Oswald Wagner, Martin Schillinger
Journal: Journal of the American College of Cardiology (2006)
Confronting the scientific obstacles to global control of tuberculosis
Authors: Douglas B. Young, Mark D. Perkins, Ken Duncan, Clifton E. Barry
Journal: Journal of Clinical Investigation (2008)

Tuberculosis (TB) is a major threat to global health, recently exacerbated by the emergence of highly drug-resistant forms of the disease-causing pathogen and synergy with HIV/AIDS. In 2006, the Stop TB Partnership published "The global plan to stop TB: 2006--2015," which set out a vision of halving the prevalence of and mortality caused by the disease by 2015, followed by eliminating the disease as a public health problem by 2050. This vision depends on the development of improved diagnostics, simpler treatment, and more effective vaccination. Recently, active translational research pipelines directed toward each of these goals have been established, but improved understanding of the fundamental biology of this complex disease will prove to be the key to radical advances in TB control.
Photosensitive Pt(IV)–azide prodrug-loaded nanoparticles exhibit controlled drug release and enhanced efficacy in vivo
Authors: Haihua Xiao, Gavin T. Noble, Jared F. Stefanick, Ruogu Qi, Tanyel Kiziltepe, Xiabin Jing, Basar Bilgicer
Journal: Journal of Controlled Release (2013)
Regulation of bile acid synthesis. II. Effect of bile acid feeding on enzymes regulating hepatic cholesterol and bile acid synthesis in the rat
Authors: Douglas M. Heuman, Reno Z. Vlahcevic, Marsha L. Bailey, Phillip B. Hylemon
Journal: Hepatology (1988)

Bile acid synthesis is believed to be regulated by bile salts returning to the liver via the portal vein and suppressing cholesterol 7α-hydroxylase, the rate-limiting enzyme in the bile acid biosynthesis pathway. In order to characterize the relative effectiveness of bile salts in regulating bile acid synthesis, seven different bile acids were administered (1% w/w in chow) to rats over a 14-day period. Biliary bile salt composition was determined from bile samples obtained prior to killing; in all cases, the fed bile acid became the predominant bile salt in bile. The specific activities of microsomal cholesterol 7α-hydroxylase, HMG-CoA reductase and acylcoenzyme A:cholesterol acyltransferase were determined after killing. Hydrophilic bile salts (ursocholic, hyocholic, ursodeoxycholic and hyodeoxycholic) did not inhibit HMG-CoA reductase or cholesterol 7α-hydroxylase activities. By contrast, more hydrophobic bile salts (cholic, chenodeoxycholic and deoxycholic) inhibited the activities of these two enzymes in order of increasing hydrophobicity. Neither hydrophobic nor hydrophilic bile salts inhibited acylcoenzyme A:cholesterol acyltransferase activity. No consistent effect of bile acid feeding on total microsomal cholesterol was observed. Based on the results of these studies, we propose that the hydrophilic-hydrophobic balance of the bile acid pool may play an important role in the regulation of bile acid synthesis. We postulate that the activities of cholesterol 7α-hydroxylase and HMG-CoA reductase may be regulated by hydrophobic bile acid-induced changes in the lipid composition and physicochemical properties (fluidity) of the microsomal membranes to which both of these rate-limiting enzymes are attached. Alternatively, hydrophobic bile salts by increasing biliary cholesterol secretion and suppressing HMG-CoA reductase activity may reduce the availability of cholesterol substrate for bile acid synthesis.
Association between the Estrogen Receptor α A908G Mutation and Outcomes in Invasive Breast Cancer
Authors: Matthew H. Herynk, Irma Parra, Yukun Cui, Amanda Beyer, Meng-Fen Wu, Susan G. Hilsenbeck, Suzanne A.W. Fuqua
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Estrogen receptor α (ERα) predicts the natural history of breast cancer without intervening therapy. Here, we have optimized the detection of a somatic mutation, an A908G transition of ERα, and examined its association with clinical and biological features of invasive breast cancer. Experimental Design: We compared two methods of sequencing to detect the A908G ERα mutation. We then used primer extension sequencing with genomic DNA isolated from invasive breast tumors to determine whether the mutation was associated with clinical outcome in 267 axillary node–negative and axillary node–positive breast tumors. The presence of the mutation and clinical variables were analyzed for association with recurrence-free survival and overall survival by Cox proportional hazards regression models. Results: We determined that dye-labeled terminator sequencing was not adequate for detection of the A908G ERα mutation. The mutation was detected at a high frequency (50%) in invasive breast tumors using primer extension sequencing, and was found to be associated with clinical measures of poor outcome, including larger tumor size and axillary lymph node positivity. Although the mutation was associated with recurrence-free survival in univariate analysis, it was not an independent predictor of outcomes in multivariate analysis. Conclusions: Consistent with our previous finding of this somatic ERα mutation in breast ductal hyperplasias, we now present evidence that the A908G mutation is present in invasive breast tumors using an optimized sequencing method. We find that the mutation is significantly associated with aggressive biological tumor features, and with an unfavorable prognosis, but was not an independent prognostic marker in untreated patients.
WHO to set up international task force on counterfeit drugs
Authors: John Zarocostas
Journal: BMJ (2006)

Experts from more than 60 countries have urged the World Health Organization to establish a task force to lead global efforts in combating the growing problem of counterfeit drugs.

“The vile and serious criminal offence” puts human lives at risk and undermines the credibility of health systems worldwide, the experts noted in a declaration.

“It's very likely that [the task force] will happen,” said Howard Zucker, WHO's assistant director general for health technology and pharmaceuticals.

Dr Zucker said that “there was unanimous support” at a WHO conference in Rome last week on combating counterfeit drugs for the agency to establish the international task force to fight counterfeiting. …
Easier Said Than Done: Moral Decisions in Medical Uncertainty
Authors: Marilyn M. Schapira
Journal: JAMA (1993)

The premise of<i>Easier Said Than Done: Moral Decisions in Medical Uncertainty</i>is that clinicians can make ethical decisions by balancing nonmaleficence, autonomy, the common good, and beneficence. Will a working knowledge of principles of ethical behavior improve the decision-making process in clinical medicine? Milton Heifetz' book provides a theoretical foundation of medical ethics and an approach to several difficult moral dilemmas in clinical medicine. He suggests that physicians employ formal ethical reasoning in clinical situations, balancing the impact a decision has on various ethical dilemmas. "Will a working knowledge of principles of ethical behavior improve the decision-making process in clinical medicine?" The first chapter of the book considers the development of basic principles of ethics. Although somewhat pedantic, the chapter is comprehensive and considers religious, biological, and intellectual origins of human moral behavior. The book does pick up some needed speed as the next several chapters address an array
Adrenergic Receptors as Models for G Protein-Coupled Receptors
Authors: B Kobilka
Journal: Annual Review of Neuroscience (1992)

Approximately 80% of known hormones and neurotransmitters activate cellular signal transduction mechanisms by activating G protein-coupled receptors (Birnbaumer et al 1990). Studying the structure and function of these receptors has been challenging because they are not naturally abun­ dant proteins and they require a lipid environment to be fully active. The eDNA or genomic clones for many members of this class of receptors have recently been obtained. Applying the techniques of molecular biology to the study of G protein-coupled receptors has helped circumvent many of the technical difficulties that had complicated previous efforts to charac­ terize these proteins biochemically. The adrenergic receptors have been one of the most extensively studied classes of G protein-coupled receptors. Genomic and/or cDNA clones for nine types of adrenergic receptors have been obtained: two types of (XI receptors (Cotecchia et al 1988; Schwinn et al 1990); three types of C(2 receptors (Kobilka et al 1987; Lomasney et al 1990; Regan et al 1988; Weinshank et aI 1990); the /31 receptor (Frielle et aI 19 87); the /32 receptor (Dixon et al 1986); the /3 3 receptor (Emorine et al 1989) ; and the avian /3 receptor (Yarden et al 1986). Significant progress has been made in eluci­ dating the structural domains involved in ligand binding, G protein acti­ vation, and desensitization, and much of what is learned about the mech­ anism of action of adrenergic receptors will likely apply to the other
Toward Better Logic
Authors: Bernard J. Rumsch
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Your editorial "Medical Logic" (<i>JAMA</i><b>187</b>:946 [March 21] 1964) passes lightly over "... those who concern themselves with philosophy of medicine." However medical logic is more than just mere algebraic symbolic classification. The physician may tabulate the history, symptoms, signs, physical findings, and laboratory data, and arrive at an erroneous conclusion—which may or may not be corrected by the electronic computer—and yet remain within the strict limits of objective scientific evaluation. But the art of medicine also entails evaluation of the patient's "psyche-soma," which is beyond the scope of the electronic computer. We, as "trained Homines sapientes," must ne'er forget the numerous cases where RxA from Dr. X brings the ailing patient back to normal function and activity, whereas RxA from Dr. Y has little or no effect on the same ailing patient. This indicates some error in evaluation of the patient
Report Urges Addressing Barriers to Reimbursement for Mental Health Care
Authors: Bridget M. Kuehn
Journal: JAMA (2008)

STATE AND FEDERAL REIMBURSEment policies create barriers that prevent many primary care physicians from offering screening and intervention for mental disorders, despite growing evidence suggesting such efforts by frontline clinicians may reduce the burden of mental illness in the United States, according to a recent report by the Substance Abuse and Mental Health Services Administration (SAMHSA), and the Health Resources and Services Administration (HRSA). The report provides an overview of the challenges physicians face in trying to bill for mental health services and recommends steps that federal and state agencies can take to make the process easier (http://download.ncadi.samhsa.gov/ken /pdf/SMA08-4324/SMA08-4324.pdf). The Centers for Medicare & Medicaid Services provided technical guidance to the group that drafted the report. Physician organizations applaud the report’s call to overcome barriers to compensation for mental health services and its emphasis on providing incentives for offering evidence-based care. Some caution, however, that the recommendations will do little to alleviate reimbursement problems stemming from an underfunded system, and that they will do nothing to improve reimbursement for mental health specialists, who, like primary care clinicians, also face substantial barriers to being paid for providing care.
An Acute Asthma Attack Induces Tissue Remodeling By Hypersecretion Of Epidermal Growth Factor (egf) And Amphiregulin (areg) In The Airway
Authors: T. Takamasu, Y. Enomoto, K. Orihara, A. Matsuda, Y. Gon, H. Saito, C. Ra, Y. Okayama
Journal: Journal of Allergy and Clinical Immunology (2011)
A Case of Tubercular Leprosy
Authors: G. Gaskoin
Journal: BMJ (1873)

THE BRITISH MEDICAL 7OUrA-Al.. 65S well corked bottle, for a long time.It is, in fact, a kind of tbick varnish.To make the resin.cloth,as I term it, for the sake of distin- puishing it from the cere-cloth dressing for wounds, which I described in a paper read at the Leeds meeting of the British Medical Association in 1869, it is needful to select a very thin, cheap, porous calico, or calico-muslin, known in the trade as " mulls", which costs at wholesale price about four sbillings per piece of twenty yards.This, divided into strips, each about nine mches wide and six yards long, is reduced to a conirenient form for general use.The calico should be unbleached and free from stiffening, and each of the strips should be carefuUy folded up, so as just to lie flatly in the press, as I am about to explain.An ordinary square tincture press may be used to press the cloth, or on the subject of this disease, and published in the second report (1859) of the medical officer to tlhe Privy Council, do not seem to justify any definite conclusion on this particular point; but, in reporting a subse- quent investigation, published in the eightlh report (1865) of the medical officer to the Piivy Couincil, Dr. Santderson states, in reference to an outbreak ol diphtheria, that " it is not possible to avoid the conclusion that it was due to local causes, and that it would have been prevented if the nuisance had been effectually abated.
The Kidney in Congestive Heart Failure
Authors: A. C. BARGER
Journal: Circulation (1960)

As a more detailed picture of the pathogenesis of salt and water retention in congestive heart failure evolves, it appears that increased tubular reabsorption of sodium occurs very early in heart disease, with further enhancement of the fluid accumulation as filtration rate decreases later in the disease process. Increase in sympathetic activity in the kidney can be demonstrated before the development of frank failure, and probably is initiated reflexly by decreased baroreceptor activity, a response that occurs in various types of circulatory insufficiency. Blocking the adrenergic nerves of the kidney produces profound diuresis and natriuresis. Evidence is presented that the pressoreceptors may also play an important role in regulating aldosterone secretion. Thus, the change in body fluids seen in congestive heart failure may be part of the normal reflex adjustments maintaining blood pressure.
Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
Authors: Gert C Scheper, Thom van der Klok, Rob J van Andel, Carola G M van Berkel, Marie Sissler, Joél Smet, Tatjana I Muravina, Sergey V Serkov, Graziella Uziel, Marianna Bugiani, Raphael Schiffmann, Ingeborg Krägeloh-Mann, Jan A M Smeitink, Catherine Florentz, Rudy Van Coster, Jan C Pronk, Marjo S van der Knaap
Journal: Nature Genetics (2007)
Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection
Authors: O. Burkhardt, S. Ewig, U. Haagen, S. Giersdorf, O. Hartmann, K. Wegscheider, E. Hummers-Pradier, T. Welte
Journal: European Respiratory Journal (2010)

Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL −1 . Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73–0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.
Detection of a Urinary-bladder Leiomyosarcoma as a Filling Defect on a 99 mTc-Pyrophosphate Image
Authors: VED PRAKASH, MAX S. LIN, INDER PERKASH
Journal: Clinical Nuclear Medicine (1978)

From the Spinal Cord Injury Service and Department of Nuclear Medicine, Veterans Administration Hospital and Stanford University School of Medicine, Palo Alto, California
Prognosis for Patients with Severe Brain Injuries
Authors: M. Vapalahti, H. Troupp
Journal: BMJ (1971)

Intraventricular pressure recording has been a standard procedure in the neurosurgical clinic, University Central Hospital, Helsinki, Finland, since 1964. Up to 31 December 1970, 250 recordings had been performed, 90 of these on brain-injured patients. Intraventricular pressure correlates well with survival or death of the patient but will not predict the quality of survival. However, other criteria seem to correlate well with the quality of survival.The results of a prospective study of 50 patients between 1 January 1967 and 31 December 1969 are reported. Clues to vegetative survival are very low arterial Pco(2) after a free airway has been established, a high respiratory minute volume, temperature above 39 degrees C, Cheyne-Stokes breathing, and extension rigidity in adults.When a reliable prognosis can be established that the patient is going to survive only as a vegetative wreck it is highly doubtful if the whole might of modern intensive therapy should be applied.
Inhibition of cultured cell growth by vascular endothelial cadherin (cadherin-5/VE-cadherin).
Authors: L Caveda, I Martin-Padura, P Navarro, F Breviario, M Corada, D Gulino, M G Lampugnani, E Dejana
Journal: Journal of Clinical Investigation (1996)

Endothelial cell proliferation is inhibited by the establishment of cell to cell contacts. Adhesive molecules at junctions could therefore play a role in transferring negative growth signals. The transmembrane protein VE-cadherin (vascular endothelial cadherin/cadherin-S) is selectively expressed at intercellular clefts in the endothelium. The intracellular domain interacts with cytoplasmic proteins called catenins that transmit the adhesion signal and contribute to the anchorage of the protein to the actin cytoskeleton. Transfection of VE-cadherin in both Chinese hamster ovary (CHO) and L929 cells confers inhibition of cell growth. Truncation of VE-cadherin cytoplasmic region, responsible for linking catenins, does not affect VE-cadherin adhesive properties but abolishes its effect on cell growth. Seeding human umbilical vein endothelial cells or VE-cadherin transfectants on a recombinant VE-cadherin amino-terminal fragment inhibited their proliferation. These data show that VE-cadherin homotypic engagement at junctions participates in density dependent inhibition of cell growth. This effect requires both the extracellular adhesive domain and the intracellular catenin binding region of the molecule.
Physical fitness and blood pressure in school children.
Authors: G E Fraser, R L Phillips, R Harris
Journal: Circulation (1983)

We studied the relationship between physical fitness and blood pressure in 228 school children. The data were collected as part of the Loma Linda Child-Adolescent Blood Pressure Study. Systolic and diastolic blood pressures were lower in children above average fitness than in children below average fitness among preadolescent and adolescent boys and girls. On multivariate analysis, adjusting for skinfold thickness, an index of lean arm mass, height and age, the relationship between fitness and systolic blood pressure was statistically significant for preadolescent boys and for adolescents of both sexes. The multivariate relationship was not clearly seen for diastolic blood pressure. Multivariate techniques showed that significant correlates of fitness were obesity in preadolescents, age in adolescent boys and height in adolescent girls. Predicted pulse rates for stages 6-10 of a modified Balke treadmill protocol are given in appendix 1 for preadolescent and adolescent boys and girls.
The Liver in the IgA Secretory Immune System. Dogs, But Not Rats and Rabbits, Are Suitable Models for Human Studies
Authors: Dominique L. Delacroix, Gildo Furtado-Barreira, Bernard De Hemptinne, Jan Goudswaard, Charles Dive, Jean-Pierre Vaerman
Journal: Hepatology (1983)

The liver transport of polymeric IgA (plgA) from plasma into bile and the immunohistochemical distribution of secretory component (SC) in the liver were studied in dogs, and compared to those in humans, rats, and rabbits. Results were as follows: (i) according to bile and serum protein concentrations and specific activities, plasma plgA in dogs, like in humans, is transported into bile cv˜10 times more efficiently than albumin, as compared to 320 and 1060 times in rabbits and rats, respectively, (ii) Only ˜1% of an i.v. dose of [125I]pIgA is transported into bile over 8 hr in dogs, like in humans, as compared to ˜50% over 3 hr in rats and rabbits. These results agree with much smaller daily fractional catabolic rates of intravascular plgA in dogs (0.28) and humans (0.48) than in rats (24.0). (iii) Total bile IgA contributes daily about 1.5 mg per kg to intestinal plgA in dogs, a figure similar in humans (0.8 mg per kg) but much smaller than in rats (38 mg per kg) and rabbits (35 mg per kg), (iv) Biliary obstruction in dogs, like in humans, results only in minor and late increases in serum plgA levels, contrasting with &gt;8-fold increases within 24 hr in rats and rabbits, (v) Unlike in rats and rabbits, SC in dog liver as well as in human liver cannot be detected in hepatocytes although clearly present in bile duct cells. To conclude: (i) major species differences in plasma-to-bile transport of plgA exist, most probably related to species differences in the ability of hepatocytes to synthetize SC. (ii) Bile duct cells, despite their membranous SC, are much less efficient than hepatocytes to transport plgA from plasma to bile, (iii) Dogs, but not rats and rabbits, provide a suitable experimental model for further studies on the relationships between the liver and the secretory IgA immune system in humans.
TRANSRADIAL PCI IS ASSOCIATED WITH LOWER COST IN MEDICARE FEE–FOR–SERVICE BENEFICIARIES FOLLOWING ELECTIVE PCI
Authors: Amit P. Amin, Mark Patterson, John House, kevin kennedy, Andreas Bremer, Helmut Giersiefen, John Spertus, Dmitri Baklanov, Adnan Chhatriwalla, David Safley, David Cohen, Sunil Rao, Steven P. Marso
Journal: Journal of the American College of Cardiology (2013)
1133 INTERFERON-β PREVENTS HBX-TRIGGERED HEPATOCARCINOGENESIS BY DOWN-REGULATING CYTOPLASMIC P21 OVEREXPRESSION
Authors: M. Yano, S. Ohkoshi, Y. Aoki, K. Yamazaki, S. Kurita, K. Suzuki, S. Fujimaki, A. Sanpei, Y. Matsuda, Y. Aoyagi
Journal: Journal of Hepatology (2011)