tbuckley/cabot-search huggingface dataset:
Gender Differences in Coronary Artery Diameter Involve Estrogen, Nitric Oxide, and Ca <sup>2+</sup> -Dependent K <sup>+</sup> Channels
Authors: George C. Wellman, Adrian D. Bonev, Mark T. Nelson, Joseph E. Brayden
Journal: Circulation Research (1996)

During their reproductive years, women have a much lower incidence of coronary heart disease compared with men of similar age. Estrogen appears to be largely responsible for this decrease in cardiovascular mortality in women. In the present study, isolated pressurized coronary arteries from rats were used to assess the role of gender and circulating estrogen on coronary vascular function. Pressure-induced constrictions (“myogenic tone”) were greater (≈2-fold) in isolated coronary arteries from estrogen-deficient male or ovariectomized (OVX) rats compared with similar arteries obtained from female rats or OVX rats receiving physiological levels of estrogen replacement (OVX+E group). These differences in coronary artery diameter were abolished by removal of the vascular endothelium or chemical inhibition of NO synthase. The anti-estrogen, tamoxifen, increased pressure-induced constrictions of coronary arteries from female and OVX+E rats. Dilations of pressurized coronary arteries from female and OVX animals to sodium nitroprusside, a nitrovasodilator that generates NO, were reduced by &gt;50% by iberiotoxin (IBTX), an inhibitor of Ca 2+ -dependent K + (K Ca ) channels. Sodium nitroprusside (10 μmol/L) hyperpolarized coronary arteries by 13±2 mV, an effect that was greatly diminished (≈80%) by IBTX. Coronary arteries isolated from female rats produced greater constrictions in response to IBTX and KT 5823, an inhibitor of cGMP-dependent protein kinase, compared with coronary arteries from OVX rats. cGMP-dependent protein kinase increased the activity of K Ca channels 16.5±5-fold in excised membrane patches from smooth muscle cells enzymatically isolated from these small coronary arteries. We propose that physiological levels of circulating 17β-estradiol elevate basal NO release from the endothelial cells, which increases the diameter of pressurized coronary arteries. Further, our results suggest that part of the effect of this NO is through activation of K Ca channels in the smooth muscle cells of the coronary arteries.
Hairy Cells and Isoenzymes
Authors: W. J. Mitus
Journal: New England Journal of Medicine (1971)

Fancy phrases readily capture headlines, and fancy names stick better. The field of medicine is no exception. Confusing and poorly understood syndromes frequently hide behind the names of people who describe them or suffer from them. Occasionally, the diseases acquire mysterious names, and then everybody seems to remember them better. "Histiocytosis X" may serve as a good example. Hematologists also use spectacular terms for some of their cells. Flame cells, a colorful combination of red and blue in secreting plasma cells, or sea-blue histiocytes (if not "buttock cells"), add an artistic touch to hematology and may even stimulate dulled recall . . .
Cardiovascular Risk and Body-Fat Abnormalities in HIV-Infected Adults
Authors: Steven Grinspoon, Andrew Carr
Journal: New England Journal of Medicine (2005)

Metabolic complications such as dyslipidemia, insulin resistance, and altered fat distribution (loss of subcutaneous fat and relatively increased central fat) are common in adults infected with the human immunodeficiency virus who are receiving highly active antiretroviral therapy and may increase their risk of cardiovascular disease. This review discusses progress in understanding the pathogenetic mechanisms and treatment strategies for addressing cardiovascular risk in this population.
US citizens score poorly on ratings of cardiovascular risk factors
Authors: J. H. Tanne
Journal: BMJ (2012)

More than 90% of Americans score poorly on at least one of the American Heart Association’s seven factors defining ideal cardiovascular health, the association reports in Circulation (doi:10.1161/CIR.0b013e31823ac046).

The seven factors are smoking status, weight, physical activity, healthy diet, cholesterol concentration, blood pressure, and fasting glucose concentration, together with lack of a diagnosis of heart or blood vessel disease.

The new statistical update is prepared by the association together with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies.

The new data show that 94% of US adults score at a “poor” level on at least one of those factors and that 38% have at least three factors at a poor level.

A fifth (21.2%) of men …
Identification of CD22 Ligands on Bone Marrow Sinusoidal Endothelium Implicated in CD22-dependent Homing of Recirculating B Cells
Authors: Lars Nitschke, Helen Floyd, David J.P. Ferguson, Paul R. Crocker
Journal: The Journal of Experimental Medicine (1999)

CD22 is a B cell–specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of α2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an ∼50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M–secreting plasma cells in the bone marrow.
Combined Screening: Blood Pressure and Cholesterol-Reply
Authors: N. Burgess Record
Journal: JAMA (1988)

<h3>In Reply.</h3> —High blood cholesterol levels and high blood pressure share many similarities, including day-to-day individual variation and regression to the mean. Determining a stable baseline against which to measure change is difficult. The SD of repeated measurements in an individual over time has been reported as 0.5 mmol/L (18 mg/dL) for total cholesterol level. The National Cholesterol Education Program<sup>1</sup>recommends using the average of two values obtained one to eight weeks apart to guide subsequent decisions in patients whose initial cholesterol level is above 5.15 mmol/L (200 mg/dL). The intent of our letter was not to report an experiment but to describe our early experience with an innovative blood pressure/cholesterol screening program. Others have already demonstrated that prudent dietary change will lower cholesterol levels an average of 10% to 15%; that those with the highest levels will drop the most; and that each 1% lowering of cholesterol level
Targeting EGFR in Non–Small-Cell Lung Cancer
Authors: James H. Doroshow
Journal: New England Journal of Medicine (2005)

The development of small-molecule inhibitors of the epidermal growth factor receptor (EGFR), such as erlotinib and gefitinib, for the treatment of advanced non–small-cell lung cancer illustrates a pattern of initial overly enthusiastic interest, subsequent critical disappointment, and eventual renewed appreciation of the clinical and mechanistic complexities surrounding the introduction of a new therapy for cancer. Such a pattern has been regrettably common in the history of oncologic therapeutics.The initial safety and efficacy studies of erlotinib and gefitinib evoked a remarkable degree of optimism that was based on prolonged remissions and, in some cases, dramatic improvements in the quality of . . .
A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling
Authors: David J. Kennedy, Sai Kuchibhotla, Kristen M. Westfall, Roy L. Silverstein, Richard E. Morton, Maria Febbraio
Journal: Cardiovascular Research (2010)

Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia.Adipose tissue from CD36(-/-) mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36(-/-) mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages.These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia.
Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent
Authors: Tomonori Aoyama, Yong-Han Paik, Sumio Watanabe, Benoît Laleu, Francesca Gaggini, Laetitia Fioraso-Cartier, Sophie Molango, Freddy Heitz, Cédric Merlot, Cédric Szyndralewiez, Patrick Page, David A. Brenner
Journal: Hepatology (2012)

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) generates reactive oxygen species (ROS) in hepatic stellate cells (HSCs) during liver fibrosis. In response to fibrogenic agonists, such as angiotensin II (Ang II), the NOX1 components form an active complex, including Ras-related botulinum toxin substrate 1 (Rac1). Superoxide dismutase 1 (SOD1) interacts with the NOX-Rac1 complex to stimulate NOX activity. NOX4 is also induced in activated HSCs/myofibroblast by increased gene expression. Here, we investigate the role of an enhanced activity SOD1 G37R mutation (SODmu) and the effects of GKT137831, a dual NOX1/4 inhibitor, on HSCs and liver fibrosis. To induce liver fibrosis, wild-type (WT) and SOD1mu mice were treated with CCl4 or bile duct ligation (BDL). Then, to address the role of NOX-SOD1-mediated ROS production in HSC activation and liver fibrosis, mice were treated with a NOX1/4 inhibitor. Fibrosis and ROS generation was assessed by histology and measurement of thiobarbituric acid reactive substances and NOX-related genes. Primary cultured HSCs isolated from WT, SODmu, and NOX1 knockout (KO) mice were assessed for ROS production, Rac1 activity, and NOX gene expression. Liver fibrosis was increased in SOD1mu mice, and ROS production and Rac1 activity were increased in SOD1mu HSCs. The NOX1/4 inhibitor, GKT137831, attenuated liver fibrosis and ROS production in both SOD1mu and WT mice as well as messenger RNA expression of fibrotic and NOX genes. Treatment with GKT137831 suppressed ROS production and NOX and fibrotic gene expression, but not Rac1 activity, in SOD1mut and WT HSCs. Both Ang II and tumor growth factor beta up-regulated NOX4, but Ang II required NOX1. Conclusions: SOD1mu induces excessive NOX1 activation through Rac1 in HSCs, causing enhanced NOX4 up-regulation, ROS generation, and liver fibrosis. Treatment targeting NOX1/4 may be a new therapy for liver fibrosis. (HEPATOLOGY 2012)
Acute Silent Cerebral Ischemic Events in Children With Sickle Cell Anemia
Authors: Charles T. Quinn, Robert C. McKinstry, Michael M. Dowling, William S. Ball, Michael A. Kraut, James F. Casella, Nomazulu Dlamini, Rebecca N. Ichord, Lori C. Jordan, Fenella J. Kirkham, Michael J. Noetzel, E. Steve Roach, John J. Strouse, Janet L. Kwiatkowski, Deborah Hirtz, Michael R. DeBaun
Journal: JAMA Neurology (2012)

Irregular, sporadic episodes of ischemic brain injury are known to occur in sickle cell anemia (SCA), resulting in overt stroke and silent cerebral infarction. Ongoing ischemia in other organs is common in SCA but has never been documented in the brain.To test the hypothesis that acute silent cerebral ischemic events (ASCIEs) are frequent and potentially transient.Cross-sectional and cohort study of children with SCA screened by magnetic resonance imaging (MRI) of the brain for a randomized clinical trial.Clinical trial setting in tertiary care centers.Asymptomatic children with SCA without known stroke, neurologic injury, or epilepsy not receiving treatment with transfusions or hydroxyurea.Incidence of ASCIEs calculated using single diffusion-weighted MRI scans (acute ischemic events that occurred within 10 days of the MRI).Acute silent cerebral ischemic events were detected on 1.3% of MRIs (10 of 771) in 652 children (mean age, 10.0 years), with an incidence of 47.3 events per 100 patient-years (95% CI, 22.7-87.2). Two of 10 children with ASCIEs had follow-up MRIs of the brain; only 1 had silent cerebral infarction in the same location as the previously detected ASCIE.Children with SCA experience ongoing (chronic, intermittent) cerebral ischemia, sometimes reversible, far more frequently than previously recognized. The brain in SCA is at constant threat of ischemia.
Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones.
Authors: W H Rodgers, L M Matrisian, L C Giudice, B Dsupin, P Cannon, C Svitek, F Gorstein, K G Osteen
Journal: Journal of Clinical Investigation (1994)

Matrix metalloproteinases are a highly regulated family of enzymes, that together can degrade most components of the extracellular matrix. These proteins are active in normal and pathological processes involving tissue remodeling; however, their sites of synthesis and specific roles are poorly understood. Using in situ hybridization, we determined cellular distributions of matrix metalloproteinases and tissue inhibitor of metalloproteinase-1, an inhibitor of matrix metalloproteinases, in endometrium during the reproductive cycle. The mRNAs for all the metalloproteinases were detected in menstrual endometrium, but with different tissue distributions. The mRNA for matrilysin was localized to epithelium, while the others were detected in stromal cells. Only the transcripts for the 72-kD gelatinase and tissue inhibitor of metalloproteinases-1 were detected throughout the cycle. Transcripts for stromelysin-2 and the 92-kD gelatinase were only detected in late secretory and menstrual endometrium, while those for matrilysin, the 72-kD gelatinase, and stromelysin-3 were also consistently detected in proliferative endometrium. These data indicate that matrix metalloproteinases are expressed in cell-type, tissue, and reproductive cycle-specific patterns, consistent with regulation by steroid hormones, and with specific roles in the complex tissue growth and remodeling processes occurring in the endometrium during the reproductive cycle.
THE RECIPROCAL RELATIONS BETWEEN CONSUMPTIVES AND SOCIETY.
Authors: S. G. BONNEY
Journal: JAMA (1900)

No medical or economic problem at the present time can assume such a degree of importance on account of its almost universal application, and the degree of individual and state responsibility involved, as the prevention of pulmonary tuberculosis. This disease is known to affect approximately one-third of our population, and to constitute one-seventh of our annual deaths. Several millions of people in this country are now afflicted with a tubercular process, known to be communicable rather than hereditary. Practically, its transmission occurs, not so much from infected food-supply as from the existence of an almost ubiquitous agent disseminated by means of the sputa of infected individuals. That the disease is thus communicable should not be understood to be so much the result of direct infectin from one person to another, after the manner of certain contagious diseases, but more because of the neglect to observe necessary precautions. There is thus
Helping disabled people with travelling costs.
Authors: G S Roberts
Journal: BMJ (1981)

The problems of increasing travelling costs in maintaining the mobility of UK disabled travellers are examined. Registered severely disabled persons, unable to use public or private transport, are able to obtain financial assistance towards taxi fares. For disabled persons able to drive, car purchase and parking allowances and concessions are available. Similarly, special concessionary fare structures are offered on rail and bus services for persons receiving a mobility allowance. (TRRL)
Nonsmokers' Rights
Authors: Geoffrey E. Greene
Journal: JAMA (1978)

IN 1964, the Surgeon General of the United States reported that tobacco smoke could be harmful to the smoker. Since then, the proportion of adults who smoke cigarettes has decreased. In 1975, thirty-four percent of persons 20 years of age or older smoked cigarettes.<sup>1</sup>The percentage of physicians, dentists, and pharmacists who smoke has also decreased.<sup>2</sup>Recently, the nonsmoking majority has been asserting its right to breathe smoke-free air. This has resulted in numerous laws to restrict smoking in public places. <h3>The Howard County Experience</h3> One law, known as the<i>Howard County Indoor Clean Air Act of 1977</i>, requires restaurants, stores, offices, and many other public places in Howard County, Md, to provide separate areas for smokers and nonsmokers, or, if the business chooses, to prohibit smoking altogether. Diplomacy and tact were important in the presentation of evidence to the Council of Howard County, because one of the
Risk factors and Predictors in the Development of Pulmonary Hypertension in Scleroderma Patients
Authors: Uğur Nadir Karakulak, Naresh Maharjan, Elifcan Aladağ, Levent Kılıç, Ali Akdoğan, Ergün Barış Kaya, Lale Tokgözoğlu
Journal: Journal of the American College of Cardiology (2013)
Specific bile acids inhibit hepatic fatty acid uptake in mice
Authors: Biao Nie, Hyo Min Park, Melissa Kazantzis, Min Lin, Amy Henkin, Stephanie Ng, Sujin Song, Yuli Chen, Heather Tran, Robin Lai, Chris Her, Jacquelyn J. Maher, Barry M. Forman, Andreas Stahl
Journal: Hepatology (2012)

Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. We tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end, stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%. Conclusion: The data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease. (Hepatology 2012)
Taking of the Census, 1801-1951
Authors: A. J. Taylor
Journal: BMJ (1951)

Though not as old as the formation of the State itself, the taking of a census is one of the earliest manifesta- tions of an organized society.A Government preparing to make war or levy taxation found it useful to know the numbers of at least certain classes in its population, and in the early democratic communities electoral lists had to be compiled.The Sumerians of the third mil- lennium B.C., the Egyptians, Jews, Greeks, and Romans, all conducted surveys which merit the broad designation of census.In England the Domesday survey, though based on land rather than population, falls into the same category.The distinctive characteristic of the modern census, however, lies not in its comprehensiveness or its relative accuracy but in the regularity with which the enumeration is undertaken.Every 10 years since 1801 in Great Britain-with one notable recent exception -a census has been held, and in other countries it is an even more frequent but equally regular event. HistoryThe history of the modern census in England may be said to begin with the " Bill for taking account of the Number of People and of the total Number of Marriages, Births and Deaths; and also of the total Number of Poor receiving Alms from every Parish and extra- parochial Place in Great Britain," which was introduced into the House of Commons in March, 1753, apparently with ministerial support.Reports of eighteenth-century debates are somewhat unreliable in detail, but there is no doubt about the spirited discussion which accompanied this measure through all its stakes in the Commons.Its principal opponent was William Thornton, M.P. for York, who viewed the institution of an annual enumeration as " totally subversive of the last remains of English liberty."" An annual register of our people," he is reported to have said, " will acquaint our enemies abroad with our weakness, and a return of the poor's rate, our enemies at home with our wealth.Our enemies abroad are the Spaniards and the French, and our enemies at home are place-men and tax-masters.A census, he maintained, was the first step on the way to the estab- Eshment of a police State (" a government en police ")."We are to entrust petty tyrants with the power of oppression, in confidence that this power shall not be executed; to subject every house to a search; to register every name, age, sex, and state upon oath; record the pox as a natikonal distemper and spend annually £50,000 of the public money-for what ?To decide a wager at White's !" Any enumerator who came his way would receive " the discipline 2f the horse-pond."
Book: The Quotable Osler
Authors: D. Woods
Journal: BMJ (2003)

Eds Mark E Silverman, T Jock Murray, Charles S Bryan American College of Physicians, $30, pp 283 ISBN 1 930513 34 8 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Before offering Sir William Osler (1849–1919) the position of professor of clinical medicine at the University of Pennsylvania, the eminent and eccentric doctor and novelist Silas Weir Mitchell was asked by his colleagues to "look him over." Osler subsequently reported that "Dr Mitchell said there was only one way in which the breeding of a man suitable for such a position, in such a city as Philadelphia, could be tested: give him a cherry pie and see how he … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif