tbuckley/cabot-search huggingface dataset:
Diabetes in the Undernourished: Coincidence or Consequence?
Authors: R. HARSHA RAO
Journal: Endocrine Reviews (1988)

DIABETES is recognized as a disease that is closely linked to nutrition, both in etiology and treatment. Overnutrition was the first risk factor for diabetes to be identified. In the sixth century A.D., Hindu physicians described two forms of the disease, one hereditary and the other acquired, and two types of patients, one lean and emaciated, and the other obese, observing that the acquired type was a disease brought on by "nonconducive foods and habits," chief among which were the gluttonous ingestion of "foods which are sweet and/or fatty, a lack of exercise, laziness and lethargy" (1). The modern concept of diabetes owes much to the clinical observations of Joslin (2). He clearly recognized the importance of obesity in the etiology of diabetes, noting that "Diabetes is largely a penalty of obesity, and the greater the obesity, the more likely is Nature to enforce it" (2). Subsequently, several epidemiological studies have confirmed his clinical observations, with the exception that the duration of obesity, rather than its severity, is thought to be the determinant (3). In the words of Kelly West (4), "Obesity is the most important environmental risk factor for diabetes. Indeed there is some evidence that its importance equals or exceeds the strong influence of diabetes related genetic factors" (4). Observations such as these, although valid in themselves, have served to propagate a singularly one-dimensional view of the relationship between diabetes and nutrition. In the clinical context this view is undeniably supported by the facts: the majority of obese individuals are glucose intolerant (5–8), more than two-thirds of adult-onset diabetics in the developed world are obese (9), and weight reduction in both groups of patients can substantially improve, or even normalize glucose tolerance (8).
Development of nociceptin receptor (NOP) agonists and antagonists
Authors: Carlo Mustazza, Giuditta Bastanzio
Journal: Medicinal Research Reviews (2010)

The nociceptin opioid (NOP) receptor is the most recently discovered member of the family of the opioid receptors; its endogenous agonist is the peptide nociceptin. Due to the subsequent elucidation of its physiological role in both central and peripheral nervous system and in some non-neural tissues, there is a rapidly growing interest in the pharmacological application of substances active on this receptor. Despite the current clinical use of a morphinane-based NOP/MOP mixed ligand (buprenorphine) as an analgesic and in the treatment of drug addictions, so far just a few clinical trials have been made with selective NOP ligands. However, the perspective of their utilization is rapidly growing. Agonists can find applications in the treatment of neuropathic pain, anxiety, cough, drug addition, urinary incontinence, anorexia, congestive heart failure, hypertension; and antagonists for pain, depression, Parkinson's disease, obesity, and as memory enhancers. Besides peptide ligands, which are still subjected to many pharmacological investigations, many different chemical classes of NOP ligands have been discovered: piperidines, nortropanes, spiropiperidines, 4-amino-quinolines and quinazolines, and others. The new advances in establishing structure-activity relationships, also with the help of modeling studies, can permit the development of more active and selective molecules.
Inhibition of lipase production in Propionibacterium acnes by sub-minimal-inhibitory concentrations of tetracycline and erythromycin
Authors: G.F. WEBSTER, K.J. McGINLEY, J.J. LEYDEN
Journal: British Journal of Dermatology (1981)

Journal Article Inhibition of lipase production in Propionibacterium acnes by sub‐minimal‐inhibitory concentrations of tetracycline and erythromycin Get access G.F. WEBSTER, G.F. WEBSTER Department of Pathology, School of Dental Medicine, University of Pennsylvania G.F. Webster, Department of Dermatology, University of Pennsylvania, 36th St. Hamilton Walk, Philadelphia, Pa. 19104, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar K.J. McGINLEY, K.J. McGINLEY Department of Dermatology, School of Medicine, Medical Education Building/GM Search for other works by this author on: Oxford Academic Google Scholar J.J. LEYDEN J.J. LEYDEN University of Pennsylvania, Philadelphia, PA 19104 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 4, 1 April 1981, Pages 453–457, https://doi.org/10.1111/j.1365-2133.1981.tb15317.x Published: 01 April 1981 Article history Accepted: 29 May 1980 Published: 01 April 1981
Human papillomaviruses in anogenital warts in children: typing by in situ hybridisation.
Authors: A F Padel, V A Venning, M F Evans, A M Quantrill, K A Fleming
Journal: BMJ (1990)

We have reported that the bacterial LPS induces the activation of NF-κB and inflammatory cytokine gene expression and that this requires the activity of small GTPase, RhoA. In this study, we show that an atypical protein kinase C isozyme, PKCζ, associates functionally with RhoA and that PKCζ acts as a signaling component downstream of RhoA. Stimulation of monocytes and macrophages with LPS resulted in PKCζ activation and that inhibition of PKCζ activity blocks both LPS-stimulated activation of NF-κB and IL-1β gene expression. Our results also indicate that transforming growth factor β-activated kinase 1 acts as a signaling component downstream of PKCζ in cytokine gene transcription stimulated by LPS in human peripheral blood monocytes and macrophages. The specificity of this response suggests an important role for the Rho GTPase/PKCζ/transforming growth factor β-activated kinase 1/NF-κB pathway in host defense and in proinflammatory cytokine synthesis induced by bacterial LPS.
Review: Phenothiazines relieve acute migraine headaches in the ED and are better than other active agents for some outcomes
Authors: Benjamin W. Friedman
Journal: Annals of Internal Medicine (2010)

ACP Journal Club20 April 2010Review: Phenothiazines relieve acute migraine headaches in the ED and are better than other active agents for some outcomesBenjamin W. Friedman, MD, MSBenjamin W. Friedman, MD, MSAlbert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA (B.W.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-8-201004200-02011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationKelly AM, Walcynski T, Gunn B. The relative efficacy of phenothiazines for the treatment of acute migraine: a meta-analysis. Headache. 2009;49:1324-32. https://pubmed.ncbi.nlm.nih.gov/19496829Clinical Impact RatingsGIM/FP/GP: Emergency Med: Neurology: Reference1 Friedman BW, Grosberg BM. Diagnosis and management of the primary headache disorders in the emergency department setting. Emerg Med Clin North Am. 2009;27:71-87. [PMID: 19218020] Google Scholar Author, Article, and Disclosure InformationAffiliations: Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA (B.W.F.)This article was published at Annals.org on 6 April 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdults with Conditions Causing Chronic Pain 20 April 2010Volume 152, Issue 8Page: JC4-11KeywordsChlorpromazineEmergency departmentHeadachesHypotensionMagnesiumMigraineNeurologyNumber needed to treatOpioidsPhenothiazine ePublished: 20 April 2010 Issue Published: 20 April 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
KCNE1 mutations cause Jervell and Lange-Nielsen syndrome
Authors: Eric Schulze-Bahr, Qing Wang, Horst Wedekind, Wilhelm Haverkamp, Qiuyun Chen, Yaling Sun, Claudia Ruble, Marco Hördt, Jeffrey A. Towbin, Martin Borggrefe, Gerd Assmann, Xiangdong Qu, John C. Somberg, Günter Breithardt, Carlos Oberti, Harald Funke
Journal: Nature Genetics (1997)
Overexpression of the Serotonin 5-HT <sub>2B</sub> Receptor in Heart Leads to Abnormal Mitochondrial Function and Cardiac Hypertrophy
Authors: Canan G. Nebigil, Fabrice Jaffré, Nadia Messaddeq, Pierre Hickel, Laurent Monassier, Jean-Marie Launay, Luc Maroteaux
Journal: Circulation (2003)

Background— Identification of factors regulating myocardial structure and function is important to understand the pathogenesis of heart disease. We previously reported that 5-HT 2B receptor ablation in mice leads to dilated cardiomyopathy. In this study, we investigated the pathological consequence of overexpressing 5-HT 2B receptors in heart in vivo. Methods and Results— We have generated transgenic mice overexpressing the Gq-coupled 5-HT 2B receptor specifically in heart. We found that overexpression of 5-HT 2B receptor in heart leads to ventricular hypertrophy as the result of increased cell number and size. Increased atrial natriuretic peptide and myosin heavy chain expression demonstrated activation of the molecular program for cardiac hypertrophy. Echocardiographic analysis indicated the presence of thickened ventricular free wall without alteration of the systolic function, showing that transgenic mice have compensated hypertrophy. Electron microscopic analysis revealed structural abnormalities including mitochondrial proliferation, as also manifested by histological staining. Transgenic mouse heart displayed a specific reduction in the expression levels of the adenine nucleotide translocator associated to increase in the succinate dehydrogenase and cytochrome C oxidase mitochondrial activities. Conclusions— Our results constitute the first genetic evidence that overexpression of the 5-HT 2B receptor in the heart leads to compensated hypertrophic cardiomyopathy associated with proliferation of the mitochondria. This observation suggests a role for mitochondria in the hypertrophic signaling that is regulated by serotonin. These transgenic mice provide a new genetic model for hypertrophic heart disease.
Hepatic histology in hepatitis C virus carriers coinfected with hepatitis G virus
Authors: J Petrik, L Guella, D G D Wight, G M Pearson, J Hinton, H Parker, J-P Allain, G J M Alexander
Journal: Gut (1998)

Background —A novel flavivirus has been described recently and designated hepatitis G virus (HGV). The virus is transmitted by the parenteral route but it is uncertain whether it is associated with chronic liver disease because liver biopsy is difficult to justify in this group. Aims —To examine histological features of liver biopsy in patients infected with hepatitis C virus (HCV) according to the presence or absence of HCV and HGV RNA. Methods —One hundred and thirty one consecutive HCV carriers undergoing staging liver biopsy were studied retrospectively. In each, HCV RNA and HGV RNA were detected by reverse transcription polymerase chain reaction on serum samples collected at the time of biopsy. The presence of each RNA was correlated with histological features blind to the RNA results; individual histological features of inflammation or fibrosis were scored separately. Results —Nineteen patients were positive for both HGV and HCV RNA in serum, 91 were positive for HCV RNA alone, two were positive for HGV RNA alone, and 19 were negative for both RNA species. Neither age nor sex differed between the groups; a greater proportion of intravenous drug users were HGV RNA positive, but this was not statistically significant. There was no effect of HGV coinfection on the stage of fibrosis or any other histological parameter except steatosis; patients with HCV and HGV RNA had a higher mean score for fat than those patients with HCV RNA alone (p&lt;0.05). Conclusions —HGV coinfection has no important effects on histological features in chronic HCV carriers. It is unlikely that HGV infection causes chronic liver disease.
Hypersensitivity of lung vessels to catecholamines in systemic hypertension.
Authors: M D Guazzi, M Alimento, C Fiorentini, M Pepi, A Polese
Journal: BMJ (1986)

Among patients with primary systemic hypertension pressure and arteriolar resistance in the pulmonary circulation exceed normal values and are hyper-reactive to sympathetic stimulation. A study was therefore carried out in 16 patients with uncomplicated essential hypertension and nine healthy subjects to compare the pulmonary vascular reactivity to exogenous catecholamines. In the normotensive group the dose response relation to adrenaline (microgram: dyn) was 1 = -4, 2 = -9, 3 = -9, and 4 = -10 and to noradrenaline 2 = +3, 4 = /8, 6 = +4, and 8 = +3. The relations in the hypertensive subjects were 1 = +18, 2 = +42, 3 = +59, and 4 = +77 and 2 = +39, 4 = +54, 6 = +76, and 8 = +100, respectively. Group differences were highly significant. Cardiac output (blood flow through the lungs) was raised by adrenaline and reduced by noradrenaline. In either case the driving pressure across the lungs was significantly augmented in the hypertensive patients but not in the normotensive group. Both catecholamines had a vasoconstrictor effect on the pulmonary circulation as a result of vascular over-reactivity. The opposite changes in resistance between normal and hypertensive subjects produced by adrenaline suggest that a constrictor vascular hypersensitivity occurs in the pulmonary circulation with the development of systemic high blood pressure.
HIV Infection and AIDS in the Public Health and Health Care Systems
Authors: Lawrence O. Gostin, David W. Webber
Journal: JAMA (1998)

The AIDS Litigation Project has reviewed nearly 600 reported cases involving individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) in the federal and state courts in the United States between 1991 and 1997. Cases were identified through a federal and 50-state computer and library search. An important subset of litigation relates to HIV/AIDS in the public health and health care systems, since the law affects health care institutions and professionals, patients, and public health policy in America. This subset of HIV/AIDS litigation includes testing and reporting; privacy, the duty to warn, and the right to know; physician standards of care in prevention and treatment; and discrimination and access to health care. In broad terms, the review demonstrates a reliance on voluntary testing and protection of patient privacy through HIV-specific statutes and the common law. Negligence with potential civil and criminal liability has been alleged in cases of erroneous or missed diagnosis of HIV infection. In the first AIDS case to be considered by the Supreme Court, the Court will decide whether patients with asymptomatic HIV infection are protected under the Americans With Disabilities Act. Considerable progress has been made, both socially and legally, during the first 2 decades of the epidemic, but much still needs to be accomplished to protect privacy, prevent discrimination, and promote tolerance.
A Concept of Negative Interstitial Pressure Based on Pressures in Implanted Perforated Capsules
Authors: ARTHUR C. GUYTON, Malcolm Frank, Berry Abernathy
Journal: Circulation Research (1963)

Over 200 perforated plastic capsules were implanted in different tissues of the dog, and the wounds were allowed to heal. After one month, pressures measured by inserting a needle through the skin and then through a perforation of the capsule into its cavity were always negative in normal tissues, averaging-6.4 mm Hg. The pressure was always positive in edematous tissues. Evidence is presented to indicate that the pressure measured in the capsule is equal to, or nearly equal to, the interstitial fluid pressure in the tissue spaces surrounding the capsule. On the other hand, pressure measurements made by a needle technic failed except in rare instances to give negative values in normal tissues but in edematous tissues gave almost exactly the same values as those recorded by the capsules. Also, pressures measured by the capsules changed in accordance with Starling's law of the capillaries when (a) venous pressure was raised, (b) when arterial pressure was lowered, (c) when the tissues were dehydrated by intravenous infusion of dextran, or (d) when the tissues were hydrated by intravenous infusion of saline. Pressures measured by a needle technique failed to change in accordance with this law in these same experiments. Therefore, it is concluded that needle pressure determinations in non-edematous tissue do not measure the interstitial fluid pressure.
THE LETHAL EFFECT OF ENDOTOXINS ON THE CHICK EMBRYO
Authors: Richard T. Smith, Lewis Thomas
Journal: The Journal of Experimental Medicine (1956)

Inoculation of the CAM of the 10-day chick embryo with endotoxin preparations derived from the meningococcus and other Gram-negative microorganisms has been shown to result in multiple hemorrhages and death of the embryo within a few hours. Evidence has been presented to indicate that this lethal effect is specific for the general class of endotoxins derived from Gram-negative bacteria. Susceptibility to endotoxin was maximal in 10-day old embryos, and younger or older embryos showed little or no response. The optimal incubation temperature for the effect of endotoxin was 39.5 degrees C., and embryos incubated at 28 degrees C. were completely protected. The lethal effect was prevented by small amounts of cortisone, hydrocortisone, and 9-alpha fluorohydrocortisone, but not by cholesterol, desoxycorticosterone, or 1-dehydrocortisone.
Transforming growth factor- 1 genotype and susceptibility to chronic obstructive pulmonary disease
Authors: L Wu
Journal: Thorax (2004)

<b>Background:</b> Only a few long term smokers develop symptomatic chronic obstructive pulmonary disease (COPD) and this may be due, at least in part, to genetic susceptibility to the disease. Transforming growth factor β<sub>1</sub> (TGF-β<sub>1</sub>) has a number of actions that make it a candidate for a role in the pathogenesis of COPD. We have investigated a single nucleotide polymorphism at exon 1 nucleotide position 29 (T→C) of the TGF-β<sub>1</sub> gene that produces a substitution at codon 10 (Leu→Pro). <b>Methods:</b> The frequency of this polymorphism was determined in 165 subjects with COPD, 140 healthy blood donors, and 76 smokers with normal lung function (resistant smokers) using the polymerase chain reaction and restriction enzyme fragment length polymorphism. <b>Results:</b> The distribution of genotypes was Leu-Leu (41.8%), Leu-Pro (50.3%), and Pro-Pro (7.9%) for subjects with COPD, which was significantly different from the control subjects (blood donors: Leu-Leu (29.3%), Leu-Pro (52.1%) and Pro-Pro (18.6%), p = 0.006; resistant smokers: Leu-Leu (28.9%), Leu-Pro (51.3%) and Pro-Pro (19.7%), p = 0.02). The Pro<sup>10</sup> allele was less common in subjects with COPD (33%) than in blood donors (45%; OR = 0.62, 95% CI 0.45 to 0.86, p = 0.005) and resistant smokers (45%; OR = 0.59, 95% CI 0.40 to 0.88, p = 0.01). <b>Conclusions:</b> The proline allele at codon 10 of the TGF-β<sub>1</sub> gene occurs more commonly in control subjects than in individuals with COPD. This allele is associated with increased production of TGF-β<sub>1</sub> which raises the possibility that TGF-β<sub>1</sub> has a protective role in COPD.
Photoinactivation of Herpes Simplex Virus Continues to Look Promising
Authors: Joseph L. Melnick
Journal: JAMA (1973)

<h3>To the Editor.—</h3> This is in response to Rapp's comments on his unpublished work (225:459, 1973). First, herpes infections are often more than "superficial" and "uncomfortable." Even though in most cases superficial herpes simplex is not of serious consequence, recurrent herpes facialis may result in temporary disfiguration—important to persons whose public appearance constitutes their livelihood. In infants the disease may be fatal. Herpes genitalis is associated with a great deal of discomfort, and its recurrence often presents considerable anxiety and marital discord. Urinary retention requiring hospitalization may occur in some patients with herpes genitalis. Naturally, the judgment regarding the use of treatment rests partly on the degree of discomfort and disability produced by the disease. Second, evidence is mounting that herpes genitalis may be etiologically related to cervical cancer. If the infection can be curtailed and even eliminated when it first becomes evident, the possibility exists that this cancer might
"POLLEN THERAPY WITH PROTEIN-FREE EXTRACTS"
Authors: Gordon A. Alles
Journal: JAMA (1926)

To the Editor:  —The article by Black and Moore (The Journal, January 30) contains statements that are distinctly inaccurate and misleading.  F. W. Heyl ( J. Am. Chem. Soc.  39: 1470, 1917) found that ragweed pollen used in his work contained 4.99 per cent of total nitrogen, of which 2.6 per cent was soluble in aqueous saline solution. Of this 2.6 per cent, from 0.6 to 0.8 per cent was protein in nature, part being albumin and proteose.  H. L. Huber and K. K. Koessler ( Arch. Int. Med.  36: 751 [Dec.] 1925) obtained solutions of ragweed pollen (1: 10, or 10 per cent) which contained 1.54 and 1.61 mg. of nitrogen per cubic centimeter. According to Heyl's figures, these 10 per cent solutions would contain about 0.5 mg. of protein nitrogen per cubic centimeter, or about 3 mg. of pollen protein per cubic centimeter.  Glycerol and water have similar solvent properties.
FDA Approval of Obesity Drugs
Authors: Elaine H. Morrato, David B. Allison
Journal: JAMA (2012)

Given the obesity epidemic, patients and physicians are clamoring for new treatments. Companies are responding with significant investment in drug development. Drugs provide an important therapeutic option when lifestyle modifications are insufficient for achieving weight loss goals and when surgery is not desired or warranted. However, in the last decade, three obesity drugs were removed from the U.S. market and until last month, only one new obesity drug has been approved since 1999. How is it possible to make sense of this curious duality of circumstances?
Intracoronary Application of C1 Esterase Inhibitor Improves Cardiac Function and Reduces Myocardial Necrosis in an Experimental Model of Ischemia and Reperfusion
Authors: Georg Horstick, Axel Heimann, Otto Go¨tze, Gerd Hafner, Oliver Berg, Peter Bo¨ehmer, Phillip Becker, Harald Darius, Hans-Ju¨rgen Rupprecht, Michael Loos, Sucharit Bhakdi, Ju¨rgen Meyer, Oliver Kempski
Journal: Circulation (1997)

Background Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH). Methods and Results Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion. Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8±7.8% versus 73.4±4.0% necrosis of area at risk, P ≤.018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137° of the anteroseptal region showed significantly improved wall motion at early and 29° at late reperfusion with C1-INH treatment. Conclusions C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.