tbuckley/cabot-search huggingface dataset:
GPR109A (PUMA-G/HM74A) mediates nicotinic acid–induced flushing
Authors: Zoltán Benyó, Andreas Gille, Jukka Kero, Marion Csiky, Marie Catherine Suchánková, Rolf M. Nüsing, Alexandra Moers, Klaus Pfeffer, Stefan Offermanns
Journal: Journal of Clinical Investigation (2005)

Nicotinic acid (niacin) has long been used as an antidyslipidemic drug. Its special profile of actions, especially the rise in HDL-cholesterol levels induced by nicotinic acid, is unique among the currently available pharmacological tools to treat lipid disorders. Recently, a G-protein–coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid–induced antilipolytic effects in adipocytes. One of the major problems of the pharmacotherapeutical use of nicotinic acid is a strong flushing response. This side effect, although harmless, strongly affects patient compliance. In the present study, we show that mice lacking PUMA-G did not show nicotinic acid–induced flushing. In addition, flushing in response to nicotinic acid was also abrogated in the absence of cyclooxygenase type 1, and mice lacking prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) receptors had reduced flushing responses. The mouse orthologue of GPR109A, PUMA-G, is highly expressed in macrophages and other immune cells, and transplantation of wild-type bone marrow into irradiated PUMA-G–deficient mice restored the nicotinic acid–induced flushing response. Our data clearly indicate that GPR109A mediates nicotinic acid–induced flushing and that this effect involves release of PGE2 and PGD2, most likely from immune cells of the skin.
THE EFFECT OF GERMANIUM DIOXID ON THE RABBIT
Authors: G. H. BAILEY
Journal: JAMA (1925)

In 1922, germanium dioxid was presented by Hammett, Nowrey and Mueller,<sup>1</sup>Hammett and Nowrey,<sup>2</sup>and Mueller and Iszard,<sup>3</sup>as a relatively nontoxic chemical compound with a marked erythropoietic effect on laboratory animals and of hopeful possibilities as a therapeutic agent in cases of anemia in man. As the fundamental experiments on which these conclusions were based did not appear adequate to justify the conclusions, it seemed advisable to test the drug on an animal more suited to hematologic studies than the white rat, and give more attention to evidences of increased hematopoiesis than had apparently been given by the authors mentioned. Our experiments were begun in the spring of 1922, but, owing to a variety of circumstances, have extended intermittently over a considerable period of time. In this interval, several reports have been made of the effect of germanium dioxid, not only on laboratory animals but also
HIV Coinfection in Multidrug- and Extensively Drug-Resistant Tuberculosis Results in High Early Mortality
Authors: Neel R. Gandhi, N. Sarita Shah, Jason R. Andrews, Venanzio Vella, Anthony P. Moll, Michelle Scott, Darren Weissman, Claudio Marra, Umesh G. Lalloo, Gerald H. Friedland
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected.To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates.We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records.Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001).Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.
Synchronous occurrence of spontaneous localized calcium release from the sarcoplasmic reticulum generates action potentials in rat cardiac ventricular myocytes at normal resting membrane potential.
Authors: M C Capogrossi, S R Houser, A Bahinski, E G Lakatta
Journal: Circulation Research (1987)

Under certain conditions, spontaneous release of Ca2+ from the sarcoplasmic reticulum occurs in resting mammalian myocardium. In single rat ventricular myocytes, such spontaneous Ca2+ release appears localized rather than homogeneous. When the increase in cytosolic Ca2+ is present in a single locus within a cell, it causes a small depolarization, which, at the normal resting potential, is subthreshold for generating an action potential. However, when spontaneous Ca2+ release occurs simultaneously at more than a single discrete locus, the resultant sarcolemmal depolarization is augmented to levels that can induce an action potential, even when this depolarization begins at the normal resting membrane potential. Thus, the synchronous occurrence of multifocal localized increases in cytosolic Ca2+ due to spontaneous Ca2+ release from the sarcoplasmic reticulum within ventricular myocytes is a mechanism for "abnormal automaticity."
MODERN RESPIRATORY ADVANTAGES.
Authors: W. T. ENGLISH
Journal: JAMA (1896)

The worker in the domain of preventive medicine often has occasion to feel that there are excuses for becoming pessimistic and for regarding his efforts as unprofitable. After some acute outbreak of disease, his heart is wrung with disappointment and his mind is distracted. A good remedy for such hypochondriasis is to rehearse for himself, or have another review for him, some of the modern respiratory advantages, and trace them to their source. All men are not alike possessed of the "vision and faculty divine," but that man must be indeed prosaic whose soul is not inspired with gratitude and whose heart is not uplifted with hopefulness as he beholds the human body rapidly and surely raised from the abnormalities of life, sublimated, refined and sacred through the avails of modern respiratory advantages. The individual who labors in the realm of preventive medicine is habituated to a life amid the
Potential for Transmission of AIDS-Associated Retrovirus From Bisexual Men in San Francisco to Their Female Sexual Contacts
Authors: Warren Winkelstein
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In recent months, concern over the possibility of heterosexual transmission of the acquired immunodeficiency syndrome related-retrovirus (ARV) infection has increased.<sup>1,2</sup>A possible chain of transmission for ARV infection from homosexual men to women would be through bisexual men. The potential for such transmission can be estimated from data available from the San Francisco Men's Health Study, a prospective study of the epidemiology and natural history of the acquired immunodeficiency syndrome (supported by National Institute of Allergy and Infectious Diseases contract NO1-A1-32519).<sup>3</sup>Because the cohort is a probability sample, inferences can be extended to the entire population of single men in the study area. Of the 1,035 men aged 25 to 54 years in the cohort, 169 (16.3%) classified themselves as bisexual and 108 of them reported one or more female sexual partners during the previous two years. Table 1 indicates that 146 women were potentially
Mitochondrial Sequence Evolution in Spiders: Intraspecific Variation in tRNAs Lacking the TΨC Arm
Authors: Susan E. Masta
Journal: Molecular Biology and Evolution (2000)

Analyses of mitochondrial DNA sequences from three species of Habronattus jumping spiders (Chelicerata: Arachnida: Araneae) reveal unusual inferred tRNA secondary structures and gene arrangements, providing new information on tRNA evolution within chelicerate arthropods. Sequences from the protein-coding genes NADH dehydrogenase subunit 1 (ND1), cytochrome oxidase subunit I (COI), and subunit II (COII) were obtained, along with tRNA, tRNA, and large-subunit ribosomal RNA (16S) sequences; these revealed several peculiar features. First, inferred secondary structures of tRNA and, likely, tRNA, lack the TΨC arm and the variable arm and therefore do not form standard cloverleaf structures. In place of these arms is a 5–6-nt T arm-variable loop (TV) replacement loop such as that originally described from nematode mitochondrial tRNAs. Intraspecific variation occurs in the acceptor stem sequences in both tRNAs. Second, while the proposed secondary structure of the 3′ end of 16S is similar to that reported for insects, the sequence at the 5′ end is extremely divergent, and the entire gene is truncated about 300 nt with respect to Drosophila yakuba. Third, initiation codons appear to consist of ATY (ATT and ATC) and TTG for ND1 and COII, respectively. Finally, Habronattus shares the same ND1-tRNA-16S gene arrangement as insects and crustaceans, thus illustrating variation in a tRNA gene arrangement previously proposed as a character distinguishing chelicerates from insects and crustaceans.
Bio-Prep
Authors: Harry J. Knopke
Journal: JAMA (1986)

To address physician maldistribution in Alabama and the Southeast region, The University of Alabama established the Biomedical Sciences Preparation Program (BioPrep) in five rural high schools. Its purpose is to help rural, disadvantaged high school students develop academically and socially so that they will be motivated and able to enroll in and progress successfully through college, specifically in pre-health professional curricula. It aims to develop their desire to return eventually to rural areas of Alabama as professionals. Project students are compared with two control groups. Performance on the American College Testing Program college entrance examination revealed significantly higher achievement by the project students. The project students also chose professional careers earlier and more frequently than matched high school students not receiving this special program, but similar to medical students and premedical students. The implications of the project for increasing the size of the rural, disadvantaged student applicant pool are discussed. (<i>JAMA</i>1986;256:2548-2551)
A Cascade of Care for Diabetes in the United States: Visualizing the Gaps
Authors: Mohammed K. Ali, Kai McKeever Bullard, Edward W. Gregg, Carlos del Rio
Journal: Annals of Internal Medicine (2014)

A "cascade-of-care" concept helped to address implementation gaps in HIV care.To develop a similar cascade for U.S. diabetes care to visualize gaps in awareness of diagnosis, engagement, and treatment.Nationally representative cross-sectional surveys.2007 to 2012 NHANES (National Health and Nutrition Examination Surveys).Nonpregnant civilians aged 18 years or older.Standardized data collection and laboratory procedures. Diabetes care was benchmarked against recent diabetes and cardiovascular risk reduction guidelines.In 2012, an estimated 28.4 million (11.8%) U.S. adults had diabetes, of whom 20.5 million (72.2%) were aware of their diagnosis. Among diagnosed adults, 95.3% had a usual care provider and 91.7% made 2 or more visits in the past year. In contrast, among undiagnosed adults, 84.5% had a usual care provider and 66.5% reported 2 or more visits in the past year. Among diagnosed adults, 63.7%, 65.5%, 56.6%, and 80.6% met individualized hemoglobin A1c, blood pressure (BP <140/80 mmHg), lipid (low-density lipoprotein [LDL] cholesterol <2.6 mmol/L [<100 mg/dL]), and nonsmoking goals, respectively; 26.7% met combined ABC (hemoglobin A1c, BP, and LDL cholesterol) targets, and 21.3% met combined ABC targets and did not smoke. Among undiagnosed adults, 77.0%, 57.9%, 36.0%, and 77.9% met hemoglobin A1c, BP, lipid, and nonsmoking goals, respectively; 22.1% met combined ABC targets; and 18.8% met combined ABC targets and were nonsmokers.Institutionalized and noncivilian persons are not surveyed in NHANES.Three of 10 adults with diabetes remain undiagnosed, which may be related to less access to care. Compared with diagnosed adults, undiagnosed adults have less elevated hemoglobin A1c levels, less lipid treatment and worse control, and similarly poor BP and combined ABC control regardless of smoking status. Addressing these care gaps in both groups would prevent long-term complications.None.
The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease
Authors: Susan E. Andrew, Y. Paul Goldberg, Berry Kremer, Håkan Telenius, Jane Theilmann, Shelin Adam, Elizabeth Starr, Ferdinando Squitieri, Biaoyang Lin, Michael A. Kalchman, Rona K. Graham, Michael R. Hayden
Journal: Nature Genetics (1993)
Less of a craft, more of a science
Authors: P. Berry
Journal: BMJ (1997)

As I was about to leave the room my computer, Frank, said, “Have you got a moment to check your blood pressure, Paul?”

I glanced at my watch. “Yeah, just about.” I found the electronic sphygmomanometer and took a reading. “One hundred and fifty over one hundred.”

After a second the machine spoke again. “I've put your readings and laboratory test results into the protocol, and the advice is that you should start on some medication for your blood pressure.”

I had expected this. All my readings had been around this level, but I had hoped that my low lipids and the fact that I was a non-smoker would let me off the hook. I had already decided to do what the protocol suggested. After all, it was one of the best researched of the constantly updated protocols lodged in the University of Maryland computer. These gold standards had been available to anyone, medical or lay, machine or human, over the past 20 years. They meant that people like myself, a fibreoptic cable technician, could bypass doctors to a large extent and manage their own conditions.

“OK, I'll …
Neutrophil-mediated endothelial injury in vitro mechanisms of cell detachment.
Authors: J M Harlan, P D Killen, L A Harker, G E Striker, D G Wright
Journal: Journal of Clinical Investigation (1981)

Neutrophil-mediated endothelial injury was assessed in vitro using assays of cell lysis and cell detachment. Activation of human peripheral blood neutrophils adherent to human umbilical vein endothelial cell monolayers by serum-treated zymosan produced dose-dependent endothelial cell detachment without concomitant cell lysis. This injury was inhibited by neutral protease inhibitors, but not by catalase or superoxide dismutase. Neutrophils from a patient with chronic granulomatous disease also produced endothelial cell detachment when activated by serum-treated zymosan similar to normal neutrophils. Endothelial detachment was also produced by cell-free postsecretory media from activated neutrophils or by partially purified human neutrophil granule fraction and was inhibitable by tryptic, elastase, and serine protease inhibitors, but not by an acid protease inhibitor. Analysis of iodinated endothelial cell surface proteins that had been exposed to partially purified neutrophil granule fraction showed complete loss of proteins migrating in the region of fibronectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This result was prevented in the presence of neutral protease inhibitors. We conclude that neutrophil-derived neutral proteases mediate endothelial cell detachment in vitro through digestion of endothelial cell surface proteins including fibronectin.
Orientation in Endoscopy
Authors: L. Ivan Epstein
Journal: Endoscopy (1981)

This paper is intended to help the beginner endoscopist learn to interpret the orientation of the object seen through the endoscope. This is applicable only to an endoscope with a reflecting (side view) prism at its distal end, such as a cystoscope. A proposed counterrotation device for turning the image upright is described.
Organization of the Bovine α2-Fucosyltransferase Gene Cluster Suggests that the Sec1 Gene Might Have Been Shaped Through a Nonautonomous L1-Retrotransposition Event Within the Same Locus
Authors: Katiana Saunier, Jean-Pierre Barreaud, André Eggen, Rafael Oriol, Hubert Levéziel, Raymond Julien, Jean-Michel Petit
Journal: Molecular Biology and Evolution (2001)

By referring to the split coding sequence of the highly conserved α6-fucosyltransferase gene family (assumed to be representative of the common α2 and α6 fucosyltransferase gene ancestor), we have hypothesized that the monoexonic coding sequences of the present α2-fucosyltransferase genes have been shaped in mammals by several events of retrotransposition and/or duplication. In order to test our hypothesis, we determined the structure of the three bovine α2-fucosyltransferase genes (bfut1, bfut2, and sec1) and analyzed their characteristics compared with their human counterparts (FUT1, FUT2, and Sec1). We show that in mammals, a complex nonautonomous L1-retrotransposition event occurred within the locus of the α2-fucosyltransferase ancestor gene itself. A consequence of this event was the processing in Catarrhini of a Sec1 pseudogene via several point mutations.
Re: Persistence of Treponema pallidum Following Penicillin G Therapy
Authors: Harold W. Jaffe
Journal: JAMA (1977)

To the Editor.—  There are several errors  Dr Tramont's article entitled Persistence of Treponema pallidum Following Penicillin G Therapy, (236: 2206, 1976). The author states that in two adult patients, T pallidum was isolated from the CSF despite the fact that each received currently recommended amounts of penicillin G benzathine for secondary and neurosyphilis, respectively. However, the second case report describes isolation of T pallidum from CSF obtained before the patient received any penicillin. The author also states that this patient was later treated with 20 million units aqueous penicillin G benzathine, administered intravenously daily for three weeks. The benzathine salt of penicillin G should only be given intramuscularly. We feel these points need explanation.
Angiotensin II Enhances Interleukin-18 Mediated Inflammatory Gene Expression in Vascular Smooth Muscle Cells
Authors: Saurabh Sahar, Roopashree S. Dwarakanath, Marpadga A. Reddy, Linda Lanting, Ivan Todorov, Rama Natarajan
Journal: Circulation Research (2005)

Vascular smooth muscle cells (VSMCs) express functional interleukin-18 receptors (IL-18Rs), composed of α and β subunits. These subunits are elevated in VSMCs of atherosclerotic plaques and can be induced by inflammatory agents in cultured VSMC. Because both IL-18 and Angiotensin II (Ang II) are implicated in atherosclerosis, our objective was to analyze the role of IL-18 signaling and potential cross-talk with Ang II in VSMC. We observed that IL-18 activated Src kinase, protein kinase C, p38 and JNK MAPKs, Akt kinase, transcription factors NF-kB and AP-1, and induced expression of pro-inflammatory cytokines in VSMC. Pretreatment of VSMC with Ang II enhanced IL-18-induced NF-kB activation and cytokine gene expression. Interestingly, Ang II directly increased mRNA and cell surface protein levels of the IL-18Rα subunit. Functional relevance in an organ culture model was demonstrated by the observation that incubation of intact mouse aortas ex vivo with Ang II also significantly increased IL-18Rα expression. Furthermore, Ang II significantly stimulated transcription from a minimal IL-18Rα promoter containing putative binding sites for STAT and AP-1. Ang II also increased in vivo recruitment of STAT-3 on the IL-18Rα promoter. Finally, dominant negative STAT-3 mutant blocked Ang II-induced IL-18Rα promoter activation in CHO cells overexpressing AT1a receptor and IL-18Rα mRNA expression in HVSMC. Thus, Ang II enhances IL-18 induced inflammatory genes by increasing IL-18Rα expression. These results illustrate a novel mechanism wherein Ang II- mediated increases in inflammatory genes and proatherogenic effects in the vasculature are enhanced by a vicious loop and cross-talk with the IL-18 signaling pathway.
Introductory Address ON RESEARCH IN MEDICINE AND WOMEN IN RESEARCH: Delivered at the London School of Medicine for Women
Authors: H. T. Butlin
Journal: BMJ (1911)

LADIES AN-D GENTLEMIEN,-I imi1agin1e that an1 Iiitroduictory Address a century ago afforded tile hospital staff tlle opl)ortunity of welcoising tile lnew stldelnts aild of giving themli some idea of the scope anld niatture of the workl which lay before tlelmi.An.dI lhave io doul)t tilat the orator did soimietim-les tcll tlle younllgmIien that tlec profession they so0"lst to eilter was a great anid noble profession, and of aii interest sufficienit in itself to repay themi for thrir labours.A hulndred years ago there was amptple reasoln for the address, for, oiice admiiittecl to the school, the studenit was left liiLcli to his ow 1i resoulrces.In these days the Introcluctory Address nieeds jtustifica- tioIi.Whlat wNvith studenlts' numi)bers of the journals, wlhat witl resident colleres, wardenls, tuitors, and demonstrators, tile student las no nieed of anl address of welcomie or of warning or of genleral advice.-My own school (St.Bartllololulew's) recognized this maniy years ago and abolislhed tlle Introductory Address; it hXas niever 'WOMEN ANDI MEDICAL RESEARCH.
The alpha1beta1 integrin is expressed during neointima formation in rat arteries and mediates collagen matrix reorganization.
Authors: P J Gotwals, G Chi-Rosso, V Lindner, J Yang, L Ling, S E Fawell, V E Koteliansky
Journal: Journal of Clinical Investigation (1996)

Remodeling of the extracellular matrix by activated mesenchymal cells (myofibroblasts) is a critical aspect of wound repair in all adult organs. Collagen-dependent gel contraction, a process requiring integrin function, is an established in vitro assay thought to mimic in vivo matrix remodeling. Numerous data have implicated the alpha2beta1 integrin in various cell types as the primary collagen receptor responsible for collagen gel contraction. However, evidence from the literature suggests that the major collagen binding integrin expressed on mesenchymally derived cells in situ is the alpha1beta1 integrin, not the alpha2beta1 integrin. In this report, we use a rat vascular injury model to illustrate that the alpha1beta1 integrin is the major collagen receptor expressed on vascular smooth muscle cells after injury. Using two smooth muscle cell lines, expressing either the alpha1beta1 integrin alone or both the alpha1beta1 and alpha2beta1 integrins, along with Chinese hamster ovary cells transfected with the alpha1 integrin, we demonstrate that alpha1beta1 supports not only collagen-dependent adhesion and migration, but also gel contraction. These data suggest that in vivo the alpha1beta1 integrin is a critical collagen receptor on mesenchymally derived cells potentially involved in matrix remodeling after injury.