tbuckley/cabot-search huggingface dataset:
Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport
Authors: Kentaro Ozawa, Toshikazu Kondo, Osamu Hori, Yasuko Kitao, David M. Stern, Wolfgang Eisenmenger, Satoshi Ogawa, Tohru Ohshima
Journal: Journal of Clinical Investigation (2001)

Expression of angiogenic factors such as VEGF under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis. Local administration of ORP150 sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased VEGF antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of ORP150 expression caused retention of VEGF antigen within the endoplasmic reticulum (ER), while overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants. Taken together, these data suggest an important role for ORP150 in the setting of impaired wound repair and identify a key, inducible chaperone-like molecule in the ER. This novel facet of the angiogenic response may be amenable to therapeutic manipulation.
Influence of Norepinephrine and Digitalis on Myocardial Oxygen Consumption in the Newborn Lamb
Authors: S. EVANS DOWNING, JOHN C. LEE, JAMES F. TAYLOR, KATHERINE HALLORAN
Journal: Circulation Research (1973)

The relationships between cardiac performance and oxygen usage were explored in 19 newborn lambs (5 hours to 8 days old), and the influence of inotropic stimulation was studied. A preparation was developed to measure coronary sinus flow and myocardial oxygen consumption (MVo 2 ) under controlled hemodynamic conditions. Using a gelatin injection technique, we determined that more than 90% of the measured sinus flow originated from left heart tissue; less than 10% was derived from right ventricular myocardium. Changes in contractility were produced by intravenous infusion of norepinephrine or acetylstrophanthidin. Norepinephrine (1-2.4 µg/min kg -1 ) or acetylstrophanthidin (5 µg/min kg -1 ) produced increases in the maximal rate of rise of left ventricular pressure and large reductions in left ventricular enddiastolic pressure, but the changes in MVo 2 in lambs with constant aortic blood pressure, cardiac output, and heart rate were minimal. Ventricular function curves demonstrated a significant relationship between end-diastolic pressure and MVo 2 (P &lt; 0.01). For a given left ventricular end-diastolic pressure, MVo 2 was approximately 3 ml/min 100 g -1 left ventricle greater during the infusion of norepinephrine. Therefore, net changes in MVo 2 with inotropic stimulation represented a balance between reciprocal changes in diastolic pressure (and volume) and contractility. The enhanced oxygen cost of increased contractility might be masked by a reduction in heart size (reduced wall stress). Ventricular function was reduced below initial control values following the infusion of norepinephrine in 3 lambs. This reduction correlated with a concomitant reduction in MVo 2 and percent extraction but not with a reduction in flow. Lambs that did not show mechanical depression demonstrated no reduction in MVo 2 . These findings suggest a metabolic basis for catechol dependence which might have special importance for the newborn lamb with its incompletely developed catechol enzyme systems.
Novel Therapies Based on Mechanisms of HIV-1 Cell Entry
Authors: J. Michael Kilby, Joseph J. Eron
Journal: New England Journal of Medicine (2003)

Inhibitors of human immunodeficiency virus type 1 (HIV-1) enzymes are central to the treatment of HIV-1 infection, but the development of resistant viruses remains a problem. Another approach is to thwart the entry of the virus into cells by preventing the fusion of the viral envelope with the cell surface. This article reviews the way in which HIV-1 enters cells and potential means of denying the virus admission to cells.
The Man with No Heart
Authors: Ari Mosenkis
Journal: Annals of Internal Medicine (2005)

On Being a Doctor20 December 2005The Man with No HeartAri Mosenkis, MDAri Mosenkis, MDFrom University of Pennsylvania School of Medicine, Philadelphia, PA 19104.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-12-200512200-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As I was en route to the parking lot on a cold autumn night, my pager started beeping. I was a new renal fellow on call, and this was an all-too-familiar, yet still unnerving, occurrence. The number to call back was one I didn't recognize: the OR. When I returned the call, I learned that a heart transplant had failed with disastrous complications. The patient was hypotensive and grossly volume overloaded. The transplant team was requesting intraoperative dialysis.Minutes later, after probing unfamiliar corridors, I arrived at the scene. By perusing the patient's chart, I learned more about him. He ... Author, Article, and Disclosure InformationAffiliations: From University of Pennsylvania School of Medicine, Philadelphia, PA 19104.Corresponding Author: Ari Mosenkis, MD, University of Pennsylvania School of Medicine, 415 Curie Boulevard—700 CRB, Philadelphia, PA 19104; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 December 2005Volume 143, Issue 12Page: 915KeywordsBrainstemCardiopulmonary bypassHeartKidneysLungsMedical dialysisSurgical pathology ePublished: 20 December 2005 Issue Published: 20 December 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Angiotensin converting enzyme inhibitors and cardiovascular remodelling
Authors: D. E Vaughan, M. A Pfeffer
Journal: Cardiovascular Research (1994)

Journal Article Angiotensin converting enzyme inhibitors and cardiovascular remodelling Get access Douglas E Vaughan, Douglas E Vaughan Cardiovascular Division, Brigham and Women's Hospital and West Roxbury VA Medical Center, Harvard Medical School, Boston, Massachusetts, USA: D E Vaughan, M A Pfeffer. Correspondence to Dr Vaughan, at Cardiovascular Division, Vanderbilt University Medical School, 1161 21st Avenue South, Nashville, TN 37232, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc A Pfeffer Marc A Pfeffer Cardiovascular Division, Brigham and Women's Hospital and West Roxbury VA Medical Center, Harvard Medical School, Boston, Massachusetts, USA: D E Vaughan, M A Pfeffer. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 2, February 1994, Pages 159–165, https://doi.org/10.1093/cvr/28.2.159 Published: 01 February 1994 Article history Received: 02 July 1993 Accepted: 28 October 1993 Published: 01 February 1994
The brown fat–enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis
Authors: Guo-Xiao Wang, Xu-Yun Zhao, Zhuo-Xian Meng, Matthias Kern, Arne Dietrich, Zhimin Chen, Zoharit Cozacov, Dequan Zhou, Adewole L Okunade, Xiong Su, Siming Li, Matthias Blüher, Jiandie D Lin
Journal: Nature Medicine (2014)
THE PRESENT STATUS OF VERTIGO CONSIDERED FROM A DIAGNOSTIC STANDPOINT
Authors: GEORGE E. DAVIS
Journal: JAMA (1910)

In the discussion of suppurative labyrinthitis before this section at the Chicago meeting in June, 1908, it was my privilege and good fortune to present the first paper to appear in the medical literature of this country, reporting the recent progress made in the diagnosis and treatment of labyrinthine diseases, as taught in the Vienna schools. Since then the literature on this subject has been added to very materially, notably by Mac-Kenzie<sup>1</sup>of Philadelphia, Fridenberg,<sup>2</sup>and Richards<sup>3</sup>of New York, and Mr. Scott<sup>4</sup>of London, the last contributing some valuable new research data relating to the functions of the semicircular canals.<sup>5</sup> My first contribution was rather a foreword, very briefly outlining the methods of functional tests of the semicircular canal system developed by the researches of Barany, Alexander and Neumann of Vienna. The basis of these tests was founded on the fact that stimulation of
Multiple Subtypes of HER-2/Neu-Positive Metastatic Breast Cancer.
Authors: A. Lipton, K. Leitzel, W. Koestler, E. Fuchs, C. Singer, S. Ali, W. Huang, J. Sperinde, L. Goodman, X. Jin, J. Banerjee, J. Weston, A. Mukherjee, J. Larson, J. Weidler, A. Paquet, S. Williams, J. Winslow, G. Parry, M. Bates
Journal: Cancer Research (2009)

Abstract Background: Using IHC or FISH to select patients for trastuzumab-based therapy, only half of HER2-positive patients show evidence of response. In vitro data implicate HER2:HER3 heterodimers and p95HER2 (p95), the truncated 95-kilodalton C-terminal fragment of HER-2 lacking the trastuzumab binding site, as mediators of resistance to trastuzumab at the receptor level. We have previously reported that central FISH-positive patients with low HER2 protein expression by VeraTag had significantly reduced response to trastuzumab compared to patients who had FISH-positive tumors with high HER2 protein expression (Lipton, SABCS 2008). Adding quantitative measurements of HER3 and p95, we offer evidence for the existence of multiple sub-types of HER2-positive tumors that respond differently to trastuzumab.Methods: Using the VeraTag assay, quantitative protein measurements of HER2, HER3, and p95 were made in FFPE specimens from a cohort of patients with metastatic breast cancer (MBC) and correlated with time to progression (TTP) and overall survival (OS) following treatment with first-line trastuzumab using Kaplan-Meier (KM) and Cox proportional hazards regression analyses.Results: Measurements of HER2 (H2T), HER3 (H3T) and p95 were made in FFPE tumor samples from 95 patients treated with first-line trastuzumab for metastatic breast cancer. Within the group that overexpressed HER2 by the VeraTag Assay (n=60), a group with highly overexpressed HER2 (n=15) had shorter TTP and OS than those that had moderate HER2 overexpression (median TTP 4.6 vs. 12 mos, HR=2.1; p=0.011; median OS 29 vs. 40 mos, HR=2.0; p=0.047). Within the subgroup with moderate H2T overexpression (n=45), bivariate Cox analyses demonstrated that p95 and H3T were independent predictors of TTP (p95 HR=2.1; p=0.031; H3T HR=3.5; p=0.0037). For OS, p95 was significant and H3T showed a strong trend (p95 HR=2.5; p=0.025, H3T HR=2.2; p=0.089). Univariate KM analysis with the p95+ and H3T+ groups combined, gives the results in the table below. These data suggest that HER2-positive breast cancer patients can be classified into at least 4 sub-groups with different outcomes following trastuzumab treatment.Conclusions: These data suggest the existence of multiple subgroups of HER2-positive patients expressing varying HER2, p95, and HER3 levels that experience different clinical outcomes following treatment with trastuzumab. Furthermore, the association of HER3 and p95 overexpression with poor response to trastuzumab in otherwise HER2-positive tumors suggests possible treatment approaches with combinations of targeted therapies. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2030.
Clinical studies of styrene workers: initial findings.
Authors: W V Lorimer, R Lilis, W J Nicholson, H Anderson, A Fischbein, S Daum, W Rom, C Rice, I J Selikoff
Journal: Environmental Health Perspectives (1976)

Styrene monomer is a high volume chemical used chiefly in production of polystyrene. A clinical survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the U.S. Relative exposure durations and levels were obtained from occupational histories. Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP. Other liver function tests, chest x-ray, FVC less than 80 per cent, and hematological parameters showed no distinct pattern. A concomitant mortality study has been mounted and is in progress.
Nephrotic syndrome induced by gold therapy.
Authors: R Wilkinson, D W Eccleston
Journal: BMJ (1970)

BRnsIJUchildhood.The present patient is an adult who never gave any history of previous attacks of pain, and consulted a doctor for the first time at the age of 21 years.It seems almost certain that the abnormal lie of the small intestine was due to the sac enclosing it.This sac prevented it from taking its final definitive position.It is difficult to explain the origin of this sac.The unsolved question is why did this man have symptoms at the age of 21 and not before?With the growth of the patient his intestine also attained the adult size.It is quite possible that the sac did not grow equally fast.If the space inside the sac was inadequate to accommodate intestinal distension after meals, it might account for the colicky pains.I am grateful to Mr. D. Lincoln Lewis, under whose care the patient was admitted, and to Dr. M. R. E. Dean, who confirmed the diagnosis after the barium meal.
History of Cracow School of Medicine
Authors: Leon Tochowicz, Stanley J. G. Nowak
Journal: JAMA (1964)

ONMAY 12, 1364, King Casimir the Great founded Cracow University ("Studium Generale Cracoviense"). Already a score of great universities in Western Europe had been founded, chief among these were Paris (1110), Bologna (1158), Oxford (1167), Montpelier (1181), Cambridge (1209), Padua (1222), Naples (1224), and Valencia ( 1345-50 ). The first universities to appear east of France were Prague ( 1348) and Cracow (1364). Austrian, German, and Scandinavian universities were to come later. During the reign of Casimir III, the last of the Piast Dynasty, Poland had emerged as a world power surrounded by a disintegrating Holy Roman Empire, a strong Bohemia and Hungary, an embattled Muscovy, and a friendly Lithuania. In the West, France and England were in the throes of their Hundred Years War (1338-1453); Flanders and Netherlands were flourishing while Italy divided into City States was the center of world culture with Dante and Petrarch heralding the forthcoming Renaissance. The
Use of a Blood Substitute to Determine Instantaneous Murine Right Ventricular Thickening With Optical Coherence Tomography
Authors: Joseph W. Villard, Marc D. Feldman, Jeehyun Kim, Thomas E. Milner, Gregory L. Freeman
Journal: Circulation (2002)

A satisfactory imaging technique to determine regional wall thickening of the murine myocardium is not available. Although cardiovascular imaging with light offers a novel solution, application is problematic because scattering by erythrocytes causes significant optical attenuation.Optical coherence tomography (OCT) is a technique for detailed resolution imaging of highly scattering biological tissues. To reduce the high level of blood scattering, a method was devised whereby murine blood was replaced with a hemoglobin-based blood substitute. The scattering and absorption properties of in vitro preparations of whole blood and dilutions of blood with a blood substitute were determined with a spectrophotometer and an inverse-adding doubling algorithm. OCT imaging of the same dilutions demonstrated a significant reduction in scattering at a hematocrit <5%. A fiber-optic OCT imaging system was used to image the murine right midventricular free wall before and after isovolumic replacement with blood substitute. Strong light attenuation prevented full thickness imaging before replacement, whereas visualization of the full ventricular thickness was possible after replacement. Baseline and imaging hematocrits were 52.4+/-3.8% and 3.7+/-1.2%, respectively. End-systolic and end-diastolic thickness values were 0.458+/-0.051 mm and 0.352+/-0.047 mm. Percent thickening fraction was 30.8+/- 7.5%.Optical imaging of the intact beating murine right ventricle was substantially improved by isovolumic blood replacement with a hemoglobin-based blood substitute. Although the current study has been directed toward imaging the murine heart, a blood substitute may be applied to various optical diagnostic and therapeutic techniques under investigation in cardiovascular medicine.