tbuckley/cabot-search huggingface dataset:
Use of Metabolic Markers To Identify Overweight Individuals Who Are Insulin Resistant
Authors: Tracey McLaughlin, Fahim Abbasi, Karen Cheal, James Chu, Cindy Lamendola, Gerald Reaven
Journal: Annals of Internal Medicine (2003)

Background: Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful. Objective: To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant. Design: Cross-sectional study. Setting: General clinical research center. Patients: 258 nondiabetic, overweight volunteers. Measurements: Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power. Results: Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceridehigh-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specifity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%). Conclusions: Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceridehigh-density lipoprotein cholesterol concentration ratio.
Wider Inclusion Criteria Needed for Thrombolytic Therapy
Authors: Richard Peto
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 September 1989Wider Inclusion Criteria Needed for Thrombolytic TherapyRichard Peto, MA, MSc, Rory Collins, MBBS, Peter Sleight, MD, DMRichard Peto, MA, MSc, Rory Collins, MBBS, Peter Sleight, MD, DMAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-6-540_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:The article by Lee and colleagues (1) and the accompanying editorial by Tate and Dehmer (2) on the smallness of the proportion of patients "eligible" for thrombolytic therapy makes it clear that in deciding who should be offered thrombolytics many U.S. physicians may simply adopt the restrictive eligibility criteria of those trials (3-5) that excluded older patients, treated only those presenting within a few hours of symptom onset, and required "definite" electrocardiographic (ECG) evidence of infarction. Such "restrictive-entry" trials cannot, however, provide direct evidence as to whether their restrictions were appropriate—that is, they obviously cannot assess directly...References1. LeeWeisbergBrandRouanGoldman TMDGL. Candidates for thrombolysis among emergency room patients with acute chest pain. Ann Intern Med. 1989;110:957-62. LinkGoogle Scholar2. TateDehmer DG. New challenges for thrombolytic therapy. Ann Intern Med. 1989;110:953-5. LinkGoogle Scholar3. TopolCaliffKereiakesGeorge ERDB. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trial. J Am Coll Cardiol. 1987;10:65B-74B. CrossrefMedlineGoogle Scholar4. PassamaniHodgesHerman EMM. The Thrombolysis in Myocardial Infarction (TIMI) phase II pilot study: tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1987;10:51B-64B. CrossrefMedlineGoogle Scholar5. KennedyMartinDavis JGK. The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial. Circulation. 1988;77:345-52. CrossrefMedlineGoogle Scholar6. . Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2:349-60. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: ISIS Trial Office Radcliffe Infirmary Oxford United Kingdom PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEligibility for intravenous thrombolysis in suspected acute myocardial infarction.Optimizing thrombolytic therapy of acute myocardial infarction. 15 September 1989Volume 111, Issue 6Page: 540-540KeywordsElectrocardiographyInfarction Issue Published: 15 September 1989 PDF DownloadLoading ...
Chronicity and a low anteroposterior gradient of cerebral blood flow in schizophrenia
Authors: R J Mathew, W H Wilson
Journal: American Journal of Psychiatry (1990)

Regional cerebral blood flow (CBF) was measured with the 133xenon inhalation technique in 27 patients with schizophrenia of less than 5 years' duration and in 27 patients with schizophrenia of more than 12 years' duration, under resting conditions. Similar measurements were also performed in 54 normal control subjects matched for age and sex. Patients with schizophrenia of long duration had lower anteroposterior gradients of CBF than patients with schizophrenia of short duration and matched control subjects. Covarying out age and end-tidal levels of CO2 did not alter the results.
Sunlight and the Skin
Authors: Isaac Willis
Journal: JAMA (1971)

To avoid the sun would be to exist without one of the great pleasures of life. But, as with most enjoyable things, indiscriminate exposure can result in unhappiness and even serious illnesses.  The undesirable results of  indiscretions have been recognized from the earliest times. Scientific and medical investigations of the subject have evolved into a field known as clinical dermatologic photobiology, pioneered in the United States around the 1930's by such investigators as Blum, Epstein, Sulzberger, Stokes, and Rothman.  Through the use of modern solar simulating lamps, ultraviolet (UV) light filters, and monochromators in improved diagnostic test procedures, recent investigators have accomplished much toward a better understanding of the pathogenesis of sunlight-induced skin disorders. 1 This new knowledge has permitted increasingly better approaches to the treatment and prevention of these disorders.  The purpose of this communication is to describe the most common types of sunlight-induced skin disorders, with special
The Sensitivity of Fish ATPases to Polychlorinated Biphenyls
Authors: L. K. Cutkomp, H. H. Yap, D. Desaiah, R. B. Koch
Journal: Environmental Health Perspectives (1972)

In spite of widespread concern about the pos- sible hazards of polychlorinated biphenyls (PCBs), little is known about the action of these materials.We have therefore examined the in vitro (1, 2) and in vivo (3) effects of PCBs on the adenosine triphosphatase (ATPase) enzyme system.We have found some effects which are similar, yet distinctive, to chemically related compounds of the DDT type.A background of earlier research with DDT and closely related chemicals has shown the greatest inhibition on Mg2+ATPase and less on Na+-K+ATPase (4-7).Subsequent research showed that mitochondrial Mg2+ATPase of fish and insects was most sensitive to DDT (8).The results from testing several PCBs on the ATPase enzyme system are presented in this manuscript.
Turnover of plasma cholesterol in man
Authors: DeWitt S. Goodman, Robert P. Noble
Journal: Journal of Clinical Investigation (1968)

Cholesterol-4-14C was injected intravenously into a series of normal men, untreated hyperlipidemic patients, and hyperlipidemic patients being treated with cholestyramine. The specific radioactivity of plasma total cholesterol was measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects. Analysis of the turnover curves of plasma cholesterol revealed that in every study the turnover of plasma cholesterol conformed to a two-pool model. Each turnover curve was analyzed in terms of this model, as expressed by the equation: specific activity = CAe-αt + CBe-βt. The parameters which were calculated included the constants CA, CB, α, and β; the size of the first pool (MA); the rate constants for the total rate of removal of cholesterol from each pool (kAA and kBB); and the production rate in pool A (PRA). In two normal men and five untreated patients the average size of pool A was 25g.
Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis
Authors: S. Huber, C.J. Bruns, G. Schmid, P.C. Hermann, C. Conrad, H. Niess, R. Huss, C. Graeb, K.-W. Jauch, C. Heeschen, M. Guba
Journal: Kidney International (2007)
Nephropathy Associated with the Oral Administration of Zoxazolamine (Flexin)
Authors: Theodore Cohen
Journal: New England Journal of Medicine (1957)

ZOXAZOLAMINE (Flexin) is a relatively new skeletal-muscle relaxant that is potent and has a long duration of action, a wide margin of safety and no cumulative effects.1 Amols2 believes its site of action to be in the central nervous system, where it depresses the polysynaptic pathways and is assumed to have little, if any, effect on monosynaptic reflex arcs, motor nerves, the myoneural junction or muscle itself.Because of its spasmolytic properties, the drug will undoubtedly come into widespread use in many neurologic and musculoskeletal disorders. Smith et al.3 reported 85 per cent effectiveness in rheumatic diseases, and Rodriguez-Gomez, Valdes-Rodriguez . . .
Treatment of acute promyelocytic leukemia with all‐trans retinoic acid: Successful control of hyperleukocytosis and leukostasis syndrome with leukaphereses and hydroxyurea
Authors: Wen‐Li Hwang, Jyh‐Ping Gau, Min‐Chun Chen, Ji‐Hsiung Young
Journal: American Journal of Hematology (1993)
Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats
Authors: A. Mieke Jonker, Freke W. J. Dijkhuis, Adriana Boes, Machiel J. Hardonk, Joris Grond
Journal: Hepatology (1992)

A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury. (Hepatology 1992;15:423–431).
Bilirubin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats
Authors: HOU-DONG WANG, MUTSUO YAMAYA, SHOJI OKINAGA, YU-XIA JIA, MASAHITO KAMANAKA, HIDENORI TAKAHASHI, LI-YA GUO, TAKASHI OHRUI, HIDETADA SASAKI
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Many possible treatments for pulmonary fibrosis have been investigated, but except for some current clinical trials, none have succeeded in clinical trials. On the basis of the antioxidant action of bilirubin (BIL), we examined the effects of hyperbilirubinemia on the development of bleomycin (BLM)-induced pulmonary fibrosis in rats. The animals' plasma BIL level was kept within 3 and 10 mg/dl by repeated intravenous infusion of a high dose of BIL. We studied the inhibitory effects of hyperbilirubinemia on BLM-induced pulmonary fibrosis through histopathologic and biochemical analyses. Mortality of rats with BLM-induced pulmonary fibrosis was significantly lower in the three groups with hyperbilirubinemia. The ameliorating effect of hyperbilirubinemia on pulmonary fibrosis was shown by lung histology, as well as by a decreased lung content of hydroxyproline and reduced bronchoalveolar lavage fluid (BALF) concentration of transforming growth factor (TGF)-beta(1). The number of polymorphonuclear leukocytes and lymphocytes in BALF was also decreased in the groups with hyperbilirubinemia. Furthermore, oxidative metabolites of BIL in urine were present at significantly higher levels in BLM-treated rats with hyperbilirubinemia than in those without hyperbilirubinemia. These data suggest that the antioxidative action of BIL can attenuate BLM-induced pulmonary fibrosis, partly by inhibiting lung inflammation and production of TGF-beta1.
TARGETED DELIVERY OF VASCULAR ENDOTHELIAL GROWTH FACTOR FAVORABLY ALTERS CARDIAC REMODELING AND FUNCTION AFTER A LARGE MYOCARDIAL INFARCTION
Authors: Jenna M. Rosano, Zhanna Ivanov, Robert C. Scott, Bin Wang, Parkson Lee-Gau Chong, Mohammad Kiani, Deborah Crabbe
Journal: Journal of the American College of Cardiology (2010)
Pericapillary fibrin and venous ulceration
Authors: Graham D. Reilly, Margaret L. Wood
Journal: British Journal of Dermatology (1983)

Journal Article Pericapillary fibrin and venous ulceration Get access Graham D. Reilly, Graham D. Reilly Rupert Hallam Department of Dermatology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF Search for other works by this author on: Oxford Academic Google Scholar Margaret L. Wood Margaret L. Wood Rupert Hallam Department of Dermatology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue 6, 1 December 1983, Page 724, https://doi.org/10.1111/j.1365-2133.1983.tb00561.x Published: 01 December 1983
Isolation and characterization of expression cDNA clones encoding antigens of Onchocerca volvulus infective larvae.
Authors: T R Unnasch, M Y Gallin, P T Soboslay, K D Erttmann, B M Greene
Journal: Journal of Clinical Investigation (1988)

The isolation of recombinant cDNA clones expressing antigens found in Onchocerca volvulus infective larvae is described. To isolate such clones, an expression cDNA library constructed from adult O. volvulus RNA was screened with antiserum raised against infective larvae. One clone, designated lambda RAL-1 was characterized further. The recombinant antigen produced by lambda RAL-1 stimulates proliferation of peripheral blood mononuclear cells from O. volvulus infected humans. Lambda RAL-1 is derived from a 1450 bases message that encodes a protein with an apparent molecular weight of 42,000 in adult O. volvulus. The inserted DNA of lambda RAL-1 contains an open reading frame of 1008 bp. The amino acid sequence predicted by this open reading frame contains three repeats of the sequence KKPEDWD. The identification of clones such as lambda RAL-1 will provide quantities of purified antigens sufficient to begin to study the immune response to and explore the development of immunity against the infectious form of the parasite.
435. A Fiber-Modified, Relaxin-Expressing Oncolytic Adenovirus Prolongs Survival of Tumor Bearing Mice
Authors: Shanthi Ganesh, Melinda VanRoey, Neeraja Idamakanti, Karin Jooss
Journal: Molecular Therapy (2006)

The inefficiency of adenoviral spread through tumor tissue may be one of the major obstacles in the development of a successful oncolytic adenovirus therapy. Recent evidence has shown that connective tissue and extracellular matrix may play a prominent role in inhibiting viral spread following injection of oncolytic viruses directly into the tumor. To improve viral cell entry, distribution and penetration within the tumor, a relaxin (RLX)-expressing, replication- competent, fiber-chimeric adenovirus has been constructed (OV1209) and compared with its corresponding non-relaxin-expressing chimeric control virus (OV1194). In these oncolytic viruses, E1A expression is controlled by the tumor-specific promoter E2F-1 to limit viral replication to tumor cells with Rb pathway defects. In addition, an inert secreted transgene was inserted into the 19K gene of the E3 region. With the goal to improve infectivity, the fiber knobs of the vectors were replaced with the Ad35 knob. Significantly better efficacy and survival was demonstrated in four xenograft models with OV1194 when compared to its parental control virus containing the Ad5 fiber. To further improve the spread within the tumor, the E3 region gene encoding 14.7K was replaced with the human Relaxin-1 coding sequence, which is known to decrease the collagen bundle density present in ligaments.
Abstract 1518: Multiple myeloma cells cross talk with bone marrow stroma lead to induction of DKK1 expression and produce bortezomib resistance
Authors: Jiyeon Ryu, Woo-june Jung, Chansu Lee, Soyoung Park, Juwon Park, Eunkyung Bae, Kwang-Sung Ahn, Sung-Soo Yoon
Journal: Cancer Research (2012)

Abstract The importance of the micro-environment in tumor progression is now well established. Dynamic interaction between multiple myeloma (MM) cells and bone marrow stromal cells (BMSCs) plays critical role in the progression of MM including drug response and bone erosion. Firstly, we found that DKK1 expression was statistically increased in MM cells (MOLP8, KMS12BM, KMS12PE, NCIH929, LP1, MOLP2, EJM, U266, RPMI8226, and 536MM, respectively) co-cultured with BMSCs obtained from MM patients when compared to MM cells alone (p&amp;lt;0.05). Also, MM cells co-cultured with BMSCs were significantly more resistant against 25 nM bortezomib than MM cells alone (p&amp;lt;0.05). We, therefore, established a bortezomib-resistant cell line using U266 cells (U266/velR), and explored the characteristics of U266/velR cells. Cytotoxic effect of bortezomib in U266/velR was 1.5 folds lower than U266 cells, and the cross-resistance against thalidomide was observed. DKK1 expression in U266/velR was higher than that in parental cells. We found that elevated levels of p-p65 were detected in U266/velR, and the degree of p65 and I-κB expression levels reduced by bortezomib was different between U266/velR and U266. Elevated levels of p-p65/p65 were effectively suppressed by treating with NF-κB activator inhibitor (6-aminoquinazoline). Also, combined treatment of bortezomib and 6-aminoquinazoline reduced the expression of DKK1 in co-culture of U266 cells and BMSCs. The expression of HGF in CD138− fractions of MM bone marrow cells was higher than that in its CD138+ fractions. Whereas, IL-6 and OPN in CD138+ fraction of MM bone marrow cells was higher compared to its CD138− fractions. In co-culture of U266 and BMSCs, IL-6, OPN and HGF was dramatically increased compared to U266 alone and BMSC alone (p&amp;lt;0.01; p&amp;lt;0.05). Taken together, cytokines and growth factor regulated by dynamic interplay between MM cells and BMSCs contributes the bortezomib response and bone erosion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1518. doi:1538-7445.AM2012-1518
Characterization of the paracrine effects of human skeletal myoblasts transplanted in infarcted myocardium
Authors: Maitane Perez‐Ilzarbe, Onnik Agbulut, Beatriz Pelacho, Cristina Ciorba, Edurne San Jose‐Eneriz, Michel Desnos, Albert A. Hagège, Pablo Aranda, Enrique J. Andreu, Philippe Menasché, Felipe Prósper
Journal: European Journal of Heart Failure (2008)
Electrophysiological Modulation of Cardiomyocytic Tissue by Transfected Fibroblasts Expressing Potassium Channels
Authors: Yair Feld, Meira Melamed-Frank, Izhak Kehat, Dror Tal, Shimon Marom, Lior Gepstein
Journal: Circulation (2002)

Background — Traditional pharmacological therapies aiming to modify the abnormal electrophysiological substrate underlying cardiac arrhythmias may be limited by their relatively low efficacy, global cardiac activity, and significant proarrhythmic effects. We suggest a new approach, in which transfected cellular grafts expressing various ionic channels may be used to manipulate the local electrophysiological properties of cardiac tissue. To examine the feasibility of this concept, we tested the hypothesis that transfected fibroblasts expressing the voltage-sensitive potassium channel Kv1.3 can modify the electrophysiological properties of cardiomyocytic cultures. Methods and Results — A high-resolution multielectrode mapping technique was used to assess the electrophysiological and structural properties of primary cultures of neonatal rat ventricular myocytes. The transfected fibroblasts, added to the cardiomyocytic cultures, caused a significant effect on the conduction properties of the hybrid cultures. These changes were manifested by significant reduction in extracellular signal amplitude and by the appearance of multiple local conduction blocks. The location of all conduction blocks correlated with the spatial distribution of the transfected fibroblasts assessed by vital staining. All electrophysiological changes were reversed after the application of Charybdotoxin, a specific Kv1.3 blocker. In contrast, conduction remained uniform in the control hybrid cultures when nontransfected fibroblasts were used. Conclusions — Transfected fibroblasts are able to electrically couple with cardiac myocytes, causing a significant local and reversible modification of the tissue’s electrophysiological properties. More broadly, this study suggests that transfected cellular grafts expressing various ionic channels may be used to modify cardiac excitability, providing a possible future novel cell therapy strategy.
Platelet-endothelial cell adhesion molecule-1 (PECAM-1)–deficient mice demonstrate a transient and cytokine-specific role for PECAM-1 in leukocyte migration through the perivascular basement membrane
Authors: Richard D. Thompson, Karen E. Noble, Karen Y. Larbi, Ann Dewar, Gordon S. Duncan, Tak W. Mak, Sussan Nourshargh
Journal: Blood (2001)