tbuckley/cabot-search huggingface dataset:
Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly
Authors: Vasiliki Gkretsi, Udayan Apte, Wendy M. Mars, William C. Bowen, Jian-Hua Luo, Yu Yang, Yan P. Yu, Ann Orr, René St.-Arnaud, Shoukat Dedhar, Klaus H. Kaestner, Chuanyue Wu, George K. Michalopoulos
Journal: Hepatology (2008)

Abstract Hepatocyte differentiation and proliferation are greatly affected by extracellular matrix (ECM). Primary hepatocytes cultured without matrix dedifferentiate over time, but matrix overlay quickly restores differentiation. ECM also is critical in liver regeneration where ECM degradation and reconstitution are steps in the regenerative process. Integrin-linked kinase (ILK) is a cell-ECM-adhesion component implicated in cell–ECM signaling by means of integrins. We investigated the role of ILK in whole liver by using the LoxP/Cre model system. ILK was eliminated from the liver by mating homozygous ILK-floxed animals with mice expressing Cre-recombinase under control of the α fetoprotein enhancer and albumin promoter. After ablation of ILK, animals are born normal. Soon after birth, however, they develop histologic abnormalities characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells, and increased deposition of extracellular matrix. Cell proliferation is accompanied by increased cytoplasmic and nuclear stabilization of β-catenin. After this transient proliferation of all epithelial components, proliferation subsides and final liver to body weight ratio in livers with ILK deficient hepatocytes is two times that of wild type. Microarray analysis of gene expression during the stage of cell proliferation shows up-regulation of integrin and matrix-related genes and a concurrent down-regulation of differentiation-related genes. After the proliferative stage, however, the previous trends are reversed resulting in a super-differentiated phenotype in the ILK-deficient livers. Conclusion: Our results show for the first time in vivo the significance of ILK and hepatic ECM-signaling for regulation of hepatocyte proliferation and differentiation. (Hepatology 2008;48:1932-1941.)
Abstract 3863: Aneuploid human colonic epithelial cells are sensitive to AICAR-induced growth inhibition through EGFR degradation
Authors: Peter Ly, Sang B. Kim, Woodring E. Wright, Angelika Amon, Jerry W. Shay
Journal: Cancer Research (2012)

Abstract Trisomy for chromosome 7 is frequently observed as an initiating event in sporadic colorectal cancer. Although unstable chromosome numbers and recurrent aneuploidies drive a large fraction of human cancers, targeted therapies selective to pre-neoplastic trisomic cells are non-existent. We have previously characterized a trisomy 7 cell line (1CT+7) spontaneously derived from normal diploid human colonic epithelial cells that aberrantly express the epidermal growth factor receptor (EGFR, located on 7p11). Recent studies identified AICAR as a pharmacological inhibitor of aneuploid murine fibroblast proliferation. Here, we report that AICAR induces profound cytostatic and metabolic effects on 1CT+7 cells but not their isogenic diploid counterpart. Dose-response assays demonstrate that 1CT+7 cells are four-fold preferentially sensitive to AICAR compared to diploid cells. Unexpectedly, treatment of 1CT+7 cells with AICAR led to a reversible 3.5-fold reduction (p=0.0025) in EGFR overexpression. AICAR-induced depletion of EGFR protein can be abrogated through inhibition of the proteasome with MG132. AICAR also heavily promoted EGFR ubiquitination in cell-based immunoprecipitation assays, suggesting enhanced degradation of EGFR protein mediated by the proteasome. Moreover, treatment with AICAR reduced EGFR protein levels in a panel of human colorectal cancer cells in vitro and in xenograft tumors in vivo. Our data collectively supports the pharmacological compound AICAR as a novel inhibitor of EGFR protein abundance and as a potential therapeutic agent for aneuploidy-driven colorectal cancer. 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 3863. doi:1538-7445.AM2012-3863
Illustrations with Articles.
Authors: C. M. Tinsman
Journal: JAMA (1900)

Adin, Cal., March 7, 1901.  To the Editor:  —Can not the contributors toThe Journalbe induced to include drawings in their articles, as Dr. Stricker has with his article in the March 2 number? The articles now being published on middle ear diseases would be of unstated benefit to hundreds of young physicians who do not and can not get to see clinics of that nature. If they were accompanied by illustrations showing the anatomical parts and the different steps in the operative work of those who frequently meet and deal with them successfully, we would be far better prepared to deal with those unfortunate ones who fall into our hands as general practitioners.  Our knowledge is very limited at best, on the study of medicine and surgery, and the only way a great many of us have to learn it is by reading, being so situated that we
HBsAg-Serum Protein Complexes Stimulate Immune T Lymphocytes More Efficiently Than Do Pure HBsAg
Authors: Esteban Celis, Tse Wen Chang
Journal: Hepatology (1984)

HBsAg from plasma of chronic hepatitis B carriers was purified by affinity chromatography using a mouse monoclonal antibody specific for HBsAg. Elution with buffer at two different pH values separated HBsAg into two fractions: one contained high amounts of immune complexes associated with HBsAg; the other contained larger quantities of the HBsAg polypeptides P24 and GP27 and only small amounts of immunoglobulin. When compared for effects on stimulating the proliferative response of freshly isolated lymphocytes and an HBsAg-specific T cell clone, the HBsAg fraction containing a high proportion of immunoglobulin was much more potent than HBsAg with low amounts of immunoglobulins or pure HBsAg, which was isolated from the culture supernatant of the human hepatoma cell line (PLC/PRF/5). The plasma-derived HBsAg with low amounts of complexed immunoglobulins became more immunogenic in the presence of an anti-HBsAg monoclonal IgG. The present results, combined with earlier findings, suggest that HBsAg associated with immune complexes is a more potent stimulator of T cells than purer HBsAg preparations due to an increase in the efficiency of monocytes to capture the antigen through binding to immune complexes for subsequent processing and presentation of the antigen. These observations could be of relevance for the preparation of effective hepatitis B vaccines from recombinant DNA and peptide synthesis technologies.
Endemic Goiter and Endemic Cretinism in the Andean Region
Authors: Rodrigo Fierro-Benítez, Wilson Penafiel, Leslie J. De Groot, Ignacio Ramirez
Journal: New England Journal of Medicine (1969)

Analysis of iodide deficiency, thyroid function, altitude, neural and motor dysfunction and a variety of social and economic variables to ascertain the prevalence of endemic goiter in eight rural Andean villages showed that as many as 54 per cent of the population in certain villages had goiter, and neural and motor abnormalities characteristic of cretinism were present in up to 10 per cent of the population. All villages with goiter had severe iodine deficiency. Intercurrent unidentified socioeconomic and biologic factors in the community may have modified the severity of the endemic. High altitude seemed to depress goiter formation. With increasing severity of the endemic, there was a rising prevalence of nodular goiter, and an increase in goiter in children, in goiter in men as compared to women and in the average size of the glands. Endemic cretinism, deaf-mutism and motor abnormalities were highly correlated with the severest intensity of endemic goiter. The cretins studied did not appear to be hypothyroid.
Repair of O6-(2-chloroethyl)guanine mediates the biological effects of chloroethylnitrosoureas.
Authors: W J Bodell, T Aida, M S Berger, M L Rosenblum
Journal: Environmental Health Perspectives (1985)

Chloroethylnitrosoureas (CENUs) are alkylating and crosslinking agents used for the treatment of human cancer; they are both mutagenic and carcinogenic. We compared the levels of induction of sister chromatid exchanges (SCEs) and the cytotoxicity of nitrosoureas that alkylate only with CENUs. CENUs are 200-fold more cytotoxic and induce SCEs with 45-fold greater efficiency than agents that do not crosslink; therefore, crosslinking is probably the most important molecular event that leads to cell death and induction of SCEs. The biological and biochemical properties of both human and rat brain tumor cells that are sensitive or resistant to the cytotoxic effects of CENUs have been investigated. CENUs induce SCEs in both sensitive and resistant cells, but to induce similar levels of SCEs, resistant cells must be treated with a 5- to 14-fold higher concentration of CENUs than are used to treat sensitive cells. Resistant cells have a higher cellular level of O6-methylguanine-DNA methyl transferase, increased repair of O6-methylguanine, and 50% fewer DNA interstrand crosslinks formed than do sensitive cells treated with the same concentration of CENU. Based on these findings, we propose that cellular resistance to the cytotoxic effects of CENUs is mediated by O6-methylguanine-DNA methyltransferase and that DNA repair may also modify the mutagenic and carcinogenic properties of CENUs.
Delivery Pressure at the Catheter Tip in Selective Angiocardiography
Authors: Thomas P. K. Lim
Journal: JAMA (1967)

The delivery pressure at the catheter tip during angiography was studied by means of a miniature pressure transducer at the tip and side openings of cardiac catheters over a wide range of machine pressures (100 to 800 pounds per square inch [psi]). It is composed of a peak pressure and a plateau pressure. The peak pressure has a short duration (usually less than 0.2 seconds) but often exceeds 500 mm Hg even under a low machine pressure of 100 psi. The plateau pressure has a longer duration, lasting for two seconds or more when 60 ml of contrast substance are used. Under a high machine pressure of 500 psi or more, the plateau pressure reaches a level of 500 mm Hg. Both peak and plateau pressures fall exponentially with increased distance from catheter openings, and the flow of the surrounding fluids has no appreciable effect in the dissipation of the high velocity jet.
PSYCHIATRY IN ASIA AND THE MIDDLE EAST
Authors: HENRY P. LAUGHLIN
Journal: American Journal of Psychiatry (1958)

Perhaps the outstanding single impression has been the increasingly important contribution which American medicine and psychiatry are making in many countries. This role will certainly tend to increase, if for no other reason than because of the large proportion of foreign graduates currently in our residency training programs (2). In few of the countries visited could my welcome have been more cordial or greater interest displayed in what I could report to our overseas colleagues about American psychiatry.
Influence of Brief Vagal and Stellate Nerve Stimulation on Pacemaker Activity and Conduction within the Atrioventricular Conduction System of the Dog
Authors: JOSEPH F. SPEAR, E. NEIL MOORE
Journal: Circulation Research (1973)

Experiments were performed on open-chest anesthetized dogs to determine the quantitative effects of autonomic nerve stimulation on pacemaker activity and conduction. The lead II electrocardiogram together with bipolar electrograms were recorded from the atria, the His bundles, and the ventricles. The vagi or the stellate ganglia were stimulated in dogs which exhibited either sinus rhythm, ectopic atrial rhythm, junctional rhythm, or ectopic ventricular rhythm. The time courses of the change in heart rate in response to vagal or stellate stimulation were characteristic for each type of rhythm. The characteristic responses of different cardiac pacemaker sites to autonomic influence were demonstrated to be important factors in the production of wandering pacemakers and in the emergence of ectopic beats. Sinus pacemaker activity was more sensitive to modification by autonomic stimulation than was atrioventricular (AV) conduction. However, subliminal autonomic effects on AV transmission were brought out during conduction of premature atrial beats, thereby demonstrating a coupling interval dependency of autonomic influences on AV conduction. The present experiments also showed how fluctuations in autonomic activity could result in Mobitz type II second-degree heart block, pseudosupernormal conduction, and the concertina effect observed in the preexcitation syndrome.
Effect of Weight Loss and Triiodothyronine on Plasma Growth Hormone and Insulin in Obesity.
Authors: G. A. Bray
Journal: Annals of Internal Medicine (1969)

s1 May 1969Effect of Weight Loss and Triiodothyronine on Plasma Growth Hormone and Insulin in Obesity.G. A. Bray, M.D., J. Londono, M.D., T. F. Gallagher Jr., M.D.G. A. Bray, M.D.Search for more papers by this author, J. Londono, M.D.Search for more papers by this author, T. F. Gallagher Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1100_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwenty-three obese patients (19 females) had a reduced response to stimuli that usually increase growth hormone. They were studied before and after diethylstilbestrol, weight loss, or triidothyronine, or a combination. Diethylstilbestrol, 5 mg twice a day for 2 days, in four women did not alter their initial, flat growth, hormone response to intravenous arginine. After weight loss ranging from 6 to 60 kg, fasting plasma insulin decreased by an average of 6 µunits/ml, and the postinsulin rise in growth hormone was increased. This increase was directly proportional to the absolute weight loss. Weight loss also augmented the rise in growth... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByFettsucht und Diabetes mellitusLiteratur 1 May 1969Volume 70, Issue 5Page: 1100-1100KeywordsArginineBlood plasmaGrowth hormoneInsulinObesityOverweightTriiodothyronineWeight loss Issue Published: 1 May 1969 PDF DownloadLoading ...
Disseminated intravascular coagulation in cirrhosis
Authors: Justine Meehan Carr
Journal: Hepatology (1989)

Hemorrhagic sequelae of liver disease were recognized and described over a century ago (1). Bleeding has been a common complication and a leading cause of death in patients with cirrhosis (2, 3). The coincidence of low clotting factor levels, hypofibrinogenemia and thrombo-cytopenia has prompted many investigators to ask whether disseminated intravascular coagulation (DIC) plays a role in the pathogenesis of hemorrhage in these patients (4-16). Despite an abundance of published investigations addressing this question, however, establishing the diagnosis of DIC in an individual patient with cirrhosis continues to pose a challenge for the clinician. In an attempt to reconcile the theoretical and the practical, the present review of the role of DIC in cirrhosis will address: (i) normal coagulation and the role of the liver; (ii) coagulation defects identified in DIC and in cirrhosis; (iii) role of DIC in cirrhosis, and (iv) new approaches to this question from the research, as well as from clinical, laboratories. Although some of the new techniques are still being evaluated, preliminary results appear promising in facilitating identification of DIC patients with cirrhosis.
Animal innovation defined and operationalized
Authors: Grant Ramsey, Meredith L. Bastian, Carel van Schaik
Journal: Behavioral and Brain Sciences (2007)

Innovation is a key component of most definitions of culture and intelligence. Additionally, innovations may affect a species' ecology and evolution. Nonetheless, conceptual and empirical work on innovation has only recently begun. In particular, largely because the existing operational definition (first occurrence in a population) requires long-term studies of populations, there has been no systematic study of innovation in wild animals. To facilitate such study, we have produced a new definition of innovation: Innovation is the process that generates in an individual a novel learned behavior that is not simply a consequence of social learning or environmental induction. Using this definition, we propose a new operational approach for distinguishing innovations in the field. The operational criteria employ information from the following sources: (1) the behavior's geographic and local prevalence and individual frequency; (2) properties of the behavior, such as the social role of the behavior, the context in which the behavior is exhibited, and its similarity to other behaviors; (3) changes in the occurrence of the behavior over time; and (4) knowledge of spontaneous or experimentally induced behavior in captivity. These criteria do not require long-term studies at a single site, but information from multiple populations of a species will generally be needed. These criteria are systematized into a dichotomous key that can be used to assess whether a behavior observed in the field is likely to be an innovation.
HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up
Authors: Chia‐Ming Chu, Yun‐Fan Liaw
Journal: Hepatology (2007)

Spontaneous hepatitis B surface antigen (HBsAg) seroclearance in chronic HBV infection has long been suggested as a rare event in high endemic areas. The prevalence of HBsAg in the general population of Taiwan, however, decreased remarkably from 15%-20% before age 40 to 5%-10% after age 60 or 70. This study aimed to reexamine the rates of HBsAg seroclearance by a long-term follow-up of 1965 hepatitis B e antibody–positive asymptomatic adult carriers. Of these, 1076 (55%) were males, the mean (± SD) age was 35.6 ± 9.2 years and the mean follow-up was 10.8 ± 5.4 years. Hepatitis relapsed in 314 patients, 0.5 to 18 (mean ± SD = 5.8 ± 4.4) years after the entry. The probability of hepatitis relapse correlated positively with male sex (P < 0.0001) and age at entry (P < 0.0001). Serum HBsAg cleared in 245 patients at the mean age of 47.8 ± 9.6 years. The cumulative probabilities of HBsAg seroclearance were 8.1% after 10 years, but increased disproportionally to 24.9% and 44.7%, respectively, after 20 and 25 years. In multivariate analysis, the probability of HBsAg seroclearance correlated positively with age at entry (P < 0.0001) and sustained remission of hepatitis (P < 0.0001) and marginally significantly with male sex (P = 0.053). Conclusion: Cumulative rate of HBsAg seroclearance in asymptomatic adult carriers from high endemic areas was approximately 40% after 25 years of follow-up. The low HBsAg seroclearance rates in previous studies might be due to the relative short period of follow-up. (HEPATOLOGY 2007;45:1187–1192.)
Immune Restoration With Antiretroviral Therapies
Authors: Michael M. Lederman, Hernan Valdez
Journal: JAMA (2000)

Recent dramatic decreases in acquired immunodeficiency syndrome–related mortality are largely due to the introduction of highly active antiretroviral therapy (HAART). Although immune restoration due to suppression of human immunodeficiency virus (HIV) replication is a critical determinant of these trends, the magnitude of immune restoration seen after treatment with HAART varies substantially among treated persons and is generally incomplete. Nonetheless, even partial immune restoration is sufficient to provide protection from most major opportunistic infections; these risks can be largely predicted by the number of circulating CD4 cells. Limited data suggest that treatment earlier during the course of HIV infection may result in greater preservation of immune function, though this has not been studied in great detail. Preliminary studies performed among persons with multidrug-resistant virus whose treatment regimens are failing suggest that there is likely a benefit to continuation of therapy that may be related to diminished pathogenicity of drug-resistant virus. As deaths related to opportunistic infections diminish, the spectrum of causes of mortality in HIV infection is changing. Except for Kaposi sarcoma, there is insufficient information to conclude that the risks of non-Hodgkin lymphoma and other malignancies are diminishing among persons with HIV infection. How much immune restoration will be enough to ensure long-term survival in persons with HIV infection remains an open question.
Prevalence and Awareness of Sickle Cell Hemoglobin in a Military Population
Authors: Richard A. Binder
Journal: JAMA (1970)

On a prospective study, 1,000 Negro military recruits were screened with a new rapid differential solubility test for sickle cell hemoglobin. A total of 75 had positive screening tests: 73 had sickle cell trait, 1 had sickle cell-hemoglobin C disease, and 1 had sickle-thalassemia disease. There were no false-positive or false-negatives detected. In only five of the 150 individuals questioned was there any awareness of sickle cell states. This test is rapid and reliable and routine screening of the Negro population accompanied by education and genetic counseling is recommended.
TCT-56 Correlation Between Residual Platelet Reactivity After Clopidogrel Loading And Long Term Major Adverse Outcome Among STEMI Patients Undergoing Delayed Primary Percutaneous Coronary Intervention
Authors: Manolis Vavuranakis, Konstantinos Kalogeras, NIKOLAOS DAGRES, Maria Kariori, Maria Lavda, Carmen Moldovan, Evangelia Bei, Dimitrios A. Vrachatis, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2014)
Fat Consumption and HbA1c Levels
Authors: Anne-Helen Harding, Lincoln A. Sargeant, Ailsa Welch, Suzy Oakes, Robert N. Luben, Sheila Bingham, Nicholas E. Day, Kay-Tee Khaw, Nicholas J. Wareham
Journal: Diabetes Care (2001)

OBJECTIVE—To describe the relationship between total dietary fat and the pattern of fat intake and HbA1c. RESEARCH DESIGN AND METHODS—In this cross-sectional study, 2,759 men and 3,464 women (40–78 years of age) without a previous diagnosis of type 2 diabetes were recruited from a population-based sampling frame. Diet was assessed using a self-reported semiquantitative food frequency questionnaire. RESULTS—The HbA1c level was negatively associated with the polyunsaturated fat–to–saturated fat ratio (P:S ratio) of the diet (β = −0.0338 HbA1c% per SD change in P:S ratio; P &amp;lt; 0.001) and positively associated with the total level of fat intake (β = 0.0620 HbA1c% per SD change in total fat intake; P &amp;lt; 0.001), adjusted for age and total energy intake. The associations remained significant when adjusted for each other and for total energy, protein, age, sex, family history of diabetes, BMI, waist-to-hip ratio, physical activity, and smoking (for P:S ratio, β = −0.0200 HbA1c% per SD change in P:S ratio, P = 0.013; for total fat, β = 0.420% HbA1c% per SD change in total fat intake, P &amp;lt; 0.001). The benefits from a high P:S ratio were attributed to a lower saturated fat intake. CONCLUSIONS—These findings demonstrate independent associations between HbA1c concentration across the normal range of HbA1c and both total fat intake and the pattern of dietary fat intake. They provide further support to efforts promoting modifications in the intake of dietary fat.