tbuckley/cabot-search huggingface dataset:
A Prospective Trial of Colchicine for Primary Biliary Cirrhosis
Authors: Marshall M. Kaplan, David W. Alling, Hyman J. Zimmerman, Hubert J. Wolfe, Robert A. Sepersky, Gary S. Hirsch, Grace H. Elta, Kenneth A. Glick, Kathleen A. Eagen
Journal: New England Journal of Medicine (1986)

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.
Nitric oxide-mediated cytoprotection of hepatocytes from glucose deprivation-induced cytotoxicity: Involvement of heme oxygenase-1
Authors: Byung-Min Choi, Hyun-ock Pae, Young-Myeong Kim, Hun-Taeg Chung
Journal: Hepatology (2003)

Heme oxygenase–1 (HO–1) is the rate–limiting enzyme in heme catabolism, which leads to the generation of carbon monoxide (CO), biliverdin, and free iron. One of 3 mammalian HO isoforms, HO–1, is a stress–responsive protein and known to modulate such cellular functions as cytokine production, cell proliferation, and apoptosis to protect organs and tissues from acute injury. Although nitric oxide (NO)–mediated cytoprotective effects against cytotoxicity induced by glucose deprivation have been well recognized, the underlying mechanisms remain to be elucidated. Thus, we investigate the involvement of HO–1 in the cytoprotective effects of NO. Deprivation of glucose markedly reduced the viability of BNL CL.2 cells and primary rat hepatocytes. Pretreatment with NO donor, sodium nitroprusside (SNP), protected hepatocytes from glucose deprivation–induced cytotoxicity; zinc protoporphyrin (ZnPP) IX, an inhibitor of HO, was found to block the SNP–induced cytoprotection. SNP increased the induction of HO–1 protein as well as its activity in hepatocytes. A cytoprotective effect comparable to SNP was observed when the cells were transfected with HO–1 gene or preincubated with another HO–1 inducer, hemin. Additional experiments revealed the involvement of CO in the cytoprotective effect of SNP/HO–1 in BNL CL.2 cells. CO mediated cytoprotective effect through suppression of ERK MAPK activation. In conclusion, our results show that SNP protects hepatocytes from glucose deprivation–induced cytotoxicity through up–regulation of HO–1. Thus, HO–1 might be an important cellular target of NO donor with clinical implications for the prevention of acute liver injury in several pathological conditions.
PARAFFINOMA OF THE VAS DEFERENS: AN UNUSUAL COMPLICATION OF INGUINAL HERNIA
Authors: Leigh F. Watson
Journal: JAMA (1924)

This case is reported to call attention to a very unusual complication of the paraffin injection treatment of hernia. <h3>REPORT OF CASE</h3> A man, aged 42, had had a right oblique inguinal hernia for nine years. Eight months before I examined it, a charlatan attempted to cure it by injecting paraffin. Immediately after the injection, the patient noticed a large swelling in the region of the internal ring, and a smaller mass a little lower which involved the spermatic cord. The cord was swollen and painful, and the right testis was tender on pressure. The patient complained of constant discomfort from the paraffin masses, and said that they were much more painful than the original hernia. At operation, under local anesthesia, I removed a large mass of paraffin, measuring 1 by 1 by 2 inches, from the internal oblique muscle; another one, measuring ½ by ½ by 1 inch, from
Endothelial progenitors promote hepatocarcinoma intrahepatic metastasis through monocyte chemotactic protein-1 induction of microRNA-21
Authors: Yu-Tsung Shih, Mei-Cun Wang, Jing Zhou, Hsin-Hsin Peng, Ding-Yu Lee, Jeng-Jiann Chiu
Journal: Gut (2014)

<h3>Objectives</h3> Endothelial progenitor cells (EPCs) circulate with increased numbers in the peripheral blood of patients with highly-vascularised hepatocellular carcinoma (HCC) and contribute to angiogenesis and neovascularisation. We hypothesised that angiogenic EPCs, that is, colony forming unit-endothelial cells (CFU-ECs), and outgrowth EPCs, that is, endothelial colony-forming cells, may exert paracrine effects on the behaviours and metastatic capacities of human hepatoma cells. <h3>Design</h3> Various molecular and functional approaches ranging from in vitro cell culture studies on molecular signalling to in vivo investigations on cell invasion and orthotropic transplantation models in mice and clinical specimens from patients with HCC were used. <h3>Results</h3> Monocyte chemotactic protein-1 (MCP-1) was identified as a critical mediator released from CFU-ECs to contribute to the chemotaxis of Huh7 and Hep3B cells by inducing their microRNA-21 (miR-21) biogenesis through the C-C chemokine receptor-2/c-Jun N-terminal kinase/activator protein-1 signalling cascade. CFU-EC-induction of miR-21 in these cells activated their Rac1 and matrix metallopeptidase-9 by silencing Rho GTPase-activating protein-24 and tissue inhibitor of metalloproteinase-3, respectively, leading to increased cell mobility. MCP-1-induction of miR-21 induced epithelial-mesenchymal transformation of Huh7 cells in vitro and their intrahepatic metastatic capability in vivo. Moreover, increased numbers of MCP-1<sup>+</sup> EPCs and their positive correlations with miR-21 induction and metastatic stages in human HCC were found. <h3>Conclusions</h3> Our results provide new insights into the complexity of EPC-HCC interactions and indicate that anticancer therapies targeting either the MCP-1 released from angiogenic EPCs or the miR-21 biogenesis in HCC cells may prevent the malignant progression of primary tumours.
408 EVALUATION OF THE ROUTINE MEDICAL INTERVIEW TO IDENTIFY HEPATITIS C PATIENTS DEVELOPING MAJOR DEPRESSION DURING PEGINTERFERON ALFA-2A PLUS RIBAVIRIN TREATMENT USING THE MAJOR DEPRESSION INVENTORY
Authors: P. Leutscher, M. Buhl, M. Lagging, C. Pedersen, Å. Alsiö, G. Norkrans, N. Langenland, K. Mørch, M. Färkkillä, P. Bech
Journal: Journal of Hepatology (2009)
2D AND 3D GLOBAL LONGITUDINAL STRAIN OF RIGHT VENTRICLE AS WELL AS LEFT VENTRICLE USING TRANSTHORACIC ECHOCARDIOGRAPHY DIFFERENTIATE HYPERTROPHIC CARDIOMYOPATHY SUBJECTS FROM CONTROLS
Authors: Koya Ozawa, Nobusada Funabashi, Hiroyuki Takaoka, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2014)
Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats
Authors: Nosheen Ahmad, Carol R. Gardner, Edward J. Yurkow, Debra L. Laskin
Journal: Hepatology (1999)

Cell adhesion molecules are important for localized accumulation of phagocytes at sites of tissue damage. In the present studies, we analyzed the effects of blocking hepatic macrophages on expression of beta2 integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cells during acute endotoxemia. Flow cytometric analysis revealed distinct subpopulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intravenously) resulted in a time-dependent increase in the percentage of small, dense macrophages and a progressive loss of larger, less-dense cells. In contrast, no major effects were observed on the physical properties of hepatocytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages. Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expression on hepatocytes, which was observed within 3 hours and reached a maximum after 24 hours. An increase in ICAM-1 expression was also observed on endothelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expressed beta2 integrins. Induction of acute endotoxemia had no effect on beta2 integrin expression by these cells. Pretreatment of rats with gadolinium chloride (GdCl3), a macrophage inhibitor known to block endotoxin-induced liver injury, abrogated the effects of endotoxin on ICAM-1 expression by hepatocytes and macrophages. In contrast, ICAM-1 expression on endothelial cells increased. Interestingly, treatment of rats with GdCl3 alone resulted in a marked increase in expression of ICAM-1 on endothelial cells and hepatocytes, and of beta2 integrins on macrophages and endothelial cells. Taken together, these data suggest that ICAM-1 is involved in mediating macrophage adherence and accumulation in the liver during endotoxemia. Furthermore, macrophages appear to regulate expression of this cell adhesion molecule on parenchymal cells.
ISOLATION OF A TUMOR FACTOR RESPONSIBLE FOR ANGIOGENESIS
Authors: Judah Folkman, Ezio Merler, Charles Abernathy, Gretchen Williams
Journal: The Journal of Experimental Medicine (1971)

Human and animal solid tumors elaborate a factor which is mitogenic to capillary endothelial cells. This factor has been called tumor-angiogenesis factor. The important components of TAF are RNA and protein. It is suggested that blockade of this factor (inhibition of angiogenesis) might arrest solid tumors at a tiny diameter of a few millimeters.
In vitro hemocompatibility of thin film nitinol in stenotic flow conditions
Authors: C.P. Kealey, S.A. Whelan, Y.J. Chun, C.H. Soojung, A.W. Tulloch, K.P. Mohanchandra, D. Di Carlo, D.S. Levi, G.P. Carman, D.A. Rigberg
Journal: Biomaterials (2010)
Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector
Authors: Karla J. Helbig, Daryl T.-Y. Lau, Ljiljana Semendric, Hugh A. J. Harley, Michael R. Beard
Journal: Hepatology (2005)

Abstract Interferon (IFN) α inhibits hepatitis C virus (HCV) replication both clinically and in vitro ; however, the complete spectrum of interferon-stimulated genes (ISGs) expressed in the HCV-infected liver or the genes responsible for control of HCV replication have not been defined. To better define ISG expression in the chronically infected HCV liver, DNA microarray analysis was performed on 9 individuals with chronic hepatitis C (CHC). A total of 232 messenger RNAs were differentially regulated in CHC compared with nondiseased liver controls. A significant proportion of these were potential ISGs that were transcriptionally elevated, suggesting an ongoing response to endogenous IFN and/or double-stranded RNA. One ISG significantly elevated in all patients was viperin, an evolutionary conserved ISG that has antiviral activity against human cytomegalovirus. Stimulation of Huh-7 and HepG2 cells with IFN-α or -γ revealed viperin is predominantly a type I ISG. Furthermore, viperin expression could also be induced following transfection of Huh-7 cells with either poly(I:C) or HCV RNA. Transient expression of viperin in cells harboring the HCV genomic replicon resulted in a significant decrease in HCV replication, suggesting that viperin has anti-HCV activity. In conclusion , even in the face of a persistent HCV infection, there is an active ISG antiviral cellular response, highlighting the complexity of the host viral relationship. Furthermore, ISG viperin has anti-HCV activity in vitro ; we postulate that viperin, along with other ISGs, acts to limit HCV replication. (Hepatology 2005.)
Prospective Study of Dietary Patterns and Persistent Cough with Phlegm among Chinese Singaporeans
Authors: Lesley M. Butler, Woon-Puay Koh, Hin-Peng Lee, Marilyn Tseng, Mimi C. Yu, Stephanie J. London
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Using principal components analysis to examine dietary patterns complements the evaluation of individual food and nutrient intake in relation to health outcomes, but has not yet been applied to nonmalignant respiratory disease or symptoms.To examine the relation between patterns of dietary intake at baseline and new onset of persistent cough with phlegm in a population-based cohort of Singapore Chinese.A 165-item validated food frequency questionnaire was administered in-person at baseline in 1993. We identified 623 cases of incident cough with phlegm among 52,325 subjects by telephone interview from 1999 through 2004. We identified two distinct food patterns: a "meat-dim sum" pattern characterized by pork and chicken dim sum foods and noodle dishes, and a "vegetable-fruit-soy" pattern characterized by vegetables, fruit, and soyfood items.The meat-dim sum pattern was positively associated with new-onset cough with phlegm (odds ratio, 1.43; 95% confidence interval, 1.08, 1.89; comparing fourth to first quartile, p for trend = 0.02), after adjustment for age, sex, total energy intake, smoking, education, and nonstarch polysaccharide intake, a protective factor for cough with phlegm in this cohort. Weaker associations were seen for more chronic symptoms and for incident asthma. A weak inverse association for the vegetable-fruit-soy pattern disappeared after adjustment for nonstarch polysaccharide intake.A diet rich in meats, sodium, and refined carbohydrates may increase risk of developing cough with phlegm, independently of the apparent beneficial effects of a diet high in fiber in this Singapore Chinese cohort.
Strong Evidence for Lineage and Sequence Specificity of Substitution Rates and Patterns in Drosophila
Authors: N. D. Singh, P. F. Arndt, A. G. Clark, C. F. Aquadro
Journal: Molecular Biology and Evolution (2009)

Rates of single nucleotide substitution in Drosophila are highly variable within the genome, and several examples illustrate that evolutionary rates differ among Drosophila species as well. Here, we use a maximum likelihood method to quantify lineage-specific substitutional patterns and apply this method to 4-fold degenerate synonymous sites and introns from more than 8,000 genes aligned in the Drosophila melanogaster group. We find that within species, different classes of sequence evolve at different rates, with long introns evolving most slowly and short introns evolving most rapidly. Relative rates of individual single nucleotide substitutions vary ∼3-fold among lineages, yielding patterns of substitution that are comparatively less GC-biased in the melanogaster species complex relative to Drosophila yakuba and Drosophila erecta. These results are consistent with a model coupling a mutational shift toward reduced GC content, or a shift in mutation–selection balance, in the D. melanogaster species complex, with variation in selective constraint among different classes of DNA sequence. Finally, base composition of coding and intronic sequences is not at equilibrium with respect to substitutional patterns, which primarily reflects the slow rate of the substitutional process. These results thus support the view that mutational and/or selective processes are labile on an evolutionary timescale and that if the process is indeed selection driven, then the distribution of selective constraint is variable across the genome.
Endothelial dysfunction in women with premature ovarian failure
Authors: Katerina K. Naka, Nikolaos Kazakos, Evangelos Papanikolaou, Maria Kravariti, Christos Bourantas, Sophia Kalantaridou, Agathoklis Tsatsoulis, Lampros K. Michalis
Journal: Journal of the American College of Cardiology (2003)
An Elemental Education
Authors: M. A. Elliott
Journal: JAMA (1990)

I took birth control pills for 2 1/2 years, starting when I was about 20. Within months after stopping, I began having lumps in my breasts. I was in college then; I remember the doctor at the college infirmary telling me that some women just have breasts like beanbags, and I happened to be one of them. He actually showed me a little beanbag that he tossed from hand to hand and then let me hold, maybe to give me something to relate to.  It is a dozen years later. I am on my back in an examination room, trying to memorize the ceiling while the surgeon goes in search of a pathologist. The lump I have found in my breast this time is different from the others, different even from the cysts he has aspirated in the past. It is solid, so he decides to do a needle biopsy
Suppression of Endothelial Progenitor Cells in Human Coronary Artery Disease by the Endogenous Nitric Oxide Synthase Inhibitor Asymmetric Dimethylarginine
Authors: Thomas Thum, Dimitrios Tsikas, Sylvia Stein, Maximilian Schultheiss, Martin Eigenthaler, Stefan D. Anker, Philip A. Poole-Wilson, Georg Ertl, Johann Bauersachs
Journal: Journal of the American College of Cardiology (2005)
Efficacy of lenalidomide in <scp>POEMS</scp> syndrome: A retrospective study of 20 patients
Authors: Bruno Royer, Lavinia Merlusca, Julie Abraham, Lucile Musset, Julien Haroche, Sylvain Choquet, Xavier Leleu, Catherine Sebban, Olivier Decaux, Lionel Galicier, Muriel Roussel, Christian Recher, Anne Banos, Isabelle Guichard, Jean‐Marie Brisseau, Pascal Godmer, Olivier Hermine, Gaël Deplanque, Thierry Facon, Bouchra Asli, Véronique Leblond, Jean‐Paul fermand, Jean Pierre Marolleau, Arnaud Jaccard
Journal: American Journal of Hematology (2012)

POEMS syndrome is a rare disorder characterized by polyneuropathy, monoclonal gammopathy, multiorgan involvement, and elevated vascular endothelial growth factor levels. Localized bone lesions require irradiation, whereas young patients with disseminated disease receive intensive treatment with stem cell support. Treatment of older and non responding patients is not yet standardized. We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed, and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18-FDG-PET/CT at diagnosis (11 with positive findings), and nine patients during follow-up. The number of lesions fell markedly in five cases and remained stable in two cases, while two patients became negative. During a median follow-up of 22 months, four patients relapsed. Toxicity, predominantly hematological, was mild and manageable. Lenalidomide thus appears to be effective in POEMS syndrome, inducing high rate of clinical and biological responses.
420 INTERLEUKIN-28B POLYMORPHISMS, IP-10 AND VIRAL LOAD PREDICT VIROLOGICAL RESPONSE TO THERAPY IN CHRONIC HEPATITIS C UNDER REAL-LIFE CONDITIONS
Authors: G. Fattovich, L. Covolo, S. Bibert, G. Askarieh, M. Lagging, S. Clément, G. Malerba, M. Pasino, M. Guido, M. Puoti, G.B. Gaeta, T. Santantonio, G. Raimondo, R. Bruno, P.-Y. Bochud, F. Donato, F. Negro
Journal: Journal of Hepatology (2011)
SHORT CHILDREN: TO TREAT OR NOT TO TREAT
Authors: S. DOUGLAS FRASIER
Journal: Annals of Internal Medicine (1964)

Letters and Comments1 December 1964SHORT CHILDREN: TO TREAT OR NOT TO TREATS. DOUGLAS FRASIER, M.D., FRED G. SMITH JR., M.D.S. DOUGLAS FRASIER, M.D.Search for more papers by this author, FRED G. SMITH JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-6-1194 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Stimulation of growth of short children with anabolic agents is an area of great controversy and confusion. Unfortunately, the article, "The Use of Androgens and Thyroid for Stimulation of Growth in Short Children," by Storment, Escamilla, and Williams (ANNALS OF INTERNAL MEDICINE 60: 962, 1964) only adds to this confusion. This study is open to extensive criticism and raised numerous questions.There is no suitable control group of untreated children of the same chronological age, height age, and bone age who have the same predicted mature height as the treatment group prior to therapy. Such controls were... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: S. DOUGLAS FRASIER, M.D.; FRED G. SMITHJR., M.D.Affiliations: University of California School of Medicine Los Angeles, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1964Volume 61, Issue 6Page: 1194-1197KeywordsAndrogensBoneChildrenThyroid ePublished: 1 December 2008 Issue Published: 1 December 1964 PDF downloadLoading ...
Myocardial infarct extension: incidence and relationship to survival.
Authors: J T Baker, D A Bramlet, R M Lester, D G Harrison, C R Roe, F R Cobb
Journal: Circulation (1982)

Myocardial infarct extension, defined as reelevation or reappearance of creatine phosphokinase-MB (CK-MB) 48 hours after the onset of symptoms, was evaluated prospectively in 56 consecutive patients with acute myocardial infarction. Myocardial infarct extension occurred in eight patients (14%). The sensitivity, specificity and predictive accuracy in the diagnosis of myocardial infarct extension were 63%, 85% and 42%, respectively, for recurrent chest pain requiring morphine; 50%, 65% and 19% for recurrent ST-segment elevation on routine 12-lead ECGs; and 88%, 63% and 28% for reelevation of total CK. Three of the eight episodes of extension were clinically silent. Four of eight patients (50%) with extension died, compared with one of 46 patients (2%) without extension (p = 0.0009). CK-MB persisted for 72 hours or longer in 16 patients and identified seven of eight patients who subsequently had infarct extension. We conclude that myocardial infarct extension is an infrequent complication of acute myocardial infarction and is associated with a very high mortality rate. Persistence of CK-MB for 72 hours or more identifies a subgroup of patients at high risk for subsequent infarct extension and death.