tbuckley/cabot-search huggingface dataset:
Connective tissue growth factor and integrin αvβ6: A new pair of regulators critical for ductular reaction and biliary fibrosis in mice
Authors: Liya Pi, Paulette M. Robinson, Marda Jorgensen, Seh‐Hoon Oh, Alicia R. Brown, Paul H. Weinreb, Thu Le Trinh, Protopapadakis Yianni, Chen Liu, Andrew Leask, Shelia M. Violette, Edward W. Scott, Gregory S. Schultz, Bryon E. Petersen
Journal: Hepatology (2014)

Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell-matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin αvβ6 in hepatic progenitor/oval cell activation, which often occurs in the form of ductular reactions (DRs) when hepatocyte proliferation is inhibited during severe liver injury. CTGF and integrin αvβ6 proteins were highly expressed in DRs of human cirrhotic livers and cholangiocarcinoma. Confocal microscopy analysis of livers from Ctgf promoter-driven green fluorescent protein reporter mice suggested that oval cells and cholangiocytes were the main sources of CTGF and integrin αvβ6 during liver injury induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Deletion of exon 4 of the Ctgf gene using tamoxifen-inducible Cre-loxP system down-regulated integrin αvβ6 in DDC-damaged livers of knockout mice. Ctgf deficiency or inhibition of integrin αvβ6, by administrating the neutralizing antibody, 6.3G9 (10 mg/kg body weight), caused low levels of epithelial cell adhesion molecule and cytokeratin 19 gene messenger RNAs. Also, there were smaller oval cell areas, fewer proliferating ductular epithelial cells, and lower cholestasis serum markers within 2 weeks after DDC treatment. Associated fibrosis was attenuated, as indicated by reduced expression of fibrosis-related genes, smaller areas of alpha-smooth muscle actin staining, and low collagen production based on hydroxyproline content and Sirius Red staining. Finally, integrin αvβ6 could bind to CTGF mediating oval cell adhesion to CTGF and fibronection substrata and promoting transforming growth factor (TGF)-β1 activation in vitro.CTGF and integrin αvβ6 regulate oval cell activation and fibrosis, probably through interacting with their common matrix and signal partners, fibronectin and TGF-β1. CTGF and integrin αvβ6 are potential therapeutic targets to control DRs and fibrosis in related liver disease.
Abstract 2928: AZD6244 inhibits cisplatin induced ERK1/2 activation and potentiates its cytotoxic effects in NSCLC preclinical models
Authors: Eun Young Kim, Arum Kim, Min Kwang Byun, Se Kyu Kim, Hyung Jung Kim, Joon Chang, Chul Min Ahn, Yoon Soo Chang
Journal: Cancer Research (2014)

Abstract Introduction; Lung cancer is still the leading cause of cancer death worldwide, indicating that there are urgent needs for elucidating the mechanisms of resistance and developments of strategies to overcome it. Cisplatin is still one of the most commonly used drugs for the treatment of advanced lung cancer and, however, the underlying mechanism of activation of MAPK/ERK1/2 after cisplatin administration is still complex and elusive. It is considered one of the main mechanisms mediating resistance to cisplatin based doublet chemotherapy. In this study we aimed to evaluate the effectiveness of combination of MAPK inhibitor, AZD6244, with cisplatin in NSCLC models. Materials and Methods; NSCLC cells harbouring oncogenic RAS mutation, NCI-H1299, -H2009, -H460, and A549 cells, and LSL K-Ras G12D mouse model was used. Protein expression was evaluated by immunoblotting and cytotoxicity was measured by FACS followed by annexin-V and PI staining. LSL Kras G12D mouse were inhaled 5X 107 PFU AdCre virus at 8 weeks after birth and, in 24 weeks after inhalation, were taken microCT, randomized into 4 groups, and then treated with AZD6244 (25mg/kg bid by oral gavage) and/or cisplatin (5 mg/kg weekly) for two weeks. Results; There was a dose dependent increase of pERK1/2, which is most prominent at 24 hr after cisplatin treatment. Expression of proapoptotic protein, BIM, was decreased whereas that of antiapoptotic proteins, BCL-2 and MCL-1, was increased with cisplatin treatment. Treatment of AZD6244 prevented phosphorylation mediated degradation of BIM after cisplatin treatment. AZD6244 itself did not show cytotoxic effects up to 10 uM whereas combination of 1 uM of AZD6244 potentiates cytotoxic effects of cisplatin. Combined treatment of AZD6244 with cisplatin showed significant tumor reduction in 2 weeks in LSL K-ras G12D mouse model when compared those treated with single agents or vehicle. Conclusion; Combination of AZD6244 with cisplatin potentiates cytotoxic effects and anti-tumor activities in NSCLC preclinical models. These findings suggest that clinical trials using combination with AZD6244 and cisplatin may be beneficial in advanced NSCLC patients. Citation Format: Eun Young Kim, Arum Kim, Min Kwang Byun, Se Kyu Kim, Hyung Jung Kim, Joon Chang, Chul Min Ahn, Yoon Soo Chang. AZD6244 inhibits cisplatin induced ERK1/2 activation and potentiates its cytotoxic effects in NSCLC preclinical models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2928. doi:10.1158/1538-7445.AM2014-2928
VINYL ETHER: A NEW METHOD OF ADMINISTRATION
Authors: V. Goldman
Journal: BMJ (1936)

MEDICAL JOURNAL -2 as, however, once .opened the contents of the bottle '.rapidly decompose I suggested that ampoules would be ,more convenient.It can now be obtained in this form, each ampoule containing 3 c.cm. TechniqueAfter a considerable number of experiments a " closed " method was adopted, using a special inhaler, as by this method great economy of anaesthetic is effected and the resulting anaesthesia is more rapid and certain in its onset than by an open method.Apparatus.-Theinhaler is a modification of Ormsby's ,ether inhaler.It consists of a sponge container made of two metal tubes, one of which slides into the other ; at ": -'._'.
The pulmonary vasopressor response to decreases in blood pH in intact dogs
Authors: Albert L. Hyman, William C. Woolverton, Paul S. Guth, Herbert Ichinose
Journal: Journal of Clinical Investigation (1971)

The pulmonary vasopressor response to acidemia was studied in intact dogs in a hemodynamically separated lobe which was pump perfused with systemic arterial or venous blood at a fixed rate. The magnitudes of the lobar vasopressor responses to perfusion with blood rendered acidic by infusions of hydrochloric lactic, and acetic acids, and by hypercapnia (membrane oxygenator) were significantly different. Although the PH of the perfusing blood in each group fell to similar extents (pH 7.1-7.0), the lobar pressor response was greatest with hydrochloric acid (HCl), smaller with lactic and acetic acids, and absent with hypercapnia. A lobar vasopressor response also occurred during lobar perfusion with blood which had been extracorporeally acidified with HCl or acetic acid, but then returned to control pH by infusions of sodium bicarbonate and Tris before reaching the lung. A lobar vasopressor response also resulted from pump perfusion of the lobar artery with femoral venous blood during perfusion of the isolated ipsilateral femoral artery with similarly treated aortic blood. However, no lobar vasopressor response resulted from pump perfusion of the lobar artery with blood removed transseptally from a right pulmonary vein during acidification (HCl) of the right pulmonary artery (to pH 7.0).The data indicate that, in this experimental preparation involving closed-chest dogs spontaneously breathing air or 35% oxygen, the lobar vasopressor response to infusions of acidifying agents is not directly related to the pH of blood actually perfusing the lobar vessels. Additionally, the vasopressor response is prevented by prior perfusion of the acidified blood through a pulmonary vascular bed but not by prior perfusion through the femoral vascular bed. Although these experiments do not establish the mediation of the lobar vasopressor response, activation of vasoactive agents in blood at or near the acidification site is suggested. In these experiments, the acidemia was produced under conditions which are not like the usual ones of developing metabolic acidosis or alveolar hypercapnia, in that strong acids were directly infused into blood which perfused only one lung lobe. The mediation of the present pressor responses and of those found in the more usual forms of experimental and clinical acidosis may therefore be dissimilar.
Authorship and Clinical Trials
Authors: ZALMEN A. ARLIN
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 March 1988Authorship and Clinical TrialsZALMEN A. ARLIN, M.D.ZALMEN A. ARLIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-3-495_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The objective of clinical research is to develop a better understanding of disease and how to treat it. In clinical trials, the objective is to develop new treatments for diseases without definitive effective therapy. Clinical trials by nature involve many participants each doing a different task. The current practice of assigning the sequence of authors is sometimes arbitrary and leads to conflicts among investigators. Five functions can be defined that lead to publishing the results of a clinical trial. They include the design, execution, data analysis, statistical analysis, and writing of the paper detailing the accomplishments of...Reference1. HUTH E. Guidelines on authorship of medical papers. Ann Intern Med. 1986;104:269-74. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ZALMEN A. ARLIN, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAuthorshipAngelo Taranta, MD 1 March 1988Volume 108, Issue 3Page: 495-496KeywordsClinical trialsStatistical data ePublished: 1 December 2008 Issue Published: 1 March 1988 PDF downloadLoading ...
BI-03 * DLX HOMEOBOX GENES REGULATE NEURONAL VS OLIGODENDROGLIAL CELL FATE DECISIONS: POTENTIAL RELEVANCE TO PEDIATRIC GLIONEURONAL TUMORS AND HIGH GRADE GLIOMAS
Authors: J. Zagozewski, S. Japoni, Q. Jiang, F. van Landeghem, P. Nozza, A. Raso, D. Eisenstat
Journal: Neuro-Oncology (2015)

BACKGROUND: Pediatric high grade gliomas (pHGG) are localized to different neuroanatomic compartments with significant differences in their gene expression profiles. In Histone H3.3 G34V/R mutants, DLX2 homeobox gene expression is increased with a corresponding decrease in myelin transcription factor (MYT1) expression. DLX genes are necessary for tangential migration and differentiation of inhibitory interneurons during CNS development. Neural progenitors derived from DLX1/DLX2 double knockout (DKO) mice transplanted into a wild-type forebrain differentiate into oligodendrocytes, providing support for the DLX homeobox genes in neuronal-glial cell fate decisions. METHODS: Chromatin immunoprecipitation (ChIP) assays using a DLX2 antibody were followed by qPCR. ChIP-reChIP assays were performed using antibodies that recognize specific histone modifications. Electrophoretic mobility shift assays (EMSA) were performed using recombinant DLX2 protein and oligonucleotide probes from ChIP-specified promoter regions. Reporter gene assays provided functional assessment of protein-DNA interactions in vitro. Target gene expression was assessed comparing wild-type (WT) and DLX1/DLX2 DKO tissues. RESULTS: Homeodomain binding sites were localized to the promoters of Olig2, Myt1, Nkx2.2 and others in silico. ChIP assays confirmed promoter occupancy by DLX2. ChIPseq experiments are underway. EMSA studies demonstrated specific DLX2-promoter complexes. Luciferase assays showed repression of Olig2 and Nkx2.2 reporter gene expression, consistent with co-occupancy of H3K27me3 in WT and increased target gene expression in DLX1/DLX2 DKO embryonic tissues. We also demonstrated DLX2 expression in a cohort of gangliogliomas. CONCLUSIONS: Our results support a role for DLX transcription factors in controlling neural progenitor specification by activating GABAergic and inhibiting oligodendroglial cell fates through transcriptional repression of a suite of genes required for oligodendrocyte differentiation. Understanding how pHGG and glioneuronal tumors co-opt these neurodevelopmental programs will lead to novel pharmacologic approaches that promote glioma differentiation.
Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children
Authors: Thomas Müller, Smita Koppikar, Rachel M. Taylor, Fiona Carragher, Barbara Schlenck, Peter Heinz-Erian, Florian Kronenberg, Peter Ferenci, Stuart Tanner, Uwe Siebert, Roland Staudinger, Giorgina Mieli-Vergani, Anil Dhawan
Journal: Journal of Hepatology (2007)
Guillaume Lam Shang (“Bill”) Leen
Authors: Alex E Clason
Journal: BMJ (2006)

Organization Dr Lee Jong-wook continued the revival of the agency begun by his predecessor, Gro Harlem Brundtland.Having taken over from the formidable Norwegian in 2003, Dr Lee continued to push health to the top of the global political agenda, winning plaudits for his style, which was based on action not words.He entered office as the threat of severe acute respiratory syndrome was subsiding, and it was bird flu-a pandemic that has yet to emerge-that was to dominate much of his time as leader of WHO.However, in the long term it is likely to be his bold, if ultimately unattainable, pledges on HIV treatment that will be remembered.Apart from his expertise in public health Dr Lee was a consummate politician-a characteristic that raised a few eyebrows at the time of his candidature.A number of health experts remarked that Dr Lee had acted more like a politician than a scientist in his extensive lobbying for the top job.As part of his strategy to get elected he persuaded more than 50 members of the US Congress to write to the US government backing his candidacy.He also remarked in an interview later that year that "you can't make it to this position without being a politician."Conversely, some commentators thought that this poor public speaker with a modest demeanour would be out of his depth on the world stage.But he was soon able to build personal contacts with George Bush, Jacques Chirac, and China's president, Hu Jintao.This July he had been due to address the G8 summit in St Petersburg at the personal invitation of Vladimir Putin.Dr Lee understood that the steps he had publicly avowed he would take against infectious diseases and tobacco related illnessfrom which his father had died-would not be possible without the support of world leaders.He declared that tuberculosis, polio, malaria, and above all, AIDS, would be key battlegrounds during his leadership.He introduced the "3 by 5" campaign, in which WHO pledged that three million HIV patients-most of whom were in the developing world-would have access to
Incidence and risk factors of hepatocellular carcinoma in patients with primary biliary cirrhosis
Authors: Carole Macaron, Ibrahim A. Hanouneh, Nizar N. Zein
Journal: Hepatology (2010)

We read with great interest the article by Cavazza et al.,1 who demonstrated that an advanced histological stage was the only risk factor associated with the development of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) from two European centers. Similar results were described in a Japanese multicenter study by Shibuya et al.2 Although these studies suggest screening for HCC in patients with advanced-stage PBC, it is still uncertain whether there is a significantly increased risk of HCC development in patients with stage IV PBC cirrhosis versus patients with cirrhosis of other etiologies. We assessed in a single-center study the incidence of HCC in North American patients with stage IV PBC or autoimmune hepatitis (AIH) cirrhosis and compared it to the incidence of HCC in patients with hepatitis C virus (HCV) cirrhosis. Three hundred fifteen patients with HCV cirrhosis, 49 patients with AIH cirrhosis, and 52 patients with stage IV PBC were evaluated at the Cleveland Clinic between 2001 and 2007. Stage IV PBC cirrhosis was diagnosed when patients had positive serological and histological findings of cirrhosis or biochemical and radiological evidence of portal hypertension. Cirrhosis due to AIH was defined by positive serological and histological findings of cirrhosis or biochemical and radiological evidence of portal hypertension. HCC-free survival was analyzed from the moment of the diagnosis of cirrhosis in HCV, AIH, and PBC patients until death or transplantation. During a median follow-up of 3.6 years (with 25th and 75th percentiles of 1.8 and 6.3, respectively), 64 of 315 patients (20.3%) with HCV cirrhosis, 2 of 49 patients (4.1%) with AIH cirrhosis, and 4 of 52 patients (7.7%) with PBC cirrhosis developed HCC. The annual cumulative incidence of HCC was 1.1% in patients with AIH cirrhosis, 1.5% in patients with PBC cirrhosis, and 4.0% in patients with HCV cirrhosis (Fig. 1). Incidence of HCC in patients with AIH, PBC, or HCV. This study has shown that although patients with stage IV PBC cirrhosis develop liver cancer, the risk is significantly lower in comparison with the risk for patients with HCV cirrhosis. The results of our study are discordant with a previously reported Spanish series in which the risks of HCC were similar in patients with late-stage PBC and in patients with HCV cirrhosis.3 We agree with Cavazza et al.1 that the low prevalence of PBC and the possible influence of geography on disease progression are confounding factors that may explain the divergent results in the literature. Future multicenter studies in North America with a longer follow-up period are necessary to validate these findings and better estimate the risk of HCC in PBC patients at an advanced histological stage. Carole Macaron M.D.*, Ibrahim A. Hanouneh M.D. , Nizar N. Zein M.D. , * Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH.
Postoperative Ischemic Jejunal Stenosis Treated with Balloon Catheter Dilation and Wallstent Implantation
Authors: J. Solt, M. Moizs, A. Orovica, A. Gárdos, I. Battyányi, B. Bogneár
Journal: Endoscopy (1997)

Ischemic stenosis of the jejunum is rare. For technical, anatomical, and pathological reasons, ischemic stenosis of the jejunal segment used for the replacement of the esophagus or the stomach, or both, represents a special entity. The present study reports a case of balloon catheter dilation of ischemic strictures of the jejunal segment, used for substitution after gastrectomy. In this patient, an occlusion of the blood vessels supplying the affected segment was observed at its aortic origin, and a Wallstent was implanted. A rare late complication, aortoesophageal fistula, appeared one year after placement of the Wallstent. The case presented in this study suggests that using balloon catheters and implanting a Wallstent may be a useful approach to the management of postoperative ischemic strictures of the jejunum in selected cases. The minimally invasive technique with special indications used here has not previously been described. The rare complication mentioned, however, requires special attention.
Viral diversity in children with diarrhea in Gambia
Authors: Irina Astrovskaya, Bo Liu, Mihai Pop
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
The Biologic &amp;amp; Clinical Basis of Infectious Diseases
Authors: David G. Rupar
Journal: JAMA (1992)

Midway through the standard medical school curriculum there is an abrupt transition from the classroom study of basic science to the hands-on study of patient care. Many schools design courses to ease the transition, either by providing the students earlier contact with patients or by bringing aspects of clinical medicine to the classroom. This textbook was written to accompany a course of the latter type, taught to sophomores at Northwestern University Medical School. The course and, thus, the book represent an attempt to integrate the basic science disciplines of microbiology and immunology within the framework of the clinical study of infectious diseases. The book can be divided roughly into three sections. The introductory chapters focus on the interaction of microbes with the human immune system and on basic diagnostic methods. The second section, which is the bulk of the book, consists of chapters on various infectious diseases. The short final
The moral philosopher's view The victim should decide
Authors: G. Gillett
Journal: BMJ (1995)

Professor Shepherd recommends a cooperative arrangement between accident and emergency and criminal justice services such as the police in an attempt to prevent injury. The justification for this arrangement is that increasing rates of conviction is an effective public health measure to prevent injury. The problem is then to reconcile this goal with victims' reluctance to pursue their complaint. This is not easy. It requires consideration of the ethics of disclosure of patient information beyond the therapeutic relationship, the conflict between respect for autonomy and protection from harm, and the ethics of intervention in the face of uncertainty.

A patient's willingness to have the results of medical communications shared is, in general, the determining factor in deciding what a doctor or …
X-ray examination of NHS employees.
Authors: J B Deasy
Journal: BMJ (1978)

<h3>Abstract</h3> Chronic alcohol consumption and alcohol use disorder (AUD) have a tremendous impact on the patient’s psychological and physiological health. There is some evidence that chronic alcohol consumption influences SARS-CoV2 infection risk, but the molecular mechanism is unknown. Here, we generated expression data of SARS-CoV2 infection relevant genes (Ace2, Tmprss2 and Mas) in different organs in rat models of chronic alcohol exposure and alcohol dependence. ACE2 and TMPRSS2 represent the virus entry point whereas Mas is activating the anti-inflammatory response once the cells are infected. Across three different chronic alcohol test conditions, we found a consistent upregulation of Ace2 in the lung, which is the most affected organ in Covid-19 patients. Other organs such as liver, ileum, kidney, heart, and the brain showed also up-regulation of Ace2 and Mas but in a less consistent manner across the different animal models, while Tmprss2 was unaffected in all conditions. We suggest that alcohol-induced up-regulation of Ace2 can lead to an elevated stochastic probability of cellular virus entry and may thus confer a molecular risk factor for a SARS-CoV2 infection.