tbuckley/cabot-search huggingface dataset:
Activation of the transforming growth factor‐β/SMAD transcriptional pathway underlies a novel tumor‐promoting role of sulfatase 1 in hepatocellular carcinoma
Authors: Renumathy Dhanasekaran, Ikuo Nakamura, Chunling Hu, Gang Chen, Abdul M. Oseini, Elif Sezin Seven, Alexander G. Miamen, Catherine D. Moser, Wei Zhou, Toin H. van Kuppevelt, Jan M. van Deursen, Taofic Mounajjed, Martin E. Fernandez‐Zapico, Lewis R. Roberts
Journal: Hepatology (2014)

In vitro studies have proposed a tumor suppressor role for sulfatase 1 (SULF1) in hepatocellular carcinoma (HCC); however, high expression in human HCC has been associated with poor prognosis. The reason underlying this paradoxical observation remains to be explored. Using a transgenic (Tg) mouse model overexpressing Sulf1 (Sulf1‐Tg), we assessed the effects of SULF1 on the diethylnitrosamine model of liver carcinogenesis. Sulf1‐Tg mice show a higher incidence of large and multifocal tumors with diethylnitrosamine injection compared to wild‐type mice. Lung metastases were found in 75% of Sulf1‐Tg mice but not in wild‐type mice. Immunohistochemistry, immunoblotting, and reporter assays all show a significant activation of the transforming growth factor‐β (TGF‐β)/SMAD transcriptional pathway by SULF1 both in vitro and in vivo . This effect of SULF1 on the TGF‐β/SMAD pathway is functional; overexpression of SULF1 promotes TGF‐β‐induced gene expression and epithelial–mesenchymal transition and enhances cell migration/invasiveness. Mechanistic analyses demonstrate that inactivating mutation of the catalytic site of SULF1 impairs the above actions of SULF1 and diminishes the release of TGF‐β from the cell surface. We also show that SULF1 expression decreases the interaction between TGF‐β1 and its heparan sulfate proteoglycan sequestration receptor, TGFβR3. Finally, using gene expression from human HCCs, we show that patients with high SULF1 expression have poorer recurrence‐free survival (hazard ratio 4.1, 95% confidence interval 1.9‐8.3; P = 0.002) compared to patients with low SULF1. We also found strong correlations of SULF1 expression with TGF‐β expression and with several TGF‐β‐related epithelial–mesenchymal transition genes in human HCC. Conclusion : Our study proposes a novel role of SULF1 in HCC tumor progression through augmentation of the TGF‐β pathway, thus defining SULF1 as a potential biomarker for tumor progression and a novel target for drug development for HCC. (H epatology 2015;61:1269–1283)
Tensions Remain Over tPA for Stroke
Authors: Mike Mitka
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Glaucoma: Pathology and Therapy
Authors: Paul Weinstein
Journal: JAMA (1953)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
OBSERVATIONS IN THE MANAGEMENT OF LATE ARTERIOSCLEROSIS OBLITERANS WITH GANGRENE
Authors: H L MYERS
Journal: Annals of Internal Medicine (1957)

Article1 June 1957OBSERVATIONS IN THE MANAGEMENT OF LATE ARTERIOSCLEROSIS OBLITERANS WITH GANGRENEHARVEY L. MYERS, M.D., F.A.C.P.HARVEY L. MYERS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-46-6-1137 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOne rarely has the opportunity to observe the panorama of a single ailment unfold itself over a broad span of years. It has been my privilege to follow, at first hand, the clinical picture of arteriosclerosis obliterans associated with gangrene and/or ulceration of the extremities for the years following World War II, 1946 through 1956. During that decade 1,158 patients, 643 males and 515 females, were hospitalized at the Queens General Hospital with varying degrees of gangrene of the extremities associated with arteriosclerosis obliterans. Seventy-nine per cent of these people were over 60 years of age.Observations of these patients...Bibliography1. BollmanPreston VFW: The effects of experimental administration of dicoumarin, J. A. M. A. 129: 1021, 1942. CrossrefGoogle Scholar2. BarkerHinesKvale NWEAWF: The treatment of acute arterial occlusion of the extremities with special reference to anticoagulant therapy, Minnesota Med. 29: 250, 280, 1946. MedlineGoogle Scholar3. WesslerSilberg SNR: Studies in peripheral arterial occlusive disease, Circulation 7: 810, 1953. CrossrefMedlineGoogle Scholar4. DotterSteinbergBall CTIRB: Angiography, Circulation 3: 606, 1951. CrossrefMedlineGoogle Scholar5. Myers HL: Enzymatic debridement in the treatment of arteriosclerosis obliterans with gangrene, New York State J. Med. 53: 981, 1953. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cedarhurst, N. Y.*Presented at the Thirty-eighth Annual Session of The American College of Physicians, Boston, Massachusetts, April 9, 1957.Requests for reprints should be addressed to Harvey L. Myers, M.D., 431 Broadway, Cedarhurst, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1957Volume 46, Issue 6Page: 1137-1142KeywordsAntibioticsAnticoagulant therapyAnticoagulantsCellulitisThrombosisUlcersVasodilation ePublished: 1 December 2008 Issue Published: 1 June 1957 PDF downloadLoading ...
Reduced secreted clusterin as a mechanism for Alzheimer-associated CLU mutations
Authors: Karolien Bettens, Steven Vermeulen, Caroline Van Cauwenberghe, Bavo Heeman, Bob Asselbergh, Caroline Robberecht, Sebastiaan Engelborghs, Mathieu Vandenbulcke, Rik Vandenberghe, Peter Paul De Deyn, Marc Cruts, Christine Van Broeckhoven, Kristel Sleegers
Journal: Molecular Neurodegeneration (2015)

The clusterin (CLU) gene has been identified as an important risk locus for Alzheimer's disease (AD). Although the actual risk-increasing polymorphisms at this locus remain to be identified, we previously observed an increased frequency of rare non-synonymous mutations and small insertion-deletions of CLU in AD patients, which specifically clustered in the β-chain domain of CLU. Nonetheless the pathogenic nature of these variants remained unclear. Here we report a novel non-synonymous CLU mutation (p.I360N) in a Belgian Alzheimer patient and have explored the pathogenic nature of this and 10 additional CLU mutations on protein localization and secretion in vitro using immunocytochemistry, immunodetection and ELISAs.Three patient-specific CLU mutations in the β-chain (p.I303NfsX13, p.R338W and p.I360N) caused an alteration of the subcellular CLU localization and diminished CLU transport through the secretory pathway, indicative of possible degradation mechanisms. For these mutations, significantly reduced CLU intensity was observed in the Golgi while almost all CLU protein was exclusively present in the endoplasmic reticulum. This was further confirmed by diminished CLU secretion in HEK293T and HEK293 FLp-In cell lines.Our data lend further support to the contribution of rare coding CLU mutations in the pathogenesis of neurodegenerative diseases. Functional analyses suggest reduced secretion of the CLU protein as the mode of action for three of the examined CLU mutations. One of those is a frameshift mutation leading to a loss of secreted protein, and the other two mutations are amino acid substitutions in the disulfide bridge region, possibly interfering with heterodimerization of the α- and β-chain of CLU.
Abstract 759: Inhibition Of Pro-inflammatory Cytokine Il-17 Reduces Atherosclerotic Lesion Development In Apo E −/ − Mice
Authors: Christian Erbel, Roland Klingenberg, Sultan Celik, Nadine Wambsganss, Benjamin Funke, Dittmar Boeckler, Thomas J Dengler
Journal: Circulation (2007)

Atherosclerotic plaque typically contains infiltrates of activated macrophages and T cells. In human carotid artery plaques, we previously showed the presence of IL-17 producing T cells (Th17) and IL-23. Effects of inhibition of the pro-inflammatory Th1 cytokine IL-17 on atherosclerosis development was studied in a rodent model. 25 female ApoE −/ − mice fed a normal diet were treated with a specific blocking antibody against IL-17 for 12 weeks (100 μg intraperitoneally once per week). For analysis, aortic root was embedded in OCT and serially cryosectioned in 5μm intervals; distal aorta was snap frozen for mRNA analysis. Sections every 75μm were stained with Oil RedO, the lesion area was quantified using PC-based image analysis. In IL-17 treated mice no changes in LDL cholesterol and anti-ox LDL antibodies were seen. Subsets of immune cells, surface marker expression and fraction of regulatory T cells in peripheral blood / spleen were unchanged. Inhibition of IL-17 markedly reduced atherosclerotic plaque volume by 65% (p=0.004) and fractional stenosis by 68% (p=0.01). Immunohistochemistry revealed significant reduction of cellular infiltration by T cells and macrophages in atherosclerotic lesions. By quantitative RT-PCR, significantly reduced expression was shown (among others) for CD3ϵ, egr-1, Akt and RANKL (all p&lt; 0.01). Functional blockade of Th1 cytokine IL-17 reduces atherosclerotic lesion development in an established animal model without major derangement of peripheral cellular immunity. Our findings suggest a relevant role for IL17-producing T cells in atherosclerosis warranting further study of pathogenic mechanisms and therapeutic potential.
Abstract 22: Visit-to-Visit Variability in Blood Pressure is Related to Late-Life Cognitive Decline
Authors: Bo Qin, Anthony J Viera, Linda S Adair, Brenda L Plassman, Lloyd J Edwards, Barry M Popkin, Michelle A Mendez
Journal: Circulation (2015)

Introduction: Recent studies suggest higher visit-to-visit variability of blood pressure (BP) is associated with worse cognitive function, but evidence based on longitudinal cognitive testing has not been reported. Hypothesis: We assessed the hypothesis that higher visit-to-visit variability in BP, but not mean BP, would be associated with faster decline in cognitive function among community-dwelling older adults. Methods: This prospective cohort study comprised 1213 adults who had two or more waves of BP measurements as part of the China Health and Nutrition Survey from 1991, up to their first cognitive tests, and completed a cognitive screening test at two or more waves in 1997, 2000 or 2004. Mean (SD) age at first cognitive test was 64 (6) y. Outcomes were repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), standardized composite cognitive and verbal memory scores (standardized units [SU]). Visit-to visit BP variability was expressed as the standard deviation [SD] or as the variation independent of mean (SD/mean^x, with x derived from curve fitting) in BP measures obtained at a mean interval of 3.6 years. Multivariable-adjusted linear mixed-effects models were used to determine the association of changes in cognitive scores with visit-to visit BP variability. Results: Higher visit-to-visit variability in systolic BP, but not mean systolic BP, was associated with a faster decline of cognitive function (adjusted mean difference [95% CI] for high vs. low tertile of SD in variability (Figure): global score -0.23 points/y [-0.41 to -0.04], composite scores -0.029 SU/y [-0.056 to -0.002] and verbal memory -0.044 SU/y [-0.075 to -0.012]). Higher visit-to-visit variability in diastolic BP was associated with a faster decline of global cognitive function only among adults 55-64 years, independent of mean diastolic BP. Conclusion: Higher long-term BP visit-to-visit variability predicted a faster rate of cognitive decline among older adults.
Helping Their Homeland
Authors: Rebecca Voelker
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
REFLECTIONS FROM OUR MIRROR
Authors: H P LEWIS
Journal: Annals of Internal Medicine (1960)

An Address30 December 1960REFLECTIONS FROM OUR MIRRORHOWARD P. LEWIS, M.D., F.A.C.P.HOWARD P. LEWIS, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-53-6-1204 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is a privilege and a pleasure for me to participate in this delightful and significant ceremony of the Gold-Headed Cane. To him who receives the cane and to those who are honored by mention, I extend my congratulations. This is an honor and a distinction that you should cherish forever.That this award is unique and at the same time of deep significance was expressed by your respected Professor of Medicine Emeritus, Dr. William J. Kerr, when he wrote in 1953 in the preface of the book,"The Gold-Headed Cane,"these words: "The award is based upon the student's... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Address delivered at the Gold-Headed Cane Ceremony, University of California School of Medicine, San Francisco, on June 9, 1960.†Professor of Medicine, University of Oregon Medical School.Requests for reprints should be addressed to Howard P. Lewis, M.D., 3181 Southwest Sam Jackson Park Road, Portland 1, Oregon. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 30 December 1960Volume 53, Issue 6Page: 1204-1210 Issue Published: 30 December 1960 PDF downloadLoading ...
ALLERGIC CONTACT DERMATITIS FROM PYRETHRUM (CHRYSANTHEMUM SPP.).
Authors: JOHN C. MITCHELL, GILLES DUPUIS, G. H. NEIL TOWERS
Journal: British Journal of Dermatology (1972)

Summary.— In a patient with allergic contact dermatitis from pyrethrum (Chrysanthemum spp., family Compositae), pyrethrosin produced strong, and pyrethrin II weak, positive patch test responses. Some other compounds derived from pyrethrum, viz. chrysanthemumic acid, the ethyl ester of this acid and its naturally occurring insecticidal esters, pyrethrin I, cinerin I and II, jasmolin I and II, and the synthetic ester allethrin and chrysanthemin, taraxasterol (pyrethrol) and tiglic acid produced negative patch test responses. In this patient, pyrethrosin, a sesquiterpene lactone which does not have insecticidal properties, was the principal allergenic fraction of pyrethrum derived from species of Chrysanthemum. Of the 8 esters of chrysanthemumic acid which were tested, pyrethrin II was also allergenic in this case.
Clinical profiles of multiple myeloma in Asia—An Asian Myeloma Network study
Authors: Kihyun Kim, Jae Hoon Lee, Jin Seok Kim, Chang Ki Min, Sung Soo Yoon, Kazuyuki Shimizu, Takaaki Chou, Hiroshi Kosugi, Kenshi Suzuki, Wenming Chen, Jian Hou, Jin Lu, Xiao‐Jun Huang, Shang‐Yi Huang, Wee Joo Chng, Daryl Tan, Gerrard Teoh, Chor Sang Chim, Weerasak Nawarawong, Noppadol Siritanaratkul, Brian G. Durie
Journal: American Journal of Hematology (2014)

The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However, the differences in clinical characteristics between ethnic groups are not well‐defined. In Asian countries, although the incidence of MM has been lower than that of Western countries, there is growing evidence that MM is increasing rapidly. The Asian Myeloma Network decided to initiate the first multinational project to describe the clinical characteristics of MM and the clinical practices in Asia. Data were retrospectively collected from 23 centers in 7 countries and regions. The clinical characteristics at diagnosis, survival rates and initial treatment of 3,405 symptomatic MM patients were described. Median age was 62 years (range, 19–106), with 55.6% of being male. Median overall survival (OS) was 47 months (95% CI 44.0–50.0). Stem cell transplantation was performed in 666 patients who showed better survival rates (79 vs. 41 months, P &lt; 0.001). The first‐line treatments of 2,970 patients were analyzed. The overall response rate was 71% including very good partial response or better in 31% of the 2,660 patients those were able to be evaluated. New drugs including bortezomib, thalidomide, and lenalidomide were used in 36% of 2,970 patients and affected OS when used as a first‐line treatment. Am. J. Hematol. 89:751–756, 2014. © 2014 Wiley Periodicals, Inc.
Abstract 4540: SAC abrogation by MPS1 kinase inhibition: preclinical proof of concept of a novel approach to tumor treatment
Authors: Dominik Mumberg, Gerhard Siemeister, Antje M. Wengner, Marcus Koppitz, Volker Schulze, Benjamin Bader, Stefan Prechtl, Bertolt Kreft, Karl Ziegelbauer
Journal: Cancer Research (2014)

Abstract Cell cycle deregulation represents one of the classical hallmarks of cancer and consequently cell cycle arrest is the predominant mode of action of a number of antimitotic cancer drugs (e.g. taxanes and vinca alkaloids). Targeted disruption of the cell cycle checkpoint offers a novel approach to cancer treatment: driving tumor cells into cell division despite DNA damage or unattached/misattached chromosomes resulting in a lethal degree of DNA damage or aneuploidy. MPS1, a mitotic kinase that is overexpressed in several human cancers, has been shown to function as the key kinase which activates the spindle assembly checkpoint (SAC) to secure proper distribution of chromosomes to daughter cells. Here, we report the identification and functional characterization of novel inhibitors of MPS1 from two structurally unrelated chemical classes. In biochemical assays, these molecules inhibited the kinase activity of MPS1 with IC50 values in the single digit nanomolar range and have shown an exquisite selectivity against a panel of kinases. In cellular assays the compounds were able to abrogate nocodazole-induced SAC, to reduce time in mitosis, to induce multinuclearity and apoptotic cell death, and to inhibit tumor cell proliferation with IC50 values in the low nanomolar range. In combination experiments MPS1 inhibitors showed cooperativity with low concentrations of paclitaxel. MPS1 inhibitors showed limited efficacy in monotherapy (T/C ca. 0.6) in tumor xenograft studies. However, when combined with paclitaxel dosed at the maximal tolerated dose, low doses of MPS1 inhibitor strongly improved efficacy over paclitaxel or MPS inhibitor monotreatment in intrinsically paclitaxel-insensitive xenograft models. The combination treatment was well tolerated. These results validate the concept of SAC abrogation preclinically and pave the way to a clinical proof of concept. Citation Format: Dominik Mumberg, Gerhard Siemeister, Antje M. Wengner, Marcus Koppitz, Volker Schulze, Benjamin Bader, Stefan Prechtl, Bertolt Kreft, Karl Ziegelbauer. SAC abrogation by MPS1 kinase inhibition: preclinical proof of concept of a novel approach to tumor treatment. [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 4540. doi:10.1158/1538-7445.AM2014-4540
Corrao's syndrome- a diagnostic dilemma in occupational setting
Authors: Agnieszka Lipinska-Ojrzanowska, Marta Wiszniewska, Jolanta Walusiak-Skorupa
Journal: European Respiratory Journal (2014)

Objectives: A cough-variant asthma (syn. Corrao9s syndrome) is defined as the presence of chronic non-productive cough in patients with bronchial hyperreactivity (BHR) and good response to bronchodilator therapy. This variant of asthma generates a diagnostic problem in occupational field. Exposure tests performed at the workplace are conventionally accepted as a diagnostic tool in occupational asthma (OA), however their findings may outcome in a false-negative result of cough-type asthma recognition.  Methods: A female beauty-professional was admitted to Occupational Diseases Department with suspicion of occupational allergic rhinitis and asthma. Number of objective clinical procedures were performed, including a single-blind, placebo-controlled specific inhalation challenge test (SICT) with cyanoacrylates glues used for applying artificial eyelashes and nails.  Results: Although the patient complained about sneezing, blocked-nose and stubborn cough, after the SICT with cyanoacrylates, declines of forced expiratory volume in one-second (FEV 1 ) and peak expiratory flow (PEF) in 24 hour-monitoring were not observed. Cytological assessment of nasal lavage revealed an increase in the percentage of eosinophils in samples collected 4 and 24h after the SICT. We found out a significant increase in BHR.  Conclusion:Positive clinical response to the SICT validated the diagnosis of a cough-type OA. Serial monitoring PEF as well as the FEV 1  measurements were not useful in the process of medical certification in this variant of OA.