tbuckley/cabot-search huggingface dataset:
Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma
Authors: Yasuhito Arai, Yasushi Totoki, Fumie Hosoda, Tomoki Shirota, Natsuko Hama, Hiromi Nakamura, Hidenori Ojima, Koh Furuta, Kazuaki Shimada, Takuji Okusaka, Tomoo Kosuge, Tatsuhiro Shibata
Journal: Hepatology (2013)

Cholangiocarcinoma is an intractable cancer, with limited therapeutic options, in which the molecular mechanisms underlying tumor development remain poorly understood. Identification of a novel driver oncogene and applying it to targeted therapies for molecularly defined cancers might lead to improvements in the outcome of patients. We performed massively parallel whole transcriptome sequencing in eight specimens from cholangiocarcinoma patients without KRAS/BRAF/ROS1 alterations and identified two fusion kinase genes, FGFR2-AHCYL1 and FGFR2-BICC1. In reverse-transcriptase polymerase chain reaction (RT-PCR) screening, the FGFR2 fusion was detected in nine patients with cholangiocarcinoma (9/102), exclusively in the intrahepatic subtype (9/66, 13.6%), rarely in colorectal (1/149) and hepatocellular carcinoma (1/96), and none in gastric cancer (0/212). The rearrangements were mutually exclusive with KRAS/BRAF mutations. Expression of the fusion kinases in NIH3T3 cells activated MAPK and conferred anchorage-independent growth and in vivo tumorigenesis of subcutaneous transplanted cells in immune-compromised mice. This transforming ability was attributable to its kinase activity. Treatment with the fibroblast growth factor receptor (FGFR) kinase inhibitors BGJ398 and PD173074 effectively suppressed transformation. FGFR2 fusions occur in 13.6% of intrahepatic cholangiocarcinoma. The expression pattern of these fusions in association with sensitivity to FGFR inhibitors warrant a new molecular classification of cholangiocarcinoma and suggest a new therapeutic approach to the disease.
Anatomic Basis of Tumor Surgery
Authors: Daniel J. Kacey
Journal: JAMA (2010)

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
The Clinical Course of Idiopathic Membranous Nephropathy.
Authors: James V. Donadio
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973The Clinical Course of Idiopathic Membranous Nephropathy.James V. Donadio Jr., M.D., F.A.C.P., Donald T. Erwin, M.D., Keith E. Holley, M.D.James V. Donadio Jr., M.D., F.A.C.P.Search for more papers by this author, Donald T. Erwin, M.D.Search for more papers by this author, Keith E. Holley, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-827_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIdiopathic membranous nephropathy, well defined morphologically, is usually associated with the nephrotic syndrome and has a variable disease course. We describe 36 patients with clinically and renal-biopsy defined idiopathic membranous nephropathy and the nephrotic syndrome and compare the effects of steroid treatment in one group (19 patients) with those of another group who did not receive steroids (17 patients) on the long-term clinical course (mean, 4.7 years). A third group of 7 patients with asymptomatic proteinuria is defined in whom none has developed either the nephrotic syndrome or renal failure after an average follow-up of 8.8 years.From known disease... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 827-828KeywordsProteinuriaRenal failure Issue Published: 1 May 1973 PDF DownloadLoading ...
Are increased individual susceptibility and environmental factors both necessary for the development of primary biliary cirrhosis?
Authors: J G Douglas, N D Finlayson
Journal: BMJ (1979)

A daughter, her mother, and an unrelated close friend developed primary biliary cirrhosis (PBC). The mother and the close friend nursed the daughter through her terminal illness and presented with PBC PBC within 21 months after her death. Half of the asymptomatic first-degree relatives in the two families had serum autoantibodies, including one with antimitochondrial antibody, suggesting some genetic susceptibility to abnormal immune reactions. It is concluded that some environmental factor may be present in PBC, perhaps in addition to a genetic susceptibility to that factor.
CANCER STATISTICS AS THEY APPEAR TO A PATHOLOGIST
Authors: H. GIDEON WELLS
Journal: JAMA (1927)

<h3>IS CANCER A GROWING MENACE?</h3> All statistics agree in indicating that the proportion of deaths recorded in civilized communities as the result of cancer has been increasing for several years, but the exact significance of this fact is not yet agreed on. It is perfectly evident that the average age of the people of these communities has also been increasing during the same period, partly from lowered birth rate, partly from reduction in the mortality from tuberculosis, typhoid, diphtheria and numerous other infectious diseases that attack the young, especially the infantile diseases. Obviously, every person saved from death in youth becomes a potential victim of cancer in later years, and consequently every improvement in public health leads to an increased cancer mortality. Should a means be found to cure or prevent effectively the last remaining large group of infectious diseases, the acute respiratory infections, there would result a marked augmentation
Who speaks for whom?
Authors: T. Richards
Journal: BMJ (1992)

the arrangements envisaged by the draft law could effectively force "moonlighting" (more accurately "daylighting") into a separately identifiable and independent subsystem. Vote in favourWith the need to enact the draft law becoming more urgent as each day passed, its sponsors showed that they had learnt how to succeed in the rough and tumble of parliamentary democracy.In a heated debate they not only argued the case but also, apparently, showed flexibility by accepting several amendments.They were rewarded by an overwhelming vote.For the record, the main opponents spoke for the Federation ofIndependent Trade Unions ofRussia; their criticisms turned on considerations of social justice.As Meditsinskaya Gazeta saw the matter, the vote was a victory for the committee chaired by Dr Askalonov, and consequently it devoted some column inches to his comments.These are remarkable for the absence of what is often identified as a failing of the Russian intelligentsia-namely, the tendency to assume that a theoretically consistent scheme can be made to work well in practice.By contrast, Dr Askalonov did not claim that insurance medicine will provide the cure for all ills.He recognised that its introduction, by 1993, must be preceded not only by the creation of the appropriate infrastructure but also by a public information programme, mention of which may be evidence of far more than concern with practical details: it may be held to flow from his acceptance that the scheme can only work well if it gains "social acceptability."7Fairly self evidently, the general public are more likely to have positive attitudes towards "insurance medicine" if they experience a clear improvement in the quality of care provided by the rank and file of Russian doctors.And in this connection it is reasonable to conclude that under the new scheme consumer choice and the forces of the market place should turn out to be powerful incentives for professional self improvement. 1Bliev Yu.
Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6
Authors: Qing Zhang, Baohui Zhao, Wei Li, Naoki Oiso, Edward K. Novak, Michael E. Rusiniak, Rashi Gautam, Sreenivasulu Chintala, Edward P. O'Brien, Yuke Zhang, Bruce A. Roe, Rosemary W. Elliott, Eva M. Eicher, Ping Liang, Christian Kratz, Eric Legius, Richard A. Spritz, T. Norene O'Sullivan, Neal G. Copeland, Nancy A. Jenkins, Richard T. Swank
Journal: Nature Genetics (2003)
Abdominal wound healing: a prospective clinical study.
Authors: T T Irvin, C J Stoddard, M G Greaney, H L Duthie
Journal: BMJ (1977)

The incidence of wound dehiscence and incisional hernia after two methods of abdominal wound closure (layered closure with retention sutures and single-layer "mass closure") was studied in a randomised prospective clinical trial in a consecutive series of 200 patients. Dehiscence occurred in 1% of patients and herniation in 4-7%; the incidence of these complications was similar with both methods of closure. Seven of the 11 cases of dehiscence or herniation occurred in infected wounds, and wound infection was associated with a tenfold increase in the incidence of these complications. The prevention of wound infection would reduce substantially the incidence of dehiscence and herniation in abdominal wounds.
TCT-873 Results of Transfemoral Aortic Valve Implantation (TF-TAVI) performed by External Cardiologists in Collaboration with an Experienced Multidisciplinary Heart Team at a Specialized Center
Authors: Philipp Kahlert, Fadi Al-Rashid, Stefan Möhlenkamp, Rainer Wessely, Bjoern Plicht, Daniel Wendt, Matthias Thielmann, Heinz Jakob, Raimund Erbel, Thomas Konorza
Journal: Journal of the American College of Cardiology (2012)
Isoform-specific regulation of myocardial Na,K-ATPase alpha-subunit in congestive heart failure. Role of norepinephrine.
Authors: C H Kim, T H Fan, P F Kelly, Y Himura, J M Delehanty, C L Hang, C S Liang
Journal: Circulation (1994)

BACKGROUND Myocardial ouabain-binding sites and Na,K-ATPase activity are reduced in congestive heart failure (CHF), but the mechanisms by which CHF reduces the Na,K-ATPase remain unknown. We proposed to investigate whether the changes are accompanied by isoform-specific reductions of the Na,K-ATPase alpha-subunit proteins in CHF and whether similar changes could be produced by exogenous norepinephrine administration. METHODS AND RESULTS CHF was induced in dogs by rapid ventricular pacing at a rate of 225 beats per minute for 8 weeks (protocol 1). A second group of dogs were paced at 100 beats per minute and served as controls. In protocol 2, norepinephrine was infused in normal dogs using a subcutaneous osmotic minipump for 8 weeks. The control dogs received normal saline through the pump. Animals were studied after 8 weeks of pacing or norepinephrine infusion. After the baseline hemodynamics and interstitial norepinephrine concentration had been obtained, the hearts were removed for measuring [3H]ouabain-binding sites and Na,K-ATPase alpha-subunit proteins using isoform-specific monoclonal antibodies. RESULTS Myocardial [3H]ouabain-binding sites were reduced in dogs with CHF and chronic norepinephrine infusion. The Western blot analysis showed that adult canine hearts possess both alpha 1 and alpha 3 isoforms of the Na,K-ATPase alpha-subunit but not the alpha 2 isoform protein. CHF and NE infusion had no effect on the Na,K-ATPase alpha 1-subunit protein but did reduce the alpha 3 isoform protein significantly. In addition, there was a significant inverse correlation between the amount of myocardial alpha 3 isoform protein and interstitial norepinephrine content in the dogs. In contrast, the specific activity of the sarcolemmal marker 5'-nucleotidase did not differ among the groups of animals. CONCLUSIONS The reduction of myocardial Na,K-ATPase in CHF is limited to the alpha 3 isoform. Furthermore, because similar changes in myocardial ouabain-binding sites and Na,K-ATPase alpha 3 isoform were produced by chronic norepinephrine infusion, the decrease in the Na,K-ATPase in CHF is most likely mediated via excess sympathetic stimulation.
Apolipoprotein CIII Induces Expression of Vascular Cell Adhesion Molecule-1 in Vascular Endothelial Cells and Increases Adhesion of Monocytic Cells
Authors: Akio Kawakami, Masanori Aikawa, Pilar Alcaide, Francis W. Luscinskas, Peter Libby, Frank M. Sacks
Journal: Circulation (2006)

Background— Activation of vascular endothelial cells (ECs) plays an important role in atherogenesis and plaque instability. Lipoproteins containing apolipoprotein CIII (apoCIII) predict coronary heart disease (CHD). We recently reported that apoCIII has a proinflammatory effect on human monocytes. In this study, we looked for a direct effect of apoCIII on EC expression of adhesion molecules, leading to monocytic cell adhesion. Methods and Results— Treatment of ECs with apoCIII or apoCIII-rich VLDL caused human monocytic THP-1 cells to adhere to them under static condition or under laminar sheer stress (1.0 dyne/cm 2 ). ApoCIII increased EC expression of vascular cell adhesion molecule-1 (VCAM-1) protein and intercellular cell adhesion molecule-1 (ICAM-1) protein (4.9±1.5-fold and 1.4±0.5-fold versus control, respectively). Furthermore, apoCIII remarkably increased membrane-bound protein kinase C (PKC) β in ECs, indicating activation. A selective inhibitor of PKCβ prevented the rise in VCAM-1 and THP-1 cell adhesion to ECs. Moreover, exposure of ECs to apoCIII induced nuclear factor-κB (NF-κB) activation. PKCβ inhibition abolished apoCIII-induced NF-κB activation, and NF-κB inhibition reduced expression of VCAM-1, each resulting in reduced THP-1 cell adhesion. ApoCIII-rich VLDL also activated PKCβ and NF-κB in ECs and increased expression of VCAM-1. Pretreatment of ApoCIII-rich VLDL with anti-apoCIII neutralizing antibody abolished its effect on PKCβ activation. Conclusions— Our findings provide the first evidence that apoCIII increases VCAM-1 and ICAM-1 expression in ECs by activating PKCβ and NF-κB, suggesting a novel mechanism for EC activation induced by dyslipidemia. Therefore, apoCIII-rich VLDL may contribute directly to atherogenesis by activating ECs and recruiting monocytes to them.
Generation of Humanized Mice Susceptible to Peptide-Induced Inflammatory Heart Disease
Authors: Kurt Bachmaier, Nikolaus Neu, Rae S. M. Yeung, Tak W. Mak, Peter Liu, Josef M. Penninger
Journal: Circulation (1999)

Background −Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death. In certain mouse major histocompatibility complex (MHC) backgrounds, myocarditis and inflammatory cardiomyopathy can be triggered by immunization with heart muscle–specific proteins. Similarly, chronic heart disease in humans has been linked to certain HLA alleles, such as HLA-DQ6. However, there is no experimental evidence showing that human MHC class II molecules and peptides derived from human proteins are involved in the pathogenesis of myocarditis and DCM. Methods and Results —We generated double CD4- and CD8-deficient mice transgenic for human CD4 (hCD4) and human HLA-DQ6 to specifically reconstitute the human CD4/DQ6 arm of the immune system in mice. Transgenic hCD4 and HLA-DQ6 expression rendered genetically resistant C57BL/6 mice susceptible to the induction of autoimmune myocarditis induced by immunization with cardiac myosin. Moreover, we identified heart-specific peptides derived from both mouse and human α-myosin heavy chains capable of inducing inflammatory heart disease in hCD4 and HLA-DQ6 double transgenic mice but not in hCD4 single transgenic littermates. The autoimmune inflammatory heart disease induced by the human heart muscle–specific peptide in hCD4 and HLA-DQ6 double transgenic mice shared functional and phenotypic features with the disease occurring in disease-susceptible nontransgenic mice. Conclusions —Our data provide the first genetic and functional evidence that human MHC class II molecules and a human α-myosin heavy chain–derived peptide can cause inflammatory heart disease and suggest that human inflammatory cardiomyopathy can be caused by organ-specific autoimmunity. The humanized mice generated in this study will be an ideal animal model to further elucidate the pathogenesis of inflammatory heart disease and facilitate the development of rational treatment strategies.
Not a bridge but an organismic (general and causal) neuropsychology should make a difference in emotion theory
Authors: Juan Pascual-Leone
Journal: Behavioral and Brain Sciences (2005)

Does Lewis imply that brain processes might be used to replace an as-yet-unavailable substantive organismic neuropsychology? To counteract this reductionist idea I argue for distinguishing between affects and emotions, and discuss a real-life example of implicit emotional appraisal. Failure to use organismic units of processing such as schemes or schemas makes the bridging attempt fall under a reductionist “mereological fallacy.”
Trends in Authorship
Authors: ROBERT S. ALEXANDER
Journal: Circulation Research (1953)

A major (rend in the organization of .scienceduring the past two decades has been an evolution away from the individual investigator in favor of research teams.Accompanying this trend, scientific publications have become afflicted with an increasing tendency towards multiple authorship of papers.Almost any scientific journal will reveal this affliction.In the case of the journal CIRCULATION, volumes 3 through 6, covering the years 1951 and 1952, included 348 papers, of which almost one third (106) had four or more authors.Of these, 35, or JO per cent of the total, had five or more authors; five papers had seven or more authors.These percentages were intermediate to the findings in the American Journal of Physiology, volumes 167 to 171, which yielded 17 per cent of 397 papers having four or more authors, and the Journal of Clinical Investigation, volumes 29 to 30, which revealed 35 per cent of 337 papers with four or more authors.These figures .shouldbe contrasted with those for the first 10 volumes of the American Journal of Physiology (1898)(1899)(1900)(1901)(1902)(1903) in which not a single paper having more than three authors could be found, and the first six volumes of the Journal of Clinical Investigation (1924)(1925)(1926)(1927)(1928)(1929) in which only five per cent of the papers had four or more authors.CIRCULATION lUisEAiicir is too much in its infancy to yield valid statistics, but it is of interest that 27 per cent of all manuscripts so far submitted to the editor have had four or more authors.Is this trend necessary or de-,sirable?At the risk of being presumptuous, we would define the requisites for authorship of a 2S1
Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure
Authors: A Cittadini
Journal: Cardiovascular Research (2003)

To investigate the effects of aldosterone receptor blockade in postinfarction heart failure.Eighty-seven rats with moderate myocardial infarction were randomized to receive either no drug or canrenone, the active metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a combination of the two drugs. Treatment was initiated 1 month after coronary ligation and lasted 4 weeks. Echocardiography was performed at baseline and after 4 weeks. LV catheterization, isolated heart studies, morphometric histology, myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the treatment period.Infarct sizes were 33+/-3, 32+/-3, 34+/-3, and 34+/-4% in the placebo, canrenone, ramipril, and combination groups, respectively. Canrenone attenuated LV remodeling, improved LV systolic and diastolic function, and markedly reduced interstitial and perivascular fibrosis. These effects were increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine content was decreased while ventricular fibrillation threshold significantly augmented by canrenone. SERCA-2 levels remained unchanged.Canrenone attenuated LV dilation and interstitial remodeling, and improved LV filling dynamics and systolic function in the rat model of postinfarction heart failure. Addition of ramipril conferred further cardioprotection. Canrenone also reduced myocardial norepinephrine content and increased ventricular fibrillation threshold. The data provide a potential explanation for the decreased sudden death observed in the RALES study. The mechanisms of action of aldosterone inhibition are still poorly understood, despite its proven efficacy in heart failure. Rats with postinfarction heart failure were randomized to receive for 1 month either no drug or canrenone, or ramipril, or a combination of canrenone and ramipril. Canrenone treatment was associated with a significant attenuation of LV dilation, better LV diastolic and systolic dynamics, and a marked reduction of reactive fibrosis. These effects were enhanced by concomitant ramipril therapy. Moreover, canrenone increased ventricular fibrillation threshold and reduced myocardial norepinephrine content. The data may explain the reduced mortality demonstrated by the RALES.
The effect of platelet rich plasma on angiogenesis in ischemic flaps in VEGFR2-luc mice
Authors: Tolga Taha Sönmez, Alexandra Vinogradov, Fatih Zor, Nisreen Kweider, Sebastian Lippross, Elisa Anamaria Liehn, Mustafa Naziroglu, Frank Hölzle, Christoph Wruck, Thomas Pufe, Mersedeh Tohidnezhad
Journal: Biomaterials (2013)
A Tumorigenic Subpopulation with Stem Cell Properties in Melanomas
Authors: Dong Fang, Thiennga K. Nguyen, Kim Leishear, Rena Finko, Angela N. Kulp, Susan Hotz, Patricia A. Van Belle, Xiaowei Xu, David E. Elder, Meenhard Herlyn
Journal: Cancer Research (2005)

Abstract Recent studies suggest that cancer can arise from a cancer stem cell (CSC), a tumor-initiating cell that has properties similar to those of stem cells. CSCs have been identified in several malignancies, including those of blood, brain, and breast. Here, we test whether stem cell–like populations exist in human melanomas. In ∼20% of the metastatic melanomas cultured in growth medium suitable for human embryonic stem cells, we found a subpopulation of cells propagating as nonadherent spheres, whereas in standard medium, adherent monolayer cultures were established. Individual cells from melanoma spheres (melanoma spheroid cells) could differentiate under appropriate conditions into multiple cell lineages, such as melanocytic, adipocytic, osteocytic, and chondrocytic lineages, which recapitulates the plasticity of neural crest stem cells. Multipotent melanoma spheroid cells persisted after serial cloning in vitro and transplantation in vivo, indicating their ability to self-renew. Furthermore, they were more tumorigenic than adherent cells when grafted to mice. We identified similar multipotent spheroid cells in melanoma cell lines and found that the stem cell population was enriched in a CD20+ fraction of melanoma cells. Based on these findings, we propose that melanomas can contain a subpopulation of stem cells that contribute to heterogeneity and tumorigenesis. Targeting this population may lead to effective treatments for melanomas.