tbuckley/cabot-search huggingface dataset:
GENO-01MOLECULAR INTERROGATION OF GLIOBLASTOMA MULTIFORME TUMORS IDENTIFIES A COMPLEX NETWORK OF CELL SIGNALLING PATHWAYS WITH POSSIBLE THERAPEUTIC IMPLICATIONS
Authors: Dadasaheb Akolkar, Alok Ranjan, Shekhar Chirmade, Sasidhar Mandal, Pradeep Devhare, Pooja Fulmali, Sachin Apurva, Amit Ray
Journal: Neuro-Oncology (2015)

The precise molecular mechanism behind Glioblastoma Grade IV with extremely poor treatment outcome for patients with even intensive therapy regimen is yet to be completely understood. GBMs represent approximately 17% of all primary brain tumours diagnosed worldwide, and 60-75% of astrocytomas, increasing in frequency with age (WHO and IARC, 2008). Recent research has revealed four distinct subtypes based on multiple genetic alterations which have prognostic and therapeutic implications. Present study was performed to characterize global genomic analysis from ten GBM patients to study the molecular mechanisms and pathways associated with tumorigenesis and to understand the cause of therapy failure. Here we show that molecular interrogation clearly identifies GBM subtypes which seem to have distinct prognostic outcomes. Importantly, pathways known to play a role in the cancer stem cell (CSC) proliferation were found to be activated in several tumor specimens. Significantly, CSCs have been implicated in tumor maintenance and relapse after surgical resection. Most current anti-cancer drugs, small molecule inhibitors and monoclonal antibodies are designed to target rapidly proliferating cells which represent committed cancer cells but not CSCs and hence may partly explain cause of therapy failure. Further, multiple pathway activation in the GBM population calls for immediate attention to consider development of combination regimens / new target based drug development in GBMs. This could be an alternative to the template regimen which has now resulted in plateaued overall survival. We also observed a possible abetment by the metabolic engine in tumor progression and would need more study to consider its importance in GBM grading. Study further supports the urgent need for identifying global molecular signatures in GBM patients to align treatment for better outcomes and improved overall survivals.
Treatment of nortriptyline's side effects in elderly patients: a double- blind study of bethanechol
Authors: J Rosen, B G Pollock, L P Altieri, E A Jonas
Journal: American Journal of Psychiatry (1993)

A double-blind, placebo-controlled study of bethanechol was conducted in 26 elderly depressed patients being treated with nortriptyline. Patients receiving bethanechol had reduced subjective complaints of anticholinergic side effects and showed a trend toward improvement on an objective measure of salivary flow. The potential use of bethanechol in older patients to reduce morbidity and improve compliance with medication regimens is discussed.
OP0138 Pain at Multiple Sites Outside the Knee Predicts Knee Cartilage Volume Loss: A Prospective Study in Older Adults
Authors: F. Pan, C. Ding, L.L. Laslett, J. Tian, T. Winzenberg, F. Cicuttini, G. Jones
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Knee osteoarthritis (OA) is commonly associated with joint pain at multiple sites <sup>1,2</sup>. Whether this pain is associated with cartilage loss in the knee is unknown. <h3>Objectives</h3> To determine whether joint pain at multiple sites is a predictor of cartilage loss in the knee amongst older community–dwelling adults and whether this reflects more severe disease or shared risk factors. <h3>Methods</h3> Data from the prospective Tasmanian Older Adult Cohort study (n=394; mean age, 63 years; range from 52 to 79) was used. Pain experience in the different joints was measured by a questionnaire at baseline. T1-weighted fat saturated MRI of the right knee was performed to assess the cartilage volume at baseline and after 2.7 years. Linear regression modelling was used with adjustment for potential confounders. <h3>Results</h3> The median number of painful sites was 3 (range from 0 to 7). Participants reporting more painful joints had greater cartilage volume loss at lateral and total but not medial tibiofemoral compartments. A strong linear relationship between number of painful joints and cartilage volume loss at lateral tibiofemoral and total compartments was observed in univariate analysis, and remained significant in multivariate analysis (β = -0.28% to -0.25% per annum, P&lt;0.05 for all comparisons). In subgroup analyses, there was a dose-response relationship for lateral and total tibiofemoral cartilage volume loss with increasing number of painful joints (all adjusted P for trend&lt;0.05) in participants without radiographic OA. These significant associations were independent of severity of knee pain or radiographic OA, knee structures and body mass index as well as other potential confounding factors. However, no significant associations were found in any compartments for participants with radiographic OA. <h3>Conclusions</h3> The number of painful joints independently predicts cartilage volume loss especially in people without radiographic OA, suggesting that widespread joint pain may be a marker of risk for more rapid early cartilage loss possibly mediated by systemic, central or genetic factors. <h3>References</h3> Dieppe PA, Lohmander LS. Pathogenesis and management of pain in osteoarthritis. Lancet 2005;365:965-73. Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol 2013;9:654-64. <h3>Disclosure of Interest</h3> None declared
Behavioral predictors of amitriptyline response in depression
Authors: C J Ranelli, R E Miller
Journal: American Journal of Psychiatry (1981)

In this study of 18 female depressed patients and 18 age- and sex-matched control subjects, the authors examined the relationship between nonverbal behavior and treatment outcome with amitriptyline. A behavioral analysis indicated that amitriptyline responders could be differentiated from nonresponders before drug treatment on the basis of discrete nonverbal behaviors. Nonresponders showed a high frequency of body-focused self-adaptors, posture shifts, and pauses and a low frequency of smiles, while responders displayed long speech pauses and long durations of head aversion.
Squeezing through the Now-or-Never bottleneck: Reconnecting language processing, acquisition, change, and structure
Authors: Nick Chater, Morten H. Christiansen
Journal: Behavioral and Brain Sciences (2016)

Abstract If human language must be squeezed through a narrow cognitive bottleneck, what are the implications for language processing, acquisition, change, and structure? In our target article, we suggested that the implications are far-reaching and form the basis of an integrated account of many apparently unconnected aspects of language and language processing, as well as suggesting revision of many existing theoretical accounts. With some exceptions, commentators were generally supportive both of the existence of the bottleneck and its potential implications. Many commentators suggested additional theoretical and linguistic nuances and extensions, links with prior work, and relevant computational and neuroscientific considerations; some argued for related but distinct viewpoints; a few, though, felt traditional perspectives were being abandoned too readily. Our response attempts to build on the many suggestions raised by the commentators and to engage constructively with challenges to our approach.
Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma
Authors: Zhang Xiao Ying, Meiyan Jin, Luke F. Peterson, Denzil Bernard, Kamlai Saiya-Cork, Mehmet Yildiz, Shaomeng Wang, Mark S. Kaminski, Alfred E. Chang, Daniel J. Klionsky, Sami N. Malek
Journal: Clinical Cancer Research (2016)

Abstract Purpose: This study was performed to further our understanding of the biological and genetic basis of follicular lymphoma and to identify potential novel therapy targets. Experimental Design: We analyzed previously generated whole exome sequencing data of 23 follicular lymphoma cases and one transformed follicular lymphoma case and expanded findings to a combined total of 125 follicular lymphoma/3 transformed follicular lymphoma. We modeled the three-dimensional location of RRAGC-associated hotspot mutations. We performed functional studies on novel RRAGC mutants in stable retrovirally transduced HEK293T cells, stable lentivirally transduced lymphoma cell lines, and in Saccharomyces cerevisiae. Results: We report recurrent mutations, including multiple amino acid hotspots, in the small G-protein RRAGC, which is part of a protein complex that signals intracellular amino acid concentrations to MTOR, in 9.4% of follicular lymphoma cases. Mutations in RRAGC distinctly clustered on one protein surface area surrounding the GTP/GDP–binding sites. Mutated RRAGC proteins demonstrated increased binding to RPTOR (raptor) and substantially decreased interactions with the product of the tumor suppressor gene FLCN (folliculin). In stable retrovirally transfected 293T cells, cultured in the presence or absence of leucine, multiple RRAGC mutations demonstrated elevated MTOR activation as evidenced by increased RPS6KB/S6-kinase phosphorylation. Similar activation phenotypes were uncovered in yeast engineered to express mutations in the RRAGC homolog Gtr2 and in multiple lymphoma cell lines expressing HA-tagged RRAGC-mutant proteins. Conclusions: Our discovery of activating mutations in RRAGC in approximately 10% of follicular lymphoma provides the mechanistic rationale to study mutational MTOR activation and MTOR inhibition as a potential novel actionable therapeutic target in follicular lymphoma. Clin Cancer Res; 22(21); 5383–93. ©2016 AACR.
<i>CYP2C8</i> and <i>SLCO1B1</i> Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes
Authors: Adem Y. Dawed, Louise Donnelly, Roger Tavendale, Fiona Carr, Graham Leese, Colin N.A. Palmer, Ewan R. Pearson, Kaixin Zhou
Journal: Diabetes Care (2016)

Thiazolidinediones (TZDs) are putatively transported into the liver by OATP1B1 (encoded by SLCO1B1) and metabolized by CYP450 2C8 enzyme (encoded by CYP2C8). While CYP2C8*3 has been shown to alter TZD pharmacokinetics, it has not been shown to alter efficacy.We genotyped 833 Scottish patients with type 2 diabetes treated with pioglitazone or rosiglitazone and jointly investigated association of variants in these two genes with therapeutic outcome.The CYP2C8*3 variant was associated with reduced glycemic response to rosiglitazone (P = 0.01) and less weight gain (P = 0.02). The SLCO1B1 521T>C variant was associated with enhanced glycemic response to rosiglitazone (P = 0.04). The super responders defined by combined genotypes at CYP2C8 and SLCO1B1 had a 0.39% (4 mmol/mol) greater HbA1c reduction (P = 0.006) than the poor responders. Neither of the variants had a significant impact on pioglitazone response.These results show that variants in CYP2C8 and SLCO1B1 have a large clinical impact on the therapeutic response to rosiglitazone and highlight the importance of studying transporter and metabolizing genes together in pharmacogenetics.
Nerve growth factor is involved in the supportive effect by bone marrow- -derived stromal cells of the factor-dependent human cell line UT-7 [published erratum appears in Blood 1996 Oct 1;88(7):2818]
Authors: I Auffray, S Chevalier, J Froger, B Izac, W Vainchenker, H Gascan, L Coulombel
Journal: Blood (1996)
Chronic Hepatitis
Authors: JAMES W. DEFORD
Journal: Annals of Internal Medicine (1975)

Comments and Correction1 October 1975Chronic HepatitisJAMES W. DEFORD, M.D.JAMES W. DEFORD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-4-581_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The editorial by Henley and Appelman (Ann Intern Med 82:840-841, 1975) focuses attention on the improved prognosis of patients with chronic active hepatitis occasioned by the evolvement of effective therapy (1). It is not my purpose to disagree with this position, but to raise certain questions regarding therapy in this disorder.While the Mayo Clinic group has shown through their careful studies that the prognosis of severe chronic active hepatitis (defined biochemically as a sustained tenfold elevation of the serum glutamic oxalacetic transaminase (SGOT) or the combination of a fivefold elevation of the SGOT with a twofold...References1. SOLOWAYSUMMERSKILLBAGGENSTOSS RWA: Clinical, biochemical and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology 63:820-833, 1972 CrossrefMedlineGoogle Scholar2. SUMMERSKILLKORMANAMMON WMH: Prednisone for chronic active liver disease (CALD): dose titration, standard dose and combination with azathioprine compared. Gastroenterology 67:830, 1974 Google Scholar1. GUDATBIANCHISONNABEND FLW: Pattern of core and surface expression in liver tissue reflects state of specific immune response in hepatitis B. Lab Invest 32:1-9, 1975 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: USAF MC Gastroenterology Service Wilford Hall USAF Medical Center Lackland Air Force Base, Texas 78236 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByChronic Hepatitis: TherapyPATRICK J. ROONEY 1 October 1975Volume 83, Issue 4Page: 581-582KeywordsAminotransferasesChronic hepatitisHepatitis ASerum glutamic oxaloacetic transaminase Issue Published: 1 October 1975 PDF DownloadLoading ...
Studies on the Blood Supply of Tumors in Man. III. Vascular Patterns of the Liver by Hepatic Arteriography &lt;italic&gt;in Vivo&lt;/italic&gt;&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Howard R. Bierman, M. D., Ralph L. Byron, Jr., M. D., Keith H. Kelley, M. D., Alice Grady, M. D.
Journal: JNCI Journal of the National Cancer Institute (1951)

Studies on the Blood Supply of Tumors in Man. III. Vascular Patterns of the Liver by Hepatic Arteriography in Vivo Get access Howard R. Bierman, M. D., Howard R. Bierman, M. D. Laboratory of Experimental Oncology, National Cancer Institute4 and the Divisions of Medicine and Radiology and Cancer Research Institute, University of California School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ralph L. Byron, Jr., M. D., Ralph L. Byron, Jr., M. D. Laboratory of Experimental Oncology, National Cancer Institute4 and the Divisions of Medicine and Radiology and Cancer Research Institute, University of California School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Keith H. Kelley, M. D., Keith H. Kelley, M. D. Laboratory of Experimental Oncology, National Cancer Institute4 and the Divisions of Medicine and Radiology and Cancer Research Institute, University of California School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alice Grady, M. D. Alice Grady, M. D. Laboratory of Experimental Oncology, National Cancer Institute4 and the Divisions of Medicine and Radiology and Cancer Research Institute, University of California School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 1, August 1951, Pages 107–131, https://doi.org/10.1093/jnci/12.1.107 Published: 01 August 1951 Article history Received: 03 April 1951 Published: 01 August 1951
Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice
Authors: Yuho Najima, Mariko Tomizawa-Murasawa, Yoriko Saito, Takashi Watanabe, Rintaro Ono, Toshiki Ochi, Nahoko Suzuki, Hiroshi Fujiwara, Osamu Ohara, Leonard D. Shultz, Masaki Yasukawa, Fumihiko Ishikawa
Journal: Blood (2015)
Paper Partition Chromatography of Free Amino Acids and Peptides of Normal Human Saliva&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: J. Rothwell Moor, M. S., D. Rourke Gilligan, M. S.
Journal: JNCI Journal of the National Cancer Institute (1951)

Paper Partition Chromatography of Free Amino Acids and Peptides of Normal Human Saliva Get access J. Rothwell Moor, M. S., J. Rothwell Moor, M. S. Laboratories of Pathology of the Harvard Cancer Commission and the New England Deaconess Hospital, Boston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Rourke Gilligan, M. S. D. Rourke Gilligan, M. S. Laboratories of Pathology of the Harvard Cancer Commission and the New England Deaconess Hospital, Boston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 3, December 1951, Pages 691–697, https://doi.org/10.1093/jnci/12.3.691 Published: 01 December 1951 Article history Received: 01 August 1951 Published: 01 December 1951
THU0268 Visual Complications in Giant Cell Arteritis – Beyond Inflammation: Table 1.
Authors: A. Hočevar, Ž. Rotar, R. Ješe, N. Potočnik, N. Gašperšič, S. Praprotnik, M. Tomšič
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Permanent visual loss, one of the most severe ischemic complications of giant cell arteritis (GCA), affects 6% of patients at our secondary/tertiary rheumatology center despite a fast track GCA diagnostic procedure. <h3>Objectives</h3> To determine potential clinical and laboratory markers forecasting visual complications in GCA. <h3>Methods</h3> We performed a paper chart review of GCA cases diagnosed between 01.09.2011 and 31.12.2014. Descriptive statistics was used to describe our cohort and appropriate post hoc tests to compare characteristics of patients with/without visual complications. <h3>Results</h3> During the 40-month observation period, 83 new GCA cases (70% female) were identified. The median (interquartile range (IQR), range) symptom duration at presentation was 30 days (IQR 14-78 days, range 2-880). 28 patients (33.7%) reported of visual symptoms: blurred vision (16), diplopia (8), amaurosis fugax (5); permanent visual loss (5; all unilateral; in 1 patient after glucocorticoids), and ptosis (1). Conventional cardiovascular risk factors: obesity, arterial hypertension, hyperlipidemia, diabetes mellitus were not associated with visual complications in our cohort. Visual manifestations were significantly more common in patients with permanent atrial fibrillation (AF) (p=0.027). 80% of patients with AF were on anticoagulants. The mean erythrocyte sedimentation rate (69 vs 85 mm/h; p=0.007), C reactive protein (31 vs 93 mg/l, p=0.011) and platelet count (372 vs 405×10<sup>9</sup>/l, p=0.001) were lower in patients with visual symptoms than in those without them. Antiphospholipid antibodies were not associated with visual symptoms. <h3>Conclusions</h3> Visual complications were significantly more common in patients with AF which has so far not been reported. The presence of the conventional cardiovascular risk factors, antiphospholipid antibodies seem not to contribute to visual complications. <h3>Disclosure of Interest</h3> None declared
A confirmation of NIMH training objectives for consultation-liaison residents
Authors: S M Saravay, H Steinberg, S P Solomon, G K Hong
Journal: American Journal of Psychiatry (1984)

Data from a 4-year prospective study suggest that the objectives of the NIMH Psychiatry Education Branch for psychiatry residents in regard to consultation-liaison training can be achieved. Residents developed a more positive view about consultation-liaison psychiatry and saw themselves more as integral members of the general hospital; some were influenced to pursue postgraduate consultation-liaison positions.
Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012
Authors: J A Bettinger, I Rouleau, M C Gariépy, W R Bowie, L Valiquette, O G Vanderkooi, J D Kellner, B L Coleman, S A McNeil, A McCarthy, G De Serres
Journal: Eurosurveillance (2015)

Preview this article: Successful methodology for large-scale surveillance of severe events following influenza vaccination in Canada, 2011 and 2012, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/20/29/art21189-en-1.gif
P0640 : Effect of the combination of the HBV core inhibitor NVR 3-778 with nucleoside analogs or other HBV core inhibitors on the inhibition of HBV DNA replication in HepG2.2.15 cells
Authors: A. Lam, C. Espiritu, O. Flores, G. Hartman, K. Klumpp
Journal: Journal of Hepatology (2015)
Effect of Experimental Congestive Heart Failure and Acetyl Strophanthidin on Myocardial Electrolyte and Water Content
Authors: HARRY A. BLISS, ROBERT J. ADOLPH
Journal: Circulation Research (1963)

The syndrome of chronic congestive heart failure was produced in female dogs by progressive pulmonary artery constriction. A factorial experimental design, containing seven experiments of four dogs each, was employed. Each experiment was completed in one day and consisted of two groups of two dogs each, one group containing dogs with heart failure and the other, normal dogs. One animal from each group received intravenous acetyl strophanthidin, 0.015 mg/kg ascites-free weight, while the other was given an injection of inert material. The heart was quickly removed from the chest nine minutes after the injection and the right ventricle was taken for analysis. Previous work indicated that this dose of the drug produced and inotropic effect both in normal animals and in dogs with heart failure without producing digitalis toxicity. The myocardium from animals with congestive heart failure contained significantly less potassium but more sodium, chloride, and water per kilogram of dry fat-free blood-free myocardium than the myocardium from normal dogs. The concentration of sodium plus potassium in tissue water was subnormal in failing hearts. The sodium and chloride composition of the fluid gained by failing hearts differed significantly from that of interstitial fluid. Acetyl strophanthidin increased myocardial chloride and water. Although potassium in the myocardium was unchanged in treated control dogs, it increased significantly after acetyl strophanthidin in animals with heart failure. The findings are consistent with myocardial cellular swelling in congestive heart failure. The quantity of blood in each kilogram of failing myocardial tissue was severely reduced, probably because of muscle fiber hypertrophy. The possibility is considered that this alteration, together with the increased tissue water, may lead to lowered oxygen tension in failing heart muscle. It is suggested that digitalis exerts two opposing effects on ion transport through the myocardial cell membrane and that neither of these is fundamental to its inotropic action.