tbuckley/cabot-search huggingface dataset:
Discovery in Context: Leveraging Multidimensional Glioblastoma Datasets to Identify Targetable Regulatory Networks
Authors: Ivan Babic, Paul S. Mischel
Journal: Cancer Discovery (2012)

Abstract Summary: The Cancer Genome Atlas (TCGA) promises to transform the treatment of patients with cancer by identifying new drug targets. However, extracting mechanistically insightful, therapeutically actionable information from complex multidimensional datasets remains a significant challenge. In this issue of Cancer Discovery, Genovese and colleagues apply a context-dependent modeling algorithm to the glioblastoma TCGA datasets and couple it with functional genetic screens and experimental validation to identify a novel, and potentially targetable, microRNA-mediated regulatory pathway. Cancer Discov; 2(8); 676–8. ©2012 AACR. Commentary on Genovese et al., p. 736.
Secretory Leukocyte Protease Inhibitor Antagonizes Paclitaxel in Ovarian Cancer Cells
Authors: Nabila Rasool, William LaRochelle, Haihong Zhong, Gulshan Ara, Joshua Cohen, Elise C. Kohn
Journal: Clinical Cancer Research (2010)

Ovarian cancer recurrence with the development of paclitaxel resistance is an obstacle to long-term survival. We showed that secretory leukocyte protease inhibitor (SLPI) is a survival factor for ovarian cancer. We hypothesize that SLPI may antagonize paclitaxel injury.Differential SLPI induction in response to paclitaxel and in response to stable forced expression of SLPI was shown in A2780-1A9 cells and their paclitaxel-resistant sublines, PTX10 and PTX22, and confirmed with HEY-A8 cells. SLPI-mediated survival was reduced by the MAP/extracellular signal-regulated kinase (ERK) kinase inhibitor, U0126, and a humanized neutralizing monoclonal anti-SLPI antibody, CR012. OVCAR3 xenographs tested the role of CR012 in vivo.SLPI expression was lower in A2780-1A9 ovarian cancer cells than in PTX10 and PTX22, and SLPI was induced by paclitaxel exposure. Stable SLPI expression yielded a proliferation advantage (P = 0.01); expression of and response to SLPI in OVCAR3 cells were abrogated by exposure to CR012. SLPI reduced the paclitaxel susceptibility of 1A9 and HEY-A8 cells (P <or= 0.05), and SLPI expression did not increase the resistance of PTX10 and PTX22 cells. Both paclitaxel and SLPI overexpression induced ERK activation. Inhibition of MAP/ERK kinase with U0126 increased paclitaxel injury and overcame SLPI-mediated cell protection. It did not reinstate PTX10 sensitivity to paclitaxel, which was associated with AKT activation. Significant inhibition of OVCAR3 xenograft growth was observed with CR012 and paclitaxel, over single agents (P <or= 0.001).A two-pronged approach confirmed that SLPI overcomes paclitaxel in part through activation of ERK1/2. These results credential SLPI as a molecular target for ovarian cancer and suggest CR012 as a tool for proof of concept.
Women who regret sterilisation.
Authors: B Alderman
Journal: BMJ (1977)

In an attempt to compensate for a lack of a control group in R.M.L. Winston's paper concerning women who regret sterilization, data are presented from the information gathered on a total of 1081 women sterilized consecutively at the Women's Hospital at Liverpool. 614 of the 1081 were traced 24-42 months later. 8.8% of the women indicated that they regretted having been sterilized. The most common reason for regretting the sterilization was a desire to bear children with a new partner. The age distribution at the time of the sterilization of patients who subsequently regretted the procedure suggests that sterilization performed at a young age is more likely to lead to regret. These "regrets" did not all result in requests for reversal of the procedure, which is in accord with Winston's findings. The association between parity and subsequent regret of the procedure was not as clear. It would not be wise to refuse young women sterilization, although patients sterilized at a young age appear to run an increased risk of regretting their sterilization. Instead, there should be careful counseling of the very young prior to sterilization, particularly with a view to predicting the likely divorce.
Labile A1C Is Inversely Correlated With the Hemoglobin Glycation Index in Children With Type 1 Diabetes
Authors: Stuart A. Chalew, Robert J. McCarter, Jeanine Ory-Ascani, James M. Hempe
Journal: Diabetes Care (2009)

OBJECTIVE We hypothesized that labile A1C (LA1C) is directly correlated with stable A1C (SA1C) and between-patient differences in SA1C, which are independent of mean blood glucose (MBG). RESEARCH DESIGN AND METHODS We measured SA1C, LA1C, MBG, and a single clinic capillary glucose (CCG) from 152 pediatric patients with type 1 diabetes. Patients were grouped as high, moderate, or low glycators by hemoglobin glycation index (HGI). RESULTS LA1C and SA1C were correlated with CCG and MBG. LA1C was not correlated with SA1C (r = 0.06, P = 0.453). LA1C level was significantly associated with glycator group status (P &amp;lt; 0.0019) and CCG (P &amp;lt; 0.0001). Adjusted LA1C levels were highest in the low-HGI patients and lowest in the high-HGI group. CONCLUSIONS A conventional model of SA1C being directly correlated with LA1C concentration was not confirmed. Between-patient differences in SA1C at the same MBG may be due to complex intracellular factors influencing formation of SA1C from LA1C.
Eliminating Tobacco Use in Mental Health Facilities
Authors: Jill M. Williams
Journal: JAMA (2008)

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
Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study
Authors: M Wright
Journal: Gut (2003)

<b>Introduction:</b> The rate of development of liver fibrosis in hepatitis C virus (HCV) infection varies between individuals. This accounts for the variation in duration of progression to cirrhosis. The aims of this study were: (1) to determine whether fibrosis progresses linearly through the grading scales and (2) to identify factors which influence the rate of fibrosis. <b>Methods:</b> HCV infected patients who had undergone at least one liver biopsy were identified. Biopsies were scored using the modified HAI (Ishak) and METAVIR systems, which were compared. Patients were treatment naïve at first biopsy. Demographic features were examined for their relationship to fibrosis rate (defined as fibrosis stage/infection duration) using univariate and multivariate analysis. A subgroup of patients with two biopsies was examined to test the assumption that fibrosis progresses in a linear fashion. <b>Results:</b> A total of 917 patients were included. Male sex (p&lt;0.00001), older age at infection (p⩽0.00001), and viral genotype non-1 (p=0.005) were all associated with a rapid rate of fibrosis. On multiple linear regression they accounted for 29.5% of the variability in fibrosis rate (<i>r</i><sup>2</sup>=0.295). METAVIR and Ishak scores were highly correlated (<i>r</i>=0.935, p&lt;0.0001). In 137 patients who had two biopsies, the predicted probability for an increase of 1 on the fibrosis score was too low to assess linearity. <b>Conclusions:</b> Demographic features account for a minority of fibrosis rate variability. The Ishak and METAVIR scoring systems are equivalent. Linearity of fibrosis progression cannot be assessed in biopsies only a few years apart.
Repeated Bone-Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial With the New, High-Energy Radiopharmaceutical Rhenium-188 Hydroxyethylidenediphosphonate
Authors: Holger Palmedo, Agnieska Manka-Waluch, Peter Albers, Ingo G.H. Schmidt-Wolf, Michael Reinhardt, Samer Ezziddin, Alexius Joe, Roland Roedel, Rolf Fimmers, F.F. Knapp, Stefan Guhlke, Hans-Jürgen Biersack
Journal: Journal of Clinical Oncology (2003)

We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments.Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death.In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043).Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.
Graduated compression and its relation to venous refilling time.
Authors: J V Cornwall, C J Dore, J D Lewis
Journal: BMJ (1987)

Graduated compression is important in improving venous function, but the pressure profiles of different brands of stockings in situ and effects on a direct measure of venous function have not been investigated. The pressure profiles of 15 different types of below knee compression stockings were established with a medical stocking tester in 13 healthy volunteers. Analysis of variance was performed for each stocking separately, considering the factors of size of stocking, site of measurement, and their interaction. The criteria used to define satisfactory function were that the stockings should have a significant linear trend with site--that is, graduation--and no other significant effects. Only five types of stockings met these standards. Venous function was then assessed by photoplethysmography in 19 patients with defined venous abnormalities. For each patient the effect on venous refilling time of three satisfactory and three unsatisfactory stockings was assessed. The three satisfactory stockings gave refilling times that were not significantly different from normal in patients with both superficial and deep vein incompetence, while refilling times with the three unsatisfactory stockings remained significantly below normal in all patients with deep vein incompetence; one stocking had no significant effect on refilling times in either group. Functional testing of compression hosiery should form part of future British Standards specifications.
Non-Respiratory Oscillations in Systemic Arterial Pressure of Dogs
Authors: David Race, Maurice Rosenbaum
Journal: Circulation Research (1966)

In dogs the condition of the cardiovascular control system was investigated quantitatively during haemorrhage, by using a system of transient inputs and by recording arterial blood pressure. The analysis of our results using standard control system techniques demonstrates a probable increase in open loop gain and a reduction of natural frequency. The implications of these findings are discussed.
Intermediates in the Assembly and Degradation of Class I Major Histocompatibility Complex (MHC) Molecules Probed with Free Heavy Chain–specific Monoclonal Antibodies
Authors: Robert P. Machold, Hidde L. Ploegh
Journal: The Journal of Experimental Medicine (1996)

Unassembled (free) heavy chains appear during two stages of the class I MHC molecule's existence: immediately after translation but before assembly with peptide and β2-microglobulin, and later, upon disintegration of the heterotrimeric complex. To characterize the structures of folding and degradation intermediates of the class I heavy chain, three monoclonal antibodies have been produced that recognize epitopes along the H-2Kb heavy chain which are obscured upon proper folding and subsequent assembly with β2-microglobulin (KU1: residues 49-54; KU2: residues 23-30; KU4: residues 193-198). The Kb heavy chain is inserted into the lumen of the endoplasmic reticulum in an unfolded state reactive with KU1, KU2, and KU4. Shortly after completion of the polypeptide chain, reactivity with KU1, KU2 and KU4 is lost synchronously, suggesting that folding of the class I heavy chain is a rapid, cooperative process. Perturbation of the folding environment in intact cells with the reducing agent dithiothreitol or the trimming glucosidase inhibitor N-7-oxadecyl-deoxynojirimycin prolongs the presence of mAb-reactive Kb heavy chains. At the cell surface, a pool of free Kb heavy chains appears after 60–120 min of chase, whose subsequent degradation, but not their initial appearance, is impaired in the presence of concanamycin B, an inhibitor of vacuolar acidification. Thus, free heavy chains that arise at the cell surface are destroyed after internalization.
Extension of borderzone myocardium in postinfarction dilated cardiomyopathy
Authors: Benjamin M Jackson, Joseph H Gorman, Sina L Moainie, T.Sloane Guy, Navneet Narula, Jagat Narula, Martin G St. John-Sutton, L.Henry Edmunds, Robert C Gorman
Journal: Journal of the American College of Cardiology (2002)
Cancer Risk Among Danish Male Seventh-Day Adventists and Other Temperance Society Members&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ole Møller Jensen
Journal: JNCI Journal of the National Cancer Institute (1983)

Cancer risk was studied in 781 male Seventh-Day Adventists (SDA) and 808 male members of other temperance societies. Standardized morbidity ratios for all cancers were 0.69 among SDA and 1.05 among other temperants. Significantly decreased risks of cancers were noted among SDA for cancer of the colon [observed/expected (O/E): 0.13], cancer of the respiratory system (O/E: 0.17), cancer of the lung (O/E: 0.15), and cancer of the bladder including papilloma (O/E: 0.13). No significant deviations from expectations were noted among members of other temperance societies. Thus risks of tobacco-associated cancers were markedly decreased among SDA. The risk of alcohol-associated cancers (cancers of the oral cavity, pharynx, esophagus, and larynx) taken together was also decreased (O/E: 0.7), although not significantly so. When the results were compared with those of a previous study of Danish brewery workers who had a high average daily beer intake, the present investigation provides further support that the alleged association between beer consumption and the occurrence of rectal cancer is of a noncausal nature. The explanation for the decreased risk of colon cancer should probably be sought in the dietary practices of SDA.
Human papillomavirus infection of the uterine cervix of women without cytological signs of neoplasia.
Authors: P G Toon, J R Arrand, L P Wilson, D S Sharp
Journal: BMJ (1986)

One hundred and six patients were studied whose cervical smears showed only non-specific inflammatory changes. Screening for genital pathogens yielded only a few positive cases. Histological examination of biopsy specimens taken by colposcopically directed tissue sampling showed cervical intraepithelial neoplasia in 13 of the women (12.3%). Deoxyribonucleic acid (DNA) hybridisation techniques were used to detect human papillomavirus, which was found in 24 patients (22.6%). In a second group of 104 patients with normal cervical cytology tissue biopsy samples were obtained and examined histologically but in no case was cervical intraepithelial neoplasia found. On DNA hybridisation, however, 12 patients (11.5%) were found to be positive for human papillomavirus. In this group finding human papillomavirus DNA was usually associated with a columnar ectopy. An association between human papillomavirus type 16 DNA and both cervical intraepithelial neoplasia and cervical cancer is well established. In this study it was type 16 which occurred most frequently in both groups.
Visualization of pseudogenes in intracellular bacteria reveals the different tracks to gene destruction
Authors: Hans-Henrik Fuxelius, Alistair C Darby, Nam-Huyk Cho, Siv GE Andersson
Journal: Genome biology (2008)

Abstract Background Pseudogenes reveal ancestral gene functions. Some obligate intracellular bacteria, such as Mycobacterium leprae and Rickettsia spp., carry substantial fractions of pseudogenes. Until recently, horizontal gene transfers were considered to be rare events in obligate host-associated bacteria. Results We present a visualization tool that displays the relationships and positions of degraded and partially overlapping gene sequences in multiple genomes. With this tool we explore the origin and deterioration patterns of the Rickettsia pseudogenes and find that variably present genes and pseudogenes tend to have been acquired more recently, are more divergent in sequence, and exhibit a different functional profile compared with genes conserved across all species. Overall, the origin of only one-quarter of the variable genes and pseudogenes can be traced back to the common ancestor of Rickettsia and the outgroup genera Orientia and Wolbachia . These sequences contain only a few disruptive mutations and show a broad functional distribution profile, much like the core genes. The remaining genes and pseudogenes are extensively degraded or solely present in a single species. Their functional profile was heavily biased toward the mobile gene pool and genes for components of the cell wall and the lipopolysaccharide. Conclusion Reductive evolution of the vertically inherited genomic core accounts for 25% of the predicted genes in the variable segments of the Rickettsia genomes, whereas 75% stems from the flux of the mobile gene pool along with genes for cell surface structures. Thus, most of the variably present genes and pseudogenes in Rickettsia have arisen from recent acquisitions.
A warning to the GMC
Authors: I. Heath
Journal: BMJ (2001)

The history of the political subversion of medicine is long, dishonourable, and continuing. It includes the active participation of doctors in the “racial hygiene” policies of Nazi Germany, the involvement of doctors in covering up deaths in custody under apartheid in South Africa, and the current use of doctors to medicalise and thereby sanitise the death penalty in the United States. The extent of the social construction of disease means that medicine will always be political and therefore at risk of political coercion.

> It is not impossible to imagine extremists seeking to marginalise the healthcare needs of minorities or dissidents 

In the United Kingdom, the General Medical Council (GMC) is considering the responses to its recent consultation process on its future constitution. The primary responsibility of the GMC is to regulate doctors and thereby assure the maintenance of professional standards. There is no doubt that lay people have an essential role to play in this process. However, the …
Diagnostic utility of reflux disease symptoms
Authors: M Shaw
Journal: Gut (2004)

Symptom assessment, by structured interview or questionnaire, is central to the diagnosis of gastro-oesophageal reflux disease (GORD). However, empiric support for the diagnostic utility of reflux symptom measures is lacking. Reliable reflux symptom questionnaires have been developed with content validity. These questionnaires need to be evaluated in terms of diagnostic accuracy, support for application of specific treatment, and improved outcomes resulting from their use. The impact on clinical outcomes of GORD diagnosis by valid questionnaires or structured interview has not been studied.
Rat myocardial tissue lipids and their effect on ventricular electrical activity: influence on dietary lipids
Authors: J Reig, E Domingo, R Segura, J L Tovar, M Vinallonga, M Borrell
Journal: Cardiovascular Research (1993)

Journal Article Rat myocardial tissue lipids and their effect on ventricular electrical activity: influence on dietary lipids Get access J Reig, J Reig Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Correspondence to Dr Reig. Search for other works by this author on: Oxford Academic PubMed Google Scholar E Domingo, E Domingo Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Search for other works by this author on: Oxford Academic PubMed Google Scholar R Segura, R Segura Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Search for other works by this author on: Oxford Academic PubMed Google Scholar J L Tovar, J L Tovar Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Search for other works by this author on: Oxford Academic PubMed Google Scholar M Viñallonga, M Viñallonga Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Search for other works by this author on: Oxford Academic PubMed Google Scholar M Borrell M Borrell Departament de Fisiologia Medica, Facultat de Medicina, Universitat Autonoma de Barcelona, Bellaterra 08193, Barcelona, Spain: J Reig, E Domingo, R Segura, J L Tovar, M Viñallonga, M Borrell. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 3, March 1993, Pages 364–370, https://doi.org/10.1093/cvr/27.3.364 Published: 01 March 1993 Article history Received: 01 May 1992 Accepted: 10 July 1992 Published: 01 March 1993
A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells
Authors: T. Matsuo, N. Osumi-Yamashita, S. Noji, H. Ohuchi, E. Koyama, F. Myokai, N. Matsuo, S. Taniguchi, H. Doi, S. Iseki, Y. Ninomiya, M. Fujiwara, T. Watanabe, K. Eto
Journal: Nature Genetics (1993)
The Effect of IL-13R·2 on IL-13 Transgene-Induced Experimental Eosinophilic Esophagitis
Authors: L. Zuo, M. Mingler, E. Cole, C. Blanchard, F.D. Finkelman, P.C. Fulkerson, M.E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2009)