tbuckley/cabot-search huggingface dataset:
Generation of a Concise Gene Panel for Outcome Prediction in Urinary Bladder Cancer
Authors: Anirban P. Mitra, Vincenzo Pagliarulo, Dongyun Yang, Frederic M. Waldman, Ram H. Datar, Donald G. Skinner, Susan Groshen, Richard J. Cote
Journal: Journal of Clinical Oncology (2009)

This study sought to determine if alterations in molecular pathways could supplement TNM staging to more accurately predict clinical outcome in patients with urothelial carcinoma (UC).Expressions of 69 genes involved in known cancer pathways were quantified on bladder specimens from 58 patients with UC (stages Ta-T4) and five normal urothelium controls. All tumor transcript values beyond two standard deviations from the normal mean expression were designated as over- or underexpressed. Univariate and multivariable analyses were conducted to obtain a predictive expression signature. A published external data set was used to confirm the potential of the prognostic gene panels.In univariate analysis, six genes were significantly associated with time to recurrence, and 10 with overall survival. Recursive partitioning identified three genes as significant determinants for recurrence, and three for overall survival. Of all genes identified by either univariate or partitioning analysis, four were found to significantly predict both recurrence and survival (JUN, MAP2K6, STAT3, and ICAM1); overexpression was associated with worse outcome. Comparing the favorable (low or normal) expression of > or = three of four versus < or = two of four of these oncogenes showed 5-year recurrence probability of 41% versus 88%, respectively (P < .001), and 5-year overall survival probability of 61% versus 5%, respectively (P < .001). The prognostic potential of this four-gene panel was confirmed in a large independent external cohort (disease-specific survival, P = .039).We have documented the generation of a concise, biologically relevant four-gene panel that significantly predicts recurrence and survival and may also identify potential therapeutic targets for UC.
Enhanced Generation of Reactive Oxygen Species in the Limb Skeletal Muscles From a Murine Infarct Model of Heart Failure
Authors: Hiroyuki Tsutsui, Tomomi Ide, Shunji Hayashidani, Nobuhiro Suematsu, Tetsuya Shiomi, Jing Wen, Kei-ichiro Nakamura, Kazuhiro Ichikawa, Hideo Utsumi, Akira Takeshita
Journal: Circulation (2001)

The generation of reactive oxygen species (ROS) is enhanced in the failing myocardium. We hypothesized that ROS were also increased in the limb skeletal muscles in heart failure. Methods and Results-- Myocardial infarction (MI) was created in mice by ligating the left coronary artery. After 4 weeks, the left ventricle was dilated and contractility was diminished by echocardiography. Left ventricular end-diastolic pressure was elevated after MI in association with an increase in lung weight/body weight and the presence of pleural effusion. The generation of ROS in the limb muscles, including the soleus and gastrocnemius muscles, which were excised after MI, was measured by electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO). Overall, generation was increased, but it was attenuated in the presence of dimethylthiourea or 4,5-dihydroxy-1,2-benzenedisulfonic disodium salt in the reaction mixture, indicating increased generation of hydroxyl radicals originating from superoxide anion. Thiobarbituric acid-reactive substance formation was also increased in muscles after MI. Mitochondrial complex I and III activities were both decreased after MI, which may have caused the functional uncoupling of the respiratory chain and ROS production. Antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, were comparable between groups.Skeletal muscle in post-MI heart failure expressed an increased amount of ROS in association with ROS-mediated lipid peroxidation. This supports the hypothesis that oxidative stress may cause (at least in part) skeletal muscle dysfunction in heart failure.
HLA DR antigens and disease expression in rheumatoid arthritis.
Authors: A J Griffin, P Wooley, G S Panayi, J R Batchelor
Journal: Annals of the Rheumatic Diseases (1984)

Ninety-four patients with rheumatoid arthritis who possessed one or more of the HLA DR alloantigens 2, 3, or 4 were studied to investigate the genetic influence on disease severity and prognosis. In those with a disease duration of less than 10 years radiological damage was less in patients with DR2 than in those without this antigen. When current joint scores were compared, patients with this antigen had less evidence of disease than patients with DR3 or 4, DR3 patients having the highest scores. The presence of nodules and Sjögren's syndrome were less common in the DR2 patients. Variability in response to disease modifying drugs according to the patient's HLA DR antigen status may explain these differences. It is concluded, however, that possession of HLA DR2 may be an indicator of good prognosis in patients with rheumatoid arthritis.
Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1.
Authors: M D Wewers, S I Rennard, A J Hance, P B Bitterman, R G Crystal
Journal: Journal of Clinical Investigation (1984)

Interleukin-1 (IL-1) is a mediator released by stimulated mononuclear phagocytes that is thought to play an important role in modulating T and B lymphocyte activation as well as in contributing to the febrile response and other inflammatory processes. Circulating mononuclear phagocytes, blood monocytes, readily release IL-1 when stimulated. However, the ability of lung mononuclear phagocytes, alveolar macrophages, to dispose of the large daily burden of inhaled antigens without stimulating an inflammatory response suggests that the release of IL-1 by alveolar macrophages may differ significantly from that of blood monocytes. To evaluate this hypothesis, normal autologous alveolar macrophages, obtained by bronchoalveolar lavage, were compared with blood monocytes for their ability to release IL-1 in response to a standard stimulus, lipopolysaccharide (LPS). Alveolar macrophages were found to be at least 1,000 times less sensitive to LPS than blood monocytes. Furthermore, alveolar macrophages released significantly less IL-1 than blood monocytes (26 +/- 11 vs. 128 +/- 21 U/10(6) cells X 24 h, respectively, after stimulation with 10 micrograms/ml of LPS, P less than 0.001). This difference was not due to the release of substances by macrophages, which inhibited lymphocyte proliferation in response to IL-1, or to degradation of IL-1 by macrophages. Culturing macrophages in the presence of indomethacin and dialysis of macrophage supernatants did not affect the difference, and culturing macrophages with monocytes did not decrease detectable IL-1 activity from the monocytes. The IL-1 produced by the two cell types was indistinguishable by anion-exchange chromatography, gel filtration, and isoelectric focusing. In addition, consistent with the findings for alveolar macrophages, macrophages generated by the in vitro maturation of blood monocytes were also deficient in their ability to release IL-1. These findings suggest that if the population of alveolar macrophages obtained by bronchoalveolar lavage represents the total in vivo population of alveolar macrophages, although normal human macrophages are capable of IL-1 release, they are relatively limited in this ability, and this limitation seems to be linked to the maturational state of the mononuclear phagocyte. These observations may explain, in part, the ability of alveolar macrophages to clear the airspaces of foreign antigens without extensive activation of other pulmonary inflammatory and immune effector cells.
Interleukin-16 in tuberculous and malignant pleural effusions
Authors: X-J. Qin, H-Z. Shi, Z-X. Huang, L-F. Kang, W-N. Mo, C. Wu
Journal: European Respiratory Journal (2005)

The aim of this study was to explore the presence of interleukin (IL)-16 in pleural effusions, the correlation between IL-16 levels and cytological parameters, as well as the chemoattractant activity of IL-16 on CD4+ T-lymphocytes. Total nucleated cell and differential counts, and IL-16 concentrations in the pleural effusion from 32 patients with tuberculous pleurisy and 30 patients with lung cancer were determined. Three-colour flow cytometry was performed to determine T-lymphocyte subsets in cell pellets of pleural effusion. The chemoattractant activity of IL-16 for CD4+ T-lymphocytes was also analysed. The levels of IL-16 were significantly higher in tuberculous than in malignant effusions. However, IL-16 levels could not be used for diagnostic purposes due to significant overlap between the two groups. Positive correlations were found between the IL-16 levels and CD4+ T-cells, and pleural fluid was chemotactic for CD4+ T-cells in vitro . Intrapleural administration of IL-16 to patients produced a marked progressive influx of CD4+ T-cells into the pleural space. Compared with malignant pleural effusion, interleukin-16 appeared to be increased in tuberculous pleural effusion. Interleukin-16 levels were positively related to the numbers of CD4+ T-cells, and interleukin-16 could directly induce CD4+ T-cell infiltration into the pleural space.
Genome and virulence determinants of high virulence community-acquired MRSA
Authors: Tadashi Baba, Fumihiko Takeuchi, Makoto Kuroda, Harumi Yuzawa, Ken-ichi Aoki, Akio Oguchi, Yoshimi Nagai, Natsuko Iwama, Kazuyuki Asano, Timothy Naimi, Hiroko Kuroda, Longzhu Cui, Kenji Yamamoto, Keiichi Hiramatsu
Journal: The Lancet (2002)
Effect of Ranolazine, an Antianginal Agent With Novel Electrophysiological Properties, on the Incidence of Arrhythmias in Patients With Non–ST-Segment–Elevation Acute Coronary Syndrome
Authors: Benjamin M. Scirica, David A. Morrow, Hanoch Hod, Sabina A. Murphy, Luiz Belardinelli, Chester M. Hedgepeth, Peter Molhoek, Freek W.A. Verheugt, Bernard J. Gersh, Carolyn H. McCabe, Eugene Braunwald
Journal: Circulation (2007)

Ranolazine, a piperazine derivative, reduces ischemia via inhibition of the late phase of the inward sodium current (late I(Na)) during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload. Increased intracellular calcium leads to both mechanical dysfunction and electric instability. Ranolazine reduces proarrhythmic substrate and triggers such as early afterdepolarization in experimental models. However, the potential antiarrhythmic actions of ranolazine have yet to be demonstrated in humans.The Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome (MERLIN)-Thrombolysis in Myocardial Infarction (TIMI) 36 (MERLIN-TIMI 36) trial randomized 6560 patients hospitalized with a non-ST-elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG (Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. Of the 6560 patients in MERLIN-TIMI 36, 6351 (97%) had continuous ECG recordings that could be evaluated for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting > or = 8 beats (166 [5.3%] versus 265 [8.3%]; P<0.001), supraventricular tachycardia (1413 [44.7%] versus 1752 [55.0%]; P<0.001), or new-onset atrial fibrillation (55 [1.7%] versus 75 [2.4%]; P=0.08). In addition, pauses > or = 3 seconds were less frequent with ranolazine (97 [3.1%] versus 136 [4.3%]; P=0.01).Ranolazine, an inhibitor of late I(Na), appears to have antiarrhythmic effects as assessed by continuous ECG monitoring of patients in the first week after admission for acute coronary syndrome. Studies specifically designed to evaluate the potential role of ranolazine as an antiarrhythmic agent are warranted.
Insurance Expenditures on Bipolar Disorder: Clinical and Parity Implications
Authors: Pamela B. Peele, Ying Xu, David J. Kupfer
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study assessed treatment rates and expenditures for behavioral health care by employers and behavioral health care patients in a large national database of employer-sponsored health insurance claims. METHOD: Insurance claims from 1996 from approximately 1.66 million individuals were examined. Average annual charges per person and payments for behavioral health care were calculated along with patient out-of-pocket expenses and inpatient hospital admission rates. Behavioral health care expenditures for bipolar disorder were compared to expenditures for other behavioral health care diagnoses in these same insurance plans. RESULTS: A total of 7.5% of all covered individuals filed a behavioral health care claim. Of those, 3.0% were identified as having bipolar disorder, but they accounted for 12.4% of total plan expenditures. Patients with bipolar disorder incurred annual out-of-pocket expenses of $568, more than double the $232 out-of-pocket expenses incurred by all claimants. The inpatient hospital admission rate for patients with bipolar disorder was also higher (39.1%) compared to 4.5% for all other behavioral health care claimants. Furthermore, annual insurance payments were higher for covered medical services for individuals with bipolar disorder than for patients with other behavioral health care diagnoses. CONCLUSIONS: Bipolar disorder is the most expensive behavioral health care diagnosis, both for patients with bipolar disorder and for their insurance plans. For every behavioral health care dollar spent on outpatient care for patients with bipolar disorder, $1.80 is spent on inpatient care, suggesting that better prevention management could decrease the financial burden of bipolar disorder.
Evolution of a Membrane Protein Regulon in Saccharomyces
Authors: H. C. Martin, J. I. Roop, J. G. Schraiber, T. Y. Hsu, R. B. Brem
Journal: Molecular Biology and Evolution (2012)

Expression variation is widespread between species. The ability to distinguish regulatory change driven by natural selection from the consequences of neutral drift remains a major challenge in comparative genomics. In this work, we used observations of mRNA expression and promoter sequence to analyze signatures of selection on groups of functionally related genes in Saccharomycete yeasts. In a survey of gene regulons with expression divergence between Saccharomyces cerevisiae and S. paradoxus, we found that most were subject to variation in trans-regulatory factors that provided no evidence against a neutral model. However, we identified one regulon of membrane protein genes controlled by unlinked cis- and trans-acting determinants with coherent effects on gene expression, consistent with a history of directional, nonneutral evolution. For this membrane protein group, S. paradoxus alleles at regulatory loci were associated with elevated expression and altered stress responsiveness relative to other yeasts. In a phylogenetic comparison of promoter sequences of the membrane protein genes between species, the S. paradoxus lineage was distinguished by a short branch length, indicative of strong selective constraint. Likewise, sequence variants within the S. paradoxus population, but not across strains of other yeasts, were skewed toward low frequencies in promoters of genes in the membrane protein regulon, again reflecting strong purifying selection. Our results support a model in which a distinct expression program for the membrane protein genes in S. paradoxus has been preferentially maintained by negative selection as the result of an increased importance to organismal fitness. These findings illustrate the power of integrating expression- and sequence-based tests of natural selection in the study of evolutionary forces that underlie regulatory change.
506 Pegylated interferon alpha-2b monotherapy and in combination with ribavirin in chronic hepatitis delta
Authors: G.A. Niro, A. Ciancio, G.B. Gaeta, A. Marrone, A. Olivero, M. Stanzione, G. Stornaiuolo, A. Smedile, A. Andriulli, M. Rizzetto
Journal: Journal of Hepatology (2006)
Severe acute interstitial pneumonia and gefitinib
Authors: Akira Inoue, Yasuo Saijo, Makoto Maemondo, Kazunori Gomi, Yutaka Tokue, Yuichiro Kimura, Masahito Ebina, Toshiaki Kikuchi, Takuya Moriya, Toshihiro Nukiwa
Journal: The Lancet (2003)
Some Reactions of the Nervous System to Trauma
Authors: W. R. Russell
Journal: BMJ (1964)

I should like first to thank most warmly the staff of the famous Birmingham Accident Service for granting me the privilege of giving this important lecture.I am a great admirer of hospital accident services, and we will all agree, as Ruscoe Clarke demonstrated by his devoted example, that to provide a service is not enough: for it is necessary and expected of the leading exponents that they will also teach others and will pioneer new developments and organize research.Trauma to the nervous system provides many opportunities for research, and in the course of this talk I hope to refer to some of these.Students of the nervous system and its diseases are dull indeed if they fail to use their great clinical opportunities to advance knowledge, and the effects of injury are particularly valuable for this purpose.Research on the nervous system, whether concerned with the brain or the peripheral nerve, is a leading challenge to man in the second half of this twentieth century.This is, I think, more appreciated in some other countries than here, and during the past 10 years, for example, research on the nervous system in the U.S.A. has come to be supported most lavishly by national funds.In this country there seems to be something wrong with our research allocations, for the funds of the University Grants Committee, which are supposed to support research related to clinical specialties, rarely reach beyond the insatiable needs of the professorial units.In the U.S.A., on the other hand, the clinical specialties such as orthopaedics and neurology seem
A novel activating, germline JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis
Authors: S. Leah Etheridge, Megan E. Cosgrove, Veena Sangkhae, Lana M. Corbo, Michelle E. Roh, Markus A. Seeliger, Edward L. Chan, Ian S. Hitchcock
Journal: Blood (2013)
Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ
Authors: A. Bardaji, J. Cinca, F. Worner, A. Schoenenberger
Journal: Cardiovascular Research (1990)

Journal Article Effects of anaesthesia on acute ischaemic arrhythmias and epicardial electrograms in the pig heart in situ Get access Alfredo Bardaji, Alfredo Bardaji Laboratorio de Cardiologia Experimental, Servicio de Cardiologia, Hospital General, Ciudad Sanitaria Valle de Hebron, 08035 Barcelona, Spain Correspondence to: Dr Cinca Search for other works by this author on: Oxford Academic PubMed Google Scholar Juan Cinca, Juan Cinca Laboratorio de Cardiologia Experimental, Servicio de Cardiologia, Hospital General, Ciudad Sanitaria Valle de Hebron, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Fernando Worner, Fernando Worner Laboratorio de Cardiologia Experimental, Servicio de Cardiologia, Hospital General, Ciudad Sanitaria Valle de Hebron, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonio Schoenenberger Antonio Schoenenberger Laboratorio de Cardiologia Experimental, Servicio de Cardiologia, Hospital General, Ciudad Sanitaria Valle de Hebron, 08035 Barcelona, Spain Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 3, March 1990, Pages 227–231, https://doi.org/10.1093/cvr/24.3.227 Published: 01 March 1990 Article history Received: 05 April 1989 Accepted: 31 October 1989 Published: 01 March 1990
So who's teaching whom?
Authors: L. Smith
Journal: BMJ (2000)

VSO (Voluntary Service Overseas) sends skilled men and women to work in partnership with people in developing countries. The organisation has seen a dramatic surge in inquiries from health professionals interested in working overseas—figures released in February 1999 show that applications from the health sector have gone up by 55%.

In the wake of the Stephen Lawrence report the health service's capacity to deliver care to multicultural Britain is under scrutiny. Cultural awareness and sensitivity are at a premium, yet the skills of health workers who have worked overseas remain undervalued.

> My colleagues still find it difficult to communicate how they have developed 

A widely held assumption that volunteering is a one way learning process rather than an exchange of ideas, skills, and information means that a large proportion of my colleagues still find it difficult to communicate how they have developed professionally from their experience.

I spent two years in Zambia with VSO as a nurse tutor. My aims and motivation were misunderstood by many …
Distinct roles for E12 and E47 in B cell specification and the sequential rearrangement of immunoglobulin light chain loci
Authors: Kristina Beck, Mandy M. Peak, Takayuki Ota, David Nemazee, Cornelis Murre
Journal: The Journal of Experimental Medicine (2009)

The E2A gene products, E12 and E47, are critical regulators of B cell development. However, it remains elusive whether E12 and E47 have overlapping and/or distinct functions during B lymphopoiesis. We have generated mice deficient for either E12 or E47 and examined their roles in B cell maturation. We show that E47 is essential for developmental progression at the prepro–B cell stage, whereas E12 is dispensable for early B cell development, commitment, and maintenance. In contrast, both E12 and E47 play critical roles in pre–B and immature B cells to promote immunoglobulin λ (Igλ) germline transcription as well as Igλ VJ gene rearrangement. Furthermore, we show that E12 as well as E47 is required to promote receptor editing upon exposure to self-antigen. We demonstrate that increasing levels of E12 and E47 act to induce Igλ germline transcription, promote trimethylated lysine 4 on histone 3 (H3) as well as H3 acetylation across the Jλ region, and activate Igλ VJ gene rearrangement. We propose that in the pre–B and immature B cell compartments, gradients of E12 and E47 activities are established to mechanistically regulate the sequential rearrangement of the Ig light chain genes.