tbuckley/cabot-search huggingface dataset:
Coexpression of Mutant p53 and p193 Renders Embryonic Stem Cell–Derived Cardiomyocytes Responsive to the Growth-Promoting Activities of Adenoviral E1A
Authors: Kishore B. S. Pasumarthi, Shih-Chong Tsai, Loren J. Field
Journal: Circulation Research (2001)

Expression of adenoviral E1A in cardiomyocytes results in the activation of DNA synthesis followed by apoptosis. In contrast, expression of simian virus 40 large T antigen induces sustained cardiomyocyte proliferation. Previous studies have shown that T antigen binds to 2 proapoptotic proteins in cardiomyocytes, namely the p53 tumor suppressor and p193 (a new member of the BH3-only proapoptosis subfamily). Structure-function analyses identified a p193 C-terminal truncation mutant that encodes prosurvival activity. This mutant was used to test the role of p193 in E1A-induced cardiomyocyte apoptosis. E1A induced apoptosis in cardiomyocytes derived from differentiating embryonic stem cells. Expression of the prosurvival p193 mutant alone or a mutant p53 alone did not block E1A-induced apoptosis. In contrast, combinatorial expression of mutant p193 and mutant p53 blocked E1A-induced apoptosis, resulting in a proliferative response indistinguishable from that seen with T antigen. These results confirm the hypothesis that there are 2 proapoptotic pathways, encoded by p53 and p193, respectively, which restrict cardiomyocyte cell cycle activity in differentiating embryonic stem cell cultures. Furthermore, these results explain in molecular terms the phenotypic differences of E1A versus T-antigen gene transfer in cardiomyocytes.
Adverse Reaction Preparedness for Allergen Immunotherapy in the Primary Care Setting
Authors: V. Reddy, P. Jhaveri, T.J. Craig
Journal: Journal of Allergy and Clinical Immunology (2012)

Fatal reactions due to allergen immunotherapy (AIT) are estimated to occur in 1 per 2.5 million injections (average of 3.4 deaths per year). Factors contributing to fatal reactions are uncontrolled asthma, inadequate post injection wait time, and administration in settings not equipped to handle anaphylactic reactions. The preferred setting is the prescribing allergist's office. However, patients may receive AIT at primary care facilities equipped to manage systemic reactions. This study was administered to determine whether primary care offices are prepared to handle adverse reactions to AIT. After IRB approval, a referring physician database was obtained. Each physician office was called, verbal consent was obtained, and a questionnaire was administered via phone to nursing staff. One hundred and ninety four physicians were represented by 43 offices administering AIT. Forty one offices (95%) felt comfortable administering AIT. Fourteen offices (32.6%) monitored patients for at least 30 minutes post injection. Twenty three offices (53%) assessed asthma patients for active symptoms and ten (23%) measured peak flow prior to administering AIT. Thirteen offices (30%) reported adverse reactions. Thirty offices (70%) had the ability to administer intravenous fluid. Eighteen offices (42%) stated they would benefit from additional education on administering AIT. The majority of primary care offices are not fully equipped to handle adverse reactions to AIT. There is insufficient wait time after injection, lack of assessment of asthmatic patients, and insufficient equipment in case of anaphylaxis. Primary care offices would benefit from further education on administration of AIT to ensure adherence to allergy practice parameters and patient safety.
Assay of Anti-Anginal Agents
Authors: SEYMOUR L. COLE, HARRY KAYE, GEORGE C. GRIFFITH
Journal: Circulation (1957)

The measure of an anti-anginal agent is its ability to decrease chest pain. Because of the subjective character of pain, extreme care is necessary in choosing patients upon whom anti-anginal medication is to be tested. We have used the double-blind technic and an initial control period to neutralize the many extraneous mental and physical factors, such as bias or the patient-physician relationship itself, that might interfere with an accurate appraisal. This study shows, in addition, that proper evaluation of an anti-anginal agent requires that its effect be measured against multiple control periods without medication throughout the various phases of angina pectoris.
Pulmonary Compliance Following Open-Heart Surgery and Its Relationship to Ventilation and Gas Exchange
Authors: LOIS T. ELLISON, JOHN F. DUKE, ROBERT G. ELLISON
Journal: Circulation (1967)

Pulmonary function was studied preoperatively and postoperatively in 71 patients undergoing 41 open-heart operations, ten thoracic operations not requiring cardiopulmonary bypass, ten intra-abdominal, and ten peripheral procedures. After operation total respiratory compliance was significantly reduced below the preoperative value for ten days in the open-heart group. Decreases of lesser degree and of shorter duration were noted in the thoracic and intra-abdominal patients with no significant reduction in the peripheral cases. Tidal volume decreased proportionately to the decrease in compliance, and respiratory rate increased, while total ventilation usually remained the same or was slightly increased. Oxygen uptake was significantly increased after open-heart operations, and there was a significant negative correlation between oxygen uptake and compliance. Abnormal venous admixture, not corrected by oxygen inhalation, was observed after cardiopulmonary bypass with a return to preoperative level coinciding with that of compliance. Cardiac output did not correlate with any other measurement. The data suggest that the postoperative breathing pattern after open-heart surgery is a compensatory adjustment to decreased compliance and that reduced compliance is one of the causes of the increased work of breathing and oxygen demands after open-heart surgery.
Medical Information Bureau
Authors: Paul S. Entmacher
Journal: JAMA (1975)

The Medical Information Bureau (MIB) is a nonprofit trade association with approximately 700 life insurance companies as members in the United States and Canada. A computer bank that contains primarily medical information is maintained by the MIB. Safeguards are taken to assure confidentiality, and there is no linkage with other computer banks. Information is submitted to the MIB only after the individuals involved give authorization, and they have access to their records and can make corrections if necessary. Dissemination of computer information is made only to member companies when they have a bona fide application or claim and then only with the consent of the person involved. Medical directors of member companies have the primary responsibility for maintaining integrity and seeing that their companies adhere to the rules of the MIB.
<i>HNF1B</i>deficiency causes ciliary defects in human cholangiocytes
Authors: Philip Roelandt, Aline Antoniou, Louis Libbrecht, Werner Van Steenbergen, Wim Laleman, Chris Verslype, Schalk Van der Merwe, Frederik Nevens, Rita De Vos, Evelyne Fischer, Marco Pontoglio, Frédéric Lemaigre, David Cassiman
Journal: Hepatology (2012)

Heterozygous deletion or mutation in hepatocyte nuclear factor 1 homeobox B/transcription factor 2 ( HNF1B/TCF2 ) causes renal cyst and diabetes syndrome (OMIM #137920). Mice with homozygous liver-specific deletion of Hnf1 β revealed that a complete lack of this factor leads to ductopenia and bile duct dysplasia, in addition to mild hepatocyte defects. However, little is known about the hepatic consequences of deficient HNF1B function in humans. Three patients with heterozygous HNF1B deficiency were found to have normal bile duct formation on radiology and routine liver pathology. Electron microscopy revealed a paucity or absence of normal primary cilia. Therefore, heterozygous HNF1B deficiency is associated with ciliary anomalies in cholangiocytes, and this may cause cholestasis.
Critique of Success with Methadone Maintenance
Authors: JAMES F. MADDUX, CHARLES L. BOWDEN
Journal: American Journal of Psychiatry (1972)

Examination of the data supporting the claims of success for methadone maintenance reveals a number of problems, including the choice of criteria to represent "success," exclusion of dropouts from the samples studied, and insufficient comparisons. The authors give examples of each of these methodological flaws and conclude that reports of success with methadone maintenance appear both ambiguous and exaggerated.
Comparison of Bedtime NPH or Preprandial Regular Insulin Combined With Glibenclamide in Secondary Sulfonylurea Failure
Authors: Lena Landstedt-Hallin, Ulf Adamson, Peter Arner, Jan Bolinder, Per-Eric Lins
Journal: Diabetes Care (1995)

To compare the effect of bedtime NPH insulin or preprandial regular insulin combined with glibenclamide on metabolic control in non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure to sulfonylurea therapy.Eighty NIDDM patients were randomized to treatment with either three preprandial doses of regular insulin (daytime group D) or a bedtime dose of NPH insulin (nocturnal insulinization, group N), both regimens being combined with 10.5 mg of glibenclamide. Metabolic profiles were obtained at 0, 6, 16 weeks.Glycemic control had improved significantly in both groups after 4 months. Fasting blood glucose was significantly lower compared with baseline in both groups. The mean change +/- SD in group D was -2.8 +/- 3.5 mmol/l and in group N -6.4 +/- 3.0 mmol/L, the reduction being more pronounced in group N compared with group D (P < 0.0001). HbA1c was lowered similarly, from 9.2 +/- 1.4 to 7.1 +/- 1.2% in group D (P < 0.0001) and from 9.1 to 1.1 to 7.5 +/- 1.5% in group N (P < 0.0001). The total daily insulin doses were similar, 29 +/- 11 U in group D and 26 +/- 9 U in group N, and the circulating insulin levels during daytime were higher in group D than in group N. Total serum cholesterol and triglycerides were similarly and significantly lowered compared with baseline in both groups. Weight gain was more pronounced in group D (3.4 +/- 0.3 kg) than in group N (1.9 +/- 1.9 kg; D vs. N, P < 0.002), and the change was inversely correlated with initial eight but not with the improvement in HbA1c.The two insulin regimens exert similar effect on glucose metabolism and serum lipids in NIDDM patients on combination therapy. Weight gain is more pronounced in patients given insulin during the daytime when preprandial doses of short-acting insulin are used.
Abstract 1071: Repression of ERK1/2 signaling by RanBPM
Authors: Elnaz Atabakhsh, Caroline Schild-Poulter
Journal: Cancer Research (2011)

Abstract Ran binding protein-M (RanBPM, also called RanBP9) is a nucleo-cytoplasmic protein that has been implicated in a multitude of cellular roles, including the regulation of transcription, protein modifications and stability, and extracellular receptor signaling pathways. However the precise mechanism by which RanBPM functions within the cell remains largely unknown. Previous studies in our lab have identified RanBPM as a pro-apoptotic protein that mediates its effects through modulation of Bcl-2 levels. Here we present evidence that the effect of RanBPM on apoptosis is mediated, at least in part, through regulation of the ERK1/2 signaling pathway. First, we determined that in addition to Bcl-2, RanBPM also regulated the expression of a second anti-apoptotic factor, Bcl-XL. siRNA-mediated knockdown of RanBPM expression led to elevated Bcl-2 and Bcl-XL mRNA expression, suggesting regulation by RanBPM at the transcriptional level. Conversely, we found that expression of RanBPM also affected ectopically expressed Bcl-2 protein levels. Together, these findings suggested that RanBPM regulated the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels. One pathway that has previously been shown to regulate the expression of Bcl-2 and Bcl-XL at both the transcriptional and post-translational levels is the ERK1/2 signaling pathway. We found that RanBPM-deficient cells exhibited enhanced ERK1/2 phosphorylation and activation, while re-expression of RanBPM led to a marked decrease in the levels of phosphorylated ERK1/2. Further analyses indicated that enhanced ERK1/2 activation in RanBPM-deficient cells contributed to the elevated levels of Bcl-2 expression observed in these cells, as inhibition of ERK1/2 activation correlated with decreased Bcl-2 protein expression. These findings suggested that RanBPM acts as a novel negative regulator of ERK1/2 signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1071. doi:10.1158/1538-7445.AM2011-1071
Baseline Potency in Candidates for Bilateral Nerve-Sparing Radical Retropubic Prostatectomy
Authors: Andrea Salonia, Giuseppe Zanni, Andrea Gallina, Antonino Saccà, Mattia Sangalli, Richard Naspro, Alberto Briganti, Elena Farina, Marco Roscigno, Luigi F. DaPozzo, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2006)
Population Pharmacokinetics and Pharmacogenetics of Imatinib in Children and Adults
Authors: Aurélie Petain, Darouna Kattygnarath, Julie Azard, Etienne Chatelut, Catherine Delbaldo, Birgit Geoerger, Michel Barrois, Sophie Séronie-Vivien, Axel LeCesne, Gilles Vassal
Journal: Clinical Cancer Research (2008)

The aim of this study was to explore the effect of several demographic, biological, and pharmacogenetic covariates on the disposition of imatinib and its main metabolite (CGP74588) in both adults and children.Thirty-three children with solid malignancies included in a phase II exploratory study and 34 adults with gastrointestinal stromal tumors received 340 mg/m(2) and 400 mg imatinib, respectively. Plasma imatinib and CGP74588 concentrations observed on day 1 and at steady-state were analyzed by a population pharmacokinetic method (NONMEM) to evaluate the effect of age, body weight, age, sex, albuminemia, plasma alpha1-acid glycoprotein (AGP), and eight polymorphisms corresponding to ABCB1, ABCG2, CYP3A4, CYP3A5, and AGP (pharmacogenetic data available for 46 of 67 patients).Analysis of the whole data set in 67 patients showed that apparent clearance (CL/F) of imatinib was positively correlated with body weight and albuminemia and negatively with AGP. By considering these three covariates, the interindividual variability on CL/F decreased from 47% to 19%. The apparent clearance of CGP74588 was similarly dependent on both body weight and AGP and significantly lower (30% reduction) at steady-state. By adding genotype status to the final covariate imatinib model, a 22% reduction in CL/F was observed in heterozygous compared with wild-type patients corresponding to ABCG2 c.421C>A (P<0.05).By considering morphologic and biological covariates, a unique covariate model could be used to accurately describe imatinib pharmacokinetics in patients ages 2 to 84 years. Morphologic and biological characteristics have a stronger influence than pharmacogenetics on imatinib pharmacokinetics.
Deregulation of p27 and Cyclin D1/D3 Control Over Mitosis Is Associated with Unfavorable Prognosis in Non-small Cell Lung Cancer, as Determined in 405 Operated Patients
Authors: William Sterlacci, Michael Fiegl, Wolfgang Hilbe, Herbert Jamnig, Wilhelm Oberaigner, Thomas Schmid, Florian Augustin, Jutta Auberger, Ellen C. Obermann, Alexandar Tzankov
Journal: Journal of Thoracic Oncology (2010)
Models of unexplained symptoms associated with occupational and environmental exposures.
Authors: Anne Spurgeon
Journal: Environmental Health Perspectives (2002)

Unexplained illnesses characterized by nonspecific, multisystem complaints are often attributed to occupational or environmental chemical exposures. This raises difficulties for the regulatory authorities, who are frequently unable to agree on the existence, nature, or source of such illnesses. It is proposed that many of these difficulties derive from an adherence to a traditional medical model of disease and that the application of a biopsychosocial approach would be more effective for both research and individual case management. A number of models derived from the field of health psychology are discussed in terms of their application to occupational and environmental syndromes. A specific example is described that relates to the health problems experienced by sheep farmers in the United Kingdom who are exposed to organophosphate-based pesticides. The source of their complaints and the responses of the health professionals and the regulatory authorities are discussed within the context of a biopsychosocial approach that focuses on illness rather than on organic disease as the unit of study and explores the interaction between the various physical and psychosocial variables involved. It is proposed that this approach, which is already well established in the fields of human and social sciences, should be adopted more readily by those concerned with occupational and environmental epidemiology.
"Hanging from the Masthead": Reflections on Authorship
Authors: KENNETH D. BURMAN
Journal: Annals of Internal Medicine (1982)

Authorship of a scientific article should imply expertise on its content and thorough knowledge of the investigation reported. Because the number of authors per article has dramatically increased, I question whether these criteria for authorship are applied. Another explanation for this increase is that authors add names to the byline without reference to any set of criteria, resulting in the designation of coauthorship when not warranted. The medical community needs to redefine the proper procedure and criteria for deciding on authorship and to strictly abide by these procedures. Specific recommendations center around the protocol as the initial instrument of communication. Who should be designated as author, and the order of names, should be negotiated before and during the study, and written communication with other involved laboratories should result in more appropriate authorship attribution.
Heuristics all the way up?
Authors: Adam Morton
Journal: Behavioral and Brain Sciences (2000)

I investigate whether heuristics similar to those studied by Gigerenzer and his co-authors can apply to the problem of finding a suitable heuristic for a given problem. I argue that not only can heuristics of a very similar kind apply but they have the added advantage that they need not incorporate specific trade-off parameters for balancing the different desiderata of a good decision-procedure.
Prognostic Impact of Coronary Vasodilator Dysfunction on Adverse Long-Term Outcome of Coronary Heart Disease
Authors: Volker Schächinger, Martina B. Britten, Andreas M. Zeiher
Journal: Circulation (2000)

Background —Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospectively investigated whether coronary endothelial dysfunction predicts disease progression and cardiovascular event rates. Methods and Results —Coronary vasoreactivity was assessed in 147 patients using the endothelium-dependent dilator acetylcholine, sympathetic activation by cold pressor testing, dilator responses to increased blood flow, and dilation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral artery revascularization) served as outcome variables over a median follow-up period of 7.7 years. Patients suffering from cardiovascular events during follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion ( P =0.009) and cold pressor testing ( P =0.002), as well as significantly blunted vasodilator responses to increased blood flow ( P &lt;0.001) and the intracoronary injection of nitroglycerin ( P =0.001). Impaired endothelial and endothelium-independent coronary vasoreactivity were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis. By multivariate analysis, all tests of coronary vasoreactivity were significant, independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors or the presence of atherosclerosis itself. Conclusions —Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates. Thus, the assessment of coronary endothelial vasoreactivity can provide pivotal information as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.
Generation of Splenic Follicular Structure and B Cell Movement in Tumor Necrosis Factor–deficient Mice
Authors: Matthew C. Cook, Heinrich Körner, D. Sean Riminton, Frances A. Lemckert, Jhagvaral Hasbold, Michelle Amesbury, Philip D. Hodgkin, Jason G. Cyster, Jonathon D. Sedgwick, Antony Basten
Journal: The Journal of Experimental Medicine (1998)

Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin α (LTα). The role of TNF in B cell positioning and formation of follicular structure was studied by comparing the location of newly produced naive recirculating and antigen-stimulated B cells in TNF−/− and TNF/LTα−/− mice. By creating radiation bone marrow chimeras from wild-type and TNF−/− mice, formation of normal splenic B cell follicles was shown to depend on TNF production by radiation-sensitive cells of hemopoietic origin. Reciprocal adoptive transfers of mature B cells between wild-type and knockout mice indicated that normal follicular tropism of recirculating naive B cells occurs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor–IgG fusion protein administered in vivo failed to prevent B cell localization to the follicle or the germinal center reaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF−/− recipients, but not into TNF/LTα−/− recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LTα−/− mice because TNF/LTα−/− B cells, when stimulated in vitro, switched isotypes normally. Thus, TNF is necessary for creating the permissive environment for B cell movement and function, but is not itself responsible for these processes.
POSTGRADUATE COURSE FOR COUNTY SOCIETIES
Authors: JOHN H. BLACKBURN
Journal: JAMA (1910)

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