tbuckley/cabot-search huggingface dataset:
Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study
Authors: Maryam Fouladi, Clinton F. Stewart, James Olson, Lars M. Wagner, Arzu Onar-Thomas, Mehmet Kocak, Roger J. Packer, Stewart Goldman, Sridharan Gururangan, Amar Gajjar, Tim Demuth, Larry E. Kun, James M. Boyett, Richard J. Gilbertson
Journal: Journal of Clinical Oncology (2011)

To estimate the maximum-tolerated dose (MTD), describe dose-limiting toxicities (DLTs), and characterize pharmacokinetic properties of MK-0752, a gamma secretase inhibitor, in children with refractory or recurrent CNS malignancies.MK-0752 was administered once daily for 3 consecutive days of every 7 days at escalating dosages starting at 200 mg/m(2). The modified continual reassessment method was used to estimate the MTD. A course was 28 days in duration. Pharmacokinetic analysis was performed during the first course. Expression of NOTCH and hairy enhancer of split (HES) proteins was assessed in peripheral-blood mononuclear cells (PBMCs) before and following treatment with MK-0752.Twenty-three eligible patients were enrolled: 10 males (median age, 8.1 years; range, 2.6 to 17.7 years) with diagnoses of brainstem glioma (n = 6), ependymoma (n = 8), medulloblastoma/primitive neuroectodermal tumor (n = 4), glioblastoma multiforme (n = 2), atypical teratoid/rhabdoid tumor (n = 1), malignant glioma (n = 1), and choroid plexus carcinoma, (n = 1). Seventeen patients were fully evaluable for toxicity. No DLTs occurred in the three patients enrolled at 200 mg/m(2)/dose. At 260 mg/m(2)/dose, DLTs occurred in two of six patients, both of whom experienced grade 3 ALT and AST. There were no grade 4 toxicities; non-dose-limiting grade 3 toxicities included hypokalemia and lymphopenia. Population pharmacokinetic values (% coefficient of variation) for MK-0752 were apparent oral clearance, 0.444 (38%) L/h/m(2); apparent volume of distribution, 7.36 (24%) L/m(2); and k(a), 0.358 (99%) hr(-1).MK-0752 is well-tolerated in children with recurrent CNS malignancies. The recommended phase II dose using the 3 days on followed by 4 days off schedule is 260 mg/m(2)/dose once daily.
Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype
Authors: A. Abrahamov, D. Elstein, A. Zimran, B. Farber, Y. Glaser, V. Gross-Tsur, I. Hadas-Halpern, S. Ronen, M. Horowitz, M. Tafakjdi
Journal: The Lancet (1995)
Re-expansion pulmonary oedema.
Authors: M Waqaruddin, A Bernstein
Journal: Thorax (1975)

Clinical details are given of two patients who developed ipsilateral pulmonary oedema following re-expansion of their spontaneous pneumothoraces by intercostal drainage of air. The possible mechanisms underlying the oedema are discussed, and prior literature is analysed. Reference is made particularly to its predictability and to precautions recommended to minimize the frequency of this potentially fatal complication in the management of spontaneous pneumothorax.
Religion and Health: Public Health Research and Practice
Authors: Linda M. Chatters
Journal: Annual Review of Public Health (2000)

▪ Abstract Research examining the relationships between religion and the health of individuals and populations has become increasingly visible in the social, behavioral, and health sciences. Systematic programs of research investigate religious phenomena within the context of coherent theoretical and conceptual frameworks that describe the causes and consequences of religious involvement for health outcomes. Recent research has validated the multidimensional aspects of religious involvement and investigated how religious factors operate through various biobehavioral and psychosocial constructs to affect health status through proposed mechanisms that link religion and health. Methodological and analytical advances in the field permit the development of more complex models of religion's effects, in keeping with proposed theoretical explanations. Investigations of religion and health have ethical and practical implications that should be addressed by the lay public, health professionals, the research community, and the clergy. Future research directions point to promising new areas of investigation that could bridge the constructs of religion and health.
European Code Against Cancer and scientific justification: third version (2003)
Authors: P. Boyle, P. Autier, H. Bartelink, J. Baselga, P. Boffetta, J. Burn, H.J.G. Burns, L. Christensen, L. Denis, M. Dicato, V. Diehl, R. Doll, S. Franceschi, C.R. Gillis, N. Gray, L. Griciute, A. Hackshaw, M. Kasler, M. Kogevinas, S. Kvinnsland, C. La Vecchia, F. Levi, J.G. McVie, P. Maisonneuve, J.M. Martin-Moreno, J. Newton Bishop, F. Oleari, P. Perrin, M. Quinn, M. Richards, U. Ringborg, C. Scully, E. Siracka, H. Storm, M. Tubiana, T. Tursz, U. Veronesi, N. Wald, W. Weber, D.G. Zaridze, W. Zatonski, H. zur Hausen
Journal: Annals of Oncology (2003)
Microtubule-Associated Protein Mdp3 Promotes Breast Cancer Growth and Metastasis
Authors: None Tala, Songbo Xie, Xiaodong Sun, Xiaoou Sun, Jie Ran, Linlin Zhang, Dengwen Li, Min Liu, Gang Bao, Jun Zhou
Journal: Theranostics (2014)

Breast cancer is the most prevalent cancer in women worldwide with a high mortality rate, and the identification of new biomarkers and targets for this disease is greatly needed.Here we present evidence that microtubule-associated protein (MAP) 7 domain-containing protein 3 (Mdp3) is highly expressed in clinical samples and cell lines of breast cancer.The expression of Mdp3 correlates with clinicopathological parameters indicating breast cancer malignancy.In addition, Mdp3 promotes breast cancer cell proliferation and motility in vitro and stimulates breast cancer growth and metastasis in mice.Mechanistic studies reveal that γ-tubulin interacts with and recruits Mdp3 to the centrosome and that the centrosomal localization of Mdp3 is required for its activity to promote breast cancer cell proliferation and motility.These findings suggest a critical role for Mdp3 in the growth and metastasis of breast cancer and may have important implications for the management of this disease.
Peripheral Arterial Circulation in Individuals with Impaired Glucose Tolerance
Authors: Olga Vaccaro, Paolo Pauciullo, Paolo Rubba, Giovanni Annuzzi, Angela A Rivellese, Gabriele Riccardi, Mario Mancini
Journal: Diabetes Care (1985)

Employees of a telephone company in Naples (N = 1376) were screened by oral glucose tolerance test (OGTT, 75 g). All those with impaired glucose tolerance (IGT) (N = 69) plus 138 normoglycemic controls, matched by sex, age, and body mass index (BMI, kg/m2), were selected to participate in this study. All participants were retested by OGTT under the same conditions as the first test. The prevalence of signs of impaired peripheral arterial circulation (IPAC) were investigated by different methods: Rose questionnaire on intermittent claudication, digital pulse plethysmography (inclination time), and ankle blood pressure measurement (ankle/arm systolic blood pressure). Very few persons had symptoms of IPAC: 2 (3.1%) and 3 (2.4%), respectively, in IGT subjects and controls. No difference in the prevalence of abnormal vascular parameters was detected between IGT and normoglycemic individuals according to either digital pulse plethysmography (6.1% versus 8.8%, P = 0.36) or ankle blood pressure measurement (10.8% versus 9.6%, χ2 = 0.06, NS); similar results were obtained when the prevalence of abnormalities was evaluated according to both methods combined (16.9% versus 16.8%). The finding remained very much the same after controlling for the effect of smoking. Individuals with IGT at both OGTTs were compared with individuals with normoglycemia at both tests: once again no significant difference was detected between the two groups in the prevalence of abnormal vascular findings (22.6% versus 16.7%, χ2 = 0.66, NS). This suggests that IGT is not associated with increased prevalence of atherosclerotic peripheral arterial disease.
Development of hyperdynamic circulation and response to β‐blockers in compensated cirrhosis with portal hypertension
Authors: Càndid Villanueva, Agustín Albillos, Joan Genescà, Juan G. Abraldes, Jose L. Calleja, Carles Aracil, Rafael Bañares, Rosa Morillas, María Poca, Beatriz Peñas, Salvador Augustin, Joan Carles Garcia‐Pagan, Oana Pavel, Jaume Bosch
Journal: Hepatology (2015)

Nonselective β-blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to β-blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to β-blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross-sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG ≥10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End-Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 ± 423 versus 1469 ± 335 dyne · s · cm(-5) , P < 0.05) and higher cardiac index (3.3 ± 0.9 versus 2.8 ± 0.4 L/min/m(2) , P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (-16 ± 12% versus -8 ± 9%, P < 0.01). The HVPG decreased ≥10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased ≥20% in 40% versus 13%, respectively (P = 0.001).Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute β-blockade than those with CSPH, suggesting that β-blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages.
Phorbol Ester Induction of Angiotensin-Converting Enzyme Transcription Is Mediated by Egr-1 and AP-1 in Human Endothelial Cells via ERK1/2 Pathway
Authors: Mélanie Eyries, Monique Agrapart, Amalia Alonso, Florent Soubrier
Journal: Circulation Research (2002)

Angiotensin-converting enzyme (ACE) is an enzyme that plays a major role in vasoactive peptide metabolism, and it has been implicated in various cardiovascular diseases. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, has been shown to increase ACE mRNA at the transcriptional level in human umbilical vein endothelial cells. We have investigated the transcriptional mechanism involved in protein kinase C induction of the ACE gene. Deletion and transfection analyses have revealed that two regions are required for PMA-inducible gene expression. The first is a G+C-rich region located in the proximal ACE promoter bearing overlapping consensus recognition sequences for stimulatory protein-1 (Sp1) and early growth response gene 1 (Egr-1). Electrophoretic mobility shift assay and supershift experiments have shown that Egr-1 is present in the specific nucleoprotein complex induced by PMA in human umbilical vein endothelial cells. The second region is located in the distal ACE promoter. DNase I footprinting analysis restricted this region to a 21-bp element containing a cAMP-responsive element/12-O-tetradecanoylphorbol 13-acetate-responsive element sequence. Electrophoretic mobility shift assays and supershift analyses have revealed that activating protein 1 (AP-1) is the transcription factor binding the cAMP-responsive element/12-O-tetradecanoylphorbol 13-acetate-responsive element located in the ACE promoter after PMA stimulation. Mutations of either Egr-1 or AP-1 binding sites partially abrogate ACE expression induced by PMA, whereas mutation of both sites totally abrogates PMA-induced ACE expression. Treatment of cells with PD98059, a mitogen-activated protein kinase kinase-1-specific inhibitor, inhibited PMA-induced ACE expression. Our results demonstrate that the two transcription factors, Egr-1 and AP-1, are involved in the PMA-induced ACE transcriptional activation in human endothelial cells via the activation of the extracellular signal-regulated kinase 1/2 signaling pathway.
Scimitar sign with normal pulmonary venous drainage and anomalous inferior vena cava.
Authors: B Herer, F Jaubert, C Delaisements, G Huchon, J Chretien
Journal: Thorax (1988)

A case of the scimitar sign due to an anomaly of the right sided pulmonary vein with normal drainage into the left atrium was associated with an azygos continuation of the inferior vena cava. Digital subtraction angiography allows the identification of these rare congenital vascular malformations.
GlialCAM, a Protein Defective in a Leukodystrophy, Serves as a ClC-2 Cl− Channel Auxiliary Subunit
Authors: Elena Jeworutzki, Tania López-Hernández, Xavier Capdevila-Nortes, Sònia Sirisi, Luiza Bengtsson, Marisol Montolio, Giovanni Zifarelli, Tanit Arnedo, Catrin S. Müller, Uwe Schulte, Virginia Nunes, Albert Martínez, Thomas J. Jentsch, Xavier Gasull, Michael Pusch, Raúl Estévez
Journal: Neuron (2012)
Risk of Hodgkin's Disease and Other Cancers After Infectious Mononucleosis
Authors: H. Hjalgrim
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. Methods: Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were followed for cancer occurrence. The ratio of observed-to-expected numbers of cancers (standardized incidence ratio [SIR]) served as a measure of the relative risk for cancer. SIRs of Hodgkin's disease in different subsets of patients were compared with the use of Poisson regression analysis. All statistical tests including the trend tests were two-sided. Results: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1.03; 95% confidence interval [CI] = 0.98–1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1.87–3.40; n = 46), only skin cancers (SIR = 1.27; 95% CI = 1.13–1.43; n = 291) occurred in statistically significant excess. In contrast, the SIR for lung cancer was reduced (SIR = 0.71; 95% CI = 0.58–0.86; n = 102). The SIR for Hodgkin's disease remained elevated for up to two decades after the occurrence of infectious mononucleosis but decreased with time since diagnosis of infectious mononucleosis (P for trend <.001). The SIR for Hodgkin's disease tended to increase with age at diagnosis of infectious mononucleosis (P for trend = .05). Following infectious mononucleosis, the SIR for Hodgkin's disease at ages 15–34 years was 3.49 (95% CI = 2.46–4.81; n = 37), which was statistically significantly higher than the SIR for any other age group (P for difference = .001). Conclusion: The increased risk of Hodgkin's disease after the occurrence of infectious mononucleosis appears to be a specific phenomenon.
Oesophageal intramural pseudodiverticulosis.
Authors: S Sabanathan, F D Salama, W E Morgan
Journal: Thorax (1985)

Twelve cases of oesophageal intramural pseudodiverticulosis are described and the findings in 85 previously reported cases are reviewed. The condition occurs in all age groups, predominantly in the sixth and seventh decades, with a slight predilection for males. The characteristic radiographic appearance is of multiple flask shaped outpouchings of 1-4 mm with narrow necks communicating with the oesophageal lumen. The source of the pseudodiverticula has been shown to be pathologically dilated excretory ducts of the submucous glands due to chronic submucosal inflammation. The distribution was segmental in 57 cases (59%) and diffuse in 40 (41%). Dysphagia is the main symptom and was found in 85 cases (88%); 88 cases out of 97 had radiological narrowing of the oesophagus; of these, 39 (44%) were in the upper oesophagus, 20 (23%) in the middle oesophagus, and 29 (33%) in the lower oesophagus. Treatment is directed towards management of the associated disorder, as the diverticula themselves rarely cause problems.
Regrow or Repair
Authors: Melissa H. Little
Journal: Journal of the American Society of Nephrology (2006)

Regenerative medicine is being heralded in a similar way as gene therapy was some 15 yr ago. It is an area of intense excitement and potential, as well as myth and disinformation. However, with the increasing rate of end-stage renal failure and limited alternatives for its treatment, we must begin to investigate seriously potential regenerative approaches for the kidney. This review defines which regenerative options there might be for renal disease, summarizes the progress that has been made to date, and investigates some of the unique obstacles to such treatments that the kidney presents. The options discussed include in situ organ repair via bone marrow recruitment or dedifferentiation; ex vivo stem cell therapies, including both autologous and nonautologous options; and bioengineering approaches for the creation of a replacement organ.
Effect of Decreasing the Force of Right Atrial Contraction on Right Ventricular Stroke Volume
Authors: DANIEL L. BOYD, JOHN W. WILLIAMS
Journal: Circulation Research (1967)

The effect of reducing the force of right atrial contraction on right ventricular stroke volume was determined in anesthetized open-chest dogs. Atrial contractile force, measured directly with a strain-gauge arch, was decreased by electrical stimulation of the right vagus nerve; right ventricular stroke volume was measured with an electro-magnetic flowmeter. Heart rate was maintained constant by electrical stimulation of the right atrium. Vagal stimulation decreased atrial contractile force by an average of 47±2.6 (SEM)% of the control, and stroke volume fell by 4.0±0.9%. During vagal stimulation, no change was observed in right ventricular contractile force. In addition, no consistent change was noted in mean right atrial or right ventricular pressures. The relation between the decrease in atrial force and stroke volume was not altered significantly by the rate of right atrial pacing. In 7 of 10 experiments, increasing the inhibition of atrial force produced a further decrease in stroke volume. Since neural, mechanical, and humoral factors modify atrial contractile force in the intact animal, the present study provides more definitive evidence that the ability to alter atrial force represents another adaptive mechanism in the regulation of cardiac performance.
215 A PHASE II OPEN LABEL TRIAL EVALUATING SAFETY AND EFFICACY OF A TELOMERASE PEPTIDE VACCINATION IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
Authors: T.F. Greten, A. Forner, F. Korangy, G. N'Kontchou, N. Barget, C. Ayuso, L. Ormandy, M. Manns, M. Beaugrand, J. Bruix
Journal: Journal of Hepatology (2010)
p53/HMGB1 Complexes Regulate Autophagy and Apoptosis
Authors: Kristen M. Livesey, Rui Kang, Philip Vernon, William Buchser, Patricia Loughran, Simon C. Watkins, Lin Zhang, James J. Manfredi, Herbert J. Zeh, Luyuan Li, Michael T. Lotze, Daolin Tang
Journal: Cancer Research (2012)

Abstract The balance between apoptosis (“programmed cell death”) and autophagy (“programmed cell survival”) is important in tumor development and response to therapy. Here, we show that high mobility group box 1 (HMGB1) and p53 form a complex that regulates the balance between tumor cell death and survival. We show that knockout of p53 in HCT116 cells increases expression of cytosolic HMGB1 and induces autophagy. Conversely, knockout of HMGB1 in mouse embryonic fibroblasts increases p53 cytosolic localization and decreases autophagy. p53 is thus a negative regulator of the HMGB1/Beclin 1 complex, and HMGB1 promotes autophagy in the setting of diminished p53. HMGB1-mediated autophagy promotes tumor cell survival in the setting of p53-dependent processes. The HMGB1/p53 complex affects the cytoplasmic localization of the reciprocal binding partner, thereby regulating subsequent levels of autophagy and apoptosis. These insights provide a novel link between HMGB1 and p53 in the cross-regulation of apoptosis and autophagy in the setting of cell stress, providing insights into their reciprocal roles in carcinogenesis. Cancer Res; 72(8); 1996–2005. ©2012 AACR.
Health‐related quality of life of food allergic patients: comparison with the general population and other diseases
Authors: B. M. J. Flokstra‐de Blok, A. E. J. Dubois, B. J. Vlieg‐Boerstra, J. N. G. Oude Elberink, H. Raat, A. DunnGalvin, J. O’B. Hourihane, E. J. Duiverman
Journal: Allergy (2009)

To cite this article: Flokstra‐de Blok BMJ, Dubois AEJ, Vlieg‐Boerstra BJ, Oude Elberink JNG, Raat H, DunnGalvin A, Hourihane JO’B, Duiverman EJ. Health‐related quality of life of food allergic patients: comparison with the general population and other diseases. Allergy 2010; 65 : 238–244. Abstract Background: To date no studies have compared generic health‐related quality of life (HRQL) of food allergic patients from childhood to adulthood with that of the general population or patients with other chronic diseases. The aim of this study was to compare generic HRQL of food allergic patients with the general population and other diseases. Methods: Generic HRQL questionnaires (CHQ‐CF87 and RAND‐36) were completed by 79 children, 74 adolescents and 72 adults with food allergy. The generic HRQL scores were compared with scores from published studies on the general population and patients with asthma, irritable bowel syndrome (IBS), diabetes mellitus (DM) and rheumatoid arthritis (RA). Results: Food allergic children and adolescents reported fewer limitations in school work due to behavioural problems ( P ≤ 0.013), but food allergic adolescents and adults reported more pain ( P = 0.020), poorer overall health ( P &lt; 0.001), more limitations in social activities ( P &lt; 0.001) and less vitality ( P = 0.002) than individuals from the general population. Food allergic patients reported poorer generic HRQL than patients with DM, but better generic HRQL than patients with RA, asthma and IBS. Conclusion: HRQL is impaired in food allergic adolescents and adults, compared to the general population, and it is intermediate in magnitude between DM and RA, asthma and IBS. Children show the least impact on generic HRQL from food allergy.
International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology
Authors: Richard R. Neubig, Michael Spedding, Terry Kenakin, Arthur Christopoulos
Journal: Pharmacological Reviews (2003)

The recommendations that follow have been updated from the proposals of a Technical Subcommittee set up by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (Jenkinson DH, Barnard EA, Hoyer D, Humphrey PPA, Leff P, and Shankley NP (1995) International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. IX. Recommendations on terms and symbols in quantitative pharmacology. <i>Pharmacol Rev</i> 47:255–266).