tbuckley/cabot-search huggingface dataset:
Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion
Authors: D. Hussein, W. Punjaruk, L. C. D. Storer, L. Shaw, R. T. Othman, A. Peet, S. Miller, G. Bandopadhyay, R. Heath, R. Kumari, K. J. Bowman, P. Braker, R. Rahman, G. D. D. Jones, S. Watson, J. Lowe, I. D. Kerr, R. G. Grundy, B. Coyle
Journal: Neuro-Oncology (2010)

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC component of 7 newly established primary pediatric cell lines (2 ependymomas, 2 medulloblastomas, 2 gliomas, and a CNS primitive neuroectodermal tumor) was thoroughly characterized. Comparison of DNA copy number with the original corresponding tumor demonstrated that genomic changes present in the original tumor, typical of that particular tumor type, were retained in culture. In each case, the CSC component was approximately 3-4-fold enriched in neurosphere culture compared with monolayer culture, and a higher capacity for multilineage differentiation was observed for neurosphere-derived cells. DNA content profiles of neurosphere-derived cells expressing the CSC marker nestin demonstrated the presence of cells in all phases of the cell cycle, indicating that not all CSCs are quiescent. Furthermore, neurosphere-derived cells demonstrated an increased resistance to etoposide compared with monolayer-derived cells, having lower initial DNA damage, potentially due to a combination of increased drug extrusion by ATP-binding cassette multidrug transporters and enhanced rates of DNA repair. Finally, orthotopic xenograft models reflecting the tumor of origin were established from these cell lines. In summary, these cell lines and the approach taken provide a robust model system that can be used to develop our understanding of the biology of CSCs in pediatric brain tumors and other cancer types and to preclinically test therapeutic agents.
Differences in spirometry reference values: a statistical comparison of a Mongolian and a Caucasian study
Authors: RO Crapo, RL Jensen, M Oyunchimeg, T Tsh, C DuWayne Schmidt
Journal: European Respiratory Journal (1999)

New reference value studies for spirometry are commonly compared to existing reference value studies using average data derived from existing reference equations. Such comparisons are inherently flawed because they do not account for differences in distributions of the independent and dependent variables and they do not have identical methodologies. This study was undertaken 1) to derive reference equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) for natives of Mongolia and 2) to compare the Mongolian data with data from a 1981 reference study of Caucasians in Salt Lake City, UT, USA. Spirometry was performed on 344 (176 male, 168 female) healthy, nonsmoking urban natives of Mongolia to generate reference equations for FVC, FEV1, and FEV1/FVC. These data were compared with data from a 1981 reference study of Caucasians in Salt Lake City, using both an analysis of covariance of the raw data and parametric and nonparametric comparisons of a matched pair subset. Average measured forced vital capacity and forced expiratory volume in one second in native Mongolians were within 1-2% of the Caucasian predicted values. These small differences are not statistically significant in any of the multiple methods of comparisons. Power analysis suggests that, if real differences exist, the differences in forced vital capacity are &lt;155 mL for males, &lt;105 mL for females, and the differences in forced expiratory volume in one second are &lt;107 mL for males and &lt;76 mL for females.
Weight Change and Health Outcomes at 3 Years After Bariatric Surgery Among Individuals With Severe Obesity
Authors: Anita P. Courcoulas
Journal: JAMA (2013)

Severe obesity (body mass index [BMI] ≥35) is associated with a broad range of health risks. Bariatric surgery induces weight loss and short-term health improvements, but little is known about long-term outcomes of these operations.To report 3-year change in weight and select health parameters after common bariatric surgical procedures.The Longitudinal Assessment of Bariatric Surgery (LABS) Consortium is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. PARTICIPANTS AND EXPOSURE: Adults undergoing first-time bariatric surgical procedures as part of routine clinical care by participating surgeons were recruited between 2006 and 2009 and followed up until September 2012. Participants completed research assessments prior to surgery and 6 months, 12 months, and then annually after surgery.Three years after Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), we assessed percent weight change from baseline and the percentage of participants with diabetes achieving hemoglobin A1c levels less than 6.5% or fasting plasma glucose values less than 126 mg/dL without pharmacologic therapy. Dyslipidemia and hypertension resolution at 3 years was also assessed.At baseline, participants (N = 2458) were 18 to 78 years old, 79% were women, median BMI was 45.9 (IQR, 41.7-51.5), and median weight was 129 kg (IQR, 115-147). For their first bariatric surgical procedure, 1738 participants underwent RYGB, 610 LAGB, and 110 other procedures. At baseline, 774 (33%) had diabetes, 1252 (63%) dyslipidemia, and 1601 (68%) hypertension. Three years after surgery, median actual weight loss for RYGB participants was 41 kg (IQR, 31-52), corresponding to a percentage of baseline weight lost of 31.5% (IQR, 24.6%-38.4%). For LAGB participants, actual weight loss was 20 kg (IQR, 10-29), corresponding to 15.9% (IQR, 7.9%-23.0%). The majority of weight loss was evident 1 year after surgery for both procedures. Five distinct weight change trajectory groups were identified for each procedure. Among participants who had diabetes at baseline, 216 RYGB participants (67.5%) and 28 LAGB participants (28.6%) experienced partial remission at 3 years. The incidence of diabetes was 0.9% after RYGB and 3.2% after LAGB. Dyslipidemia resolved in 237 RYGB participants (61.9%) and 39 LAGB participants (27.1%); remission of hypertension occurred in 269 RYGB participants (38.2%) and 43 LAGB participants (17.4%).Among participants with severe obesity, there was substantial weight loss 3 years after bariatric surgery, with the majority experiencing maximum weight change during the first year. However, there was variability in the amount and trajectories of weight loss and in diabetes, blood pressure, and lipid outcomes.clinicaltrials.gov Identifier: NCT00465829.
OP16 Evidence for compartmentalised endotoxaemia and its effect on neutrophil function in the portal circulation in cirrhosis
Authors: J Macnaughtan, N Davies, V Stadlbauer, S Olde Damink, R Mookerjee, R Jalan
Journal: Gut (2010)

Introduction  Bacterial translocation and endotoxaemia are important in the pathogenesis of neutrophil dysfunction in cirrhosis. At present, it is not clear whether systemic endotoxaemia occurs as a consequence of a defect at the gut barrier interface or diminished hepatic function and associated portosystemic shunting.  Aim  The aims of this study were (1) to quantify the degree of portal endotoxaemia and the contribution of the liver in the regulation of systemic endotoxin (ET) levels, (2) to determine intestinal production of cytokines and adhesion molecules and (3) to determine whether the portal and hepatic milieu modulates neutrophil function.  Method  12 patients with cirrhosis (54±3.2 yr, Pugh 10.2±1.0, eight male, four female) were studied prior to and 1-h after TIPSS insertion. Blood was sampled from the artery, hepatic vein (HV), portal vein (PV) and its tributaries. PV blood was sampled before insertion of the TIPSS. Endotoxin (ET) (LAL assay), LBP, BPI, IL-6, IL-10, TNFR55, TNFR75, sICAM and sELAM (using ELISA) were measured. Neutrophil respiratory burst and phagocytosis was measured using FACS in neutrophils derived from the HV and PV, prior to and following cross-incubation with PV and HV plasma, respectively.  Results  TIPSS insertion resulted in a significant increase in arterial ET levels from 0.08±0.02 to 0.19±0.02 EU/ml (p=0.0001). Mean ET levels in the PV and HV pre-TIPSS insertion were 0.22±0.02 and 0.04±0.02 EU/ml respectively. Transintestinal (TI) and transhepatic (TH) ET fractional extraction (FE) rates were 2.7±0.7 and −0.5±0.06, respectively. HV neutrophil resting burst was significantly increased from 52±5.3 to 78±4.5% after incubation with PV plasma (p  Conclusion  This study provides direct evidence for portal endotoxaemia in cirrhosis. The data suggest that the liver is responsible for compartmentalising ET and associated neutrophil dysfunction within the portal circulation. Intestinal production of IL-6 and IL-10 was also demonstrated. TIPSS insertion disturbs this compartmentalisation and exposes the systemic circulation to portal endotoxaemia. Strategies to diminish portal endotoxaemia or enhance hepatic ET clearance capacity are important therapeutic targets to minimise neutrophil dysfunction in cirrhosis.
Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma
Authors: David A. Reardon, Jennifer A. Quinn, Jeremy N. Rich, Sridharan Gururangan, James Vredenburgh, John H. Sampson, James M. Provenzale, Amy Walker, Michael Badruddoja, Sandra Tourt-Uhlig, James E. Herndon, Jeannette M. Dowell, Mary Lou Affronti, Susanne Jackson, Deborah Allen, Karen Ziegler, Steven Silverman, Cindy Bohlin, Allan H. Friedman, Darell D. Bigner, Henry S. Friedman
Journal: Neuro-Oncology (2004)

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade ≥3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.
Harry Stafford Morton
Authors: C J Cameron
Journal: BMJ (2002)

Former consultant surgeon Montreal, Canada (b Nova Scotia 1905; q London 1930; OBE, MD, FRCS, FRCSC, FACS, FRCOG), d 7 December 2001.

Harry Morton was honorary attending surgeon, Royal Victoria Hospital, Montreal, from 1937 to 1970. From 1960 to 1969 he was chief surgeon at Queen Mary's Veterans Hospital, Montreal, and from 1970 to 1975 he was consultant surgeon at Fisherman's Memorial Hospital, Lunenberg, Nova Scotia. He loved the sea and sailing, and raced 14ft dinghies, winning several championships. He leaves a wife, Rachel, with whom he developed a traditional farm using sustainable agricultural practices.
Relapse of hepatitis B in HBeAg-negative chronic hepatitis B patients who discontinued successful entecavir treatment: The case for continuous antiviral therapy
Authors: Daniel Shouval, Ching-Lung Lai, Ting-Tsung Chang, Hugo Cheinquer, Paul Martin, Giampiero Carosi, Steven Han, Sabahattin Kaymakoglu, Ricardo Tamez, Joanna Yang, Daniel Tenney, Helena Brett-Smith
Journal: Journal of Hepatology (2008)
Stimulant Therapy and Risk for Subsequent Substance Use Disorders in Male Adults With ADHD: A Naturalistic Controlled 10-Year Follow-Up Study
Authors: Joseph Biederman, Michael C. Monuteaux, Thomas Spencer, Timothy E. Wilens, Heather A. MacPherson, Stephen V. Faraone
Journal: American Journal of Psychiatry (2008)

The extant literature does not provide definite answers pertaining to whether stimulant treatment increases, decreases, or does not affect the risk for subsequent substance use disorders in youths with attention deficit hyperactivity disorder (ADHD). The authors examined the association between stimulant treatment in childhood and adolescence and subsequent substance use disorders (alcohol, drug, and nicotine) into the young adult years.The authors conducted a 10-year prospective follow-up study. One hundred forty male Caucasian children with ADHD, ages 6 to 17, were examined at baseline. Of these, 112 (80%) were reassessed at the 10-year follow-up (mean age at follow-up=22 years). Assessments were made using Cox proportional hazards survival models. All models were adjusted for conduct disorder, since conduct disorder is a potent predictor of subsequent substance use disorders.Of the 112 ADHD subjects who were reassessed at the 10-year follow-up, 82 (73%) had been treated previously with stimulants and 25 (22%) were undergoing stimulant treatment at the time of the follow-up assessment. There were no statistically significant associations between stimulant treatment and alcohol, drug, or nicotine use disorders.The findings revealed no evidence that stimulant treatment increases or decreases the risk for subsequent substance use disorders in children and adolescents with ADHD when they reach young adulthood.
Nephron-sparing Techniques Independently Decrease the Risk of Cardiovascular Events Relative to Radical Nephrectomy in Patients with a T1a–T1b Renal Mass and Normal Preoperative Renal Function
Authors: Umberto Capitanio, Carlo Terrone, Alessandro Antonelli, Andrea Minervini, Alessandro Volpe, Maria Furlan, Rayan Matloob, Federica Regis, Cristian Fiori, Francesco Porpiglia, Ettore Di Trapani, Monica Zacchero, Sergio Serni, Andrea Salonia, Marco Carini, Claudio Simeone, Francesco Montorsi, Roberto Bertini
Journal: European Urology (2014)
Specificity of Genetic and Environmental Risk Factors for Use and Abuse/Dependence of Cannabis, Cocaine, Hallucinogens, Sedatives, Stimulants, and Opiates in Male Twins
Authors: Kenneth S. Kendler, Kristen C. Jacobson, Carol A. Prescott, Michael C. Neale
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Data on use and misuse of six classes of illicit substances by male twin pairs were used to examine whether genetic and shared environmental risk factors for substance use disorders are substance-specific or -nonspecific in their effect. METHOD: Lifetime history of use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates was assessed at personal interview in both members of 1,196 male-male twin pairs ascertained by the Virginia Twin Registry. Multivariate twin modeling of substance-nonspecific (common) and substance-specific genetic, shared environmental, and unique environmental risk factors was performed by using the program Mx. RESULTS: High levels of comorbidity involving the different substance categories were observed for both use and abuse/dependence. One common genetic factor was found to have a strong influence on risk for illicit use and abuse/dependence for all six substance classes. A modest influence of substance-specific genetic factors was seen for use but not for abuse/dependence. Shared environmental factors were more important for use than for abuse/dependence and were mediated entirely through a single common factor. CONCLUSIONS: In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.
Contrasting effects of an angiotensin converting enzyme inhibitor and a calcium antagonist on calcium transients in isolated rat cardiac myocytes
Authors: T. Kuramochi, M. Honda, K. Tanaka, A. M Mansoor, K.-i. Enomoto, M. Hashimoto, S. Morioka
Journal: Cardiovascular Research (1994)

The aim was to examine the effects of an angiotensin converting enzyme (ACE) inhibitor and a calcium antagonist on intracellular calcium transients in isolated cardiac myocytes from a monocrotaline induced right ventricular hypertrophy model.One week after monocrotaline injection, Sprague-Dawley rats were given either an ACE inhibitor (delapril-HCl) or a calcium antagonist (nilvadipine) for two weeks. Using fura-2/AM, calcium transients were measured in single myocytes separated from the right ventricle.The severe right ventricular hypertrophy observed in untreated rats was significantly reduced in drug treated animals. The inhibitory effects of delapril were more prominent than those of nilvadipine, although both drugs reduced right ventricular pressure to the same extent. Calcium transients in delapril treated rats were similar to those in control rats. On the other hand, the calcium transient in nilvadipine treated rats was decreased and its time course was prolonged. The changes were similar to those found in monocrotaline treated rats. The responsiveness of calcium transients to isoprenaline in delapril treated rats was similar to that in control rats. The responsiveness in nilvadipine treated rats was decreased, and was similar to that in monocrotaline treated rats. Delapril improved developed tension and the beta adrenoreceptor responsiveness of developed tension to isoprenaline.Although delapril and nilvadipine inhibited cardiac hypertrophy in monocrotaline treated rats, significant improvement of contractile function and beta adrenoreceptor responsiveness was observed only in the delapril treated rats. This improvement was partially due to the improvement in calcium transients and the restoration of the beta adrenoreceptor responsiveness of the calcium transient to beta adrenergic stimulation.
Nuclear Factor-κB Regulates Induction of Apoptosis and Inhibitor of Apoptosis Protein-1 Expression in Vascular Smooth Muscle Cells
Authors: Wolfgang Erl, Göran K. Hansson, Rainer de Martin, Georg Draude, Kim S. C. Weber, Christian Weber
Journal: Circulation Research (1999)

Abstract —Apoptosis is important in normal development as well as in diseases such as atherosclerosis. However, the regulation of apoptosis is still not completely understood. We now show that the transcription factor nuclear factor-κB (NF-κB) controls the induction of apoptosis in human and rat vascular smooth muscle cells (SMCs). SMCs in high-density culture exhibited a high NF-κB activity and were insensitive to induction of apoptosis. Inhibition of NF-κB by adenovirus-mediated overexpression of its inhibitor IκBα caused a marked increase in cell death at low but not high cell density. Elevating endogenous IκBα levels by inhibiting its degradation with proteasomal inhibitors resulted in induction of apoptosis in low-density SMCs, as detected by increased binding of annexin V, reduced mitochondrial membrane potential, and increased hypodiploid DNA. In high-density cultures, protection against apoptosis was associated with the expression of inhibitor of apoptosis protein-1 (IAP-1). Transfer of IκBα reduced human IAP-1 mRNA levels, which suggested that IAP-1 is transcriptionally regulated by NF-κB. This was confirmed through identification of a motif with NF-κB–like binding activity in the human IAP-1 promoter region. Moreover, antisense inhibition of IAP-1 sensitized high-density SMCs to the induction of cell death. Together, our data imply that SMCs at high density are protected by an antiapoptotic mechanism that involves increased expression of NF-κB and IAP-1. Interference with pathways that control the susceptibility to programmed cell death may be helpful in the treatment of diseases where dysregulation of apoptosis is involved, eg, atherosclerosis and restenosis.
Randomized Phase III Study Comparing Paclitaxel–Bleomycin, Etoposide, and Cisplatin (BEP) to Standard BEP in Intermediate-Prognosis Germ-Cell Cancer: Intergroup Study EORTC 30983
Authors: Ronald de Wit, Iwona Skoneczna, Gedske Daugaard, Maria De Santis, August Garin, Nina Aass, Alfred J. Witjes, Peter Albers, Jeffery D. White, José R. Germa-Lluch, Sandrine Marreaud, Laurence Collette
Journal: Journal of Clinical Oncology (2012)

To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m(2) in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual.Accrual was from November 1998 to April 2009. A total of 169 patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different.T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.