tbuckley/cabot-search huggingface dataset:
Electrophysiological Studies on Preexcitation in the Dog Using an Electronically Simulated Atrioventricular Bypass Pathway
Authors: E. Neil Moore, Joseph F. Spear, John P. Boineau
Journal: Circulation Research (1972)

Experiments were performed on open-chest dogs. In the in situ heart, electronic circuits were used to simulate atrioventricular (AV) bypass pathways as they are found in the preexcitation syndrome. Bipolar electrograms were recorded from the atria, His bundle, Purkinje system, and ventricles. A Systron-Donner SD-80 computer was used to simulate conduction over the Kent or the James bundle and over Mahaim fibers. The electronic bypass circuits had the properties of an excitation threshold, conduction delay, and refractoriness and the ability to conduct in the antegrade or retrograde directions. Simulated lateral accessory AV pathways at various regions of the base of the left and right AV margin produced electrocardiogram (ECG) patterns corresponding to type A, type B, and intermediate types of the Wolff-Parkinson-White syndrome. Stimulation of the ventricular septum along that region of the His bundle corresponding to Mahaim fibers did not produce prominent delta waves or obvious fusion of ECG complexes when the timing of ventricular septal stimulation was coincident with His bundle activation or preceded it by 18 msec. The characteristics of the fusion beats during introduction of premature atrial beats and during phasic changes in vagal tone were also investigated. Retrograde conduction through a simulated Kent bundle caused the development of a self-sustained supraventricular tachycardia. Spontaneously occurring echo beats during simulated preexcitation exhibited distorted ECG complexes and verified the possibility of a nodal reentrant atrial tachycardia with rapid antegrade conduction over the Kent bundle. The danger of atrial tachyarrhythmias in individuals with preexcitation was demonstrated by showing that, with the proper conduction parameters across a bypass tract, atrial fibrillation could lead to ventricular fibrillation.
Enhancement of photodynamic therapy in gastric cancer cells by removal of iron.
Authors: W C Tan, N Krasner, P O'Toole, M Lombard
Journal: Gut (1997)

Aminolaevulinic acid (ALA) is an endogenous substrate in the haem biosynthetic pathway. Protoporphyrin IX (PPIX), the immediate haem precursor in the pathway, has photoexcitable properties. Exogenous ALA has been used previously as a precursor agent in photodynamic therapy (PDT). Its main advantage is a short half-life and hence reduced incidence of skin photosensitivity. ALA can be toxic, however, causing, for example, transient increases in liver enzyme concentrations when given systemically and this may be dose related.To assess whether accumulation of PPLX and ultimately the efficacy of PDT could be improved by modulating both ends of the haem biosynthetic pathway.Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mumolar) and desferrioxamine (0-800 mumolar) for 24 hours before exposure to argon-pumped dye laser (630 nm) at different energy levels (0-40 J/cm2). Cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light.Total PPIX accumulation increased linearly with increasing extracellular concentrations of ALA up to 1 mmolar (r = 0.973, p < 0.005). Adding 200 molar of desferrioxamine trebled PPIX accumulation over the same period of incubation. Cell viability after exposure to light decreased with low doses (0-30 mumolar) of desferrioxamine (r = 0.976, p = 0.024). However, higher doses of desferrioxamine (more than 40 molar) seemed to confer a protective effect against PDT.PDT using ALA can be improved by removal of available iron with desferrioxamine. The reason for the protective effect of desferrioxamine seen at higher doses is not clear.
Overcoming Methodological Weakness in Dose-Intense Alkylating Agent Studies through Pharmacology
Authors: Roy B. Jones
Journal: Clinical Cancer Research (2004)

The importance of alkylating-agent dose intensity to cancer treatment is the subject of considerable comment. In recent years, this debate has often centered on the value of hematopoietic progenitor cell-supported high-dose alkylating agent regimens used in the treatment of hematopoietic cancers,
Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data
Authors: Yvonne JK Edwards, Anna E Lobley, Melissa M Pentony, David T Jones
Journal: Genome biology (2009)

Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins. In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed. Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function.
Phenotypic and functional characterisation of myofibroblasts, macrophages, and lymphocytes migrating out of the human gastric lamina propria following the loss of epithelial cells
Authors: K C Wu, L M Jackson, A M Galvin, T Gray, C J Hawkey, Y R Mahida
Journal: Gut (1999)

BACKGROUND The basement membrane of human colonic mucosa contains numerous discrete pores. We have recently shown that following loss of the surface epithelium, many cells migrate out of the colonic lamina propria via basement membrane pores. AIMS To characterise cells migrating out via basement membrane pores of the human gastric lamina propria, following loss of the surface epithelium. METHODS Fresh human gastric mucosal samples were completely denuded of epithelial cells and placed in culture. Tissue samples were studied by electron microscopy (EM) and cells by EM, FACS analysis, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR). RESULTS EM showed numerous discrete pores (0.65–8.29 μm in diameter) in the subepithelial basement membrane. During culture of mucosal samples denuded of epithelial cells, lymphocytes, macrophages, and myofibroblasts migrated out of the lamina propria via the basement membrane pores. The lymphocytes were predominantly CD45RO+ and CD69+ T cells. Macrophages were shown to express cyclooxygenase (COX) 1 and 2 enzymes. Myofibroblasts were established in culture and, despite prolonged culture and passage, retained their phenotype. They expressed mRNA and protein for COX 1 and 2 enzymes and their release of prostaglandin E 2 was inhibited by selective COX 1 and 2 inhibitors. CONCLUSIONS Lamina propria cells migrating out of cultured denuded gastric mucosal samples have been characterised phenotypically and functionally. Such cells would be suitable for studies of their interactions with epithelial cells and also with Helicobacter pylori and its products.
Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse
Authors: Stephanie J. Lee, John P. Klein, A. John Barrett, Olle Ringden, Joseph H. Antin, Jean Yves Cahn, Matthew H. Carabasi, Robert Peter Gale, Sergio Giralt, Gregory A. Hale, Osman Ilhan, Philip L. McCarthy, Gerard Socie, Leo F. Verdonck, Daniel J. Weisdorf, Mary M. Horowitz
Journal: Blood (2002)
Long-term Outcomes of 1,263 Patients with Mycosis Fungoides and Sézary Syndrome from 1982 to 2009
Authors: Rakhshandra Talpur, Lotika Singh, Seema Daulat, Ping Liu, Sarah Seyfer, Tanya Trynosky, Wei Wei, Madeleine Duvic
Journal: Clinical Cancer Research (2012)

The purpose of this prospectively collected single center study cohort of 1,263 patients with mycosis fungoides (MF)/Sézary syndrome (SS) is to evaluate the significance of stage and risk of disease progression from initial presentation and to examine other prognostic factors.The prognostic variables effecting overall survival (OS) were examined in a unique prospective cohort of 1,263 patients with MF and SS seen by one investigator at MD Anderson Cancer Center (Houston, TX) from 1982 to 2009. Kaplan-Meier estimates were used to determine median OS, progression-free survival (PFS), and disease-specific survival (DSS). Cox proportional hazards regression model assessed prognostic factors.Mean age at diagnosis was 55.33 years. Early mycosis fungoides (stage IA-IIA) represented 71.5% (903 of 1,263) and advanced (stage IIB-IVB) 28.5% (360 of 1,263) patients. Progression to a higher stage occurred in 147 patients (11.6%) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from disease occurred in 102 of 1,263 (8.1%) patients. Median OS was 24.44 years, PFS was 16 years, and median DSS was not reached. OS and PFS were significantly better for early-stage patients with patches (T1a/T2a) than with patches/plaques (T1b/T2b). The PFS analyzed in 1,241 patients found that only 337 (27.2%) had disease progression or had died from disease. Risk factors associated with progression or deaths were advanced age, plaque stage, lactate dehydrogenase (LDH) level, and tumor area.Improved outcome of MF/SS, reflected by OS and PFS for all stages, may result from earlier diagnosis, new therapies, and aggressive treatment of infections.
A variant in FTO shows association with melanoma risk not due to BMI
Authors: Mark M. Iles, Matthew H. Law, Simon N. Stacey, Jiali Han, Shenying Fang, Ruth Pfeiffer, Mark Harland, Stuart Macgregor, John C. Taylor, Katja K. Aben, Lars A. Akslen, Marie-Françoise Avril, Esther Azizi, Bert Bakker, Kristrun R. Benediktsdottir, Wilma Bergman, Giovanna Bianchi Scarra, Kevin M. Brown, Donato Calista, Valérie Chaudru, Maria Concetta Fargnoli, Anne E. Cust, Florence Demenais, Anne C. De Waal, Tadeusz Dębniak, David E. Elder, Eitan Friedman, Pilar Galan, Paola Ghiorzo, Elizabeth M. Gillanders, Alisa M. Goldstein, Nelleke A. Gruis, Johan Hansson, Per Helsing, Marko Hočevar, Veronica Hoiom, John L. Hopper, Christian Ingvar, Marjolein Janssen, Mark A. Jenkins, Peter A. Kanetsky, Lambertus A. Kiemeney, Julie Lang, G. Mark Lathrop, Sancy Leachman, Jeffrey E. Lee, Jan Lubinski, Rona M. Mackie, Graham J. Mann, Nicholas G. Martin, Jose I. Mayordomo, Anders Molven, Suzanne Mulder, Eduardo Nagore, Srdjan Novakovic, Ichiro Okamoto, Jon H. Olafsson, Haan Olsson, Hubert Pehamberger, Ketty Peris, Maria Pilar Grasa, Dolores Planelles, Susana Puig, Joan Anton Puig-Butille, Juliette Randerson-Moor, Celia Requena, Licia Rivoltini, Monica Rodolfo, Mario Santinami, Bardur Sigurgeirsson, Helen Snowden, Fengju Song, Patrick Sulem, Kristin Thorisdottir, Rainer Tuominen, Patricia van Belle, Nienke van Der Stoep, Michelle M. van Rossum, Qingyi Wei, Judith Wendt, Diana Zelenika, Mingfeng Zhang, Maria Teresa Landi, Gudrnar Thorleifsson, D. Timothy Bishop, Christopher I. Amos, Nicholas K. Hayward, Kari Stefansson, Julia A. Newton Bishop, Jennifer H. Barrett
Journal: Nature Genetics (2013)
Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes.
Authors: J C Rogers
Journal: The Journal of Experimental Medicine (1976)

The DNA released into the culture medium after phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes has been purified and characterized. It is double stranded, sediments at 7-8S in alkaline sucrose, and has a Tm determined optically and by thermal elution from hydroxyapatite that is substantially lower than that found for lymphocyte cell DNA. Media DNA contains a major component reassociating with an average Cot-1/2 of 87 mol X s/liter, compared to a Cot-1/2 of 770 mol X s/liter for the unique fraction of cell DNA as measured by reassociation in 0.6 M Na+. This component of media DNA consists of unique sequence elements which are largely shared in media DNA preparations from cultures derived from different cell donors. The marked difference between media DNA and cell DNA indicates that media DNA is not derived from cell death and lysis, rather than some unique portion of lymphocyte DNA is apparently excreted from the cells during PHA-stimulated growth.
Association of ICU or Hospital Admission With Unintentional Discontinuation of Medications for Chronic Diseases
Authors: Chaim M. Bell, Stacey S. Brener, Nadia Gunraj, Cindy Huo, Arlene S. Bierman, Damon C. Scales, Jana Bajcar, Merrick Zwarenstein, David R. Urbach
Journal: JAMA (2011)

Patients discharged from acute care hospitals may be at risk for unintentional discontinuation of medications prescribed for chronic diseases. The intensive care unit (ICU) may pose an even greater risk because of the focus on acute events and the presence of multiple transitions in care.To evaluate rates of potentially unintentional discontinuation of medications following hospital or ICU admission.A population-based cohort study using administrative records from 1997 to 2009 of all hospitalizations and outpatient prescriptions in Ontario, Canada; it included 396,380 patients aged 66 years or older with continuous use of at least 1 of 5 evidence-based medication groups prescribed for long-term use: (1) statins, (2) antiplatelet/anticoagulant agents, (3) levothyroxine, (4) respiratory inhalers, and (5) gastric acid-suppressing drugs. Rates of medication discontinuation were compared across 3 groups: patients admitted to the ICU, patients hospitalized without ICU admission, and nonhospitalized patients (controls). Odds ratios (ORs) were calculated and adjusted for patient demographics, clinical factors, and health services use.The primary outcome was failure to renew the prescription within 90 days after hospital discharge.Patients admitted to the hospital (n = 187,912) were more likely to experience potentially unintentional discontinuation of medications than controls (n = 208,468) across all medication groups examined. The adjusted ORs (AORs) ranged from 1.18 (95% CI, 1.14-1.23) for discontinuing levothyroxine in 12.3% of hospitalized patients (n = 6831) vs 11.0% of controls (n = 7114) to an AOR of 1.86 (95% CI, 1.77-1.97) for discontinuing antiplatelet/anticoagulant agents in 19.4% of hospitalized patients (n = 5564) vs 11.8% of controls (n = 2535). With ICU exposure, the AORs ranged from 1.48 (95% CI, 1.39-1.57) for discontinuing statins in 14.6% of ICU patients (n = 1484) to an AOR of 2.31 (95% CI, 2.07-2.57) for discontinuing antiplatelet/anticoagulant agents in 22.8% of ICU patients (n = 522) vs the control group. Admission to an ICU was associated with an additional risk of medication discontinuation in 4 of 5 medication groups vs hospitalizations without an ICU admission. One-year follow-up of patients who discontinued medications showed an elevated AOR for the secondary composite outcome of death, emergency department visit, or emergent hospitalization of 1.07 (95% CI, 1.03-1.11) in the statins group and of 1.10 (95% CI, 1.03-1.16) in the antiplatelet/anticoagulant agents group.Patients prescribed medications for chronic diseases were at risk for potentially unintentional discontinuation after hospital admission. Admission to the ICU was generally associated with an even higher risk of medication discontinuation.
Treatment of nocturnal asthma with nedocromil sodium.
Authors: L Clancy, S Keogan
Journal: Thorax (1994)

BACKGROUND--The association of nocturnal asthma symptoms with a diurnal increase in inflammatory activity suggests a role for anti-inflammatory therapy in nocturnal asthma. METHODS--Fifty patients with asthma with nocturnal symptoms entered a randomised, double blind, placebo controlled, crossover study. After a two week baseline period patients received nedocromil sodium (4 mg) or placebo four times daily. After eight weeks of treatment patients crossed to the alternative treatment for a further eight weeks. Symptom severity was recorded on a scale of 0-4 and inhaled bronchodilator use and peak flow (PEFR) were also recorded daily by the patients. Asthma severity, pulmonary function (FEV1, PEFR, FVC), and adverse events were recorded at clinic visits (baseline and after four and eight weeks of treatment). Global effectiveness was rated by clinician and patient, and treatment preference was recorded. RESULTS--Efficacy was assessed from data from 28 patients. Night-time asthma (mean (SE) difference between nedocromil sodium and placebo: -0.52 (0.13)), total nocturnal symptom severity defined as night-time asthma plus morning tightness (-0.72 (0.20)), and night-time bronchodilator use (-0.62 (0.23)) were reduced with nedocromil sodium compared with placebo treatment during the primary efficacy period (weeks 5-8) and during weeks 1-4 (-0.36 (0.12), -0.63 (0.20), and -0.55 (0.28), respectively). Morning and evening PEFR values improved slightly--but not significantly--compared with placebo. Patient and clinician opinions favoured nedocromil sodium treatment. Daytime asthma, daytime cough, and clinic assessment of asthma severity (secondary efficacy variables) were improved with nedocromil sodium treatment; day-time bronchodilator use and clinic pulmonary function were not. CONCLUSIONS--Nedocromil sodium was more effective than placebo in reducing nocturnal symptoms of asthma and bronchodilator use in this group of patients.
Counterpoint: Postprandial Glucose Levels Are Not a Clinically Important Treatment Target
Authors: Mayer B. Davidson
Journal: Diabetes Care (2010)

The recently published randomized controlled Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study evaluated the effect of nateglinide in people with impaired glucose tolerance (IGT) who also had cardiovascular disease (CVD) or CVD risk factors (1). After a median of five years, there was no effect on either incident diabetes or CVD. In five studies (2–6) in which the development of diabetes in subjects with IGT was delayed by lifestyle intervention or drugs, the beneficial effect was postulated to be mainly due to decreasing insulin resistance with resulting less demands on β-cell insulin secretion. On the other hand, subjects with IGT in an older small study treated with tolbutamide (a first-generation sulfonylurea agent) (7) or in the more recent Study To Prevent Noninsulin-Dependent Diabetes Mellitus (STOP-NIDDM) given acarbose (8), there was significantly less incident diabetes than in their control groups. (The STOP-NIDDM study, however, has been severely criticized [9]). Neither tolbutamide nor acarbose are thought to primarily affect insulin resistance. It is very possible, of course, that all of these drugs were simply masking the development of diabetes by treating hyperglycemia (10). If so, nateglinide was unable to accomplish this.

The rationale for the CVD end point in the NAVIGATOR study might have been that glucose levels after a glucose challenge, extending all the way down into the midnormal range, are associated with CVD (11). It is important to point out that in many articles postprandial glucose is used mistakenly to describe glucose levels after the …
Commentary: octreotide and hypertrophic pulmonary osteoarthropathy
Authors: R. T. Penson, R. M. Rudd
Journal: Thorax (1997)

Case reports sequence of treatment with stilboestrol for prostate cancer.Reduction of the metabolism of Department of over study 200 g octreotide by subcutaneous The pathogenesis of HPOA remains un-Medical Oncology, St Bartholomew's bolus was found to be no better than placebo in certain.Although a common factor appears to Hospital, London nine out of 10 patients in the relief of advanced be local hyperaemia, no specific endocrine, EC1A 7BE, UK cancer pain. 11peptide or cytokine mediator has been con-R T Penson Disparate hypotheses abound regarding the R M Rudd sistently linked with the condition.Raised levels aetiology of HPOA.As yet there is little inof hormones such as oestrogen have been Correspondence to: Dr R M Rudd.blamed but clubbing was not seen as a con-formation about the value, if any, of bis-on July 22
Asthma Genetics: From Linear to Multifactorial Approaches
Authors: Stefano Guerra, Fernando D. Martinez
Journal: Annual Review of Medicine (2007)

Asthma risk has a clear hereditary component but, unexpectedly, the majority of reported associations between genetic variants and asthma have not been consistently replicated across studies. Methodological flaws have been indicated as a possible explanation for these inconsistencies. However, an alternative explanation is that the effects of genetic variants depend on other factors whose frequency and distribution vary, both across individuals and across populations. Within this framework, we review recent advances in asthma genetics and conclude that a paradigm shift is needed, because a static model in which the DNA sequence is associated with disease risk in a linear fashion fails to consider the interdependence of the diverse components of asthma risk. We propose an integrated approach, linking sequence variation to specific phenotypic manifestations of the disease by taking into account concurrent influences from biological systems and environmental factors that interact within specific developmental windows of opportunity.