tbuckley/cabot-search huggingface dataset:
Transgenic Myocardial Overexpression of Fibroblast Growth Factor-1 Increases Coronary Artery Density and Branching
Authors: Borja Fernandez, Alexandra Buehler, Swen Wolfram, Sawa Kostin, Gudrun Espanion, Wolfgang M. Franz, Heiner Niemann, Pieter A. Doevendans, Wolfgang Schaper, René Zimmermann
Journal: Circulation Research (2000)

Fibroblast growth factor (FGF)-1 plays important roles during myocardial and coronary morphogenesis. FGF-1 is also involved in the physiological response of the adult heart against ischemia, which includes cardiomyocyte protection and vascular growth. In the present study, we have generated transgenic mice with specific myocardial overexpression of the gene. Transgene expression was verified by Northern blot, and increased FGF-1 protein content was assessed by Western blot and immunoconfocal microscopy. Anatomic, histomorphological, and ultrastructural analyses revealed no major morphological or developmental abnormalities of transgenic hearts. Capillary density was unaltered, whereas the density of coronary arteries, especially arterioles, was significantly increased, as was the number of branches of the main coronary arteries. In addition, the coronary flow was significantly enhanced in transgenic mice ex vivo. These differences in the anatomic pattern of the coronary vasculature are established during the second month of postnatal life. The present findings demonstrate an important role of FGF-1 in the differentiation and growth of the coronary system and suggest that it is a key regulatory molecule of the differentiation of the arterial system.
Receptor-effector coupling pathway for alpha 1-adrenergic modulation of abnormal automaticity in 'ischemic' canine Purkinje fibers.
Authors: E P Anyukhovsky, S F Steinberg, I S Cohen, M R Rosen
Journal: Circulation Research (1994)

We studied the receptor-effector coupling mechanism responsible for alpha 1-adrenergic receptor-induced increases in abnormal automaticity (AA) occurring at low membrane potentials in "ischemic" Purkinje fibers, superfused with Tyrode's solution containing [K+]o 10 mmol/L, pH 6.8, PO2 &lt; 25 mm Hg. To exclude beta-adrenergic actions, propranolol was added to all solutions. We derived membrane slope resistance (Rsl) from the current-voltage relation obtained with two microelectrodes for intracellular current injection and transmembrane voltage recording. We also measured the membrane time constant, Tm, to assess changes in membrane resistance (Rm). Phenylephrine effects on Rsl in simulated ischemia were studied in the absence or presence of the alpha 1-subtype blockers WB 4101 (WB) or chloroethylclonidine (CEC), both 0.1 mumol/L, and in Purkinje fibers from dogs injected with pertussis toxin (PTX) (30 micrograms/kg i.v., 60 to 72 hours before study). There were no significant differences in mean values of Rsl before phenylephrine superfusion among all groups of Purkinje fibers. Tm increased by 23% during phenylephrine 0.1 mumol/L superfusion, and Rsl increased by 11%. These two results suggest a 23% increase in Rm with no concordant change in longitudinal resistance. In the presence of CEC, phenylephrine increased Rsl by 12%. In contrast, WB blocked phenylephrine effects on Rsl (0.3%). In PTX-treated Purkinje fibers, the levels of PTX-sensitive G protein as well as phenylephrine effects on Rsl (3%) were significantly reduced. In the absence of WB and of CEC, the phenylephrine effects both on Rsl and on the incidence of AA were directly related to the level of PTX-sensitive substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophysiological observations on the digitalis-potassium interaction in canine Purkinje fibers.
Authors: G J Anderson, J C Bailey, J Reiser, A Freeman
Journal: Circulation Research (1976)

We studied the effects of elevating potassium concentration on the membrane potential of Purkinje cells exposed to toxic concentrations of acetylstrophanthidin or ouabain. Conventional intracellular microelectrode techniques were employed. Rapid elevation of [K+]o from 2.7 to 5.4 mEq/liter resulted in an initial increase (more negative) in membrane potential of cells demonstrating ouabain-induced phase 4 depolarization. The increase in maximal diastolic potential occurred initially without suppression of phase 4 depolarization. In cells rendered inexcitable by ouabain or acetylstrophanthidin, elevation of [K+]o consistently increased membrane potential and restored excitability. In four experiments automaticity was initiated within 2 minutes after the increase in [K]o. Although automaticity reappeared, as maximal diastolic potential increased, the automatic rate slowed and then pacemaker activity was suppressed. Studies with 3H-ouabain showed that the increase in membrane potential paralleled K+-induced release of 3H-ouabain from Purkinje cells. These studies suggest that elevation of [K+]o reverses digitalis toxic manifestations in canine Purkinje fibers by causing release of cardiac glycosides bound to the membrane. The observed increase in membrane potential of ouabain-treated Purkinje fibers that occurred after [K+]o elevation was considered to be mediated in part by restoration of the Na pump and by electrogenic pumping.
Tracking Evolution of BRCA1-Associated Breast Cancer: Figure 1.
Authors: Jos Jonkers
Journal: Cancer Discovery (2012)

Abstract Summary: Single-cell profiling and computational identification of evolutionary paths to BRCA1-associated tumorigenesis predict that PTEN loss and TP53 mutation precede loss of wild-type BRCA1 in basal-like and luminal tumors, respectively. Cancer Discov; 2(6); 486–8. ©2012 AACR. Commentary on Martins et al., p. 503.
Macrolides, quinolones and amoxicillin/clavulanate for chronic bronchitis: a meta-analysis
Authors: I. I. Siempos, G. Dimopoulos, I. P. Korbila, K. Manta, M. E. Falagas
Journal: European Respiratory Journal (2007)

The comparative effectiveness and safety of macrolides, quinolones and amoxicillin/clavulanate (A/C) for the treatment of patients with acute bacterial exacerbation of chronic bronchitis (ABECB) was evaluated in the present study. PubMed, Current Contents and the Cochrane Central Register of Controlled Trials were searched to identify relevant randomised controlled trials (RCTs). In total, 19 RCTs (20 comparisons) were included in the present analysis. There was no difference regarding treatment success in intention-to-treat and clinically evaluable patients between macrolides and quinolones, A/C and quinolones or A/C and macrolides. The treatment success in microbiologically evaluable patients was lower for macrolides compared with quinolones (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.31–0.69). Fewer quinolone-recipients experienced a recurrence of ABECB after resolution of the initial episode compared with macrolide-recipients during the 26-week period following therapy. Adverse effects in general were similar between macrolides and quinolones. Administration of A/C was associated with more adverse effects (mainly diarrhoea) than quinolones (OR 1.36, 95% CI 1.01–1.85). Macrolides, quinolones and amoxicillin/clavulanate may be considered equivalent for the treatment of patients with an acute bacterial exacerbation of chronic bronchitis in terms of short-term effectiveness. Quinolones are associated with better microbiological success and fewer recurrences of acute bacterial exacerbation of chronic bronchitis than macrolides, while amoxicillin/clavulanate is associated with more adverse effects than both comparators.
Gabapentin for refractory chronic cough
Authors: Alison M MacKenzie
Journal: Thorax (2013)

Gabapentin for refractory chronic coughThis randomised controlled trial from Australia reported on the efficacy of gabapentin in chronic refractory cough and investigated its role in modulating central sensitisation (CS) of the cough reflex.Recruitment of 62 patients was conducted over 2 years.Fifty-two patients completed the trial.All were non-smokers with a cough of more than 8 weeks' duration and had negative investigation and trials of treatment for asthma, rhinitis, gastro-oesophageal reflux and respiratory tract infection.Participants were randomised to placebo or gabapentin for a 12-week period, with objective serial assessments of cough severity, sensitivity and quality of life.Dose range was 300 -1800 mg.Patient groups, although well matched for efficacy variables, did not reach the target sample size at trial completion and had discrepancies in pre-trial cough frequency.The primary outcome, change in the Leicester Cough Questionnaire (LCQ) score, showed significant improvement in 74% of patients in the gabapentin group versus 46% in the placebo group (number needed to treat 3.58).Secondary end points, change in cough frequency and cough severity score showed significant improvements in the gabapentin cohort.CS screening questions and capsaicin sensitivity were used to assess the mechanism of action of gabapentin.In the gabapentin group, participants with symptoms of CS had significant improvements in LCQ score in comparison to those without CS symptoms, supporting the neuromodulatory effect of gabapentin on CS.These promising results provide an evidence base for further research into the role of gabapentin in chronic cough and cough of established aetiology, with potential for it to be considered as an attractive treatment alternative to opiates.
Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8+ T cells
Authors: Seth M Pollack, Robin L Jones, Erik A Farrar, Ivy P Lai, Sylvia M Lee, Jianhong Cao, Venu G Pillarisetty, Benjamin L Hoch, Ashley Gullett, Marie Bleakley, Ernest U Conrad, Janet F Eary, Kendall C Shibuya, Edus H Warren, Jason N Carstens, Shelly Heimfeld, Stanley R Riddell, Cassian Yee
Journal: Journal for ImmunoTherapy of Cancer (2014)

Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer. Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY-ESO-1 limit the applicability of this approach to other solid tumors. To overcome this, we tested a strategy combining IL-21 modulation during in vitro stimulation with first-in-class use of tetramer-guided cell sorting to generate NY-ESO-1 specific cytotoxic T lymphocytes (CTL).CTL generation was evaluated in 6 patients with NY-ESO-1 positive sarcomas, under clinical manufacturing conditions and characterized for phenotypic and functional properties.Following in vitro stimulation, T cells stained with NY-ESO-1 tetramer were enriched from frequencies as low as 0.4% to >90% after single pass through a clinical grade sorter. NY-ESO-1 specific T cells were generated from all 6 patients. The final products expanded on average 1200-fold to a total of 36 billion cells, were oligoclonal and contained 67-97% CD8(+), tetramer(+) T cells with a memory phenotype that recognized endogenous NY-ESO-1.This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy. This approach, when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer-Testis antigens will enhance the scope and feasibility of adoptive T cell therapy.
The timing of cranial radiation in elderly patients with newly diagnosed glioblastoma multiforme
Authors: R. Lai, D. L. Hershman, T. Doan, A. I. Neugut
Journal: Neuro-Oncology (2009)

There are few and conflicting studies on the optimal timing of initial cranial radiation in the treatment of glioblastoma multiforme (GBM) but none of them have addressed this issue in the elderly population. We used the linked Surveillance, Epidemiology, and End Results (SEER) Medicare database to investigate whether the time interval from surgery to initiation of radiation is a significant prognostic factor for survival in subjects aged ≥65 years with newly diagnosed GBM. Cox modeling was used to assess the effect of waiting time on overall survival. We identified a total of 1,375 patients, 296 with biopsies and 1,079 with resections. The median time to the initiation of radiotherapy was 15 days post operation (interquartile range 12–21). In the univariate Cox analysis of those who had debulking surgeries, a waiting time of >22 days showed a significant inverse relationship with survival (hazard ratio [HR] = 0.82, 95% CI 0.70–0.97, p = 0.02), but after adjustment for confounders, it was not a statistically significant factor in the final Cox model (HR = 0.99, 95% CI 0.97–1.01, p = 0.14). Therefore, waiting time was not a significant prognostic factor for subjects with biopsies in both the univariate and multivariate analyses. Although effort should be made to initiate radiotherapy as soon as possible after surgical resection/biopsy, a brief delay similar to that experienced by our cohort does not have a significant impact on survival.
Specific adsorption of IgM antibody onto H-2-activated mouse T lymphocytes.
Authors: L Hudson, J Sprent
Journal: The Journal of Experimental Medicine (1976)

Evidence is presented to support the contention that IgM demonstrable by surface immunofluorescent staining on H-2-activated T cells represents specifically adsorbed B-cell-derived alloantibody. T cells activated to H-2 determinants expressed surface IgM only when the progenitor cell populations contained B lymphocytes. IgM was not detected on T cells activated to determinants which fail to stimulate alloantibody production (e.g., M-locus determinants). In addition, IgM-negative H-2 activated T cells (derived from B-cell-depleted lymphoid cells), unlike M-locus-activated T cells, adsorbed IgM in a specific manner when incubated in vitro with "early bleed" antisera raised against the activating H-2 determinants.
Acute myeloid leukemia ontogeny is defined by distinct somatic mutations
Authors: R. Coleman Lindsley, Brenton G. Mar, Emanuele Mazzola, Peter V. Grauman, Sarah Shareef, Steven L. Allen, Arnaud Pigneux, Meir Wetzler, Robert K. Stuart, Harry P. Erba, Lloyd E. Damon, Bayard L. Powell, Neal Lindeman, David P. Steensma, Martha Wadleigh, Daniel J. DeAngelo, Donna Neuberg, Richard M. Stone, Benjamin L. Ebert
Journal: Blood (2014)
High amplitude contractions in the middle third of the oesophagus: a manometric marker of chronic alcoholism?
Authors: L Grande, R Monforte, E Ros, V Toledo-Pimentel, R Estruch, G Lacima, A Urbano-Marquez, C Pera
Journal: Gut (1996)

BACKGROUND--Oesophageal motor abnormalities have been reported in alcoholism. AIM--To investigate the effects of chronic alcoholism and its withdrawal on oesophageal disease. PATIENTS--23 chronic alcoholic patients (20 men and three women; mean age 43, range 23 to 54). METHODS--Endoscopy, manometry, and 24 hour pH monitoring 7-10 days and six months after ethanol withdrawal. Tests for autonomic and peripheral neuropathy were also performed. Motility and pH tracings were compared with those of age and sex matched control groups: healthy volunteers, nutcracker oesophagus, and gastro-oesophageal reflux disease. RESULTS--14 (61%) alcoholic patients had reflux symptoms, and endoscopy with biopsy showed oesophageal inflammation in 10 patients. One patient had an asymptomatic squamous cell carcinoma. Oesophageal motility studies in the alcoholic patients showed that peristaltic amplitude in the middle third was &gt; 150 mm Hg (95th percentile (P95) of healthy controls) in 13 (57%), the ratio lower/ middle amplitude was &lt; 0.9 in 15 (65%) (&gt; 0.9 in all control groups), and the lower oesophageal sphincter was hypertensive (&gt; 23.4 mm Hg, P95 of healthy controls) in 13 (57%). All three abnormalities were present in five (22%). Abnormal reflux (per cent reflux time &gt; 2.9, P95 of healthy controls) was shown in 12 (52%) alcoholic patients, and was unrelated to peristaltic dysfunction. Subclinical neuropathy in 10 patients did not effect oesophageal abnormalities. Oesophageal motility abnormalities persisted at six months in six patients with ongoing alcoholism, whereas they reverted towards normal in 13 who remained abstinent; reflux, however, was unaffected. CONCLUSIONS--Oesophageal peristaltic dysfunction and reflux are frequent in alcoholism. High amplitude contractions in the middle third of the oesophagus seem to be a marker of excessive alcohol consumption, and tend to improve with abstinence.
Multivitamins improve weight gain in pregnant women with HIV
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Multivitamin supplements increased weight gain during pregnancy in a randomised, placebo controlled study of 957 HIV positive women in Dar es Salaam, Tanzania, reports a study in the American Journal of Clinical Nutrition (2002;76:1082-90).

About 13 million women of childbearing age in sub-Saharan Africa are HIV positive. The infection causes weight loss through wasting, and weight loss or poor weight gain during pregnancy leads to fetal loss, intrauterine growth retardation, prematurity, and low birthweight babies.

The study was a collaboration between Harvard School of Public Health in Boston, …
Myeloid growth factors.
Authors: Jeffrey Crawford, Jeffrey Allen, James Armitage, Douglas W Blayney, Spero R Cataland, Mark L Heaney, Sally Htoy, Susan Hudock, Dwight D Kloth, David J Kuter, Gary H Lyman, Brandon McMahon, David P Steensma, Saroj Vadhan-Raj, Peter Westervelt, Michael Westmoreland
Journal: Journal of the National Comprehensive Cancer Network (2011)

Febrile neutropenia, a common side effect of myelosuppressive chemotherapy in patients with cancer, can result in prolonged hospitalization and broad-spectrum antibiotic use, often prompting treatment delays or dose reductions of drug regimens. Prophylactic use of myeloid growth factors (mainly the colony-stimulating factors filgrastim and pegfilgrastim) in patients of heightened risk can reduce the severity and duration of febrile neutropenia. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid Growth Factors provide recommendations on the use of these agents mainly in the oncology setting based on clinical evidence and expert consensus. This version includes revisions surrounding the issue of timing of pegfilgrastim administration. It also includes new sections on tbo-filgrastim, a recently approved agent that is biologically similar to filgrastim, and the role of myeloid growth factors in the hematopoietic cell transplant setting.
Expression of Inducible Nitric Oxide Synthase by Macrophages in Rat Lung
Authors: HONG-WEN LIU, AMIT ANAND, KENNETH BLOCH, DAVID CHRISTIANI, RICHARD KRADIN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary macrophages (Mø). An inducible isoform of NO synthase (iNOS) catalyses the production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1 cytokines, including interferon- γ and TNF- α . In the present study, iNOS+ interstitial cells were demonstrated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1+ interstitial Mø (IM) were iNOS+ and secreted modest amounts of NO without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS− and showed no basal NO secretion. When incubated with heat-killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM. Recombinant murine GM-CSF stimulated production of NO by AM but not by IM. However, when IM were costimulated with GM-CSF and IFN- γ , they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by IM. We conclude that iNOS+ IM are present in normal rat lung, where they regulate the pulmonary cell-mediated immune response to antigen.
Phase II Study of Clofarabine Monotherapy in Previously Untreated Older Adults With Acute Myeloid Leukemia and Unfavorable Prognostic Factors
Authors: Hagop M. Kantarjian, Harry P. Erba, David Claxton, Martha Arellano, Roger M. Lyons, Tibor Kovascovics, Janice Gabrilove, Michael Craig, Dan Douer, Michael Maris, Stephen Petersdorf, Paul J. Shami, Andrew M. Yeager, Stephen Eckert, Rekha Abichandani, Stefan Faderl
Journal: Journal of Clinical Oncology (2009)

This phase II study assessed clofarabine monotherapy in older adults (>or= 60 years of age) with untreated acute myeloid leukemia (AML) and at least one unfavorable baseline prognostic factor.Clofarabine was administered intravenously for 5 days at 30 mg/m(2)/d during induction and 20 mg/m(2)/d during reinduction/consolidation (six cycles maximum). The primary end point was overall remission rate (ORR; ie, complete remission [CR] plus CR with incomplete platelet recovery [CRp]).In 112 evaluable patients who were treated (median age, 71 years; range, 60 to 88 years), the ORR was 46% (38% CR, 8% CRp). ORR by unfavorable prognostic factor was 39% for patients >or= 70 years of age; 32% for Eastern Cooperative Oncology Group (ECOG) performance status 2; 51% for antecedent hematologic disorder; 54% for intermediate karyotype; 42% for unfavorable karyotype; and 48%, 51%, and 38% for one, two, and three risk factors, respectively. The median disease-free survival was 37 weeks (95% CI, 26 to 56 weeks). Median duration of remission was 56 weeks (95% CI, 33 to not estimable). The estimated median overall survival was 41 weeks (95% CI, 28 to 53 weeks) for all patients, 59 weeks for patients with CR/CRp, and 72 weeks for patients with CR. The 30-day all-cause mortality was 9.8%. The most common non-laboratory drug-related toxicities (>or= 20% patients) were nausea, febrile neutropenia, vomiting, diarrhea, rash, and fatigue.Clofarabine is an active agent with acceptable toxicity in patients age 60 years or older with untreated AML who have at least one unfavorable prognostic factor. ORR did not seem affected by the presence of multiple unfavorable prognostic factors.
Hereditary progressive mucinous histiocytosis
Authors: D. Wong, M. Killingsworth, G. Crosland, S. Kossard
Journal: British Journal of Dermatology (1999)

Journal Article Hereditary progressive mucinous histiocytosis Get access D. Wong, D. Wong Skin and Cancer Foundation, 277 Bourke Street, Darlinghurst, NSW 2010, Australia Search for other works by this author on: Oxford Academic Google Scholar M. Killingsworth, M. Killingsworth Electron Microscope Unit, South‐western Area Pathology Service, Liverpool, NSW, Australia Search for other works by this author on: Oxford Academic Google Scholar G. Crosland, G. Crosland Department of Dermatology, Royal North Shore Hospital, St Leonards, NSW, Australia Search for other works by this author on: Oxford Academic Google Scholar S. Kossard S. Kossard Skin and Cancer Foundation, 277 Bourke Street, Darlinghurst, NSW 2010, Australia Steven Kossard. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 6, 1 December 1999, Pages 1101–1105, https://doi.org/10.1046/j.1365-2133.1999.03212.x Published: 01 December 1999