tbuckley/cabot-search huggingface dataset:
Variability of Peripheral Blood Lymphocyte Beta-2-Adrenergic Receptor Density in Humans
Authors: MICHAEL I. ANSTEAD, TRAVIS A. HUNT, SONIA L. CARLSON, NAUSHERWAN K. BURKI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

β2-adrenergic receptor ( β AR) density on peripheral blood lymphocytes has been used as an index to reflect the β AR state of the body. Lymphocytes β ARs are unequally distributed among lymphocyte subpopulations, with the highest density on CD8 + cells and the lowest on CD4 + cells. Thus, the measurement of peripheral blood lymphocyte β AR density could vary with changes in CD4 + and CD8 + cell concentrations. We examined the individual and intersubject variance of β AR density and lymphocyte subpopulations over time in 10 normal subjects, studied on 3 to 5 different d always at approximately 9:00 a.m. over a 4 - to 12-wk period. Peripheral blood lymphocytes were isolated and β2-adrenergic receptor density was determined by specific binding of [I25I] - (-) iodopindolol, and lymphocyte subpopulations were measured by flow cytometry. Average receptors per lymphocyte were 776 ± 183. Whereas the absolute values of CD4 + % and CD8 + % cell concentrations varied little in individual subjects (coefficient of variation 9.5% and 11.1%, respectively), the individual β AR variance was greater (coefficient of variation 22.4%). However there was a significant correlation between β AR and CD4 + % and CD8 + % cell concentration (correlation coefficients: − 0.58, p < 0.001; + 0.51, p < 0.001, respectively). This information is relevant to interpretations of changes in peripheral β AR in humans.
Action potential transfer in cell pairs isolated from adult rat and guinea pig ventricles.
Authors: R Weingart, P Maurer
Journal: Circulation Research (1988)

An enzymatic procedure was used to obtain ventricular cells from adult rat and guinea pig hearts. Isolated pairs of cells were selected to study the action potential transfer from cell to cell and determine the resistance of the nexal membrane, rn. For this purpose, each cell of a cell pair was connected to a patch pipette so as to enable whole-cell, tight-seal recording. Normal impulse transmission was observed when rn ranged from 5-265 M omega. In these cases, the action potential in both cells occurred virtually simultaneously. An occasional failure in action potential transfer was seen in cell pairs whose rn had increased to 155-375 M omega. In these cases, the impulse transfer across the nexal membrane occurred with considerable delay. Impulse transfer was completely blocked once rn was larger than 780 M omega. Assuming a single connexon conductance of 100 pS, this would mean that more than 13 connexons are necessary to allow impulse transfer from cell to cell. Two single myocytes, gently pushed together, neither showed electrotonic interaction nor impulse transfer, thus rendering unlikely the possibility of an ephaptic signal transmission.
Physiological changes during symptom recovery from moderate exacerbations of COPD
Authors: C. M. Parker, N. Voduc, S. D. Aaron, K. A. Webb, D. E. O'Donnell
Journal: European Respiratory Journal (2005)

Acute exacerbations of chronic obstructive disease (AECOPD) are characterised by worsening dyspnoea that is variably prolonged. In this study, physiological changes during moderate AECOPD were examined and the factors associated with dyspnoea resolution over time were determined. In total, 20 patients experiencing an AECOPD were evaluated within 72 h of initial worsening of symptoms (day 0) with pulmonary function testing, metabolic testing and symptom assessment using the dyspnoea domain of the Chronic Respiratory Disease Questionnaire (CRQ). Treatment was optimised and testing was repeated after 7, 14, 30 and 60 days. At day 0, patients were very short of breath (CRQ-dyspnoea mean± sem 2.4±0.3) and showed significant airflow obstruction (forced expiratory volume in one second (FEV 1 ) 41±3% predicted) and lung hyperinflation (forced residual capacity (FRC) 164±7% pred). By day 60 CRQ-dyspnoea improved to 4.6±0.5 (some shortness of breath); FRC and residual volume decreased by 5 and 11%, respectively; inspiratory capacity (IC) and slow vital capacity increased by 18 and 17%, respectively; and FEV 1 increased by 18% with no change in FEV 1 /FVC. Total lung capacity did not change during AECOPD, and thus, changes in IC reliably reflected changes in end-expiratory lung volume. In conclusion, moderate acute exacerbation of chronic obstructive pulmonary disease is characterised by worsening airflow obstruction and lung hyperinflation. Improvement of dyspnoea following acute exacerbations of chronic obstructive pulmonary disease was associated with reduction in lung hyperinflation and consequent increase in expiratory flow rates.
Fibulin-3 Promotes Glioma Growth and Resistance through a Novel Paracrine Regulation of Notch Signaling
Authors: Bin Hu, Mohan S. Nandhu, Hosung Sim, Paula A. Agudelo-Garcia, Joshua C. Saldivar, Claire E. Dolan, Maria E. Mora, Gerard J. Nuovo, Susan E. Cole, Mariano S. Viapiano
Journal: Cancer Research (2012)

Abstract Malignant gliomas are highly invasive and chemoresistant brain tumors with extremely poor prognosis. Targeting of the soluble factors that trigger invasion and resistance, therefore, could have a significant impact against the infiltrative glioma cells that are a major source of recurrence. Fibulin-3 is a matrix protein that is absent in normal brain but upregulated in gliomas and promotes tumor invasion by unknown mechanisms. Here, we show that fibulin-3 is a novel soluble activator of Notch signaling that antagonizes DLL3, an autocrine inhibitor or Notch, and promotes tumor cell survival and invasion in a Notch-dependent manner. Using a strategy for inducible knockdown, we found that controlled downregulation of fibulin-3 reduced Notch signaling and led to increased apoptosis, reduced self-renewal of glioblastoma-initiating cells, and impaired growth and dispersion of intracranial tumors. In addition, fibulin-3 expression correlated with expression levels of Notch-dependent genes and was a marker of Notch activation in patient-derived glioma samples. These findings underscore a major role for the tumor extracellular matrix in regulating glioma invasion and resistance to apoptosis via activation of the key Notch pathway. More importantly, this work describes a noncanonical, soluble activator of Notch in a cancer model and shows how Notch signaling can be reduced by targeting tumor-specific accessible molecules in the tumor microenvironment. Cancer Res; 72(15); 3873–85. ©2012 AACR.
<i>MECT1-MAML2</i> Fusion Transcript Defines a Favorable Subset of Mucoepidermoid Carcinoma
Authors: Mitsukuni Okabe, Satoru Miyabe, Hitoshi Nagatsuka, Akihiro Terada, Nobuhiro Hanai, Motoo Yokoi, Kazuo Shimozato, Tadaaki Eimoto, Shigeo Nakamura, Noriyuki Nagai, Yasuhisa Hasegawa, Hiroshi Inagaki
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. Mucoepidermoid carcinoma translocated gene 1-mastermind-like gene family (MECT1-MAML2) gene fusion was identified from a recurring t(11;19)(q21;p13) translocation, which is often the sole cytogenetic alteration in this disease. This fusion transcript has been frequently detected in mucoepidermoid carcinoma and shown to be involved in the transformation of epithelial cells. However, its clinicopathologic significance remains unclear. Experimental Design: Seventy-one cases of mucoepidermoid carcinoma and 51 cases of nonmucoepidermoid carcinoma salivary gland tumors (including 26 Warthin tumor cases) were retrospectively analyzed. RNA was extracted from archival materials: histologic paraffin specimens in all cases and cytologic specimens in 10 mucoepidermoid carcinoma cases. The MECT1-MAML2 fusion transcript was detected by a reverse transcription-PCR assay, which can be applied to both histologic and cytologic specimens. The presence of the fusion transcript was correlated with relevant clinicopathologic and survival data of the mucoepidermoid carcinoma patients. Results: The MECT1-MAML2 fusion transcript was detected in 27 of the 71 (38%) mucoepidermoid carcinoma cases but not in any case of nonmucoepidermoid carcinoma tumors. The reverse transcription-PCR results showed no difference between histologic and cytologic specimens. Detection of the MECT1-MAML2 fusion transcript was associated with a less advanced clinical stage and a low-grade tumor histology. The presence of the transcript was associated with longer disease-free and overall survivals on univariate analysis and emerged as an independent prognostic factor for longer overall survival on multivariate analysis. Conclusions: The MECT1-MAML2 fusion transcript may be specific to mucoepidermoid carcinoma and associated with a distinct mucoepidermoid carcinoma subset that exhibits favorable clinicopathologic features and an indolent clinical course.
Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review
Authors: Lee Hooper, Rachel L Thompson, Roger A Harrison, Carolyn D Summerbell, Andy R Ness, Helen J Moore, Helen V Worthington, Paul N Durrington, Julian P T Higgins, Nigel E Capps, Rudolph A Riemersma, Shah B J Ebrahim, George Davey Smith
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer. <b>Data sources</b> Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies. <b>Review methods</b> Review of RCTs of omega 3 intake for 3 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate. <b>Results</b> Of 15 159 titles and abstracts assessed, 48 RCTs (36 913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded. <b>Conclusion</b> Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.
Ferritin in Crohn's disease tissue: detection by electron microscopy.
Authors: P J Whorwell, R C Baldwin, R Wright
Journal: Gut (1976)

Using immune electron microscopy, an attempt has been made to visualise viral particles in Crohn9s disease tissue and faeces. No particles resembling viruses were observed, but in the absence of a specific antiserum a negative result does not exclude the presence of a virus, particularly if it is sparsely distributed. Compared with controls, an abundance of a 12 nm particle was found in all Crohn9s disease tissue and one small intestinal lymphoma. This particle has been identified as ferritin and is unlikely to be of aetiological significance.
Meta-analysis for the Association between Overall Survival and Progression-Free Survival in Gastrointestinal Stromal Tumor
Authors: Ipek Özer-Stillman, Lauren Strand, Jane Chang, Ateesha F Mohamed, Katherine E Tranbarger-Freier
Journal: Clinical Cancer Research (2014)

Gastrointestinal stromal tumor (GIST) is a relatively rare tumor that is treated with targeted therapies in advanced stages. Randomized clinical trials (RCT) often require long follow-up and large sample sizes to evaluate overall survival (OS), the gold-standard measure of treatment efficacy. However, changes in therapy following disease progression may complicate survival assessments. Establishing surrogate endpoints may facilitate the drug approval and availability of new efficacious treatments; however, no published studies have investigated this topic in unresectable and/or metastatic GIST.A systematic literature review identified 14 RCTs and five observational studies of sufficient methodologic quality published between January 1995 and December 2013 (29 treatment arms; 2,189 patients). Weighted linear regression was used to evaluate the relation between median OS and median progression-free survival (PFS) for all arms combined and stratified by treatment line, treatment type, and quality score.Median OS and PFS were positively related with a correlation of 0.91. The association was still moderate (correlation 0.72) after eliminating four influential data points. In stratified analyses, correlation of OS and PFS was greater in later lines of therapy (first line = 0.52; second line = 0.80; third- and later-line = 0.70) and imatinib showed a stronger association (0.91) than other evaluated treatments (-0.26 to 0.69).This analysis identified a strong relationship between median OS and PFS, especially in later lines of therapy. Findings suggest that PFS could serve as a surrogate marker for OS; however, analyses of patient-level data are needed to establish its validity in GIST.
Free-Floating Thrombus in Right Heart and Massive Pulmonary Embolism Migrating Into Pulmonary Artery
Authors: Yoshihiro Noji, Tohru Kojima, Takahiko Aoyama, Masato Yamaguchi, Tsutomu Araki, Susumu Fujino, Katsuaki Yokota, Noriko Kumamoto, Takakiyo Nakaya, Keiichiro Takase, Masami Shimizu, Hiroshi Mabuchi
Journal: Circulation (2005)
Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells
Authors: Yutaka Yatomi, Tsukasa Ohmori, Ge Rile, Fuminori Kazama, Hirotaka Okamoto, Takamitsu Sano, Kaneo Satoh, Shoji Kume, Gabor Tigyi, Yasuyuki Igarashi, Yukio Ozaki
Journal: Blood (2000)
Reducing Smoking in Hospitals
Authors: Anthony M. H
Journal: JAMA (1985)

THE FACT that cigarette smoking is widespread in hospitals is a paradox. Smoking, voluntary and involuntary, is a major risk factor associated with respiratory and cardiovascular disease, a growing list of malignancies, adverse outcomes of pregnancy, and impaired healing of peptic ulcers. This has been documented in the past two decades by several US Surgeon General's reports, and some 30,000 articles. 1 As quoted in a recent editorial inThe Journal, 2 the 350,000 premature deaths per year attributable to smoking in the United States exceeds the number of American lives lost in all the wars this country has fought in the 20th century. Medical care expenditures and productivity loss cost Americans at least $49 billion a year. 3 Worldwide, the annual toll of over 1 million tobacco-related early deaths is expected to rise as a result of aggressive cigarette promotion in the Third World. 4 Briefly stated, the tremendous
RADIATION INJURY FOLLOWING AN A-BOMB EXPLOSION
Authors: Colin F. Vorder Bruegge
Journal: Annals of Internal Medicine (1952)

Article1 June 1952RADIATION INJURY FOLLOWING AN A-BOMB EXPLOSIONCOLIN F. VORDER BRUEGGECOLIN F. VORDER BRUEGGESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-6-1444 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRadiation injury to large numbers of people had never occurred before the atomic bomb explosions in Japan. Consequently, reports of the thermal and ionizing radiation effects of this unique weapon awakened universal concern. It must be remembered, however, that from the standpoint of military effectiveness an air burst atomic bomb is primarily a blast and burn weapon. Ionizing radiation injury, in particular, has often provoked emphasis out of proportion to its real danger. Logical evaluation will lead to proper respect for these phenomena and serve to dispel the air of mystery and feeling of defenselessness sometimes evoked by inadequate understanding...Bibliography1. Lang D: The man in the thick lead suit, The New Yorker, July 16, 1949. Google Scholar2. Joint Commission for the Investigation of the Effects of the Atomic Bomb in Japan, 1947. Medical Report. (To be published.) Google Scholar3. The Effects of Atomic Weapons, prepared for and in coöperation with the U. S. Department of Defense and the U. S. Atomic Energy Commission, under the direction of the Los Alamos Scientific Laboratory, 1950. Google Scholar4. LiebowWarrenDeCoursey AASE: Pathology of atomic bomb casualties, Am. J. Path. 25: 853-1027, 1949. MedlineGoogle Scholar5. PearsePayne HEJT: Mechanical and thermal injury from the atomic bomb, New England J. Med. 241: 647-653, 1949. CrossrefMedlineGoogle Scholar6. WilderMaynard HCRM: Ocular changes produced by total body irradiation, Am. J. Path. 27: 1-19, 1951. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C.*Presented at the Thirty-second Annual Session of the American College of Physicians, St. Louis, Mo., April 10, 1951.From the Armed Forces Institute of Pathology, Washington, D. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDosimetrie und StrahlenschutzPhänomenologie der Strahlenwirkungen auf Organe und OrgansystemeThe physiology and physiopathology of the male sexual glandsDer Hypogonadismus im Knaben- und Mannesalter 1 June 1952Volume 36, Issue 6Page: 1444-1458KeywordsArmed forcesBurnsEmotionsIonizing radiation Issue Published: 1 June 1952 PDF downloadLoading ...
Cardiac-Specific Deletion of Acetyl CoA Carboxylase 2 Prevents Metabolic Remodeling During Pressure-Overload Hypertrophy
Authors: Stephen C. Kolwicz, David P. Olson, Luke C. Marney, Lorena Garcia-Menendez, Robert E. Synovec, Rong Tian
Journal: Circulation Research (2012)

Decreased fatty acid oxidation (FAO) with increased reliance on glucose are hallmarks of metabolic remodeling that occurs in pathological cardiac hypertrophy and is associated with decreased myocardial energetics and impaired cardiac function. To date, it has not been tested whether prevention of the metabolic switch that occurs during the development of cardiac hypertrophy has unequivocal benefits on cardiac function and energetics.Because malonyl CoA production via acetyl CoA carboxylase 2 (ACC2) inhibits the entry of long chain fatty acids into the mitochondria, we hypothesized that mice with a cardiac-specific deletion of ACC2 (ACC2H-/-) would maintain cardiac FAO and improve function and energetics during the development of pressure-overload hypertrophy.ACC2 deletion led to a significant reduction in cardiac malonyl CoA levels. In isolated perfused heart experiments, left ventricular function and oxygen consumption were similar in ACC2H-/- mice despite an ≈60% increase in FAO compared with controls (CON). After 8 weeks of pressure overload via transverse aortic constriction (TAC), ACC2H-/- mice exhibited a substrate utilization profile similar to sham animals, whereas CON-TAC hearts had decreased FAO with increased glycolysis and anaplerosis. Myocardial energetics, assessed by 31P nuclear magnetic resonance spectroscopy, and cardiac function were maintained in ACC2H-/- after 8 weeks of TAC. Furthermore, ACC2H-/--TAC demonstrated an attenuation of cardiac hypertrophy with a significant reduction in fibrosis relative to CON-TAC.These data suggest that reversion to the fetal metabolic profile in chronic pathological hypertrophy is associated with impaired myocardial function and energetics and maintenance of the inherent cardiac metabolic profile and mitochondrial oxidative capacity is a viable therapeutic strategy.
Clusterin, a Haploinsufficient Tumor Suppressor Gene in Neuroblastomas
Authors: Olesya Chayka, Daisy Corvetta, Michael Dews, Alessandro E. Caccamo, Izabela Piotrowska, Giorgia Santilli, Sian Gibson, Neil J. Sebire, Nourredine Himoudi, Michael D. Hogarty, John Anderson, Saverio Bettuzzi, Andrei Thomas-Tikhonenko, Arturo Sala
Journal: JNCI Journal of the National Cancer Institute (2009)

Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma.We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription-polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided.Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026).We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.