tbuckley/cabot-search huggingface dataset:
Overexpression of Mitochondrial Peroxiredoxin-3 Prevents Left Ventricular Remodeling and Failure After Myocardial Infarction in Mice
Authors: Shouji Matsushima, Tomomi Ide, Mayumi Yamato, Hidenori Matsusaka, Fumiyuki Hattori, Masaki Ikeuchi, Toru Kubota, Kenji Sunagawa, Yasuhiro Hasegawa, Tatsuya Kurihara, Shinzo Oikawa, Shintaro Kinugawa, Hiroyuki Tsutsui
Journal: Circulation (2006)

Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process.We created MI in 12- to 16-week-old, male Prx-3-transgenic mice (TG+MI, n=37) and nontransgenic wild-type mice (WT+MI, n=39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TG+MI than in WT+MI mice (mean+/-SEM, 1.5+/-0.2 vs 2.2+/-0.2 nmol/mg protein; n=8 each, P<0.05). LV cavity dilatation and dysfunction were attenuated in TG+MI compared with WT+MI mice, with no significant differences in infarct size (56+/-1% vs 55+/-1%; n=6 each, P=NS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TG+MI mice were also larger than those in WT+sham-operated mice but smaller than those in WT+MI mice. Improvement in LV function in TG+MI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WT+MI mice, and this decrease was also ameliorated in TG+MI mice.Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.
Cigarette Smoking and Progression of Atherosclerosis
Authors: George Howard
Journal: JAMA (1998)

Context.-Cigarette smoking is a powerful risk factor for incident heart disease and stroke, but the relationship of active and passive smoking with the progression of atherosclerosis has not been described.Objective.-Toexamine the impact of active smoking and exposure to environmental tobacco smoke (ETS) on the progression of atherosclerosis.Design.-A longitudinal assessment of the relationship between smoking exposure evaluated at the initial visit and the 3-year change in atherosclerosis.Setting.-A population-based cohort of middle-aged adults from 4 communities in the United States.Participants.-A total of 10 914 participants from the Atherosclerosis Risk in Communities (ARIC) study enrolled between 1987 and 1989.Main Outcome Measure.-Change in atherosclerosis from baseline to the 3-year follow-up as indexed by intimal-medial thickness of the carotid artery assessed by ultrasound and adjusted for demographic characteristics, cardiovascular risk factors, and lifestyle variables.Results.-Exposure to cigarette smoke was associated with progression of atherosclerosis.Relative to never smokers and after adjustment for demographic characteristics, cardiovascular risk factors, and lifestyle variables, current cigarette smoking was associated with a 50% increase in the progression of atherosclerosis (mean progression rate over 3 years, 43.0 µm for current and 28.7 µm for never smokers, regardless of ETS exposure), and past smoking was associated with a 25% increase (mean progression rate over 3 years, 35.8 µm for past smokers and 28.7 µm for never smokers).Relative to those not exposed to ETS, exposure to ETS was associated with a 20% increase (35.2 µm for those exposed to ETS vs 29.3 µm for those not exposed).The impact of smoking on atherosclerosis progression was greater for subjects with diabetes and hypertension.Although more pack-years of exposure was independently associated with faster progression (PϽ.001), after controlling for the number of pack-years, the progression rates of current and past smokers did not differ (P=.11).Conclusions.-Bothactive smoking and ETS exposure are associated with the progression of an index of atherosclerosis.Smoking is of particular concern for patients with diabetes and hypertension.The fact that pack-years of smoking but not current vs past smoking was associated with progression of atherosclerosis suggests that some adverse effects of smoking may be cumulative and irreversible.
Two separate genes regulate self-Ia and carrier recognition in H-2-restricted helper factors secreted by hybridoma cells.
Authors: P Lonai, S Bitton, H F Savelkoul, J Puri, G J Hämmerling
Journal: The Journal of Experimental Medicine (1981)

H-2 heterologous T cell hybridomas were used to study the genetic control of dual, anti-nominal antigen and anti-self H-2 specificity of H-2 restricted T cell factors. Each of four hybridoma clones produced two helper factors. One was restricted for the Ia type of the normal T cell partner (H-2b), whereas the other was restricted for the ia type of the lymphoma partner (H-2k) of the somatic hybrid. This was shown by affinity separation on parental type spleen cells and on monoclonal anti-I-A-Sepharose. Both factors had carrier (chicken gamma globulin; CGG)-specific helper effect, and both bound to anti-VH-315-Sepharose. Because the lymphoma (BW-5147) partner could not contribute a CGG-specific locus, the H-2k-restricted, CGG-specific factor had to be the product of segregating anti-nominal and anti-self loci. This suggests that dual specificity is due to two independent loci and support the validity of dual recognition concepts. Anti-self specificity was associated with homologous Ia alloantigens in the individual factors. Therefore, Ia and anti-self might be linked. Implications of the major histocompatibility complex or VH nature of anti-self receptors and the relationship of T cell factors and receptors was discussed.
Randomized Clinical Trial of Adenosine 5'-Triphosphate in Patients With Advanced Non-Small-Cell Lung Cancer
Authors: H. J. Agteresch
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND: Extracellular adenosine 5′-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). METHODS: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. RESULTS: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were −1.0 kg (95% confidence interval[ CI] = −1.5 to −0.5) in the control group and 0.2 kg (95% CI= −0.2 to +0.6) in the ATP group (P = .002). Serum albumin concentration declined by −1.2 g/L (95% CI= −2.0 to −0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = −0.3 to +0.3) in the ATP group (P = .006). Elbow flexor muscle strength declined by− 5.5% (95% CI = −9.6% to −1.4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI=− 1.4% to +1.4%) in the ATP group (P = .01). A similar pattern was observed for knee extensor muscles (P = .02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P = .0002, P = .0001, and P = .0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group—physical scores (−0.2% versus− 2.4%; P = .0002); functional scores (+0.4% versus− 5.5%; P = .02); psychologic scores (−0.7% versus− 2.4%; P = .11); overall QOL score (+0.1% versus− 3.5%; P = .0001). CONCLUSIONS: This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.
Combined DNA Methyltransferase and Histone Deacetylase Inhibition in the Treatment of Myeloid Neoplasms
Authors: Steven D. Gore, Stephen Baylin, Elizabeth Sugar, Hetty Carraway, Carole B. Miller, Michael Carducci, Michael Grever, Oliver Galm, Tianna Dauses, Judith E. Karp, Michelle A. Rudek, Ming Zhao, B. Douglas Smith, Jasper Manning, Anchalee Jiemjit, George Dover, Abbie Mays, James Zwiebel, Anthony Murgo, Li-Jun Weng, James G. Herman
Journal: Cancer Research (2006)

Abstract Optimal reexpression of most genes silenced through promoter methylation requires the sequential application of DNA methyltransferase inhibitors followed by histone deacetylase inhibitors in tumor cell cultures. Patients with myelodysplastic syndrome or acute myeloid leukemia (AML) were treated with the methyltransferase inhibitor 5-azacitidine (aza-CR) followed by the histone deacetylase inhibitor sodium phenylbutyrate. Major responses associated with cytogenetic complete response developed in patients receiving prolonged dosing schedules of aza-CR. Bisulfite sequencing of the p15 promoter in marrow DNA during the first cycle of treatment showed heterogeneous allelic demethylation in three responding patients, suggesting ongoing demethylation within the tumor clone, but no demethylation in two nonresponders. Six of six responding patients with pretreatment methylation of p15 or CDH-1 promoters reversed methylation during the first cycle of therapy (methylation-specific PCR), whereas none of six nonresponders showed any demethylation. Gene demethylation correlated with the area under the aza-CR plasma concentration-time curve. Administration of both drugs was associated with induction of acetylation of histones H3 and H4. This study provides the first demonstration that molecular mechanisms responsible for responses to DNA methyltransferase/histone deacetylase inhibitor combinations may include reversal of aberrant epigenetic gene silencing. The promising percentage of major hematologic responses justifies the testing of such combinations in prospective randomized trials. (Cancer Res 2006; 66(12): 6361-9)
Panniculitis complicating gallstone pancreatitis with subsequent resolution after therapeutic endoscopic retrograde cholangiopancreatography
Authors: A.A. Riaz, F. Smith, L. Phylactides, N.W. Law
Journal: British Journal of Dermatology (2000)

Journal Article Panniculitis complicating gallstone pancreatitis with subsequent resolution after therapeutic endoscopic retrograde cholangiopancreatography Get access A.A. Riaz, A.A. Riaz Department of Surgery, Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, U.K. Correspondence: A.A.Riaz, 20 Sidmouth Road, London NW2 5JX, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. Smith, F. Smith Department of Surgery, Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, U.K. Correspondence: A.A.Riaz, 20 Sidmouth Road, London NW2 5JX, U.K. Search for other works by this author on: Oxford Academic Google Scholar L. Phylactides, L. Phylactides Department of Surgery, Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, U.K. Correspondence: A.A.Riaz, 20 Sidmouth Road, London NW2 5JX, U.K. Search for other works by this author on: Oxford Academic Google Scholar N.W. Law N.W. Law Department of Surgery, Chase Farm Hospital, The Ridgeway, Enfield EN2 8JL, U.K. Correspondence: A.A.Riaz, 20 Sidmouth Road, London NW2 5JX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 6, 1 December 2000, Pages 1332–1333, https://doi.org/10.1046/j.1365-2133.2000.03921.x Published: 01 December 2000
Intact fetal cells in maternal plasma: are they really there?
Authors: Farideh Z Bischoff, Sinuhe Hahn, Kirby L Johnson, Joe Leigh Simpson, Diana W Bianchi, Dorothy E Lewis, William D Weber, Katherine Klinger, Sherman Elias, Laird G Jackson, Mark I Evans, Wolfgang Holzgreve, Felix de la Cruz
Journal: The Lancet (2003)
Frequent mutations in the ligand-binding domain of PML-RARα after multiple relapses of acute promyelocytic leukemia: analysis for functional relationship to response to all-transretinoic acid and histone deacetylase inhibitors in vitro and in vivo
Authors: Da-Cheng Zhou, Soon H. Kim, Wei Ding, Cynthia Schultz, Raymond P. Warrell, Robert E. Gallagher
Journal: Blood (2002)
Beraprost therapy for pulmonary arterial hypertension
Authors: Robyn J Barst, Michael McGoon, Vallerie McLaughlin, Victor Tapson, Ronald Oudiz, Shelley Shapiro, Ivan M Robbins, Richard Channick, David Badesch, Barry K Rayburn, Robin Flinchbaugh, Jeff Sigman, Carl Arneson, Roger Jeffs
Journal: Journal of the American College of Cardiology (2003)
Interferon and Cell Division. II. Influence of Various Experimental Conditions on the Inhibition of L1210 Cell Multiplication &lt;italic&gt;In Vitro&lt;/italic&gt; by Interferon Preparations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Gresser, Ion, Brouty-Boyé, Danièle, Thomas, Marie-Thérèse, Macieira-Coelho, Alvaro
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Interferon and Cell Division. II. Influence of Various Experimental Conditions on the Inhibition of L1210 Cell Multiplication In Vitro by Interferon Preparations Get access Ion Gresser, Ion Gresser Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, and Institut de Cancérologie et d'Immunogénétique, 94-Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Danièle Brouty-Boyé, Danièle Brouty-Boyé Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, and Institut de Cancérologie et d'Immunogénétique, 94-Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Marie-Thérèse Thomas, Marie-Thérèse Thomas Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, and Institut de Cancérologie et d'Immunogénétique, 94-Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Alvaro Macieira-Coelho Alvaro Macieira-Coelho Laboratory of Viral Oncology, Institut de Recherches Scientifiques sur le Cancer, and Institut de Cancérologie et d'Immunogénétique, 94-Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 45, Issue 6, December 1970, Pages 1145–1153, https://doi.org/10.1093/jnci/45.6.1145 Published: 01 December 1970 Article history Received: 16 June 1970 Accepted: 29 July 1970 Published: 01 December 1970
β <sub>2</sub> -Adrenoceptors Activate Nitric Oxide Synthase in Human Platelets
Authors: Lindsay R. Queen, Biao Xu, Kazumi Horinouchi, Ian Fisher, Albert Ferro
Journal: Circulation Research (2000)

Abstract —Nitric oxide (NO), generated by platelets through stimulation of nitric oxide synthase (NOS), limits platelet adhesion and aggregation after a prothrombotic stimulus. Platelet β-adrenoceptors (βARs) mediate inhibition of aggregation, but no direct link has been shown between these receptors and platelet adhesion or NO production. We examined NOS activity in human platelets from the conversion of l -[ 3 H]-arginine to l -[ 3 H]-citrulline, after βAR stimulation or cAMP elevation. Basal NOS activity was 0.11±0.03 pmol l -citrulline/10 8 platelets. The βAR agonist isoproterenol 1 μmol/L and the adenylyl cyclase activator forskolin 1 μmol/L each increased NOS activity, to 0.26±0.04 and 0.23±0.03 pmol l -citrulline/10 8 platelets, respectively ( P &lt;0.01 for each). Both responses were abolished by the adenylyl cyclase inhibitor SQ22536 50 μmol/L. NOS activation by isoproterenol or forskolin was not associated with a change in intracellular Ca 2+ . In functional studies, isoproterenol inhibited U46619-induced platelet aggregation in a concentration-dependent manner, but this effect was not significantly diminished by NOS inhibition. In contrast, thrombin-stimulated platelet adhesion to cultured human umbilical vein endothelial cell monolayers was inhibited by isoproterenol, and this effect was abolished by NOS inhibition (1.3±0.2% versus 2.6±0.2% respectively; P &lt;0.001). Effects of isoproterenol on NOS activity, platelet aggregation, and adhesion were mediated exclusively through β 2 ARs, as determined by coincubation with βAR subtype-selective antagonists. We conclude that β 2 ARs activate platelet NOS by increasing cAMP, and that this activation is Ca 2+ -independent. β 2 ARs may contribute to modulation of platelet aggregation and adhesion to endothelium, and our findings suggest that activation of the l -arginine/NO system mediates the effects of β 2 ARs on adhesion but not aggregation. ( Circ Res. 2000;87:39-44.)
Induced interleukin-33 expression enhances the tumorigenic activity of rat glioma cells
Authors: Kuan-Min Fang, Chung-Shi Yang, Tzu-Chien Lin, Ti-Chun Chan, Shun-Fen Tzeng
Journal: Neuro-Oncology (2013)

Glioma development is a multistep process associated with progressive genetic alterations but also regulated by cellular and noncellular components in a tumor-associated niche. Using 2 rat C6 glioma cell clones with different tumorigenesis, named C6-1 and C6-2, this study characterized genes associated with enhanced tumorigenic features of glioma cells by comparative cDNA microarray analysis combined with Q-PCR. Neurospehere formation and clonogenicity were examined to determine the growth of tumorigenic C6 glioma cells. The lentivirus-mediated gene knockdown approach was conducted to determine the role of interleukin-33 (IL-33) in glioma cell proliferation and migration. Transwell cell invasion assay was used to examine microglia migration induced by tumorigenic C6 cells. The functional analysis of gene ontology (GO) biological processes shows that the upregulated genes found in tumorigenic C6 (C6-1) cells are closely related to cell proliferation. Tumorigenic C6 cells expressed cytokines and chemokines abundantly. Among these genes, IL-33 was profoundly induced in tumorigenic C6 cells with the expression of IL-33 receptor ST2. Furthermore, the growth rate and colony formation of tumorigenic C6 cells were attenuated by the inhibition of IL-33 and ST2 gene expression. Moreover, IL-33 was involved in tumorigenic glioma cell migration and regulation of the expression of several glioma-associated growth factors and chemokines in tumorigenic C6 cells. Accordingly, we concluded that glioma cells with abundant production of IL-33 grow rapidly; moreover, the interactions of multiple cytokines/chemokines induced by glioma cells may develop a microenvironment that facilitates microglia/macrophage infiltration and fosters glioma growth in the brain.
Relationship of Dissociation to Temperament and Character in Men and Women
Authors: H J Grabe, C Spitzer, H Juergen Freyberger
Journal: American Journal of Psychiatry (1999)

This study approaches the question of nature and nurture of dissociative phenomena. Within Cloninger's concept of personality, character traits are thought to develop in response to environmental stimuli and conditions during childhood and adolescence, whereas temperament traits are considered to be genetically predisposed. The hypothesis is tested that dissociative symptoms are associated with distinct character traits but not with temperament dimensions.Psychiatric patients (N = 191) and healthy subjects (N = 41) were evaluated for dissociative symptoms (Dissociative Experience Scale), temperament and character (Temperament and Character Inventory), and current psychopathology (SCL-90-R). Regression analyses for women and men were calculated separately.For both genders, the character traits of self-transcendence and self-directedness were significant and independent predictors for dissociation.These results support the hypothesis that dissociative symptoms are caused by environmental factors and point against a genetic predisposition in the development of dissociative symptoms.
T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity
Authors: Huaizhu Wu, Sudip Ghosh, Xiaoyuan Dai Perrard, Lili Feng, Gabriela E. Garcia, Jerry L. Perrard, John F. Sweeney, Leif E. Peterson, Lawrence Chan, C. Wayne Smith, Christie M. Ballantyne
Journal: Circulation (2007)

Obesity is associated with chronic inflammation, which includes increased macrophage accumulation in adipose tissue (AT) and upregulation of chemokines and cytokines. T cells also play important roles in chronic inflammatory diseases such as atherosclerosis but have not been well studied in obesity.Flow cytometric analysis showed higher numbers of T cells and macrophages in AT of diet-induced obese insulin-resistant male mice than in lean mice and obese females (P<0.05). RNase protection assay, ELISA, and flow cytometry indicated gender-dependent upregulation of mRNA and protein levels of regulated on activation, normal T cell expressed and secreted (RANTES) and its receptor CCR5 in AT of obese mice. Adipocytes, stromal/vascular cells from mouse AT, and human and murine adipocytes expressed RANTES. RANTES mRNA levels were negatively correlated with adiponectin in mouse AT. Adiponectin-deficient mice fed high-fat diet showed higher RANTES mRNA levels in AT than wild-type mice. Activated T cells coincubated with preadipocytes in vitro significantly suppressed preadipocyte-to-adipocyte differentiation. Obese humans with metabolic syndrome had higher mRNA levels of RANTES and CCR5 in subcutaneous AT than lean humans. RANTES and CCR5 mRNA levels were significantly higher in visceral than subcutaneous AT of morbidly obese humans. RANTES mRNA levels were positively correlated with CD3 and CD11b in human visceral AT.Obesity is associated with increased accumulation of T cells and macrophages in AT, which may play important roles in obesity-related disease by influencing preadipocyte/adipocyte functions. RANTES is an adipokine that is upregulated in AT by obesity in both mice and humans.