tbuckley/cabot-search huggingface dataset:
791. Histone Deacetylase Inhibition Up-Regulates CAR and Increases Adenovirus Infection and Transgene Expression in Skeletal Muscle
Authors: Alan R. Brooks, Linda Cashion, Kaye Reiter, Peiyin Wang, Hu Sheng Qian, Richard N. Harkins, Gabor M. Rubanyi
Journal: Molecular Therapy (2004)

Previous studies on cancer cells in culture have shown that histone deacetylase inhibitors (HDACis) can up-regulate a subset of silenced genes including the coxsackie and adenovirus receptor (CAR) that mediates binding of type 5 adenovirus (Ad5). However, little is known about the effect and mechanism of action of HDACi's on Ad5 transfection of skeletal muscle that normally expresses low levels of CAR and is therefore resistant to Ad5 infection. In the present study we used quantitative PCR to measure the effect of HDACi on CAR mRNA levels and Ad5 delivered transgene expression in vitro and in vivo. Treatment of human primary skeletal muscle cells (SkMC) with HDACi for 24 h resulted in a dose dependent increase in CAR mRNA levels that peaked as high as 250-fold over baseline. CAR protein level on the cell surface was also increased by the HDACi. Treatment of SkMC with optimal concentrations of HDACi for 24 h prior to infection was more effective than co-treatment at increasing Ad5Luc mediated luciferase expression (15-fold vs 6-fold, respectively). Treatment with HDACi at the time of infection resulted in a 5-fold increase in the amount of Ad5 DNA in the cells (measured by quantitative PCR) and a 9-fold increase in luciferase mRNA levels. Thus, HDACi treatment increased Ad5 transduction efficiency in SkMC, presumably as a result of increased CAR expression, but also increased the ratio of transgene RNA to viral DNA by 2.5-fold. This data suggest that the primary mechanism by which HDACi improve transgene expression after adenoviral delivery to skeletal muscle is via increased transduction with a smaller effect on transcription of the transgene. Administration of HDACi to mice increased CAR mRNA levels 3-fold in skeletal muscle and resulted in a 2 to 4-fold increase in luciferase activity when an AdEasy-luciferase virus was given by intramuscular injection 24 h after the HDACi. Our studies suggest that pre- or co-treatment with HDACi could be useful to improve both adenovirus delivery and transgene expression in vivo in human skeletal muscle.
Subclinical left ventricular dysfunction by echocardiographic speckle‐tracking strain analysis relates to outcome in sarcoidosis
Authors: Emer Joyce, Maarten K. Ninaber, Spyridon Katsanos, Philippe Debonnaire, Vasilis Kamperidis, Jeroen J. Bax, Christian Taube, Victoria Delgado, Nina Ajmone Marsan
Journal: European Journal of Heart Failure (2014)
The Effects of Roentgen Radiation on Tumor Incidence in Drosophila melanogaster
Authors: Ernest W. Hartung
Journal: Cancer Research (1942)

Spontaneously occurring tumors in Drosophila mdanogaster have been known for a number of years, and have been described in many strains (6-~I). In i938 Haskins and Enzmann ( I ) reported that x-radiation could modify the incidence of certain apparently hereditary tunmrs in Drosophila. In view of these facts, it was considered of interest to ascertain thc effects of roentgcn radiation on the tutnor incidence of strains of Drosophila which show an hereditary incidence, as opposed to nontumorous wild typcs. From Dr. E. S. Russell four strains of tumor-producing flies were obtained which were of the following genetic make-up:
Abstract P306: Combined Impact Of Income And Education On All-Cause And Cardiovascular Mortality In Men And Women. Prospective Results From The Moli-Sani Study.
Authors: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Mariarosaria Persichillo, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello
Journal: Circulation (2014)

Background: Education and income have been reportedly associated with mortality but their combined impact has not been extensively investigated. This study aims at evaluating the combined impact of income and education on overall and cardiovascular mortality in men and women. Methods: A prospective cohort study on a large sample of individuals (N=20,600, age ≥35) free from cardiovascular or cancer disease randomly enrolled in the Moli-sani study. The cohort was followed-up for overall mortality for 6.8 years (median 4.3 years). Education was considered as low (≤8 years of study) or high (&gt;8 years). Low income group was defined as gross income ≤25,000euros/year while high income category included subjects reporting &gt;25,000euro/years. A four-level variable was constructed to account for the combination of the two measurements: a) low income and low education group (reference group); b) high income and low education; c) low income and high education; d) high income and high education group. Hazard ratios were calculated using Cox-proportional hazard models. Results: During follow-up, 354 all-cause deaths occurred, 61 from cardiovascular causes. In a fully adjusted model, income, but not education, was significantly associated with a reduction of overall mortality. However, the group having both high income and high education levels showed a reduced risk of 54%(HR=0.46; 95CI: 0.32-0.66) compared to the reference group. Cardiovascular mortality was also reduced by 63%. Analyses stratified by sex showed that the highest combination of income and education had a stronger impact on overall mortality among women (HR=0.27; 95CI: 0.10-0.79) than among men (HR=0.50; 95CI:0.34-0.76). Conclusions: The combination of high education and high income is associated with a consistent significant reduction of either overall or cardiovascular mortality. The protective effect of the combination is apparent in both genders but is stronger in women than in men.
Heregulin: A novel modulator of telomere length maintenance via regulation of the Telomere Repeat-binding Factor (TRF-2)
Authors: Javier A. Menendez, Miguel A. Rubio, Louisa Benboudjema, Luciano Vellon, Judith Campisi, Ruth Lupu
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4988 

The growth factor Heregulin (HRG) actively promotes breast cancer tumorigenesis and metastasis, whilst it differentially modulates breast cancer cell responses to DNA-damaging drugs. HRG overexpression induces hypersensitivity to doxorubicin whereas it promotes resistance to cisplatin. An attractive molecular candidate underlying these HRG’s counterintuitive effects is the telomere and more specifically, its end-capping function: a. ) Depending on their length, telomeres serve to suppress or promote malignant transformation, and b. ) the inhibition of telomere maintenance acts to chemosensitize cancer cells to double-stranded DNA breaks inducers ( e.g ., doxorubicin), whereas long telomeres are good targets for drugs preferentially targeting the G-rich telomeric sequence ( e.g ., cisplatin). We herein characterized the ability of HRG to regulate telomere length and/or function in breast cancer cells. MCF-7-derived T6 and T7 clones stably expressing the human full-length HRG cDNA exhibited shorter telomeres (≤ 1.3 Kb shortening) relative to control cells. HRG-overexpressing MDA-MB-231 and Hs578T cells stably transfected with an anti-sense (AS)-HRG cDNA displayed longer telomeres (≥ 3.0 Kb lengthening) when compared to control cells. While no significant HRG-related differences in telomerase activity were observed, HRG-overexpressing MCF-7/T clones markedly exhibited higher levels of telomeric repeat binding factor-2 (TRF2) expression as compared to matched control cells, whereas TRF2 expression was knocked-down in AS-HRG clones. Exogenous supplementation with recombinant HRG up-regulated TRF2 expression in MCF-7 cells while it partially rescued TRF2 expression levels in AS-HRG clones. An up to 75% reduction in the amount of TRF2 protein was achieved 72 hours after transfection with HRG-specific small interference RNAs (siRNAs). These findings strongly suggest that HRG is a previously unrecognized modulator of telomere function in breast cancer cells by virtue of its ability to regulate TRF2, a specific telomeric-protein playing an essential role in protecting telomeric integrity.
Abstract 18091: Impact of Late Gadolinium Enhancement With Cardiac Magnetic Resonance on Mortality in Moderate to Severe Aortic Stenosis
Authors: Rosalyn Adigun, Kongkiat Chaikriangkrai, Mohamad Ghosn, Stephen H Little, William A Zoghbi, Faisal Nabi, Dipan J Shah
Journal: Circulation (2014)

Objective:  Our aim is to examine the association between late gadolinium enhancement (LGE) detected by cardiac magnetic resonance imaging (CMR) and mortality in patients with moderate or severe aortic stenosis (AS).   Methods:  Patients presenting for CMR assessment of aortic stenosis were prospectively enrolled into our CMR registry. This study evaluated 276 consecutive patients with moderate or severe AS who underwent delayed enhancement (DE-CMR) from June 2009 - October 2013. Exclusion criteria were moderate or severe aortic insufficiency and aortic valve replacement before CMR. Patients were categorized into LGE 0%, LGE 1-5% and LGE>5%. Median follow up was 14 months (IQR 2-27 months).   Results:  The cohort had a mean age of 70±14 years with 58% (160) men, of which 51% had severe AS. Mean LVEF was 60±19%. LGE was evident in 56% (155/276 patients) of which 105 (68%) had LGE of 1-5% and 50 (32%) had LGE > 5%. LGE pattern was consistent with CAD in 68 patients whereas 87 patients had non-CAD pattern. Patients in the LGE 1-5% and >5% group were older (p=0.02), had more males (p  5% was significantly associated with death. After adjusting for age, LVEF, LV mass, CAD, diabetes mellitus and subsequent AVR, the association between LGE >5% and mortality remained significant (HR 2.34, p=0.047).   Conclusions:  LGE detected by DE-CMR is associated with higher long term mortality in patients with moderate or severe AS. Our findings suggest a potential role of DE-CMR in risk stratification of these patients.
Scientists Probe Cancer Cell Resistance
Authors: M J Friedrich
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Does Tamoxifen Enhance Endothelial Function by Lowering the Plasma Levels of Homocysteine?
Authors: Marco Cattaneo
Journal: Circulation (2001)

To the Editor:In their interesting study, Clarke et al 1 showed that treatment with tamoxifen (40 mg/d) for 56 days caused an increase in endothelium-dependent flow-mediated dilatation (ED-FMD) of the brachial artery in men with angiographically proven coronary artery disease (CAD) and in men with angina-like symptoms but normal coronary arteries (as shown by angiography).In contrast, tamoxifen did not affect endothelium-independent FMD in the same subjects.The ED-FMD response to tamoxifen was unlikely to have been caused by the associated increase in plasma estradiol or a reduction in plasma cholesterol levels. 1 A possible mechanism for the observed enhanced endothelial function in men treated with tamoxifen could be the reduction in plasma total homocysteine (tHcy) levels.High tHcy levels are associated with increased risk for CAD and other atherothrombotic diseases. 2 Compelling evidence indicates that both long-and shortterm (induced by oral methionine loading) increases in the plasma levels of tHcy impair the ED-FMD of the brachial artery without affecting endothelium-independent FMD.Two studies showed that the oral administration of folic acid, alone 3 or in combination with vitamin B 12 , 4 improved the ED-FMD in patients with CAD.The improvement in ED-FMD correlated with the reduction in total 3 or free Hcy levels 4 caused by vitamin treatment.Tamoxifen, at oral doses ranging between 20 and 30 mg/d, reduces tHcy levels not only in patients with advanced breast cancer, 2 but also in healthy women, 5 indicating that its lowering effect is not only due to its antitumoral activity, but also to its direct effect on estrogenregulated targets.The reduction of tHcy levels by tamoxifen (20 mg/d) was seen in women with moderate hyperhomocystinemia and in women with normal tHcy levels. 5 On the basis of these considerations, it seems reasonable to hypothesize that the improvement of vascular endothelial function after treatment with tamoxifen, as described by Clarke et al, 1 can be attributed, at least in part, to the lowering effect of the drug on plasma tHcy levels.
Shortage of nurses in Japan leads to high accident rate
Authors: Joe Lamar
Journal: BMJ (2000)

Japan's biggest nursing union has called on the government to address a worrying staff shortage that it claims is responsible for the fact that two in three of its members have filed an accident report in the past year.

The All Japan Prefectural and Municipal Workers Union said that 62.7% of the 5227 nurses it surveyed had made a mistake or reported a near accident. Among the errors were mix-ups of …
Abnormal Expression of Mouse Mast Cell Protease 5 Gene in Cultured Mast Cells Derived From Mutant mi/mi Mice
Authors: Eiichi Morii, Tomoko Jippo, Tohru Tsujimura, Koji Hashimoto, Dae-Ki Kim, Young-Mi Lee, Hideki Ogihara, Kumiko Tsujino, Hyung-Min Kim, Yukihiko Kitamura
Journal: Blood (1997)
Abstract 418: Preconditioning Promotes Survival and Proliferation of Mesenchymal Stem Cells in the Infarcted Rat Heart Via Activation of NF-{kappa}B Downstream of PI3K/Akt Signaling.
Authors: Muhammad Rizwan Afzal, Husnain K Haider, Niagara Muhammad Idris, Shujia Jiang, Rafeeq Ahmed, Muhammad Ashraf
Journal: Circulation (2007)
Abstract 17751: PCSK9 is Elevated in HIV+ Patients
Authors: Payal Kohli, Peter Ganz, Yifei Ma, Rebecca Scherzer, Steven G Deeks, Kristinalisa Maka, Scott M Wasserman, Rob Scott, Priscilla Hsue
Journal: Circulation (2014)

Purpose: Proprotein convertase subtilisin kexin 9 (PCSK9) is induced by inflammation and inhibits LDL receptor expression. Increased PCSK9 might explain the dyslipidemia observed in HIV patients, which has been previously attributed to HIV medication, HIV disease, and/or chronic inflammation. We aimed to compare PCSK9 levels in HIV patients and uninfected controls and identify predictors of elevated PCSK9 in HIV. Methods: We measured PCSK9 levels in 567 participants (495 HIV, 72 controls) from an outpatient cohort in San Francisco using a high affinity ELISA assay. Poisson regression models were used to determine factors associated with PCSK9. Results: The median age of all participants was 50 years (IQR 43-55) and 89% were male; 34% were smokers, 25% had hypertension, the median LDL was 103 mg/dL (IQR 80-127), and 21% were on statins. HIV patients and controls had similar rates of traditional risk factors except prior CAD was more common in HIV patients. Half of the HIV patients were treated and suppressed on HIV medication. Unadjusted PCSK9 levels were 11% higher in HIV patients vs. controls [mean 430 ng/ml (SD 166) vs. 386 ng/ml (SD134), p=0.015] with some HIV patients having extremely elevated levels &gt;1000 ng/ml. After adjustment for demographics and statin use, HIV remained independently associated with 10% higher PCSK9 levels (p=0.03). In addition, older age, other race, statin use, Hepatitis C (HCV), higher triglycerides, current smoking and Lp(a)&gt;90 nmol/L were all independently associated with higher PCSK9 levels in adjusted analysis. In contrast, neither inflammatory markers (IL-6, hs-CRP) nor CD4+ count or HIV viral load were associated with higher PCSK9. Conclusion: PCSK9 is increased in HIV-infected individuals. Traditional risk factors, HCV, and Lp(a)&gt;90 nmol/L were also independently associated with PCSK9. Future studies should explore whether PCSK9 inhibition may be used to treat dyslipidemia and statin resistance in HIV+ patients.
Wakefulness Is Governed by GABA and Histamine Cotransmission
Authors: Xiao Yu, Zhiwen Ye, Catriona M. Houston, Anna Y. Zecharia, Ying Ma, Zhe Zhang, David S. Uygun, Susan Parker, Alexei L. Vyssotski, Raquel Yustos, Nicholas P. Franks, Stephen G. Brickley, William Wisden
Journal: Neuron (2015)

Histaminergic neurons in the tuberomammilary nucleus (TMN) of the hypothalamus form a widely projecting, wake-active network that sustains arousal. Yet most histaminergic neurons contain GABA. Selective siRNA knockdown of the vesicular GABA transporter (vgat, SLC32A1) in histaminergic neurons produced hyperactive mice with an exceptional amount of sustained wakefulness. Ablation of the vgat gene throughout the TMN further sharpened this phenotype. Optogenetic stimulation in the caudate-putamen and neocortex of "histaminergic" axonal projections from the TMN evoked tonic (extrasynaptic) GABAA receptor Cl− currents onto medium spiny neurons and pyramidal neurons. These currents were abolished following vgat gene removal from the TMN area. Thus wake-active histaminergic neurons generate a paracrine GABAergic signal that serves to provide a brake on overactivation from histamine, but could also increase the precision of neocortical processing. The long range of histamine-GABA axonal projections suggests that extrasynaptic inhibition will be coordinated over large neocortical and striatal areas.
172. In Vitro DNA Packaging and Gene Delivery Using JC Virus-Like Particles
Authors: Oliver Ast, Andrezj Citkowicz, Linda Cashion, Brent Larsen, Gabor M. Rubanyi, Richard N. Harkins, Harald Petry
Journal: Molecular Therapy (2005)

Virus-like particles (VLP) have been known for several years to be a promising alternative to the existing viral and non-viral DNA delivery systems. VLPs are self-assembled structures composed only of proteins necessary for capsid formation and DNA packaging. They are replication deficient and exhibit a similar morphology and cell tropism compared to their viral origin. One of the major differences between VLPs and traditional viral vectors is the way of DNA packaging. For viral delivery systems the use of packaging cell lines is indispensable whereas the DNA packaging into the VLP can be accomplished by controlled and reproducible in vitro methods.
EFFECTS OF CORTISONE AND ACTH IN MUMPS MENINGO-ENCEPHALITIS
Authors: John K. Spitznagel
Journal: Annals of Internal Medicine (1958)

ExcerptIt has long been recognized that central nervous system involvement, most frequently aseptic meningitis or meningo-encephalitis, may occur during mumps infection.1, 2, 3, 4The involvement may be so mild that its presence is manifested only by abnormal findings in the spinal fluid, or it may be quite violent. The meningitis has been generally regarded as benign; however, fatalities and incapacitating sequelae have been attributed to the encephalitic component, which is quite similar to that which occasionally complicates varicella, rubeola and rubella.5Because no specific treatment has been available, various palliative and supportive measures have been employed. They have not...
Etiology of the Metabolic Syndrome
Authors: Akira Taguchi
Journal: JAMA (2004)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Second neoplasm and cerebrovascular disease in over five-year survivors with CNS germ cell tumor
Authors: K. Sugiyama, K. Arita, K. Kurisu, Y. Sawamura
Journal: Journal of Clinical Oncology (2007)

9046 Background: Survivors of childhood and adolescent brain tumors are at risk for long-term effects of treatment (Tx). This study investigates details on second neoplasm and cerebrovascular disease of long-term survivors with CNS germ cell tumors (CNSGCTs). Methods: The authors reviewed clinical data on 203 institutional patients (pts) who had a CNSGCT and survived more than 5 years. Median age of initial Tx was 15.0 years and median follow-up period was 168 months (60–448 months). Results: Among these pts, 32 pts (15.4%) suffered from second neoplasm and/or cerebrovascular disease. Median age of 32 pts was 14.6 years at the initial Tx. Median interval to event was 151 months (24–456 months). The secondary events, therefore, occurred at the third decade of age. The second neoplasm included 8 cavernous angiomas, 7 GBMs, 3 meningiomas, 2 G-III glioma, 1 hemangiopericytoma, and 1 leukemia. Four cavernous angiomas caused a hematoma. The cerebrovascular disease included 14 steno-occlusive diseases of circle of Willis, 1 aneurysm, and 1 dural AVF. Four pts sufferred from both neoplasum and cerebrovascular disease. All 32 pts had previously received radiotherapy and 6 pts had undergone chemotherapy. Radiation field included whole ventricle system or whole brain involving basal cistern with the dose of more than 40 Gy, except for one who received 24 Gy followed by P-E chemotherapy. Eight of 32 pts died and 14 pts had additional sequelae due to these secondary events. Conclusions: The risk of lethal malignant neoplasm and disabling cerebarovascular disease after Tx for CNSGCTs is extremely large. Long-term follow-up system to monitor and prevent late sequelae should be established. No significant financial relationships to disclose.