tbuckley/cabot-search huggingface dataset:
Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms
Authors: Belinda A Di Bartolo, Sian P Cartland, Leonel Prado-Lourenco, Nor Saadah M Azahri, Thuan Thai, Amanda Yeung, Shane R Thomas, Mary M Kavurma
Journal: Circulation (2014)

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.
Abstract 12229: Health Literacy, Adherence to Self-Care Behaviors, and Ten-Year Cardiovascular Disease Risk in Central Appalachian Residents
Authors: Jia-rong Wu, Frances Hardin-Fanning, Darren DeWalt, Debra K Moser
Journal: Circulation (2014)

Background: Appalachian Kentucky has disproportionately higher rates of cardiovascular disease (CVD) and associated risk factors than the rest of the U.S. Health literacy and adherence to CVD risk reduction self-care behaviors are important predictors of health outcomes and may play a major role in modifying CVD risk. Objective: To examine the relationships among health literacy, adherence to self-care behaviors and 10-year CVD risk in Central Appalachian residents. Method: This was a sub-analysis of baseline data of a randomized control trial in 844 Central Appalachian residents (male 25%, age 51± 14, Caucasian 95%) without major CVD (e.g., coronary artery disease, stroke). Health literacy was assessed by the Newest Vital Sign (NVS), and adherence to self-care behaviors by the Medical Outcomes Study Specific Adherence Scale. Ten-year CVD risk points were calculated from the Framingham formula based on age, high density lipoprotein, total cholesterol, systolic blood pressure (treated &amp; untreated), smoking status, and diagnosis of diabetes. Linear regressions were used to examine the relationships among health literacy, adherence to self-care behaviors, and 10-year CVD risk. Results: Based on the NVS, 12% of residents had limited health literacy. Residents who had limited health literacy were more likely to have higher 10-year CVD risk than those with adequate health literacy ( p = .014). Health literacy was not correlated with adherence to self-care behaviors. Unadjusted regressions revealed that both health literacy and adherence to self-care behaviors predicted 10-year CVD risk ( p = .002 and &lt; .001, respectively). After adjustment for the covariates (age, gender, ethnicity, marital status, employed status), only adherence to self-care behaviors predicted 10-year CVD risk ( p = .012) Conclusion: Poor adherence to self-care behaviors predicts higher 10-year CVD risk. The lack of independent relationship between health literacy and self-care adherence, and health literacy and outcome suggests that adherence to effective self-care may be fostered despite low health literacy. It is important to design and implement effective interventions to enhance adherence to self-care behaviors to reduce 10-year CVD risks in Central Appalachian residents.
855. Stable Transduction of Hepatocytes Following Intravenous Retroviral Gene Therapy in Seven-Week-Old Dogs with Mucopolysaccharidosis (MPS) VII
Authors: Mark Haskins, Thomas O'Malley, N. Matthew Ellinwood, Patricia O'Donnell, Kristen Cullen, Karyn Cullen, Margaret Sleeper, Gustavo Aguirre, Lingfie Xu, Ping Wang, Katherine Ponder
Journal: Molecular Therapy (2004)

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disease due to deficient -glucuronidase (GUSB) activity. We previously reported that IV injection of 310E9 transducing units (TU)/kg of a retroviral vector (RV) expressing GUSB into newborn MPS VII dogs resulted in transduction of hepatocytes, which secreted GUSB into blood and has been stable for more than 3 years. One MPS VII animal that was treated with human hepatocyte growth factor (HGF) prior to neonatal IV injection of 1210E9 U/kg of the same RV had dramatically higher serum levels, possibly due to the HGF or the higher dose of RV. In all 4 of the neonatally treated dogs followed more than 3 years, clinical signs were minimal, and provirus and expression of GUSB were detected by PCR in peripheral blood indicating transduction of hematopoietic stem cells. Because most MPS patients are not diagnosed until 1–2 years of age, we tested if post-weaning, 7-week-old MPS VII dogs could be treated by injecting a total dose of 1.7-2.210E9 TU/kg of RV IV administered over 4 days. Four dogs were pre-treated over 24 h with 2.5 mg/kg of HGF divided every 3 h (HGF/RV); 3 were only given RV. At 6 months of age, the HGF/RV- and RV-treated dogs had 184+/-109 U/ml (54% normal) and 49.7+/-11 (14% normal) U/ml of serum GUSB activity, respectively (ANOVA, p=0.079). The serum activity was stable in each dog for as long as 10 months with a range of from 14% to 83% of normal. Liver biopsies at 1 week (N=4) and 12 weeks (N=3) post treatment had GUSB activity of 83.3+/48.9 U/ml (8.4% normal) and 85.5+/-65.7 U/ml (8.7% normal), respectively, with normal GAG concentration of 3.03+/-0.79 ug/mg protein and 3.77+/-0.51 ug/mg protein, respectively (normal average 4.1 ug/mg protein, affected average 12.7 ug/mg protein). Clinically, 3 of the 7 dogs could still stand or walk at 6 months of age, however, 4 could not. Cornea cloudiness was present to variable degrees from minor to severe, and all dogs had some degree of mitral valve insufficiency by ultrasound. The clinical phenotype was not correlated with the serum GUSB activity. None of these dogs had PCR-detectable provirus in peripheral blood. We conclude that 1) 7-week-old MPS VII dogs were able to achieve stable serum GUSB activity for as long as 10 months at levels that were similar to that achieved with neonatal administration of RV, 2) GUSB expression occurred in the liver by 1 week and reduced hepatic GAG storage to normal, and 3) There was only modest improvement in gait, suggesting that bone and joint disease was not as well corrected with gene therapy at 7 weeks as it was with neonatal gene therapy.
Abstract 11388: A Randomized Trial Comparing the Pleotropic Effects of Ezetimibe Plus Moderate Dose Statin versus High Dose Statin Monotherapy
Authors: Antonio E Pesaro, Carlos Serrano, Juliano L Fernandes, Alexandre B Cavalcanti, Alexandre H Campos, Herlon S Martins, Raul C Maranhao, James A de Lemos, Heraldo P Souza, Jose C Nicolau
Journal: Circulation (2010)

Background: In patients with stable coronary artery disease (CAD), it is not known if different strategies of LDL-lowering Results in different “pleotropic” antiplatelet and anti-inflammatory effec...
International Tobacco Control: An Update
Authors: D Satcher
Journal: JAMA (2001)

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
Alternative Splicing in the Mammalian Nervous System: Recent Insights into Mechanisms and Functional Roles
Authors: Bushra Raj, Benjamin J. Blencowe
Journal: Neuron (2015)

High-throughput transcriptomic profiling approaches have revealed that alternative splicing (AS) of precursor mRNAs, a fundamental process by which cells expand their transcriptomic diversity, is particularly widespread in the nervous system. AS events detected in the brain are more highly conserved than those detected in other tissues, suggesting that they more often provide conserved functions. Our understanding of the mechanisms and functions of neural AS events has significantly advanced with the coupling of various computational and experimental approaches. These studies indicate that dynamic regulation of AS in the nervous system is critical for modulating protein-protein interactions, transcription networks, and multiple aspects of neuronal development. Furthermore, several underappreciated classes of AS with the aforementioned roles in neuronal cells have emerged from unbiased, global approaches. Collectively, these findings emphasize the importance of characterizing neural AS in order to gain new insight into pathways that may be altered in neurological diseases and disorders. High-throughput transcriptomic profiling approaches have revealed that alternative splicing (AS) of precursor mRNAs, a fundamental process by which cells expand their transcriptomic diversity, is particularly widespread in the nervous system. AS events detected in the brain are more highly conserved than those detected in other tissues, suggesting that they more often provide conserved functions. Our understanding of the mechanisms and functions of neural AS events has significantly advanced with the coupling of various computational and experimental approaches. These studies indicate that dynamic regulation of AS in the nervous system is critical for modulating protein-protein interactions, transcription networks, and multiple aspects of neuronal development. Furthermore, several underappreciated classes of AS with the aforementioned roles in neuronal cells have emerged from unbiased, global approaches. Collectively, these findings emphasize the importance of characterizing neural AS in order to gain new insight into pathways that may be altered in neurological diseases and disorders.
Use of Bivalirudin During Percutaneous Coronary Intervention in Patients With Diabetes Mellitus
Authors: Hitinder S. Gurm, Ian J. Sarembock, Dean J. Kereiakes, John J. Young, Robert A. Harrington, Neal Kleiman, Frederick Feit, Kathy Wolski, John A. Bittl, Robert Wilcox, Eric J. Topol, A. Michael Lincoff
Journal: Journal of the American College of Cardiology (2005)
Researchers Buoyed by Promise of Targeted Leukemia Therapy
Authors: J Stephenson
Journal: JAMA (2000)

NEW ORLEANS—The concept that tailoring therapy to the specific molecular abnormality responsible foradiseasewill lead to safer and more effective drugs received a dramatic boost with results reported from a study of a new agent that targets the genetic flaw causing chronic myelogenous leukemia (CML). In the study, reported here at the annual meeting of the American Society of Hematology, all 31 patients with CML who were given a daily pill containing at least 300 mg of a drug called STI-571 had a complete normalization of their blood counts, indicating a remission of the disease. At the same time, the drug, which targets a tyrosine kinase enzyme found only in the leukemia cells, appeared to eliminate all cells containing the chromosomal abnormality in three patients and substantially reduced the number of such cells in another eight, said Brian J. Druker, MD, of Oregon Health Sciences University, Portland. All of the patients had failed to improve after receiving the standard therapy, interferon alfa, which causes such adverse effects as flulike symptoms, explained Druker, who led the study. Adverse effects of the experimental drug, which included mild nausea when the once-daily pill was taken without food, and muscle cramps in about 10% of patients, were minimal.
THE PSYCHE AND THE SOMA: THE SPIRITUAL AND PHYSICAL ATTRIBUTES OF THE HEART
Authors: P D WHITE
Journal: Annals of Internal Medicine (1951)

Article1 December 1951THE PSYCHE AND THE SOMA: THE SPIRITUAL AND PHYSICAL ATTRIBUTES OF THE HEARTPAUL D. WHITE, M.D., F.A.C.P.PAUL D. WHITE, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-35-6-1291 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPsychosomatic medicine is "as old as the hills," or at least as old as the earliest humans who came down from the hills to establish civilized communities in the valleys and plains. The effect of "mind over matter" was the belief of our primitive ancestors as far as health and disease were concerned. There were no bacteria for them, or lesions of the brain or nerves or viscera, but evil spirits that had to be exorcised by extensive ritual in the hands of the witch doctors, of the magician and, finally, of the priest. Even Christ cast out devils... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *The Loevenhart Lecture, University of Wisconsin, Madison, November 28, 1949. Received for publication November 3, 1950. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAssessment of Coronary Bypass Surgery and Percutaneous Transluminal Coronary AngioplastyDistress or Illness? a Study of Psychological Symptoms after Myocardial InfarctionThe quiz electrocardiogram: A new diagnostic and research technique for evaluating the relation between emotional stress and ischemic heart diseasePsychological Factors and Heart DiseaseRole of emotional stress preceding coronary occlusionComparison of Fat Intake of American Men and WomenTHE NORMALITY OF AGEINGDISCUSSION ON PALLIATION IN CANCER†Discussion on Palliation in CancerA psychomedical survey of a private outpatient clinic in a university hospitalIATROGENIC HEART DISEASE*HARRY B. WEINBERG, M.D., F.A.C.P. 1 December 1951Volume 35, Issue 6Page: 1291-1305KeywordsBacteriaBrainHeartLesionsNerves ePublished: 1 December 2008 Issue Published: 1 December 1951 PDF downloadLoading ...
Abstract 12625: Mechanical Shear Stress Restores Mitochondrial Cytoarchitecture in Human Endothelial Cells Exposed to Angiotensin II by Modulating Activity of the Fission-Inducing Protein Dynamin Related Protein 1
Authors: Matthew J Durand, David D Gutterman
Journal: Circulation (2014)

Background: The mitochondria exist in a state of balance between fission (fragmentation) and fusion (joining of mitochondrial segments). Disease is characterized by excessive fission, leading to an overproduction of mitochondrial reactive oxygen species (ROS) which mediate pathological changes in vascular endothelium. Dynamin-related protein-1 (DRP-1) is the primary mediator of mitochondrial fission. The therapeutic benefit of exercise is largely due to increased endothelial shear; however the effects of shear stress on DRP-1 expression and mitochondrial structure are unknown. Hypothesis: Shear stress reduces mitochondrial fission in cultured human umbilical vein endothelial cells (HUVECs) exposed to the fission-inducing stimulus angiotensin II (ANG II) by reducing DRP-1 expression and activity. Methods: HUVECs were treated with MitoRFP for 24 hours to fluorescently label the mitochondria, then were exposed to ANG II (10 pM; 4 hours), fixed, and 25 random cells/group were imaged with a confocal microscope. Separate groups of cells were sheared (15 dyn/cm2; 24 hours) immediately following ANG II exposure using the Ibidi Pump System. To quantify mitochondrial fission, images were converted to binary color and ImageJ was used to count non-contiguous mitochondrial fragments. This value was divided by the number of pixels in the mitochondrial network and multiplied by 1000 to yield a Mitochondrial Fragmentation Index (MFI). Total DRP-1 expression and phosphorylation of the S616 activator and S637 suppressor sites were analyzed by Western blot. Results: ANG II increased MFI (1.13±0.25 vs. 0.75±0.06), DRP-1 expression (+48%) and phosphorylation of the S616 activator site (+141%; p&lt;0.05 for all) compared to static controls. Conversely, ANG II-treated cells sheared for 24 hours showed reduced mitochondrial fission (MFI = 0.50 vs. 0.75±0.06), DRP-1 expression (-24%) and phosphorylation at S616 (-11%) compared to control. ANG II treated cells exposed to shear also showed a robust increase (+528%) in phosphorylation of the S637 suppressor site of DRP-1. Conclusions: High shear stress restores mitochondrial network integrity in HUVECs exposed to ANG II, suggesting exercise may promote vascular health by modulating mitochondrial fission.
Changing Clinicians’ Behavior
Authors: Manisha Juthani-Mehta
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Abstract 15514: Activation of Serine Exoprotease Dipeptidyl Peptidase-4 Impairs Coronary Angiogenesis by Degradation of Cardiac SDF1alfa Leading to Maladaptive Cardiac Remodeling in Diabetes.
Authors: Toshimasa Shigeta, Yasuko K Bando, Akio Monji, Xianwu Cheng, Morihiko Aoyama, Toko Mitsui, Akihiro Hirashiki, Toyoaki Murohara
Journal: Circulation (2011)

RATIONALE Dipeptidyl peptidase-4 (DPP4/CD26) is a exoprotease that degradates chemokines including SDF-1α. DPP4 inhibition has been demonstrated to improve mortality and cardiac remodeling after my...
Forecast for US Uninsured Remains Gloomy
Authors: Mike Mitka
Journal: JAMA (2004)

man fibroblasts and T24 human bladder carcinoma cells following exposure to zebularine. They found that when exposed to the drug, four genes were expressed at higher levels in the normal cells compared with 35 genes in the cancer cells. “So zebularine does in fact seem to show some level of selectivity in the sense that it preferentially activates genes in cancer cells relative to normal cells,” said Jones. Furthermore, many of the genes that were upregulated in the cancer cells were tumorassociated antigens, which might make the cancer cells susceptible to targeting by the immune system, he noted. While it remains to be seen how zebularine’s effects will play out in patients, Jones was optimistic about the therapeutic potential of targeting hypermethylation. “Even if you’re successful in activating a subset of these genes in a given cancer cell, you may still have some therapeutic benefit,” said Jones. “It’s for that reason that we’re excited about the possibility of these therapies really making it into the clinic.” Only time and rigorous clinical testing will show whether demethylation is a viable therapeutic avenue in cancer.