tbuckley/cabot-search huggingface dataset:
Abstract 216: Angiogenic Factor AGGF1 Promotes Therapeutic Angiogenesis in a Mouse Limb Ischemia Model for Peripheral Arterial Disease
Authors: Qing Wang, Qiulun Lu, Xin Tu, Qing Wang
Journal: Circulation Research (2012)

Introduction: Peripheral arterial disease (PAD) is caused by atherosclerosis. PAD is a common disease that affects 12% of the adult population and causes significant morbidity and mortality. The existing treatments for PAD, including pharmacological, interventional and surgical procedures, are not sufficient and many patients are opt for limb amputation. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. Hypothesis: In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD. Methods and Results: We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 ( AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice of hindlimb ischemia with injection of the empty vector (control group). The blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration. Four weeks after the injection of DNA, the blood flow was approximately 2.19 fold higher in AGGF1 group than that in control. With the increased blood flow in the AGGF1 group, ambulatory impairement were inhibited compared with the control group. Increased AGGF1 expression decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. CD31-positive capillary vessel density was significantly higher in AGGF1 -injected limbs than in empty vector-injected limbs. Conclusions: These data establish that plasmid DNA-based gene transfer of AGGF1 into mouse skeletal muscles is efficient in increase the expression levels of AGGF1 mRNA and protein. Increased AGGF1 expression increases blood flow by increasing density of CD31-positive vessels and by decreasing necrosis in muscle tissues. These findings suggest that AGGF1 may be used as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.
Factors Contributing to the Weekend Effect
Authors: Ugo Fedeli, Massimo Gallerani, Roberto Manfredini
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
A Personalized Model of COQ2 Nephropathy Rescued by the Wild-Type COQ2 Allele or Dietary Coenzyme Q10 Supplementation
Authors: Jun-yi Zhu, Yulong Fu, Adam Richman, Zhanzheng Zhao, Patricio E. Ray, Zhe Han
Journal: Journal of the American Society of Nephrology (2017)

Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function. Nephrocyte-specific silencing of Coq2, Coq6, and Coq8, which are genes involved in the CoQ10 pathway that have been associated with genetic nephrotic syndrome in humans, induced dramatic adverse changes in these cells. In particular, silencing of Coq2 led to an abnormal localization of slit diaphragms, collapse of lacunar channels, and more dysmorphic mitochondria. In addition, Coq2-deficient nephrocytes showed elevated levels of autophagy and mitophagy, increased levels of reactive oxygen species, and increased sensitivity to oxidative stress. Dietary supplementation with CoQ10 at least partially rescued these defects. Furthermore, expressing the wild-type human COQ2 gene specifically in nephrocytes rescued the defective protein uptake, but expressing the mutant allele derived from a patient with COQ2 nephropathy did not. We conclude that transgenic Drosophila lines carrying mutations in the CoQ10 pathway genes are clinically relevant models with which to explore the pathogenesis of podocyte injury and could serve as a new platform to test novel therapeutic approaches.
TCTAP A-142 Monitoring and Titration of Conventional and Newer Antiplatelet Therapies in Post PCI Patients Using Platelet Function Assay: A Tertiary Care Hospital Experience from Eastern India
Authors: Debdatta Bhattacharyya, Ayan Kar, Sujash Chakraborty, Saiyed Rana
Journal: Journal of the American College of Cardiology (2017)
Exosomal MicroRNA Transfer Into Macrophages Mediates Cellular Postconditioning
Authors: Geoffrey de Couto, Romain Gallet, Linda Cambier, Ervin Jaghatspanyan, Nupur Makkar, James Frederick Dawkins, Benjamin P. Berman, Eduardo Marbán
Journal: Circulation (2017)

Background: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction by distinctive macrophage (Mϕ) polarization. Here we demonstrate that CDC-secreted exosomes (CDC exo ) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning. Methods: Rats and pigs underwent myocardial infarction induced by ischemia/reperfusion before intracoronary infusion of CDC exo , inert fibroblast exosomes (Fb exo ; control), or vehicle. Two days later, infarct size was quantified. Macrophages were isolated from cardiac tissue or bone marrow for downstream analyses. RNA sequencing was used to determine exosome content and alterations in gene expression profiles in Mϕ. Results: Administration of CDC exo but not Fb exo after reperfusion reduces infarct size in rat and pig models of myocardial infarction. Furthermore, CDC exo reduce the number of CD68+ Mϕ within infarcted tissue and modify the polarization state of Mϕ so as to mimic that induced by CDCs. CDC exo are enriched in several miRNAs (including miR-146a, miR-181b, and miR-126) relative to Fb exo . Reverse pathway analysis of whole-transcriptome data from CDC exo -primed Mϕ implicated miR-181b as a significant ( P =1.3x10 −21 ) candidate mediator of CDC-induced Mϕ polarization, and PKCδ (protein kinase C δ) as a downstream target. Otherwise inert Fb exo loaded selectively with miR-181b alter Mϕ phenotype and confer cardioprotective efficacy in a rat model of myocardial infarction. Adoptive transfer of PKCδ-suppressed Mϕ recapitulates cardioprotection. Conclusions: Our data support the hypothesis that exosomal transfer of miR-181b from CDCs into Mϕ reduces PKCδ transcript levels and underlies the cardioprotective effects of CDCs administered after reperfusion.
A Randomized, Placebo-Controlled Trial of Zoledronic Acid in Patients With Hormone-Refractory Metastatic Prostate Carcinoma
Authors: F. Saad, D. M. Gleason, R. Murray, S. Tchekmedyian, P. Venner, L. Lacombe, J. L. Chin, J. J. Vinholes, J. A. Goas, B. Chen
Journal: JNCI Journal of the National Cancer Institute (2002)

Bone metastases are a common cause of morbidity in patients with prostate carcinoma. We studied the effect of a new bisphosphonate, zoledronic acid, which blocks bone destruction, on skeletal complications in prostate cancer patients with bone metastases.Patients with hormone-refractory prostate cancer and a history of bone metastases were randomly assigned to a double-blind treatment regimen of intravenous zoledronic acid at 4 mg (N = 214), zoledronic acid at 8 mg (subsequently reduced to 4 mg; 8/4) (N = 221), or placebo (N = 208) every 3 weeks for 15 months. Proportions of patients with skeletal-related events, time to the first skeletal-related event, skeletal morbidity rate, pain and analgesic scores, disease progression, and safety were assessed. All statistical tests were two-sided.Approximately 38% of patients who received zoledronic acid at 4 mg, 28% who received zoledronic acid at 8/4 mg, and 31% who received placebo completed the study. A greater proportion of patients who received placebo had skeletal-related events than those who received zoledronic acid at 4 mg (44.2% versus 33.2%; difference = -11.0%, 95% confidence interval [CI] = -20.3% to -1.8%; P =.021) or those who received zoledronic acid at 8/4 mg (38.5%; difference versus placebo = -5.8%, 95% CI = -15.1% to 3.6%; P =.222). Median time to first skeletal-related event was 321 days for patients who received placebo, was not reached for patients who received zoledronic acid at 4 mg (P =.011 versus placebo), and was 363 days for those who received zoledronic acid at 8/4 mg (P =.491 versus placebo). Compared with urinary markers in patients who received placebo, urinary markers of bone resorption were statistically significantly decreased in patients who received zoledronic acid at either dose (P =.001). Pain and analgesic scores increased more in patients who received placebo than in patients who received zoledronic acid, but there were no differences in disease progression, performance status, or quality-of-life scores among the groups. Zoledronic acid at 4 mg given as a 15-minute infusion was well tolerated, but the 8-mg dose was associated with renal function deterioration.Zoledronic acid at 4 mg reduced skeletal-related events in prostate cancer patients with bone metastases.
Gemtuzumab ozogamicin for treatment of relapsing/refractory acute myelogenous leukemia (AML)
Authors: D. C. Case, M. A. Boyd, J. A. Hedlund, T. J. Ervin
Journal: Journal of Clinical Oncology (2006)

16531 Background: Gemtuzumab ozogamicin is a calicheamicin-conjugated anti-CD 33 monoclonal antibody studied and utilized in relapsed and refractory acute myelogenous leukemia. Methods: At our center we treated a series of refractory patients (&lt;60 years old) and relapsed patients (&gt;60 years old) with gemtuzumab ozogamicin over a 3 year period. We treated 20 patients: 14 males and 6 females with an age range of 21 to 77 years (median 64 years). Seven patients were refractory to multiple regimens (&lt;60 years old) and 13 were relapsing from initial therapy (&gt;60 years old). Cytogenetic analysis revealed 60% were intermediate-risk and 40% were poor-risk. The goal of therapy was complete remission (≤ 5% leukemia blast cells in the marrow. ≥ 9 g/dl hemoglobin, ≥1500/ul absolute neutrophil count, and platelet count ≥100,000/ul). Patients received gemtuzumab ozogamicin 9 mg/m 2 I.V. days 1 and 5. All patients received at least one dose. Patients achieving complete remission were eligible to receive monthly doses of gemtuzumab ozogamicin after complete remission was obtained. Results: Of the 7 refractory patients (&lt;60 years old), there were no complete remissions. Of 13 relapsing patients (&gt;60 years old) there were 2 complete remissions. One patient was 64 and the other 67 years old. Both remissions lasted 2 months. All patients were treated in the hospital. Chills/fever with treatment occurred in 40% of patients. Fever/neutropenia was universal. Thirty percent had elevation of liver function tests. Conclusions: Gemtuzumab ozogamicin as a single agent is capable of producing complete remission in a small number of relapsing patients &gt;60 years old. Remissions are short. No significant financial relationships to disclose.
Comorbidity from Solid Tumor or Hematologic Malignancy Prior to Allogeneic Hematopoietic Cell Transplantation (HCT) May Both Increase Non-Relapse Mortality
Authors: Christopher Robert D'Angelo, Brianna Novitsky, Sang Mee Lee, Lucy A Godley, Justin Kline, Richard A. Larson, Hongtao Liu, Olatoyosi Odenike, Wendy Stock, Michael R. Bishop, Andrew Artz
Journal: Blood (2016)
Generation of Functional Regulatory T Cells By FOXP3 Gene Transfer into CD4 T Cells from Scurfy Mice and IPEX Patients
Authors: Marianne Delville, Emmanuelle Six, Florence Bellier, Nelly Sigrist, David Zemmour, Marie-André Bessard, Fabienne Mazerolles, David Gross, Axel Schambach, Frederic Rieux-Laucat, Christoph Benoist, Isabelle Andre-Schmutz, Marina Cavazzana
Journal: Blood (2016)
Feasibility of whole genome association study to find SNPs predictive of colorectal cancer outcome
Authors: Axel Walther, Enric Domingo, Elaine Johnstone, Xiao-He Chen, David Mesher, David Kerr, Ian Tomlinson
Journal: Clinical Cancer Research (2008)

B29  Purpose  Genome wide association studies (GWAS) have successfully identified low-penetrance loci associated with colorectal (CRC), breast, lung, and prostate cancer. Here we describe the use of high-density SNP arrays to perform a GWAS aimed at identifying candidate germline loci which can predict outcome and might influence success of chemotherapy in stage 2 and 3 CRC.  Methods  We typed 318,237 tagSNPs on Illumina HumanHap300duo arrays (Illumina Inc, San Diego, CA) in 933 patients enrolled in the Victor trial of AJCC stage 2 or 3 CRC treated with surgery and chemo- or radiotherapy as appropriate and randomized to rofecoxib or placebo. Two patients were excluded from the analysis due to call rates  99.97% concordance between repeats) and reliable (median call rate 99.95%). Testing each model with a q-q plot did not reveal any substructure in the population tested, with good alignment of observed and expected p-value distribution.  Of the 309200 autosomal SNPs, 180 failed and 56 were non-informative (monomorphic). 565 SNPs had p
Managing Patients With Intrauterine Devices
Journal: JAMA (1987)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-Resistant Prostate Cancer
Authors: Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floch, Sheida Hayati, Yanping Sun, Clémentine Le Magnen, Daniel Chester, Elahe A. Mostaghel, Andrea Califano, Mark A. Rubin, Michael M. Shen, Cory Abate-Shen
Journal: Cancer Discovery (2017)

Current treatments for castration-resistant prostate cancer (CRPC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here, we provide novel insights into treatment response for the antiandrogen abiraterone by analyses of a genetically engineered mouse (GEM) model with combined inactivation of
Association Between Fetal Congenital Heart Defects and Maternal Risk of Hypertensive Disorders of Pregnancy in the Same Pregnancy and Across Pregnancies
Authors: Heather Allison Boyd, Saima Basit, Ida Behrens, Elisabeth Leirgul, Henning Bundgaard, Jan Wohlfahrt, Mads Melbye, Nina Øyen
Journal: Circulation (2017)

Both pregnant women carrying fetuses with heart defects and women with hypertensive disorders of pregnancy often exhibit angiogenic imbalances, suggesting that the same mechanisms are involved in the pathogenesis of the former and the pathophysiology of the latter. We conducted a register-based cohort study to determine whether offspring congenital heart defects are associated with an increased risk of hypertensive disorders of pregnancy and whether the mechanisms driving any association are primarily maternal or fetal.Among singleton pregnancies without chromosomal abnormalities lasting ≥20 weeks in Denmark from 1978 to 2011 (n= 1 972 857), we identified pregnancies complicated by offspring congenital heart defects or early preterm preeclampsia, late preterm preeclampsia, term preeclampsia, and gestational hypertension. We used polytomous logistic regression to estimate odds ratios (ORs) for associations between offspring congenital heart defects and maternal hypertensive disorders of pregnancy overall and for specific heart defects.Offspring congenital heart defects were strongly associated with early preterm preeclampsia (OR, 7.00; 95% confidence interval [CI], 6.11-8.03) and late preterm preeclampsia (OR, 2.82; 95% CI, 2.38-3.34) in the same pregnancy and weakly associated with term preeclampsia (OR, 1.16; 95% CI, 1.06-1.27), but they were not associated with gestational hypertension (OR, 1.07; 95% CI, 0.92-1.25). Association strengths were consistent across heart defect types. Offspring congenital heart defects in a previous pregnancy were also strongly associated with preterm preeclampsia in subsequent pregnancies (early preterm preeclampsia: OR, 2.37; 95% CI, 1.68-3.34; late preterm preeclampsia: OR, 2.04; 95% CI, 1.52-2.75) but were only modestly associated with term preeclampsia and not associated with gestational hypertension. Similarly, preterm preeclampsia in a previous pregnancy, but not term preeclampsia or gestational hypertension, was associated with offspring congenital heart defects in later pregnancies (early preterm preeclampsia: OR, 7.91; 95% CI, 6.06-10.3; late preterm preeclampsia: OR, 2.83; 95% CI, 2.11-3.79; term preeclampsia: OR, 0.98; 95% CI, 0.88-1.10; gestational hypertension: OR, 1.13; 95% CI, 0.92-1.38).Linked pathophysiological mechanisms may be involved in some congenital heart defects and preterm preeclampsia. The strong associations across pregnancies support a predominantly maternal origin of effect.
Reevaluating Eligibility Criteria — Balancing Patient Protection and Participation in Oncology Trials
Authors: Julia A. Beaver, Gwynn Ison, Richard Pazdur
Journal: New England Journal of Medicine (2017)

Specific patient populations are often excluded from oncology trials without clear reasons, which renders results less clearly applicable to all patients. A more logical approach would be to study safety in a broad population and modify criteria as knowledge emerges.
Abstract 275: Berbamine Confers Cardioprotection Against Ischemia-Reperfusion Injury by Attenuating Ca <sup>2+</sup> Overload and Preventing Calpain Activation Through Protection of Mitochondria
Authors: Huang-Tian Yang, Cai-Mei Zhang, Ling Gao, Yan-Jun Zheng
Journal: Circulation Research (2012)

Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis. However, the reperfusion can also lead to additional damage. Ischemic preconditioning is a powerful way to initiate intrinsic adaptive responses protecting the heart from subsequent severe ischemia/reperfusion (I/R) injury that can be mimicked by pharmacological preconditioning. However, so far few agents are clinically available for patients with ischemia heart disease. There is a growing interest in exploring effective cardioprotective components extracted from Traditional Chinese Medicine because they have been practiced for thousands of years, providing a vast source of pharmaceutical materials. Berbamine, a kind of bisbenzylisochinoline alkaloids derived from the roots, barks and stems of Barberry , was reported to protect myocardium from ischemia/reperfusion (I/R) injury, but the underlying mechanisms are largely unknown. Here, we investigated whether berbamine confers cardioprotection via preventing calpain activation and protein degradation. We identified here that berbamine pretreatment from 10 to 100 nM concentration-dependently improved post-ischemic myocardial function in isolated Sprague-Dawley rat hearts subjected to 30 min ischemia/45 min reperfusion. Similar protection was confirmed in isolated cardiomyocytes characterized by the attenuation of I/R-induced intracellular Ca 2+ overloading and the depression of Ca 2+ transients and cell shortening. Moreover, I/R-induced decreases of Ca 2+ handling proteins were significantly attenuated by berbamine. Further analysis showed that those protections were related to the suppression of I/R-induced calpain activity and the protection of mitochondrial function by berbamine. These findings suggest that berbamine confers cardioprotections against I/R injury by attenuating Ca 2+ overloading and preventing calpain activation; and the protection of mitochondria is critical for the cardioprotection.
Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study
Authors: Belén Gutiérrez-Gutiérrez, Elena Salamanca, Marina de Cueto, Po-Ren Hsueh, Pierluigi Viale, José Ramón Paño-Pardo, Mario Venditti, Mario Tumbarello, George Daikos, Rafael Cantón, Yohei Doi, Felipe Francisco Tuon, Ilias Karaiskos, Elena Pérez-Nadales, Mitchell J Schwaber, Özlem Kurt Azap, Maria Souli, Emmanuel Roilides, Spyros Pournaras, Murat Akova, Federico Pérez, Joaquín Bermejo, Antonio Oliver, Manel Almela, Warren Lowman, Benito Almirante, Robert A Bonomo, Yehuda Carmeli, David L Paterson, Alvaro Pascual, Jesús Rodríguez-Baño, M D del Toro, J Gálvez, M Falcone, A Russo, H Giamarellou, E M Trecarichi, A R Losito, E García-Vázquez, A Hernández, J Gómez, G Bou, E Iosifidis, N Prim, F Navarro, B Mirelis, A Skiada, J Origüen, R San Juan, M Fernández-Ruiz, N Larrosa, M Puig-Asensio, J M Cisneros, J Molina, V González, V Rucci, E Ruiz de Gopegui, C I Marinescu, L Martínez-Martínez, M C Fariñas, M E Cano, M Gozalo, M Mora-Rillo, C Navarro-San Francisco, C Peña, S Gómez-Zorrilla, F Tubau, A Tsakris, O Zarkotou, A Antoniadou, G Poulakou, J Pitout, D Virmani, J Torre-Cisneros, J Guzmán-Puche, Ö Helvaci, A O Sahin, V Pintado, P Ruiz, M Bartoletti, M Giannella, E Tacconelli, F Riemenschneider, E Calbo, C Badia, M Xercavins, O Gasch, D Fontanals, E Jové
Journal: The Lancet Infectious Diseases (2017)
Efficacy of Catheter Ablation for Nonparoxysmal Atrial Fibrillation
Authors: Guy Amit, Jonathan Nyong, Carlos A. Morillo
Journal: JAMA Cardiology (2017)

Is catheter ablation better than antiarrhythmic drugs for the prevention of nonparoxysmal atrial fibrillation?Radiofrequency catheter ablation was found to be superior to antiarrhythmic drugs in preventing recurrences of nonparoxysmal atrial fibrillation and reducing hospital admissions.