tbuckley/cabot-search huggingface dataset:
Aprotinin Preserves Cellular Junctions and Reduces Myocardial Edema After Regional Ischemia and Cardioplegic Arrest
Authors: Tanveer A. Khan, Cesario Bianchi, Eugenio Araujo, Pierre Voisine, Shu-Hua Xu, Jun Feng, Jian Li, Frank W. Sellke
Journal: Circulation (2005)

Background— Cardiac surgery with cardiopulmonary bypass (CPB) and cardioplegic arrest has been associated with myocardial edema attributable to vascular permeability, which is regulated in part by thrombin-induced alterations in cellular junctions. Aprotinin has been demonstrated to prevent activation of the thrombin protease-activated receptor, and we hypothesized that aprotinin preserves myocardial cellular junctions and prevents myocardial edema in a porcine model of regional ischemia and cardioplegic arrest. Methods and Results— Fourteen pigs were subjected to 30 minutes of regional ischemia, followed by 60 minutes of CPB, with 45 minutes of crystalloid cardioplegia, then 90 minutes of post-CPB reperfusion. The treatment group (n=7) was administered aprotinin (40 000 kallikrein inhibitor units [KIU]/kg loading dose, 40 000 KIU/kg pump prime, and 10 000 KIU/kg per hour continuous infusion). Control animals (n=7) received normal saline. Myocardial vascular endothelial (VE)-cadherin, β-catenin and γ-catenin, and associated mitogen-activated protein kinase (MAPK) pathways were assessed by immunoblot and immunoprecipitation. Histologic analysis of the cellular junctions was done by immunofluorescence. Myocardial tissue water content was measured. VE-cadherin, β-catenin, and γ-catenin levels were significantly greater in the aprotinin group (all P &lt;0.05). Immunfluorescence confirmed that aprotinin prevented loss of coronary endothelial adherens junction continuity. Aprotinin reduced tyrosine phosphorylation in myocardial tissue sections. Phospho-p38 activity was ≈30% lower in the aprotinin group ( P =0.007). The aprotinin group demonstrated decreased myocardial tissue water content (81.2±0.5% versus 83.5±0.3%; P =0.01) and reduced intravenous fluid requirements (2.9±0.2 L versus 4.0±0.4 L; P =0.03). Conclusions— Aprotinin preserves adherens junctions after regional ischemia and cardioplegic arrest through a mechanism potentially involving the p38 MAPK pathway, resulting in preservation of the VE barrier and reduced myocardial tissue edema.
Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies
Authors: Diana W. Bianchi, Darya Chudova, Amy J. Sehnert, Sucheta Bhatt, Kathryn Murray, Tracy L. Prosen, Judy E. Garber, Louise Wilkins-Haug, Neeta L. Vora, Stephen Warsof, James Goldberg, Tina Ziainia, Meredith Halks-Miller
Journal: JAMA (2015)

<h3>Importance</h3> Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care. <h3>Objective</h3> To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies. <h3>Design, Setting, and Participants</h3> Case series identified from 125 426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation. <h3>Exposures</h3> NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y). <h3>Main Outcomes and Measures</h3> Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort. <h3>Results</h3> From a cohort of 125 426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident. <h3>Conclusions and Relevance</h3> In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.
Abstract 4039: Continuous Positive Airway Pressure From Out-of-hospital Setting To Cardiac Intensive Care Unit In Acute Heart Failure: A Multicenter Randomized Study
Authors: Laurent Ducros, Damien Logeart, Jean-Philippe Collet, Eric Vicaut, Patrick Henry, Gilles Montalescot, Patrick Plaisance, Didier Payen
Journal: Circulation (2008)

Purpose : Recent guidelines for acute heart failure (AHF) support the use of continuous positive airway pressure (CPAP) although its early use upstream intensive care unit (ICU) requires more evidence. The aim of this multicenter randomized study was to compare the effects of standard treatment of cardiogenic acute pulmonary oedema to CPAP when started in out-hospital setting and continued in ICU. Methods : AHF presenters with respiratory distress were enrolled by 10 emergency medical mobile services. Inclusion criteria were respiratory rate &gt;25, pulse oxygen saturation &lt;90% in air and Killip score ≥3. Each eligible patient was randomly assigned at home to receive standard treatment (ST) including oxygen, nitroglycerin, diuretic and inotropic drug as appropriate, or a combination of ST and CPAP (7.5–10 cmH 2 O). The primary end point, a composite of death, presence of intubation criteria or persistence at the second hour after inclusion, reappearance of the inclusion criteria or circulatory failure, was assessed within the first 48 hours after inclusion. The analysis was done by intention to treat. Results : 207 patients (80 ± 10 years, 59% females) were enrolled. Baseline characteristics and standard treatment were balanced between the 2 groups. The mean duration of CPAP was 1 hour prior to admission and 2 hours after admission. The primary end-point was observed in 36% of patients in ST and 21.5% in ST+CPAP (p=0.028). There was no difference in the rate of death (5% vs. 3.75% for ST and ST+CPAP, respectively), although the use of CPAP was associated with a significant reduction of persistent respiratory distress (26% vs 12%, p&lt;0.01), of haemodynamic failure (6% vs 1%, p 0.05) and in the rate of intubation criteria (14% vs 4%, p=0.01). Clinical benefits of CPAP were found irrespective of left ventricular dysfunction and of normo/hypercapnia measured at inclusion. Conclusion : the use of CPAP upstream ICU and continued after admission improves improves early clinical outcome of patients presenting with cardiogenic acute pulmonary oedema.
Abstract 18399: In vivo targeted Molecular Imaging for Activated Platelets by MRI using USPIO-Fucoidan in Rat Abdominal Aortic Aneuryms
Authors: Michimasa Suzuki, Jean-Michel Serfaty, Laure Bachelet, Liliane Louedec, Frederic Chaubet, Jean-Baptiste Michel, Didier Letourneur
Journal: Circulation (2010)
Abstract 1850: Clinical Characteristics And Early Mortality Of Patients Undergoing Coronary Artery Bypass Grafting Compared To Percutaneous Coronary Intervention - Insights From Two Large Multi-centre Australian Registries.
Authors: Bryan P Yan, David J Clark, Brian Buxton, Andrew E Ajani, Julian A Smith, Stephen J Duffy, Gil Shardy, Omar Farouque, Michael Yii, Cheng-Hon Yap, Nick Adrianopoulos, Angela Brennan, Chris Reid
Journal: Circulation (2007)

Background: The clinical characteristics, risk profile, and mortality of patients undergoing coronary artery bypass graft (CABG) compared to percutaneous coronary intervention (PCI) are thought to ...
The Juxtaposition of Population Science and Individual Treatment Recommendations for Intermittent Androgen Deprivation Therapy
Authors: Christopher J. Sweeney
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
The Cancer Genome Atlas Analysis Predicts MicroRNA for Targeting Cancer Growth and Vascularization in Glioblastoma
Authors: Hon-Kit Andus Wong, Rachid El Fatimy, Courtney Onodera, Zhiyun Wei, Ming Yi, Athul Mohan, Sindhuja Gowrisankaran, Priya Karmali, Eric Marcusson, Hiroaki Wakimoto, Robert Stephens, Erik J Uhlmann, Jun S Song, Bakhos Tannous, Anna M Krichevsky
Journal: Molecular Therapy (2015)

Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two "risky" miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two miRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1α and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of uncomplexed antagomirs in orthotopic glioma. Using in silico analysis of The Cancer Genome Atlas (TCGA), we identified microRNAs associated with glioblastoma (GBM) survival, and predicted their functions in glioma growth and progression. Inhibition of two "risky" miRNAs, miR-148a and miR-31, in orthotopic xenograft GBM mouse models suppressed tumor growth and thereby prolonged animal survival. Intracranial tumors treated with uncomplexed miR-148a and miR-31 antagomirs exhibited reduced proliferation, stem cell depletion, and normalized tumor vasculature. Growth-promoting functions of these two miRNAs were, in part, mediated by the common target, the factor inhibiting hypoxia-inducible factor 1 (FIH1), and the downstream pathways involving hypoxia-inducible factor HIF1α and Notch signaling. Therefore, miR-31 and miR-148a regulate glioma growth by maintaining tumor stem cells and their niche, and providing the tumor a way to activate angiogenesis even in a normoxic environment. This is the first study that demonstrates intratumoral uptake and growth-inhibiting effects of uncomplexed antagomirs in orthotopic glioma.
The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential
Authors: Stephen H.K. Wong, David L. Goode, Masayuki Iwasaki, Michael C. Wei, Hsu-Ping Kuo, Li Zhu, Dominik Schneidawind, Jesus Duque-Afonso, Ziming Weng, Michael L. Cleary
Journal: Cancer Cell (2015)
Large gene deletions in the mutation cluster region of the Apc gene in the ileal and colonic tumors of mice deficient in two intracellular Se-dependent glutathione peroxidases
Authors: Lixin Yang, R. Steven Esworthy, James H. Doroshow, Fong-Fong Chu
Journal: Cancer Research (2005)

1981   The ubiquitous glutathione peroxidase, Gpx1, and epithelium-specific Gpx2 are highly efficient in reducing H 2 O 2  and fatty acid hydroperoxides. Hydroperoxides are known DNA damaging agents and mutagens, and Gpx1/2-KO mice with combined disruption of both  Gpx1  and  Gpx2  genes are highly susceptible to cancer in the ileum and the colon. Since most of these tumors have nuclear accumulation of β-catenin, and mutations of the adenomatous polyposis coli ( Apc ) gene occur frequently in colorectal cancers, we investigated whether the  Apc  gene is mutated in these tumors, and whether the type of mutations matches the oxidative damage. We used snap-frozen tissues for this analysis to avoid artifacts created by formalin fixation. First, we used random hexomers to generate cDNA from total RNA isolated from intestinal tissues, and then used a set of nested PCR primers to detect mutations in mouse  Apc  gene. These PCR primers were based on human  APC  mutation cluster region as described by Traverso et al. (N. Eng. J. Med. 346:311-320, 2004). In order to detect  50 PCR reactions were performed on each sample. Protein truncation mutations were detected by  in vitro  transcription and translation (TnT) assay of the PCR product after incorporation of biotinylated leucine, resolved by SDS-PAGE, transferred to nitrocellulose, and visualized by immunoluminescent assay. Those PCR products generating truncated proteins were analyzed after gel purification from the wildtype PCR product for DNA sequence. We detected truncation mutations in seven tumors isolated from Gpx1/2-KO mice, but no mutations in six ileum samples isolated from control mice with at least one wildtype  Gpx1  or  Gpx2  allele. To determine whether the truncation mutations occur before tumorigenesis, we have analyzed the ilea from three ≥6-month-old Gpx1/2-KO mice without gross tumors, and detected Apc truncation in all three ileal samples. Since only the ileum and the colon, but not the jejunum, are often inflamed in Gpx1/2-KO mice, we have also examined Apc mutations in the jejunum from five older Gpx1/2-KO mice and did not detect any mutations. DNA sequence analysis of the DNA template for TnT assay has revealed that all protein truncation mutations are derived from large (473-840 bp) gene deletions. The sequences flanking the deletion site have microhomology, suggesting that this deletion results from non-homologous DNA recombination. Because hydroperoxides can cause double-stranded DNA breakage, and the  Apc  gene deletion is only detected in the ileum and colon, which are prone to inflammation, we conclude that Gpx prevents inflammation, which produces oxidative species including hydroperoxides causing DNA damage and breakage, and drives tumorigenesis.
RTS,S/AS01E Vaccine against Malaria
Authors: Roly D Gosling, Daniel Chandramohan
Journal: New England Journal of Medicine (2009)

To the Editor: The results of the trial reported by Bejon et al. (Dec.11 issue), 1 in which the malaria vaccine RTS,S/AS01E was administered to children in Kilifi, Kenya, and Korogwe, Tanzania, are impressive.However, there are methodologic issues in the measurement of protective efficacy in sites where the transmission of malaria is falling.In such areas, transmission becomes overdispersed, and measuring protective efficacy against malaria over short periods may be inappropriate. 2For example, the high protective efficacy of intermittent preventive treatment for malaria in infants that was observed in the first clinical trial in Tanzania was probably exaggerated by a fall in transmission during the trial. 3Administration of the RTS,S vaccine in adults was shown to give short-lived protection, 4 and in the study by Bejon et al., 1 the incidence of malaria was highest in the placebo group between 3 and 5 months after vaccination.This combination of decreasing transmission and protection over time could lead to an overestimate of efficacy.Reassuringly, the high protective efficacy was seen in both sites; however, the study was small, the risk of malaria was highly variable, and transmission was falling.Similarly, the SPf66 vaccine showed high protective efficacy in low-transmission 5 but not high-transmission settings.
Assessment of cardiac involvement in patients with sarcoidosis
Authors: Vasileios Kouranos, Aggeliki Rapti, Elias Gialafos, Konstantina Aggeli, Maria Ntouskou, Anastasios Kallianos, Ourania Anagnostopoulou, George Tzelepis
Journal: European Respiratory Journal (2011)

Background: Cardiac involvement remains an important prognostic factor in patients with sarcoidosis. However, early diagnosis of cardiac sarcoidosis has been difficult because the clinical manifestations are not specific and the sensitivity and specificity of the diagnostic modalities are limited.

Methods: Patients with biopsy proven sarcoidosis were prospectively recruited from the outpatient clinic of sarcoidosis and underwent a full cardiopulmonary monitoring including pulmonary function tests, a 12-lead electrocardiography, echocardiography, a 24-hour ambulatory ECG and cardiac magnetic resonance imaging (MRI) when appropriate. Cardiac involvement was assessed based on known established Japanese Ministry of Health (JMH) criteria and on modified criteria using MRI as a major criterion for cardiac sarcoidosis. All consecutive patients were followed for 5 years for major adverse events.

Results: Seventy patients (43 female) were enrolled with median age 49.96±12.83 years old and disease duration 4.44±5.27 years. Cardiac involvement was identified with the modified criteria in 27 patients (38.5%) while 10 (14.3%) patients were found based on the JMH criteria, showing a more than two-fold higher rate for the MRI group (p=0.005). On follow-up, 9 patients had adverse events including 5 cardiac deaths. All patients with cardiac cause of death had cardiac sarcoidosis based on the modified criteria.

Conclusion: Evaluation of myocardial involvement in sarcoidosis with the use of MRI as a major criterion appears to be more sensitive than current consensus criteria and associated with future adverse events including cardiac death. Cardiac MRI evaluation may be of great importance in the early diagnosis of cardiac sarcoidosis.
Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity
Authors: Phetcharat Chen, Christina Park, Eltayeb Karrar, Chaoyung Wang, James Liao
Journal: Circulation (2014)

Background: The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown. Methods and Result: To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2 adipoQ-/- ) and overexpression (CA-ROCK adipoQ+/+ ) of ROCK2 in mice. Compared to control mice, CA-ROCK adipoQ+/+ mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK adipoQ+/+ mice showed that UCP1 was upregulated. Furthermore, CA-ROCK adipoQ+/+ mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2 adipoQ-/- mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2 adipoQ-/- mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2 adipoQ-/- mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2 adipoQ-/- mice. Thermal imaging revealed that ROCK2 adipoQ-/- mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK adipoQ+/+ mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates. Conclusions: ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.
Clinical Impact Of The Simultaneous Detection Of Anti-Erythocytic Autoantibodies In Alloimmunization
Authors: Maria C Tenorio Nuñez, Gemma Moreno Jimenez, Manuel Hernandez Jodra, Lorena Abalo, Juan Manuel Alonso, Javier Garcia Lledo, Jose Valentin Garcia Gutierrez, Carlos Montalban, Concepcion Zamora De Pedro, Francisco Javier Lopez Jimenez
Journal: Blood (2013)
Phase II clinical study on stent therapy for unresectable malignant colorectal stenosis (JIVROSG-0206)
Authors: Y. Inaba, Y. Arai, H. Yamaura, Y. Sato, M. Najima, H. Saito, T. Aramaki, M. Sato, T. Kumada, Y. Takeuchi
Journal: Journal of Clinical Oncology (2008)

9641 Background: A phase II clinical study on stent therapy for unresectable malignant colorectal stenosis was conducted to ascertain clinical efficacy, safety and procedural feasibility. Methods: Inclusion criteria were as follows: unresectable stenosis of the rectum or sigmoid colon with large bowel obstruction; no apparent stenosis of the oral side of the gastrointestinal tract; no bleeding requiring a procedure; ECOG PS ≤3; and maintained major organ function. The treatment protocol was to place an uncovered metal stent through the anus in a stenotic portion under X-ray fluoroscopic guidance. The patient was followed for 4 weeks after therapy, and the degree of improvement in subjective symptoms lasting ≥2 weeks was assessed in significantly effective (SE), moderately effective (ME) or ineffective (IE). Rate of clinical efficacy was defined as the proportion of SE and ME cases. Adverse reactions were assessed by NCI-CTC (version 2.0). Procedural feasibility was assessed based on the rate of treatment protocol completion. Results: A total of 33 patients (13 men and 20 women, PS 1, 2, 3 in 17, 7, 9 patients) were enrolled and all satisfied the inclusion criteria. Mean patient age was 60 years (range, 34–84 years). Rate of treatment completion was 97.0% (32/33), and no procedural complications were encountered. Therapy was SE in 15 patients, ME in 12, IE in 4 and unassessable in 1, yielding a clinical efficacy rate of 81.8% (27/33). Among treatment completed cases, death (n=3), stent removal due to anal pain (n=1) and occlusion at another location (n=1) were noted during the observation period. Among clinically effective cases, recurrence was not seen. Adverse reactions included grade 2–3 diarrhea (n=12, 33.3%), pain (n=5, 15.2%), bleeding (n=1, 3.0%) and dysuria (n=1, 3.0%), but no grade 4 adverse reactions or treatment-related deaths were seen. Conclusions: Stent therapy for unresectable malignant colorectal stenosis is highly practical, safe and effective. No significant financial relationships to disclose.