tbuckley/cabot-search huggingface dataset:
Abstract 11977: Tranilast, Transient Receptor Potential Vanilloid 2 Antagonist, Ameliorates End-Stage Heart Failure of Mice With Dilated Cardiomyopathy
Authors: Yuko Iwata, Kazuo Komamura
Journal: Circulation (2014)

Introduction: Abnormal intracellular Ca2+ handling seems to be involved in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). We have found up-regulation of the expression of transient receptor potential vanilloid 2 (TRPV2), a calcium-permeable cation channel, in the sarcolemma of myocardium of animal and human DCM. Hypothesis: We hypothesized an orally active TRPV2 antagonist, tranilast, ameliorated heart failure symptoms of DCM mice. Methods: We used 4C30 mice (created by National Institute of Biomedical Innovation, Japan), which has abnormal myocardial calcium handling, as a model of DCM. Sixteen 4C30 mice of 25 weeks old with end-stage heart failure were given no drug (control) or 20 mg/kg/day of carvediol (group C) or 400 mg/kg/day of tranilast (group T) or both of them (group B) for 2 weeks. Results: Blood pressure and heart rate were similar among the 4 groups. Echocardiography demonstrated tranilast improved fractional shortening (in %). Control: 6.2±2.5; Group C: 14.2±5.6, NS; Group T: 16.6±2.3, p&lt;0.05; Group B: 17.2±3.2, p&lt;0.05. Tranilast also improved cardiac hypertrophy measured with heart-to-body weight ratio (HW/BW in mg/g). Control: 12.4±2.5; Group C: 11.5±3.4, NS; Group T: 8.6±0.9, p&lt;0.05; Group B: 5.9±1.1, p&lt;0.01. Sarcolemmal expression of TRPV2 measured with immunostaining in 4C30 mice increased twice as much as syngeneic C57BL/6J. Tranilast, not carvedilol, halved the expression of TRPV2, corresponding to reduction in [Ca2+]i of isolated cardiomyocytes. Consistent with those changes, CaMKII phosphorylation reduced in the 4C30 mice after treatment of tranilast. Conclusions: Tranilast ameliorated heart failure symptoms of 4C30 mice, possibly due to the inhibition of Ca2+ influx through TRPV2.
The prevalence of atrial fibrillation in incident stroke cases and matched population controls in Rochester, Minnesota
Authors: Teresa S.M Tsang, George W Petty, Marion E Barnes, W.Michael O’Fallon, Kent R Bailey, David O Wiebers, JoRean D Sicks, Teresa J.H Christianson, James B Seward, Bernard J Gersh
Journal: Journal of the American College of Cardiology (2003)
Abstract 12590: Usefullness of Early Release Peak of Cardiac Biomarkers for Detection of Myocardial Infarction Related to Coronary Revascularization Procedures. A Cardiac Magnetic Resonance Study
Authors: Rodrigo M Vieira de Melo, Fernando T Oikawa, Leandro M Costa, Paulo C Rezende, Thiago L Scudeler, Cesar H Nomura, Alexandre V Villa, Alexandre C Hueb, Whady Hueb, Roberto Kalil Filho
Journal: Circulation (2014)

Background: The elevation of troponin (TnI) and creatine kinase-MB (CKMB) after coronary revascularization procedures is frequent, but may not be reliable at identifying a definitive procedure-related myocardial injury. Cardiac magnetic resonance (CMR) is the gold standard in the identification of small areas of myocardial necrosis by late gadolinium enhancement (LGE). The presence of a biomarker early release peak might indicate a nonlethal transient cellular myocardial damage and help to discriminate the patients without procedure-related myocardial lesion. Thus, our objective was to evaluate the amount and pattern of release of biomarkers after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) compared with the area of new LGE on CMR. Methods: Patients with indication for coronary revascularization were included. Measurements of high-sensitivity TnI and CK-MB were obtained before and after the procedures, every 6 hours until 48 hours after PCI, and up to 72 hours after CABG. We evaluated the area under the curve (AUC) and peak release of biomarkers and stratified before and 24 hours after the procedure. CMR was performed before and after procedures with quantification of necrosis by LGE. Results: From 150 patients who completed the study, 60 (40%) underwent CABG with cardiopulmonary bypass (CPB), 44 (29.3%) without CPB, and 46 (30.7%) underwent PCI. 130 (86.7%) exhibited release of cardiac biomarkers consistent with myocardial injury, however only 32 (21.3%) had new LGE on CMR. The AUC and peak release of TnI showed a moderate correlation with the mass of new myocardial LGE on CMR (AUC: r = 0.46, P &lt; 0.0001; TnI peak: r = 0.45, P &lt; 0.0001), as well as the AUC and peak release of CKMB (AUC: r = 0.33, P &lt; 0.0001; CK-MB peak: r = 0.35, P &lt;0.0001). Patients without new LGE on CMR had more frequently an early peak release of cardiac biomarkers when compared with those with new LGE: 63 (88.7%) vs. 8 (11.3%), P = 0.004. Conclusion: The elevation of cardiac biomarkers after coronary revascularization procedures had a low diagnostic power for the detection of new myocardial areas of infarction identified by LGE on CMR. The early release of biomarkers may be useful to rule out the diagnosis of peri-procedural myocardial infarction.
Noninvasive Estimation of PA Pressure, Flow, and Resistance With CMR Imaging
Authors: Andrew J. Swift, Smitha Rajaram, Judith Hurdman, Catherine Hill, Christine Davies, Tom W. Sproson, Allison C. Morton, Dave Capener, Charlie Elliot, Robin Condliffe, Jim M. Wild, David G. Kiely
Journal: JACC. Cardiovascular imaging (2013)
Subacute Tissue Response to 3D Graphene Oxide Scaffolds Implanted in the Injured Rat Spinal Cord
Authors: Elisa López‐Dolado, Ankor González‐Mayorga, María Teresa Portolés, María José Feito, María Luisa Ferrer, Francisco del Monte, María Concepción Gutiérrez, María Concepción Serrano
Journal: Advanced Healthcare Materials (2015)

The increasing prevalence and high sanitary costs of lesions affecting the central nervous system (CNS) at the spinal cord are encouraging experts in different fields to explore new avenues for neural repair. In this context, graphene and its derivatives are attracting significant attention, although their toxicity and performance in the CNS in vivo remains unclear. Here, the subacute tissue response to 3D flexible and porous scaffolds composed of partially reduced graphene oxide is investigated when implanted in the injured rat spinal cord. The interest of these structures as potentially useful platforms for CNS regeneration mainly relies on their mechanical compliance with neural tissues, adequate biocompatibility with neural cells in vitro and versatility to carry topographical and biological guidance cues. Early tissue responses are thoroughly investigated locally (spinal cord at C6 level) and in the major organs (i.e., kidney, liver, lung, and spleen). The absence of local and systemic toxic responses, along with the positive signs found at the lesion site (e.g., filler effect, soft interface for no additional scaring, preservation of cell populations at the perilesional area, presence of M2 macrophages), encourages further investigation of these materials as promising components of more efficient material‐based platforms for CNS repair.
Cost‐effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria
Authors: Kheng Choon Lim, Vivian W. Wang, Fahad J. Siddiqui, Luming Shi, Edwin S.Y. Chan, Hong Choon Oh, Say Beng Tan, Pierce K.H. Chow
Journal: Hepatology (2014)

Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations.In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.
The Sex-Complex. A Study of the Relationships of the Internal Secretions to the Female Characteristics and Functions in Health and Disease.
Authors: William Blair Bell
Journal: JAMA (1921)

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
Combined pulmonary fibrosis and emphysema. Descriptive analysis from a specialized clinic of interstitial lung disease
Authors: M. Asunciόn Nieto, Beatriz Morales, Covadonga Feranadez-Golfín, Paola Benedetti, Gema Rodriguez-Trigo, Ina Gerasimova, José Luis Άlvarez-Sala Walther
Journal: European Respiratory Journal (2011)

The combination of pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome characterized with pulmonary fibrosis (PF) and emphysema.   Aim:  To analyze the clinical, functional, radiological and echocardiographic features in patients with CPFE.   Method:  Prospective study conducted in a specialized clinic of ILD from 01/01/2007 to 31/12/2010. PF was defined as reticular opacities with peripheral and basal predominance, honeycombing, architectural distortion and/or traction bronchiectasis without ground glass opacities in HRTC and emphysema as the presence of areas of low attenuation with a very thin or no wall and/or bullaes with upper zone predominance.   Results:  We anlized 20 patients, 90% men; mean age 74 years; 91% were smokers or ex-smokers, 60% had dyspnoea, 75% basal crackles and 25% finger clubbing. The pulmonary function tests are shown in table 1. Pulmonary hypertension was detected in 5 of 10 patients who underwent echocardiography.   Conclusions:  The finding of lung volumes normal o minimally altered in contrast to a severe reduction in TLCO and arterial hypoxemia should alert to the possibility of CPFE. The prevalence of PH in these patients is high.
LSC 2012 abstract - Effects of the Hedgehog (Hh) pathway inhibitor GDC-0449 on lung cancer cells and cisplatin resistant lung cancer cells are mediated by lung cancer stem cells (SPs)
Authors: Fei Tian, Josef Mysliwietz, Joachim Ellwart, Amanda Tufman, Albrecht Bergner, Rudolf Huber
Journal: European Respiratory Journal (2012)

We aimed at investigating if Hh pathway inhibitor GDC-0449 is effective in the lung cancer cell lines HCC (adeno-carcinoma) and H1339 (small cell lung carcinoma) and also the corresponding cisplatin resistant lung cancer cells, and if possible effects of GDC-0449 are mediated via SPs. GDC-0449 inhibited concentration dependently cell growth in both lines, and also cisplatin resistant cells. In HCC and H1339 SPs of 0.57 and 0.46 % could be identified, respectively, while in cisplatin resistant cell lines, those were identified as 2.8% and 3.4%, which were significantly higher than the non-cisplatin-resistant lung cancer cell lines. In both cisplatin resistant and non-resistant cells, SP but not non-SP cells were able to repopulate the original tumour population. The Hh receptor smoothened was detectable in SP but not in non-SP cells, showing activation of Hh only in SP. GDC-0449 considerably reduced SP in HCC and H1339 cells, and also in cisplatin resistant HCC and H1339 cells. We demonstrate for the first time that GDC-0449 effectively reduces cell growth in lung cancer cell lines, and remarkable in cisplatin resistant lung cancer cells. This effect is mediated by inhibition of stem cell-like SPs.
TLR5 expression in the small intestine depends on the adaptors MyD88 and TRIF, but is independent of the enteric microbiota
Authors: Inês Brandão, Nives Hörmann, Sven Jäckel, Christoph Reinhardt
Journal: Gut Microbes (2015)

In our recent article Hörmann and coworkers have reported a role for epithelial cell-intrinsic TLR2 signaling for proliferation and renewal of the small intestinal epithelium. In this study, MyD88 and TRIF expression in the small intestine were affected by gut microbiota. Here, we report that in contrast to TLR2 and its co-receptor TLR1, TLR5 transcripts are not changed by presence of gut microbiota nor regulated through TLR2 or TLR4. Similar to TLR2 also TLR5 depends on MyD88 and TRIF adaptors. Our results indicate that TLR adaptor molecules could be determinants of TLR expression in the small intestine.
Imaging Atherosclerotic Plaque Inflammation by Fluorodeoxyglucose With Positron Emission Tomography
Authors: James H.F. Rudd, Jagat Narula, H. William Strauss, Renu Virmani, Josef Machac, Mike Klimas, Nobuhiro Tahara, Valentin Fuster, Elizabeth A. Warburton, Zahi A. Fayad, Ahmed A. Tawakol
Journal: Journal of the American College of Cardiology (2010)
Lead Poisoning Associated with Ayurvedic Medications — Five States, 2000-2003
Authors: J Araujo, AP Beelen, LD Lewis, GG Robinson, C DeLaurier, M Carbajal, B Ericsson, Y Chin, K Hipkins, SN Kales, RB Saper, R Nordness, R Rabin, N Jeffery, J Cone, C Ramaswamy, P Curry-Johnson, KH Gelberg, J Paquin, DM Homa, RJ Roscoe
Journal: MMWR Morbidity and Mortality Weekly Report (2004)

Although approximately 95% of lead poisoning among U.S. adults results from occupational exposure (1), lead poisoning also can occur from use of traditional or folk remedies (2-5). Ayurveda is a traditional form of medicine practiced in India and other South Asian countries. Ayurvedic medications can contain herbs, minerals, metals, or animal products and are made in standardized and nonstandardized formulations (2). During 2000-2003, a total of 12 cases of lead poisoning among adults in five states associated with ayurvedic medications or remedies were reported to CDC (Table). This report summarizes these 12 cases. Culturally appropriate educational efforts are needed to inform persons in populations using traditional or folk medications of the potential health risks posed by these remedies.



TABLE

Reported cases of adult lead poisoning related to ayurvedic medications, by state and selected characteristics — United States, 2000-2003



The first three cases described in this report were reported to CDC by staff at Dartmouth Hitchcock Medical Center at Dartmouth Medical School, New Hampshire; the California Childhood Lead Poisoning Prevention Program; and the California Department of Health Services. To ascertain whether other lead poisoning cases associated with ayurvedic medicines had occurred, an alert was posted on the Epidemic Information Exchange (Epi-X), and findings from the cases in California were posted on the Adult Blood Lead Epidemiology and Surveillance (ABLES) listserv. Nine additional cases were reported by state health departments in Massachusetts, New York, and Texas (Table).
Physiologically based pharmacokinetic study on suramin
Authors: Leijun Hu, Liang Zhao, Danny Chen, Xiao Hu, Jie Wang, Jessie L.-S. Au, M. Guillaume Wientjes
Journal: Cancer Research (2005)

3991   Purpose: Suramin failed in multiple clinical trials as a chemotherapeutic agent. However, it was proved to be a chemosensitizer at low or non-toxic concentrations (10 to 50 μM) (Villalona-Calero MA, et al., Clin. Cancer Res., 2003, Aug 15; 9(9): 3303-11), which are 4 to 20 fold lower than the normal clinically desired plasma concentration (200μM). Present study aims to understand the suramin distribution characteristics in this low or non-toxic concentration range at its action site: tissues. Method: Suramin distribution in blood was done with ultracentrifuge method. And a series of tissue disposition kinetic study was performed in nude mice after 10, 30, or 200 mg/kg i.v. bolus dose. Plasma and tissue concentrations were measured with HPLC. Results: Extensive tissue binding and extremely long tissue retention of suramin were found in most tissues. Although plasma pharmacokinetics showed a dose linear pattern, suramin distribution in tissues is very likely dose nonlinear in many organs (kidney, skin, muscle, liver, and gut), where higher dose generates a lower normalized AUC value (AUC/dose). Accordingly, apparent volume of distribution decreases at higher dose (2165.8 ml at 10 mg/kg dose, 1754.3 ml at 30 mg/kg dose, and 545.0 ml at 200 mg/kg) and the saturable binding is possibly the cause. A whole-body physiologically based pharmacokinetic (PBPK) model was therefore established to better understand this process. The tissue distribution is best described with either a Michaelis-Menten kinetics based tissue binding model (heart, muscle, kidney, gut, spleen, and skin; model 1), a linear model with deep tissue binding sub-compartment (liver; model 2), or a Michaelis-Menten kinetics based tissue binding model with a supplemental tissue binding sub-compartment (lung; model 3). Simulation results agree well with experimental results in plasma and all organs. Extremely high drug binding capacity was found in kidney (BM = 1482 μg-eq/ml), spleen (BM = 1213 μg-eq/ml), and gut (BM = 3317 μg-eq/ml). The model was then up-scaled to human beings by modifying physiological parameters, protein binding value and elimination clearance. The simulated plasma concentration profiles correlate closely to experimentally measured values from our phase I clinical trial, further suggesting the validity of current model. Conclusions: Overall, the PBPK model provides a powerful tool to quantitatively link preclinical and clinical data.
Abstract 2589: In vitro activities of the cationic antitumoral peptide LTX-315 against human melanoma cells
Authors: Liv-Marie Eike, Nannan Yang, Øystein Rekdal, Baldur Sveinbjornsson
Journal: Cancer Research (2014)

Abstract The LTX-315 peptide is a lactoferricin-derived short antitumor peptide which was designed to treat solid tumors with intra-tumoral injections through a two-stage mode of action. First, the collapse of the tumor itself, then the released DAMPs from the dying tumor cell, could induce a subsequent immune protection against recurrences and metastastis. In the present study, we investigate the mechanisms behind the killing of A375 melanoma cells by LTX-315. The peptide kills the tumor cells within a few minutes by direct plasma membrane attack, but at lower concentration internalizes- and can be associated with mitochondria, ultimately leading to a lytic cell death. We show that a fluorescence-labeled peptide was internalized and localized in cytoplasmic vacuoles and accumulated around the mitochondria with subsequent rapid lysis of cells as shown by confocal live cell imaging and transmission electron microscopy. Furthermore we detected the secretion of DAMPs into the extracellular compartment minutes after peptide exposure using ELISA assay, ATP luciferase assay and western blot. Taken together, these findings suggest that LTX-315 has the ability to cause immunogenic cell death in cancer cells, and thus might have a potential as an in situ therapeutic vaccination agent Citation Format: Liv-Marie Eike, Nannan Yang, Øystein Rekdal, Baldur Sveinbjornsson. In vitro activities of the cationic antitumoral peptide LTX-315 against human melanoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2589. doi:10.1158/1538-7445.AM2014-2589
Pru p 3, the nonspecific lipid transfer protein from peach, dominates the immune response to its homolog in hazelnut
Authors: V. Schulten, B. Nagl, E. Scala, M. L. Bernardi, A. Mari, M. A. Ciardiello, I. Lauer, S. Scheurer, P. Briza, A. Jürets, F. Ferreira, B. Jahn-Schmid, G. F. Fischer, B. Bohle
Journal: Allergy (2011)

Nonspecific lipid transfer proteins (nsLTPs) are important food allergens. Often, patients allergic to the nsLTP in peach suffer from allergy to hazelnuts. We aimed to analyse the T-cell response to Cor a 8, the nsLTP in hazelnut and its immunological cross-reactivity with the nsLTP in peach, Pru p 3.Cor a 8-reactive T-cell lines (TCL) established from patients allergic to hazelnut and peach were stimulated with 12-mer peptides representing the complete amino acid sequence of Cor a 8 to identify its T-cell-activating regions and with Pru p 3 to investigate cellular cross-reactivity. T-cell clones specific for different major T-cell-activating regions of Pru p 3 were stimulated with Cor a 8. Both nsLTPs were subjected to endolysosomal degradation assays. Immunoglobulin E (IgE) cross-reactivity between Cor a 8 and Pru p 3 was assessed in inhibition enzyme-linked immunosorbent assay.No major T-cell-activating region was found among 26 T-cell-reactive peptides identified in Cor a 8. Although generated with Cor a 8, 62% of the TCL responded more strongly to Pru p 3. This cross-reactivity was mediated by T cells specific for the immunodominant region Pru p 3(61-75) . Peptide clusters encompassing this region were generated during lysosomal degradation of both nsLTPs. Cor a 8 was more rapidly degraded by lysosomal proteases than Pru p 3. Pre-incubation of sera with Pru p 3 completely abolished IgE binding to Cor a 8, which was not the case vice versa.T-cell reactivity to Cor a 8 is predominantly based on cross-reactivity with Pru p 3, indicating that the latter initiates sensitisation to its homolog in hazelnut. The limited allergenic potential of Cor a 8 seems to be associated with rapid lysosomal degradation during allergen processing and the lack of major T-cell-activating regions.