tbuckley/cabot-search huggingface dataset:
Abstract 143: Evaluation of the Paracrine Effect of Encapsulated Mononuclear Stem Cells in the Acute Myocardial Rat Model
Authors: Santiago Alonso L Tobar, Virgílio Olsen, Amanda P Phaelante, Daiane Silvello, Andréia Biolo, Luis E Rohde, Nadine O Clausell, Michael Andrades
Journal: Circulation Research (2014)

Many studies have considered stem cell-based therapy as a treatment option for acute myocardial infarction (AMI). Paracrine signaling has been proposed as an underlying mechanism, in which released cytokines and chemokines may promote angiogenesis and activation of resident stem cells. In order to characterize this paracrine action, bone marrow mononuclear stem cells (BM-MNC) collected from femur of adults GFP+ Wistar rats were encapsulated in 1.5% of sodium alginate. Animals were randomized in three groups: SHAM (n=3); Empty capsules (n=8); BM-MNC capsules (n=8). AMI was induced by permanent occlusion of the left anterior descending artery after anesthesia with 100mg/kg ketamin and 10 mg/kg xylazine. Soon after the AMI, capsules (empty or BM-MNC) were delivered intra-thoracically. SHAM group was submitted to the same surgical procedures without permanent artery occlusion or treatment given. Troponin I (cTnI) was measured 24h after AMI in order to evaluate the success of the procedures; echocardiography was also performed to assess heart morphofunctional parameters 48h and 7 days after AMI. At day 7, after echocardiography, the animals were euthanized under profound anesthesia (isoflurane 5%) and their hearts were withdrawn for biochemical analysis. Plasma and tissue levels of TNF-α and IL-6 were measured by ELISA. All technical procedures were performed by blinded operators. Statistical comparisons were made using ANOVA analysis followed by Tukey post-test or using t-Student test when appropriated. BM-MNC were viable after day 7 since GFP+ cells were detected by fluorescence microscopy. Nevertheless, the empty capsules groups showed lower levels cTnI compared to BM-MNC group (25 vs. 40 ng/mL, respectively; p=0.03). There was no difference in the shortening fraction (24% VS. 18%, respectively; p=0.08) and in the infarcted area (32% vs. 43%, respectively; p=0.10) when both AMI groups (Empty and BM-MNC) were compared. Also TNF-α and IL-6 levels showed no difference between all groups. We concluded that paracrine effects of cell-based therapy with BM-MNC was unable to modulate events associated to AMI in rat in spite of cell viability after 7 days of implantation.
Abstract 13358: LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes
Authors: Yasuhide Kuwabara, Masayasu Izuhara, Takahiro Horie, Shin Watanabe, Osamu Baba, Shunsuke Usami, Tetsushi Nakao, Masataka Nishiga, Tomohiro Nishino, Toru Kita, Takeshi Kimura, Koh Ono
Journal: Circulation (2013)

Rationale:  Recent genome-wide approaches have revealed that long intergenic non-coding RNAs (lincRNAs) are transcribed from many intervening regions of protein coding genes. Several reports indicate that lincRNAs have pivotal role in physiological and pathological conditions such as cancer and cell reprogramming. However, it is still unclear whether lincRNAs are involved in cardiac hypertrophy or cardiac remodeling resulting in heart failure.   Methods and Results:  To identify the up-regulated intervening regions of protein coding genes during cardiac remodeling, we extracted the total RNAs from the heart after transverse aortic constriction (TAC) in mice, and carried out microarray analysis. We identified 10 transcribed regions, and transcripts derived from these regions were named lincRNA-Hypertrophy (linc-hypertrophy). The levels of three lincRNA-Hypertrophys (linc-hypertrophy3, -hypertrophy5, and -hypertrophy7) were validated based on qRT-PCR (n = 4-6, p   Conclusions:  These results suggest that transcription of numerous lincRNAs were up-regulated during cardiac remodeling, and some lincRNAs were involved in neonatal mouse cardiomyocyte hypertrophy. Since ectopic expressions of lincRNA-Hypertrophy induced cardiomyocyte hypertrophy, lincRNAs may be key players in cardiac hypertrophy.
Closure of mesenteric defects in laparoscopic gastric bypass: a multicentre, randomised, parallel, open-label trial
Authors: Erik Stenberg, Eva Szabo, Göran Ågren, Johan Ottosson, Richard Marsk, Hans Lönroth, Lars Boman, Anders Magnuson, Anders Thorell, Ingmar Näslund
Journal: The Lancet (2016)
Combined effects of hypoxia and elimination of glucose on resting and postextrasystolic potentiated contractions of papillary muscle of guinea pigs.
Authors: Jun Asayama, Tetsuya Tatsumi, Itsuki Omori, Daisuke Inoue, Hiroshi Katsume, Masao Nakagawa
Journal: Circulation (1989)

We studied the combined effects of hypoxia and the absence of glucose on postextrasystolic potentiated and resting contractions in papillary muscle of guinea pigs. Postextrasystolic potentiations (PESPs) were evoked following trains of 40 externally applied continuous stimulations. During hypoxia resting (regular) contractions decreased to about 25% of baseline tension at 30°C, whereas postextrasystolic potentiated contractions decreased to about 35% of baseline measurement of postextrasystolic potentiated contraction. In contrast, with reoxygenation, PESPs recovered quickly while resting contractions recovered gradually. Caffeine abolished the potentiation of postextrasystolic contraction not only in normoxia but also in hypoxia. We speculate that calcium release from the sarcoplasmic reticulum (SR) is attributable to PESP for the most part, and that the trans-sarcolemmal calcium influx generally contributes to the steady-state tensions developed by continuous stimulations. In addition, it seems that PESP works in a ischemic heart to compensate for the decreased tension during hypoxia as a potentiation by a premature ventricular contraction. Trans-sarcolemmal calcium influx might be affected more easily than the SR calcium release, by a combination of hypoxia and the absence of glucose, that is, the sarcolemma may be more susceptible to hypoxic injury than the SR.
A phase I study of recombinant human arginase I (rhArgI) for patients with advanced hepatocellular carcinoma.
Authors: C. C. Yau, P. Chan, R. Pang, W. Chan, P. N. Cheng, R. Poon
Journal: Journal of Clinical Oncology (2010)

e13503 Background: Patients (pts) with advanced hepatocellular carcinoma (HCC) have a poor prognosis. Pre-clinical data suggest that HCC cells are auxotrophic for arginine through the lack of expression of argininosuccinate synthetase. Recombinant human arginase I (rhArgI) is a novel compound which can achieve near total depletion of plasma arginine. A phase Ia/Ib, open-label, dose-escalation study was conducted to determine the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of rhArgI in patients with advanced HCC. Methods: Eligibility criteria included unresectable and/or metastatic HCC with at least 1 target lesion, Karnofsky performance status (KPS) 80% or above, Child-Pugh A or B, and adequate organ function. Weekly doses of rhArgI were escalated from 500 U/kg to 3800 U/kg in a 3 + 3 design. Response was measured by computed tomography according to RECIST criteria. Results: 15 patients enrolled at weekly doses of 500 U/kg (3 pts), 1000 (3), 1600 (3), 2500 (6). The median age was 56 years (33-74); M/F =4:1; KPS 80/90/100 = 13%/47%/40%; 86% hepatitis B carriers; 27% with prior systemic therapy, 20% with prior TACE and 40% had prior surgery. Most common AEs were: diarrhea (14%); nausea (7%) and abdominal pain (7%). Liver function derangement was presented in 14% of enrolled patients. DLT was Gr 3 prolonged elevation of bilirubin in 2 patients at 2500 U/kg. MTD was determined to be 1600 U/kg. Median duration on study was 10 weeks overall. PK and PD studies indicated that RhArgI was efficacious in inducing arginine depletion in a dose-dependent manner and adequate arginine depletion as defined by arginine level <8mM throughout treatment period, is achieved in 1,600 – 2,500 U/kg. Eight pts were evaluable for tumor response and best response was SD > 8 weeks in 4 pts (50%). The median time-to-progression was 2.8 months and the median overall survival was 5.1 months. Conclusions: RhArgI has favorable safety profile with preliminary evidence of antitumor activity in treating patients with advanced HCC. It emerges as one of the potential promising therapeutic targets for patients with advanced HCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bio-Cancer Treatment International Bio-Cancer Treatment International Bio-Cancer Treatment International
Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism
Authors: Xiaoping Liu, Mohamed A El-Mahdy, Raed S Ismail, Sean Little, Le T Thuy, Norifumi Kawada, Jay L Zweier
Journal: Circulation (2014)

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.
Effect of Dose on Urinary Bladder Carcinogenesis Induced in F344 Rats by &lt;italic&gt;N&lt;/italic&gt;-[4-(5-Nitro-2-furyl)-2-thiazolyllformamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M Arai, S M Cohen, J B Jacobs, G H Friedell
Journal: JNCI Journal of the National Cancer Institute (1979)

Because of the utility of the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) rat model in the study of bladder cancer, the effect of dose on FANFT-induced bladder carcinogenesis was evaluated. Weanling male F344 rats were given FANFT in the diet at doses of 0.1, 0.05, 0.01, 0.005, 0.001, and 0.0005% for 30 weeks and then a control diet for 22 weeks. A control group received only the control diet throughout the experiment. Papillary tumors were present at the higher doses, hyperplasia of various degrees of severity was present at the intermediate doses, and minimal hyperplasia was observed in 4 of 16 rats at the 0.005% dose; no mucosal abnormalities were observed at the two lower doses or in the control group. Bladder epithelium from selected animals was also examined by scanning electron microscopy (SEM) aHer 10 weeks and again at the end of the experiment. Hyperplastic mucosa with pleomorphic microvilli similar to that previously demonstrated for 0.2% FANFT was observed at 10 weeks in rats fed 0.1% FANFT. Hyperplastic mucosa with pleomorphic microvilli was also observed at 52 weeks in rats fed 0.1% and 0.05% FANFT. Hyperplastic mucosa without pleomorphic microvilli was observed in rats fed 0.01 and 0.005% FAN FT. The bladder appeared normal by light microscopy and SEM at the two lower doses and in the control group at both the 10- and 52-week intervals. A dose relationship was thus demonstrated for FANFT-Induced bladder carcinogenesis in male F344 rats, and more severe surface changes were observed by SEM as the dose increased.
Thromboembolic disease and the pill. (Letter to the editor)
Authors: Inman Wh, Vessey Mp
Journal: BMJ (1970)

Dr. L.F. Nanni (September 12 p. 644) made a number of criticisms of our recent analysis (April 25 p. 203) of 977 reports of thromboembolism occurring in association with oral contraceptives routinely submitted to the Committee on Safety of  Drugs.  While the possible biases in the data and the justification for using estimates of oral contraceptive sales for comparative purposes were considered at length in the published report some of Dr. Nannis other comments require a reply.  Firstly his objection to the use of the chi-square test for examining the trend in the ratio of observed to expected numbers of reports with estrogen dose is unjustified.  Our assumption that the expected frequencies were subject to negligible sampling error is correct.  Secondly it is true that the one oral contraceptive preparation containing 150 mcg mestranol had an important influence on the results of the analysis but the omission of the data relating to this product does not eliminate the relationship  between mestranol dose and the ratio of observed to expected numbers of reports despite Dr. Nannis statement to the contrary.  When all the groups (relating to both venous and arterial thromboembolism) are combined a statistically significant relationship still exists (p less than .05).  The confusion may have arisen from the fact that Dr. Nanni transposed the ratios for the highest and lowest doses of mestranol (which should be 1.07 and .98 respectively).  It should also be noted that in making this criticism Dr. Nanni ignores the Scandinavian data the data for preparations containing ethinyl estradiol and the fact that the somewhat discrepant data relating to 50 mcg of mestranol also  represent only 1 oral contraceptive preparation.  Finally we agree with Dr. Nanni that the data provide only a very inadequate comparison between products containing mestranol and products containing ethinyl estradiol; this was pointed out in the published report.(FULL TEXT)
First independent evaluation of QuantiFERON-TB Plus performance
Authors: Lucia Barcellini, Emanuele Borroni, James Brown, Enrico Brunetti, Luigi Codecasa, Federica Cugnata, Paola Dal Monte, Clelia Di Serio, Delia Goletti, Giulia Lombardi, Marc Lipman, Paola M.V. Rancoita, Marina Tadolini, Daniela M. Cirillo
Journal: European Respiratory Journal (2016)

Tuberculosis elimination requires an effective strategy to diagnose and treat people infected with Mycobacterium tuberculosis who would otherwise be at high risk of developing and transmitting active disease [1, 2]. The diagnostic tools for latent tuberculosis infection (LTBI) are the tuberculin skin test (TST) and the T-cell interferon-γ release assays (IGRAs). Two IGRAs are commercially available, QuantiFERON-TB Gold In-Tube (QFT-GIT) (Qiagen, Hilden, Germany) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK). Compared to the TST, IGRAs offer operational advantages and higher specificity in the bacille Calmette–Guérin (BCG)-vaccinated population [3], and they are at least as sensitive for LTBI [4]. However, IGRAs have limitations: reduced sensitivity in children and immunocompromised subjects, including HIV-infected individuals [3, 4]; failure to discriminate between active tuberculosis and LTBI; and poor correlation with the risk of progression to active disease [3]. QuantiFERON-TB Plus improves sensitivity for active TB and maintains high specificity among unvaccinated controls <http://ow.ly/XjYPK> The authors thank the study subjects for their generous participation, and G. Pellicciotta, P. Erba and I. Mascherona (IRCCS San Raffaele Scientific Institute, Health Care Staff Protection Unit, Milan, Italy) for their valuable support in control enrolment.
Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy
Authors: F. A. Dilmanian
Journal: Neuro-Oncology (2002)

Neuro-OncologyRadiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues.To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 µm) planar beams (microbeams) of synchrotron-generated X rays.Rats with i.c.9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 µm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 µm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skinentrance, single-exposure doses.The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm
Abstract 226: Sex Differences in Cardiac Catheterization Following Out-of-Hospital Cardiac Arrest
Authors: Bryn E Mumma, James F Holmes, Machelle D Wilson, Deborah B Diercks
Journal: Circulation (2014)

Introduction: Cardiac catheterization is recommended for patients resuscitated from out-of-hospital cardiac arrest (OHCA) with a suspected cardiac etiology. Women are less likely than men to receive cardiac catheterization in other presentations of cardiovascular disease, but it remains unknown whether this disparity extends to OHCA. Objective: To determine whether patient sex is associated with undergoing cardiac catheterization after OHCA. Methods: We included all adult cases in the 2011 California Office of Statewide Health Planning and Development (OSHPD) database with a present-on-admission diagnosis of cardiac arrest (ICD-9-CM 427.5) or sudden cardiac death (ICD-9-CM 798) who were admitted from the emergency department to an acute care hospital. Data extracted from the OSHPD database included patient demographics, diagnoses, and procedures. ICD-9-CM procedure codes from the OSHPD database were used to identify patients who received cardiac catheterization. To determine factors associated with undergoing cardiac catheterization, we used a hierarchical logistic regression model that included age, sex, race, ethnicity, insurance type, ventricular arrest rhythm, and treatment at a hospital with 24/7 percutaneous coronary intervention capability. Results: We studied 4493 men and 3287 women admitted following OHCA. Women were older (median age 70 vs 64 years; p&lt;0.001), had had fewer ventricular arrest rhythms (21.8% vs 31.7%; p&lt;0.001), and received fewer cardiac catheterization procedures [12.5% vs 21.4%; p&lt;0.0001]. This sex difference in cardiac catheterization persisted in the multivariable hierarchical model (adjusted OR 0.65; 95% CI 0.57-0.76; p&lt;0.0001) and in a subgroup analysis including only patients with ventricular arrest rhythms (adjusted OR 0.63; 95% CI 0.51-0.78; p&lt;0.0001) Conclusion: Sex differences exist in cardiac catheterization following resuscitation from OHCA. Future efforts should focus on understanding and resolving these differences.
Influence of tumor site on cognitive deficits in children with cerebellar tumors at diagnosis
Authors: R. Riccardi, L. Peruzzi, L. Iuvone, C. Colosimo, G. Tamburrini, L. Massimi, M. Caldarelli, I. Lazzareschi, V. Ridola, A. Di Giannatale, C. Di Rocco
Journal: Journal of Clinical Oncology (2006)

9045 Background: Children with cerebellar tumor are at risk for cognitive deficits (CD) depending on surgery and radiotherapy. Only few studies analyze the role of tumor itself in mental functioning (Ellenberg et al., ‘87). Data about neuropsychological organization before any treatment are essential to understand the effect of tumor and have a baseline for analyzing the negative impact of the different treatments in the CD. Aim of this study is to prospectively analyze cognitive functions before treatment in patients (pts) with cerebellar tumors. Methods: Twenty-five pts with cerebellar tumor were assessed at diagnosis.Children with previous and severe neurological disturbances neurological were excluded. Intelligence quotient (IQ) and sectorial cognitive abilities (memory, attention, language, visuospatial and executive functions) were evaluated. Neurological examination (BUSPAR) and magnetic resonance imaging (MRI) were performed in the same period of cognitive assessment. Neurological deficits were classified as major, mild or absent in relation with the results of BUSPAR. Results: Twenty pts were selected; males/females: 12/8; age: 7.6 years (range: 18 m-14.8 y); histhology: pilocytic astrocytoma (9 pts), medulloblastoma (9), ependymoma (1) and atypical teratoid-rabdoid (1); tumor location: right cerebellar hemisphere (4), left (4), vermal (12); neurological examination: major neurological signs (2 pts), mild (10), absent (6); hydrocephalus: 50% of pts. Three pts had IQ values below the average level, although mean IQ values were normal (mean: 99.6; range: 78–118). Sixteen/20 pts had selective CD mainly involving working memory, executive functions, attention, and visual motor integration. Language processing was defective in 6 pts (2/4 right-sides lesions, 4/12 vermal lesion). Conclusions: Sectorial CD are present before treatment in about 80% of pts, mainly related to the location of tumor. Preliminar data suggest a correlation between specific sites inside cerebellum and selective CD, with language problems mainly in right hemispheric tumor. Complex cognitive impairment was present in 15% of pts before treatment. These data will represent the baseline for further analysis about the impact of treatment on cognitive outcome. No significant financial relationships to disclose.
Publication of Clinical Studies Supporting FDA Premarket Approval for High-Risk Cardiovascular Devices Between 2011 and 2013
Authors: Adam T. Phillips, Vinay K. Rathi, Joseph S. Ross
Journal: JAMA Internal Medicine (2016)

Improved publication rates, particularly among public companies, are probably a consequence of the explicit inclusion of medical devices in the 2007 FDA Amendment Act expansion of clinicaltrials.govregistration and reporting requirements.However, recent failures of high-profile cardiovascular devices may also have led patients and physicians to more frequently ask about the evidence supporting newly approved devices, prompting publication by companies seeking clinical adoption of their products. 6Although we found that results of the vast majority of clinical studies supporting recent FDA approval of high-risk cardiovascular devices are now being made available to the clinical and research communities, efforts to improve the accessibility of results through online FDA resources and within medical device labels may still be needed to ensure dissemination of historical studies.
Incidence and Characteristics of Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis in Thailand: A 5-Year Retrospective Study
Authors: Archrob Khuhapinant, Kamoltip Lertchaisataporn, Ployploen Phikulsod, Noppadol Siritanaratkul
Journal: Blood (2014)