tbuckley/cabot-search huggingface dataset:
Abstract 4883: Insulin-like Growth Factor Binding Protein-3 (IGFBP3) Modulates Vascular Tone via Scavenging Receptor-B1 (SRB1)-Dependent Nitric Oxide Release
Authors: Yagna P Jarajapu, Jennifer L Kielczewski, Robert C Baxter, Maria B Grant
Journal: Circulation (2009)

Purpose: We recently reported the vascular protective effect of IGFBP3 in experimental models of ischemic vascular injury involving increased homing of circulating endothelial progenitor cells and activation of nitric oxide synthase (eNOS). The vascular protective potential of a molecule is determined in part by its ability to facilitate perfusion to the ischemic areas by dilation of the resident vasculature. Therefore, we hypothesized that IGFBP3 regulates vascular tone by causing vasodilation and thereby, enhances the perfusion of vascular bed. Methods: We evaluated the effect of intraluminal IGFBP3 on the pressure- and agonist-induced constrictions in rat posterior cerebral arteries (PCAs) and compared with that of HDL, a known activator of SRB1. NO release and endothelial intracellular Ca2+ ([Ca2+]i) were evaluated by DAF-FM and Fura-2 fluorescence microscopy, respectively, in intact arteries and human microvascular endothelial cells (HMVECs). Signaling pathways mediating the effects of IGFBP3 were delineated in intact arteries and HMVECs. Activation of eNOS by IGFBP3 was evaluated by Western blotting of ser1177 phosphorylated eNOS in HMVECs. IGF-independent effect was confirmed by using a non-IGF-binding mutant of IGFBP3. Results: Intraluminal IGFBP3 (100ng/ml) or HDL (1mg/ml) caused significant decrease in pressure- (40, 70 and 100 mmHg) and serotonin-induced constrictions of PCAs compared to the vehicle-control. These effects were blocked by L-NAME or SRB1-function blocking antibody (SRB1-ab). NO release was stimulated in PCAs by intraluminal IGFBP3 and HDL with no change in the [Ca2+]i. NO release by IGFBP3, with no change in the [Ca2+]i, in HMVECs was blocked by SRB1-ab, PP2 (cSrc inhibitor), LY294002 (PI3-kinase inhibitor) and triciribin (akt inhibitor) not by KN-92 (CamKII inhibitor). Non-IGF-binding mutant and wild type IGFBP3 showed similar effect in stimulating NO release in HMVECs. Phosphorylation of eNOS at ser1177 was increased in a time-dependent manner by IGFBP3 that was blocked by SRB1-ab. Conclusions: These results suggest that IGFBP3 modulates vascular tone by NO release via SRB1-dependent cSrc/PI3-kinase/akt pathway and this response may significantly contribute to the vascular protective effect of IGFBP3.
Abstract 1830: Protein Quality Control Inadequacy Activates NFAT Signaling in Cardiomyocytes
Authors: Asangi R Kumarapeli, Mingxin Tang, Hanqiao Zheng, Kathleen M Horak, Manixiang Li, Jeffery D Molkentin, Xuejun Wang
Journal: Circulation (2008)

Protein Quality Control (PQC) assists proper (re)folding of nascent polypeptides, keeps normal mature proteins from denaturing or misfolding, and timely removes terminally misfolded and irreparable damaged proteins in the cell. PQC is enforced by collaboration between chaperones and targeted proteolysis. The latter is primarily mediated by the ubiquitin-proteasome system (UPS) while a large family of chaperones are heat shock proteins (HSPs), including small HSPs. α B-crystallin (CryAB) is the most abundant small HSP in cardiomyocytes. Signs of severe PQC inadequacy, including abnormal protein aggregation, reduced CryAB protein, and functional insufficiency of the proteasome, were all observed in failing human hearts, supporting a novel hypothesis that PQC inadequacy contributes to the genesis of congestive heart failure (CHF). It is well established that the calcineurin-NFAT pathway regulates the expression of a significant subset of genes associated with cardiac remodeling and failure. We present here several lines of new genetic and pharmacological evidence that PQC inadequacy suffices to activate NFAT signaling in both cultured neonatal rat cardiomyocytes (NRCMs) and intact mouse hearts. NFAT translocation from cytoplasm to the nucleus is critical to its activation. We observed in cultured NRCMs that CryAB overexpression (o/e) significantly reduced adrenergic agonists-induced NFAT nuclear translocation and myocyte hypertrophy while pharmacological inhibition of the proteasome induced significant calcineurin-dependent NFAT nuclear translocation. Using a NFAT-luciferase reporter mouse model, we detected that NFAT transactivation was increased by a factor of 3 in a mouse cardiomyopathy model that was created by transgenic o/e of a misfolded desmin protein and displayed severe PQC inadequacy. Similarly, we found that NFAT activities in the heart of CryAB/HSPB2 null mice were significantly increased. Consistently, these mice developed cardiac hypertrophy and malfunction at the baseline and displayed exacerbated cardiac hypertrophy and malfunction upon transverse aortic constriction (TAC). Finally, cardiac-specific CryAB o/e significantly attenuated NFAT activation and cardiac hypertrophic responses induced by TAC. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Maternal influenza, obstetric complications, and schizophrenia
Authors: P Wright, N Takei, L Rifkin, R M Murray
Journal: American Journal of Psychiatry (1995)

Epidemiologic studies have reported an association between prenatal exposure to influenza and adult schizophrenia. The authors studied this association in individual patients with schizophrenia and also investigated the relationship of obstetric complications, another postulated risk factor, to adult schizophrenia.Using a structured interview instrument, the authors assessed infections during pregnancy, obstetric complications, gestational age, and birth weight by interviewing the mothers of 121 patients with DSM-III-R schizophrenia.Significantly more infections were reported in the second trimester of the patients' gestations than in the combined first and third trimesters. Influenza accounted for 70% of second-trimester infections. Patients with schizophrenia whose mothers reported having influenza during the second trimester were almost five times more likely to experience at least one definite obstetric complication than were patients who were not exposed to influenza during the second trimester; the exposed patients weighed a mean of 210 g less at birth than the unexposed patients.Maternal influenza during the second trimester may impair fetal growth and predispose to obstetric complications and lower birth weight in a proportion of individuals destined to develop schizophrenia.
The Acute Effect of 25-Hydroxycholecalciferol on Renal Handling of Phosphorus
Authors: Mordecai M. Popovtzer, John B. Robinette, Hector F. Deluca, Michael F. Holick
Journal: Journal of Clinical Investigation (1974)

The acute effect of i.v. and direct intrarenal arterial infusion of 25-hydroxycholecalciferol (25HCC) and 1,25-dihydroxycholecalciferol (1,25-DHCC) on renal handling of phosphorus was evaluated in the following groups of rats: (a) intact animals, (b) parathyroidectomized (PTX) hypocalcemic rats, (c) PTX rats in which normocalcemia was maintained with calcium supplements and (d) PTX animals in which urinary phosphorus was augmented by (i) i.v. sodium phosphate, (ii) expansion of the extracellular fluid volume with normal saline, and (iii) i.v. parathyroid hormone (PTH). Clearances of inulin (C(In)), phosphorus (C(P)), and fractional clearances of phosphorus (C(P)/C(In)) of the experimental groups were compared with those of the corresponding control groups, and the clearances of the infused kidneys with those of the contralateral kidneys. In intact animals, i.v. 25HCC decreased C(P)/C(In) from 0.29+/-0.04 (mean +/-SE) to 0.19+/-0.04, and i.v. 1,25-DHCC decreased C(P)/C(In) from 0.25+/-0.04 to 0.15+/-0.02. The intrarenal infusion of both 25HCC and 1,25DHCC into intact animals failed to produce a unilateral change; however, it decreased C(P)/C(In) bilaterally. i.v. and intrarenal infusions of 25HCC or 1,25DHCC in PTX hypocalcemic and normocalcemic rats, and i.v. infusions of 25HCC in PTX rats receiving either sodium phosphate or normal saline, all failed to produce significant changes in C(P)/C(In). In contrast, 24HCC given i.v. to PTX animals receiving exogenous PTH was associated with a significant fall in C(P)/C(In), from 0.34+/-0.08 to 0.13+/-0.02. These results indicate that 25HCC enhances tubular reabsorption of phosphorus in rats, only in the presence of either endogenous or exogenous circulating PTH, but not in its absence and thus imply a PTH-dependent mechanism of 25HCC action on the kidney. This effect does not appear to be related to the conversion of 25HCC into 1,25DHCC, since the latter fails to affect tubular reabsorption of phosphorus in PTX rats.
Effects Of Five-Years Of Ruxolitinib Therapy On Bone Marrow Morphology In Patients With Myelofibrosis and Comparison With Best Available Therapy
Authors: Hans Michael Kvasnicka, Jürgen Thiele, Carlos E. Bueso-Ramos, William Sun, Jorge E. Cortes, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Blood (2013)
Safety and Efficacy Of Long-Term Open-Label Romiplostim Dosing In Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP)
Authors: Michael D. Tarantino, James B. Bussel, Amy Geddis, Michael F. Guerrera, Alan K. Ikeda, Kun Nie, Melissa Eisen
Journal: Blood (2013)
Abstract 3694: P38-MAP-Kinase-inhibition Changes Balance From Inflammation Towards Vascular Repair In Metabolic Syndrome
Authors: Florian H Seeger, Linping Chen, Alexandra Aicher, Tina Rasper, Ioakim Spyridopoulos, Judith Haendeler, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2007)

Initial trials suggest that bone marrow-derived mononuclear cells (BMC) augment neovascularization in patients after MI. However, patients with cardiovascular risk factors show reduced number and i...
Abstract 2738: Image Integration Using Intracardiac Ultrasound for Scar Mapping and Intervention of Ventricular Tachycardia
Authors: Thomas J Bunch, J P Weiss, Brian G Crandall, John D Day, John P Dimarco, John D Ferguson, Pamela K Mason, George McDaniel, Jeffrey S Osborn, Dave Wiggins, Srijoy Mahapatra
Journal: Circulation (2009)

Background. Ventricular tachycardia (VT) ablation is an effective means to reduce ICD shocks. Intracardiac ultrasound can accurately visualize all left ventricular wall segments and quantify their ...
Abstract 202: Thrombospondin-2 Protects Against Uncontrolled Cardiac Inflammation and Oxidative Stress During Doxorubicin-Induced Myocarditis
Authors: Melissa Swinnen, Davy Vanhoutte, Brigit denAdel, Peter Carmeliet, Yigal M. Pinto, Stephane Heymans
Journal: Circulation (2006)

Background Doxorubicin is a live-saving chemotherapeutic agent in young patients affected by cancer. However, its use is limited by its cardiotoxicity caused by increased oxidative stress and exagg...
The prognostic effect of lipids on early-stage breast cancer (BC) outcome
Authors: M. Bahl, M. Ennis, I. F. Tannock, J. E. Hux, K. I. Pritchard, J. Koo, P. J. Goodwin
Journal: Journal of Clinical Oncology (2005)

710 Background: The prognosis of women with early-stage BC is affected by certain metabolic factors, namely insulin and body mass index (BMI). Obesity and increased insulin are often seen together with dyslipidemia in the Insulin Resistance Syndrome, but the contribution of total cholesterol (TC) and triglycerides (TG) to BC outcome is unclear. Methods: A cohort of 535 women without known hyperlipidemia or diabetes, with stage T1-T3, N0-N1, M0 BC was assembled from July 1989 to June 1996. Information on traditional prognostic factors and anthropometrics, as well as fasting blood was collected at baseline. After completion of local and/or systemic therapy, subjects were followed prospectively, and hazard ratios (HR) for recurrence (local, regional, distant) and death from all causes based on TC and TG were calculated using Cox regression modeling. Significance for each was set at 0.025 (2-sided). Results: Adequate blood samples were available for 520 subjects. TC was significantly correlated with age (Spearman’s r=0.44), and TG with insulin (r=0.43) and BMI (r=0.45). Higher levels of TC were seen amongst those with lower grade tumors (p=0.01), but TG was not associated with grade, tumor stage, nodal group or receptor status. At a median follow-up of 8.7 years, TC and TG were not associated with outcome in age-adjusted univariate analysis, or in analysis controlling for BMI and insulin. When controlling for the effects of age, grade, tumor stage, nodal and receptor status, TG was not associated with outcome, however a trend towards significance was seen for disease recurrence, but not death, for TC (HR recurrence, 1.58 for 4th vs.1st quartile, 2-sided p=0.043). Conclusions: Fasting TG was not associated with outcome in women with early stage BC. In multivariate analysis of tumor-related characteristics, a trend towards risk of recurrence was seen with higher TC. This potential association should be explored in future studies. No significant financial relationships to disclose.
Management of Renal Failure.
Authors: Vicente Arroyo, Mónica Guevara
Journal: Annals of Internal Medicine (1971)

Renal failure is a common complication of cirrhosis with ascites. The most frequent type of renal failure in cirrhosis is that induced by diuretics. Ascites reabsorption is a rate-limited phenomenon and if diuretics increase urine volume at a rate greater than the passage of ascites from the peritoneal cavity to the systemic circulation, a contraction of the effective plasma volume occurs leading to renal hypoperfusion and reduction in GFR (1). Diuretic-induced renal failure is rapidly reversible after discontinuation of therapy and usually does not progress to more severe types of renal failure, such as hepatorenal syndrome (HRS) or acute tubular necrosis (ATN). Acute bacterial infection is also frequently associated with renal failure (2, 3), and usually reverses after infection resolves. However, renal failure associated with infections may progress to HRS.
Abstract 4181: Dual-Energy CT of the Heart for Diagnosing Coronary Artery Stenosis and Myocardial Ischemia - Comparison with SPECT
Authors: Balazs Ruzsics, Mulugeta Gebregziabher, U. Joseph Schoepf, Heon Lee, Joseph A Abro, Philip Costello, Peter L Zwerner
Journal: Circulation (2008)

A single dual-energy CT (DECT) scan can assess coronary anatomy and detect myocardial perfusion defects (PD) seen on SPECT. 28 patients underwent SPECT myocardial perfusion imaging, invasive coronary angiography (ICA), and a single contrast medium-enhanced, retrospectively ECG-gated DECT scan using a dual-source CT system with simultaneous acquisition of high and low x-ray spectra. Scan data was used to reconstruct anatomic coronary CT angiographic (cCTA) images and to map the myocardial iodine distribution on virtually non-contrast enhanced long- and short-axis views of the left ventricle. Two independent observers analyzed all DECT studies for coronary artery stenosis and myocardial blood-pool deficits. Segmental comparison was performed between DECT, ICA, and SPECT. Data were analyzed using the Bayesian model. 484 myocardial segments were evaluated. 135 segments in 21 patients showed blood-pool deficits on DECT. In all territories where DECT showed blood-pool deficits, SPECT or catheter angiography confirmed PD or critical stenosis. Overall, DECT had 94.4% sensitivity and 95.2% specificity with 95% accuracy for detecting PD seen on SPECT. In patients without significant stenosis and negative SPECT (n=7), DECT showed no sign of blood-pool deficits. Interobserver agreement was very good (weighted kappa = 0.87). Compared with ICA, cCTA reconstructions had 98% sensitivity, 88% specificity and 92% accuracy for detection of &gt;50% stenosis. Initial experience suggests that DECT may be promising for the comprehensive analysis of coronary artery morphology and the myocardial blood pool in good agreement with ICA and SPECT.
Viral encephalopathy mimicking functional psychosis
Authors: L G Wilson
Journal: American Journal of Psychiatry (1976)

Encephalitis, particularly herpes simplex encephalitis, frequently presents as a disorder with puzzling psychiatric symptoms before frank evidence of central nervous system involvement is apparent. The author describes three cases of encephalitis characterized by abrupt onset of bizarre psychological disturbance in the absence of gross neurologic dysfunction. Each patient was initially diagnosed as schizophrenic but later became critically ill and recovered only after a long and chaotic hospital course. The author warns psychiatrists and staff on psychiatric impatient units against mistakenly diagnosing cases of early encephalitis as functional psychoses.
Abstract 11265: Elevated Plasma Annexin A5 Levels in Patients after Atrial Switch Operation for Complete Transposition of the Great Arteries: Association with Impaired Systemic Ventricular Myocardial Deformation
Authors: Clare Tm Lai, Pak-cheong Chow, Sophia J Wong Wong, Koon-wing Chan, Yiu-fai Cheung
Journal: Circulation (2011)

Background: Experimental data suggest involvement of annexin A5 (AnxA5) in cardiomyocyte apoptosis. In adults with heart failure, elevated plasma AnxA5 level has been related to ventricular dysfunc...
Abstract 348: Low Radiation Dose, Prospectively ECG-Triggered Coronary CT Angiography: Can It Be Done in Patients With Cardiac Arrhythmia? Initial Experience
Authors: Elisabeth Arnoldi, Luis Ramos-Duran, Joseph A Abro, Peter Zwerner, Konstantin Nikolaou, Maximilian F Reiser, Philip Costello, U. Joseph Schoepf
Journal: Circulation (2009)
Abstract 14215: A Novel Thrombin Interacting Partner Emerges in Heart Failure
Authors: Jill M Gelow, Michael J Hayes, Rachael M Andrie, Wohaib Hasan, David J Sahn, Charles T Esmon, Antony Y Kim
Journal: Circulation (2011)

Introduction: Heart failure (HF) is a prothrombotic state that increases the risk for thromboembolic events. Thrombomodulin (TM) is an endothelial membrane protein that, in complex with thrombin, a...
Organic personality disturbance: a case of apparent atypical cyclic affective disorder
Authors: C Hellekson, R Buckland, T Price
Journal: American Journal of Psychiatry (1979)

The authors present the case report of a 19-year-old woman that contains several important points in the diagnosis and management of organic personality disturbance associated with temporal lobe epilepsy. The behavioral changes may antedate the onset of the clinical seizure. The diagnosis of complex partial seizures is a clinical diagnosis in which surface EEGs may repeatedly not demonstrate focal activity. Carbamazepine can have important psychotropic effects, in addition to its well-established anticonvulsant effects, and it may be particularly indicated if a lithium-resistant bipolar affective disorder is a differential diagnostic possibility.
Abstract 15671: Comparison between Optimal Intravascular Ultrasound Criteria and the Functional Significance of Intermediate Coronary Stenoses
Authors: Hyun-Ok Cho, Chang-Wook Nam, Seung-Ho Hur, Yun-Kyeong Cho, Hyuck-Jun Yoon, Hyoung-Seob Park, Hyung-Seop Kim, Yoon-Nyun Kim, Kwon-Bae Kim, Bon-Kwon Koo, Jun-Hyung Doh
Journal: Circulation (2011)

Background: Optimal intravascular ultrasound (IVUS) criteria for the functional significance of patients with intermediate coronary stenoses have been introduced, but not fully evaluated yet. We wo...
Abstract 2992: Repetitive Apneic Events Augment Arterial Pressure Fluctuation Associated with Severity of Sleep Apnea Syndrome
Authors: Takeshi Takamura, Kaoru Dohi, Naoto Kumagai, Tairo Kurita, Naoki Fujimoto, Takashi Tanigawa, Tetsuya Kitamura, Masaaki Ito, Naoki Isaka, Katsuya Onishi
Journal: Circulation (2006)
Abstract 19990: Identification and Characterization of an ATP-sensitive Potassium Channel in the Inner Membrane of Cardiac Mitochondria
Authors: D B Foster, Alice S Ho, Jasma J Rucker, Marjan Gucek, Robert N Cole, Brian O'Rourke
Journal: Circulation (2010)

Opening of mitochondrial potassium channels is cardioprotective, yet, to date, the pore-forming subunits of these channels remain unidentified. We therefore undertook an in-depth proteomic analysis...
Abstract 5520: Lethal Hepatic Failure with Steatosis in Liver-Sepecific 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Knockout Mice
Authors: Shuichi Nagashima, Hiroaki Yagyu, Fumiko Tazoe, Ken Ohashi, Manabu Takahashi, Kenta Okada, Michiaki Miyamoto, Shori Wang, Toshihiro Inaba, Kazuhiro Eto, Jun-ichi Osuga, Shun Ishibashi
Journal: Circulation (2008)

Three-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the late-limiting enzyme for cholesterol biosynthesis in the mevalonate pathway. Furthermore, HMGCR is involved in the generation of i...
Risperidone Treatment of Autistic Disorder: Longer-Term Benefits and Blinded Discontinuation After 6 Months
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Risperidone is effective for short-term treatment of aggression, temper outbursts, and self-injurious behavior in children with autism. Because these behaviors may be chronic, there is a need to establish the efficacy and safety of longer-term treatment with this agent. METHOD: The authors conducted a multisite, two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums, aggression, and/or self-injurious behavior who showed a positive response in an earlier 8-week trial. Part I consisted of 4-month open-label treatment with risperidone, starting at the established optimal dose; part II was an 8-week randomized, double-blind, placebo-substitution study of risperidone withdrawal. Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale. RESULTS: Part I included 63 children. The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment. The change on the Aberrant Behavior Checklist irritability subscale was small and clinically insignificant. Reasons for discontinuation of part I included loss of efficacy (N=5) and adverse effects (N=1). The subjects gained an average of 5.1 kg. Part II included 32 patients. The relapse rates were 62.5% for gradual placebo substitution and 12.5% for continued risperidone; this difference was statistically significant. CONCLUSIONS: Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums, aggression, and/or self-injurious behavior. Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects.