tbuckley/cabot-search huggingface dataset:
Abstract 1500: Gender Differences of Arteriosclerotic Cardiovascular Diseases in Mice Lacking All Nitric Oxide Synthase Isoforms
Authors: Sei Nakata, Masato Tsutsui, Hiroaki Shimokawa, Osamu Suda, Ken Sabanai, Yasuko Yatera, Kiyoko Shibata, Tsuyoshi Morishita, Hiromi Tasaki, Yasuhide Nakashima, Nobuyuki Yanagihara, Yutaka Otsuji
Journal: Circulation (2007)

Background : We have recently succeeded in developing mice lacking all 3 nitric oxide synthase (NOS) isoforms (triply n/i/eNOS-KO mice) ( PNAS 2005). Our preliminary study has revealed that those mice spontaneously develop cardiovascular diseases, including hypertension, dyslipidemia, and myocardial infarction (MI), and that there seems to be a great gender difference in those disorders. Methods and Results : Experiments were performed in both genders of wild-type (WT) and triply-KO mice. In male mice, survival rate at 11 months of age was markedly more reduced in triply-KO mice than in WT mice (15% vs. 100%, P &lt;0.001, n=34 – 41), whereas in female mice, the survival rate was slightly but significantly more reduced in triply-KO mice than in WT mice (74% vs. 100%, P &lt;0.05, n=34–38). There was a significant gender difference in the survival rate in the triply-KO mice (male 15% vs. female 74%, P &lt;0.05). A postmortem examination revealed that both genders of the triply-KO mice died mainly due to spontaneous MI associated with severe coronary arteriosclerosis (n=13–20). However, in the female triply-KO mice, as compared with the male triply-KO mice, the incidence of MI (29% vs. 56%, P &lt;0.05) and the extent of coronary lesions (intima/media ratio, 0.15±0.01 vs. 0.01±0.01, P &lt;0.05) were both significantly less. In addition, although both genders of the triply-KO mice exhibit hypertension (HT) and hyper-low density lipoproteinemia (hyperLDL), the extents of both HT (135±2 vs. 150±3 mmHg) and hyperLDL (20.6±3.9 vs. 29.4±7.9 mg/dl) were again significantly less in the female than the male mice (both P &lt;0.05, n=6–10). Importantly, ovariectomy significantly exacerbated both HT (159±3) and hyperLDL (32.1±8.8) in the female triply-KO mice (both P &lt;0.05, n=6–7). Furthermore, treatment with 17β-estradiol (10 −8 M, 2 days) significantly enhanced prostacyclin production in isolated aortas of the triply-KO mice (3.07±0.44 to 6.56±0.56 nM/g, P &lt;0.05, n=5), suggesting a novel NO-independent anti-atherogenic action of estrogen. Conclusions : These results provide the first evidence that the gender difference in the extent of arteriosclerotic cardiovascular diseases still exists even in the complete absence of NOSs system, in which estrogen may, at least in part, be involved.
Abstract 2762: Beating-Heart Patch Closure of Muscular Ventricular Septal Defects under Real-Time 3D Echo Guidance: Pre-Clinical Study
Authors: Nikolay V Vasilyev, Pedro J del Nido, Ivan Melnychenko, Kazuo Kitahori, Franz P Freudenthal, Alistair Phillips, Rainer Kozlik-Feldmann, Ivan S Salgo, Emile A Bacha
Journal: Circulation (2007)

Background: The application of percutaneous and transcardiac device closure of ventricular septal defects (VSD) without cardiopulmonary bypass (CPB) has been challenging. We have developed a patch ...
1-Year Outcomes After Transcatheter Aortic Valve Replacement With Balloon-Expandable Versus Self-Expandable Valves
Authors: Mohamed Abdel-Wahab, Franz-Josef Neumann, Julinda Mehilli, Christian Frerker, Doreen Richardt, Martin Landt, John Jose, Ralph Toelg, Karl-Heinz Kuck, Steffen Massberg, Derek R. Robinson, Mohamed El-Mawardy, Gert Richardt
Journal: Journal of the American College of Cardiology (2015)
Abstract 17048: Fifteen Year Follow-Up After Aortic Root Replacement with Stentless Biological Valve Conduits: Homograft versus Freestyle
Authors: Sandro Sponga, Francois Dagenais, Jean Perron, Pierre Voisine, Vincent Tchana-sato, Daniel Doyle, Siamak Mohammadi
Journal: Circulation (2011)

Objectives: The choice of biologic aortic valve substitute for aortic root replacement is multifaceted. Herein, we report the compared long-term outcome of two type of stentless biologic valve conduits namely homograft and Fresstyle bioprosthesis used to replace the aortic root and followed prospectively up to 15 years. Methods: Between 1993 and 2011, 188 patients underwent elective primary aortic root replacement with a stentless bioprosthetic aortic valve with (n=38) or without (n=150) CABG. Among these patients, 98 Freestyle and 90 homografts were implanted. All clinical and echocardioraphic data were collected prospectively. Mean overall follow-up was 8.5±3.9 years (range: 0.1-15). It was 8.4±3.8 years for Freestyle, and 8.5±4.0 years for homografts, and complete in all patients. Results: Patient characteristics were comparable between groups except for age and number of pre-operative diagnosis of endocarditis ( p &lt;0.0001) and moderate/severe aortic insufficiency ( p &lt;0.008). The mean age was significantly higher in the Freesstyle (65.4±8.5years) compared to homograft (48.1±13.0 years) group ( p &lt; 0.0001). Hospital mortality was comparable between the Freestyle and the homograft group (5.1% versus 7.8%, p =0.6). Ten and 15-years survival was 66.7% and 53.0% in the Freestyle versus 89.9% and 69.1% in the homograft group, respectively ( p &lt;0.001). Freedom from reoperation due to structural valve deterioration (SVD) at 10 and 15 years was 98.8% and.92.7% for the Freestyle compared to 87.4% and 68.6% in the homografts group, respectively ( p =0.009). Independent risk factors for reoperation for SVD were age (OR:1.1, CI: 1.02-1.1, p =0.002), and use of homograft (OR:7.7, CI: 1.7-35.5, p =0.008). Independent risk factors for poorer long-term survival were age (OR 1.2, CI: 1.1-1.3, p =0.001), and lenght of hospital stay (OR 2.9, CI: 1.5-3.8, p =0.0003). Mean pressure gradient at the end of follow-up was 8.5±6.2 mm Hg for the Freestyle and 9.9±9.1 mm Hg for the homograft patients. Conclusion: The choice of stentless biologic valve for aortic root reconstruction have no influence on early and long-term survival. The use of biologic root reconstruction with Freestyle bioprostheses provides a better freedom from reoperation due to SVD compared to homografts.
Abstract 8917: Dauricine Suppresses Early Afterdepolarizations and Torsade De Pointes In Rabbit Hearts with Long Qt2 Syndrome
Authors: Ashish A Parikh, Xiao-Yan Yang, Fan-Dian Zeng, Guy Salama
Journal: Circulation (2011)

Background: Dauricine (Dau) is a bisbenzylisoquinoline alkaloid derivative isolated from rhizome of Mensipermum dauricium DC, a Chinese herb. Dau has been shown to lower blood pressure, platelet aggregation, inflammatory response and arrhythmia. Dau has also been shown to inhibit the late Na + current, I NaL , I Kr and L-type Ca 2+ current, I CaL by shifting the steady state inactivation and activation curves and prolonging the τ value of recovery. Objectives: The multiple targets of Dau make it challenging to explain the suppression of early afterdepolarizations (EADs) and Torsade de Pointes (TdP) in drug-induced Long QT 2 (LQT2) model in rabbit hearts by mapping Action Potential (AP) and Ca 2+ transients (Ca i T) and to mathematically model the effect of Dau and explain its possible mode of action. Methods: Experimental (Langendorff rabbit hearts labelled with Rhod-2/AM and PGH1 to simultaneously map Action Potential (AP) and Ca 2+ transients (Ca i T)) and simulations ( Shannon et al . model) of rabbit AP and CaiT were used to investigate the effects of Dau (5µM) before and after LQT2 induced with Dofetilide (Dofe=0.5μ M) to block I Kr . Results: In controls, Dau tended to prolong AP durations (APDs), CaiT durations (CTD) (p&gt;0.5) but significantly reduced conduction velocity (CV) (p&lt;0.05; n=5) in a rate independent manner. In LQT2, Dofe prolonged APDs (318±24 to 835±32 ms; p&lt;0.01), CTDs (346±36 to 867±48ms; p&lt;0.01) elicited EADs and TdP that were suppressed by Dau (p&lt;0.01; n=5/5 hearts). Dau (5µM) reduced the Dofe-prolongation of APDs (835±32 to 542±93ms; p&lt;0.01) and CTD (867±48 to 567±103ms; p&lt;0.01) and reversed the Dofe-prolongation of Dispersion of Repolarization (DOR) (25±6 to 55± 15ms; p&lt;0.01; reversed 55±15ms to 29±15ms; p&lt;0.05). Simulations of the effects of Dofe, Dau and Dofe + Dau indicate that Dau's suppression of EADs is primarily mediated by reducing the Ca i overload by modifying the kinetics of I CaL . Conclusions: Dau (5µM) markedly reduced CV and in LQT2 significantly shortening APDs, CTDs, reduced DOR and suppressed EADs and TdP. Simulations implicate the slowing down of activation and inactivation kinetics of I CaL as the dominant anti-arrhythmic mechanism.
Abstract 443: Transcription Factor E2F2 Regulates Vessel Contractile Function and Blood Pressure via Isoform-specific Expressions of Endothelin Converting Enzyme-1
Authors: Gangjian Qin, Yan Zhu, Raj Kishore, Deepika Dinesh, Tina Thorne, Keong Kian Poh, Douglas W Losordo
Journal: Circulation (2007)

E2F transcription factors play critical roles in cell cycle regulation but their cardiovascular specific functions are not well defined. Recent studies have revealed a polymorphism in Endothelin Converting Enzyme-1b (ECE-1b) promoter (C-338A), located within E2F consensus site, which is strongly associated with blood pressure (BP) values in hypertensive women. ECE-1, with four isoforms ECE-1a/b/c/d expressed by the use of alternative promoters, is the major enzyme that catalyzes the biogenesis of the potent vessel-constricting peptide endothelin-1 (ET-1) from its inactive precursor Big-ET-1. The role of E2Fs in ECE-1 bioactivity and BP regulation, however, is unknown. Here we provide evidence that E2F2- but not E2F1-deficient mice display an elevated arterial BP. Loss of E2F2 leads to an aortic artery hypercontractility in response to Big-ET-1, indicating an increased ECE-1 bioactivity. ECE-1b promoter-reporter assays, combined with either E2F2 overexpression or knockdown, confirm that E2F2 regulates ECE-1b transcription. The incorporation of C-338A polymorphism in the promoter confers a higher basal level of the promoter activity and blunts the induction of ECE-1b by E2F2. Among all four isoforms, ECE-1b has been suggested to localize in the late endosome and heterodimerize with cell surface ECE-1a/c/d isoforms for lysosomal degradation, thereby down-regulating their activities. Indeed, we found that knockdown of E2F2 leads to a reduced cytosolic however an increased plasma membrane ECE-1 immunoactivity, corroborating with the hypercontractility of E2F2-deficient vessels. These data indicate that in the normal “non-proliferating” vessels, E2F2 plays a critical role in the maintenance of vascular tone. Deregulated E2F2 activity may contribute to the pathogenesis of hypertension.
Database proposed for patients possibly exposed to CJD.
Authors: Andrew Moscrop
Journal: BMJ (2001)

A confidential database has been proposed that would contain details of all patients who may have been exposed to Creutzfeldt-Jakob disease (CJD) through medical procedures.

Proposals were put forward last week in a consultation paper from the CJD incidents panel, a group of experts set up last year by England's chief medical officer.

At a press briefing Dr Michael Banner, the panel's chairman, said the database would be used to assess whether people who may have been exposed to CJD in healthcare procedures go on to develop the disease. The panel's job was to devise mechanisms for use when a patient with CJD, or suspected of having CJD, is found to have undergone a medical procedure in the past.

Other patients may then be considered at risk because of the “unknown but possible risk that CJD could be transmitted through surgical instruments, donated blood, or other tissues or organs, from individuals who later develop CJD,” according to Dr Banner.

Dr Banner admitted that the proposals had not been put before legal experts and that questions might arise as to the legality of holding information on patients. “The principles may not be feasible with legal restrictions,” he said.

Management of Possible Exposure to CJD through Medical Procedures is accessible at www.doh.gov.uk/cjd/consultation/
Psychological sequelae of brain damage in children
Authors: Michael Rutter
Journal: American Journal of Psychiatry (1981)

The author reviews the empirical evidence on the psychological sequelae of brain damage in childhood, concluding that brain injury causes a markedly increased risk in both intellectual impairment and psychiatric disorder. The risk is related to the severity of the brain damage, but there is little indication of locus effects. Psychiatric disorder is probably most likely to occur when there is abnormal neurophysiological activity; to some extent it may be influenced by the nature of the basic medical condition. Psychiatric consequences of brain injury are also substantially affected by the child's pre-injury behavior, psychosocial circumstances, and cognitive level. However, there are few psychological sequelae that are specific to brain damage.
Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects
Authors: C E Coffey, G S Figiel, W T Djang, R D Weiner
Journal: American Journal of Psychiatry (1990)

Subcortical hyperintensity on T2-weighted brain magnetic resonance imaging was significantly more common and more severe in elderly depressed patients referred for ECT than in a matched control group of normal elderly subjects. The potential clinical and research implications of these findings are discussed.
Cross-talk between β-adrenoreceptor and α7-nicotinic acetylcholine receptor (α7-nAChR) signaling in gastric carcinogenesis
Authors: Vivian Shin, Wai-Keung Leung, Chi-Hin Cho, Joseph Sung
Journal: Cancer Research (2008)

2238   Cigarette smoking is associated with various cancers, but it is unclear which component(s) imposed the carcinogenic effect in stomach. Nicotine, the major component in cigarette smoke, has been shown to exert mitogenic effect on tumor growth and angiogenesis. Moreover, nicotine-derived nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is carcinogenic in lung cancer. However, there are few studies that examined the effects of these two components in gastric carcinogenesis. The aim of this study is to determine if nicotine and/or NNK would promote gastric tumor growth and to delineate the molecular mechanism(s) involved, which may shed light on new gastric cancer drug discovery. Human gastric carcinoma cells (AGS) were incubated with nicotine and NNK at various concentrations for 5 hours. High dose of nicotine (200 μg/ml) and NNK (100 nM) significantly increased cell proliferation by 40% and 96%, respectively. The increased cancer growth is due to the modulation of several G1 regulatory proteins, leading to the cell cycle transitions. Cyclin D1 expression and its association with cyclin-dependent kinases (CDK4/6) was analyzed by immunoprecipitation. The complexes immunoprecipitated with anti-cyclin D1 antibody exhibited higher amounts of CDK4 in NNK than nicotine treatment. Furthermore, phosphorylation of retinoblastoma protein (Rb) was activated which released the transcription factor E2F and DP-1 to form heterodimers and facilitate cell cycle progression. Pretreatment with a selective COX-2 inhibitor (SC-236) prevented the upregulation of G1 regulatory proteins and caused cell cycle arrest at G1 phase. Furthermore, nicotine- and NNK-induced COX-2 activity and protein expressions were abrogated by SC-236. The increased production of PGE 2  was blocked by SC-236. Pretreatment of cells with propranolol (non-specific β-adrenoreceptor antagonist), but not α-bungarotoxin (α-BTX, α7nAChR antagonist), abolished the nicotine-induced cell proliferation. On the other hand, α-BTX suppressed COX-2 and PGE 2  production in NNK-induced cell proliferation, and was partially abrogated by propranolol. These results pointed to the importance of adrenergic and nicotinic receptors in gastric tumor growth promoted by cigarette smoke. These data revealed that nicotine and NNK are two major components in cigarette smoke that are responsible for the tumor promoting effects on gastric carcinogenesis through the cooperation of different receptors to regulate the progression of cell cycle via COX-2 dependent pathway.
Exclusion of close linkage of Tourette's syndrome to D1 dopamine receptor
Authors: J Gelernter, J L Kennedy, D K Grandy, Q Y Zhou, O Civelli, D L Pauls, A Pakstis, R Kurlan, R K Sunahara, H B Niznik
Journal: American Journal of Psychiatry (1993)

The authors' goal was to establish if a mutation in D1 dopamine receptor locus (DRD1), or one genetically close to it, could cause Gilles de la Tourette's syndrome.DRD1 and linked markers (D5S36, D5S61, and D5S62) were studied in a large Mennonite Tourette's syndrome kindred. Only individuals with the full Tourette's syndrome were considered to be affected in one series of analyses; in another series the diagnostic spectrum was broadened to include chronic multiple tics. Liability classes were defined to take into account age at onset and sex differences; dominant inheritance was assumed. The authors' version of the LINKMAP program of the LINKAGE package modified to run under distributed parallel processing (Linda LINKMAP) was used for the multipoint linkage analysis.Complete (theta = 0.0) linkage of Tourette's syndrome with DRD1 was ruled out (lod score of -10.1) when the disease was defined narrowly. The area of exclusion of linkage (lod score between -2 and -10.5) extended from map position -0.10 to map position 0.50. The authors conducted an additional (centromeric) multipoint analysis with D5S36 as well as glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area of exclusion to map position -0.30 when the disease was defined narrowly.This result provides strong evidence against linkage of the DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion extends the authors' earlier work with the dopamine system in Tourette's syndrome to exclude the two best characterized dopamine receptors from linkage with Tourette's syndrome.
Abstract 5368: Metarrestin effectively disassembles PNCs and inhibits metastasis
Authors: Chen Wang, Kevin Frankowski, Teper Yaroslav, Samarjit Patnaik, Frank Schoenen, Noel Southall, Wei Sun, Steve Titus, Lesley Griner, Christopher Dextras, Jamey Sultan, Irawati Kandela, Marzena Lewandowska, Yi-Ping Wen, John Norton, Jin Sol Kang, Andrew Mazar, Wei Zhang, Jeffrey Aubé, Marc Ferrer, Udo Rudloff, Juan Jose Marugan, Sui Huang
Journal: Cancer Research (2015)

Abstract The perinucleolar compartment (PNC) is a nuclear body that forms specifically in highly malignant cancer cells. PNC prevalence is shown to reflect metastatic potential of cancer cells from solid tissue origins. A high-content screen was performed to identify small molecules that reduce PNC prevalence. Medicinal chemistry optimizations of confirmed hits yield metarrestin, having 95% of oral bioavailability and a PNC disassembly IC50 between 100 to 400 nM across multiple cancer cell lines. Metarrestin inhibits soft agar growth and the invasive capabilities of cancer cells in vitro. In vivo mouse xenograft metastatic studies showed that metarrestin effectively inhibits lung and/or liver metastasis of prostate cancer (PC3M), pancreatic cancer (organotypic spheroids of PANC1), and a breast cancer patient xenograft (PDX) model derived from metastatic cells isolated from a pleural effusion. Treated animals tolerate metarrestin well with no discernable impact on animal well-being including weight compared with control animals. These data supports the idea that the pharmacological disassembly of PNC produces the inhibition of malignant behavior of cancer cells both in vitro and in vivo. Cellular and molecular analyses of the mechanisms of action of metarrestin show that this compound induces significant and reversible changes in the nucleolar structure, accompanied by a selective reduction of pol I transcription. These studies suggest that PNC structural integrity directly associates with pol I function and nucleolar structure. Experiments are currently underway to identify the cellular factors and pathways by which metarrestin reduces PNCs, disrupts nucleolar structure, regulates transcriptions, and blocks malignant behaviors. Citation Format: Chen Wang, Kevin Frankowski, Teper Yaroslav, Samarjit Patnaik, Frank Schoenen, Noel Southall, Wei Sun, Steve Titus, Lesley Griner, Christopher Dextras, Jamey Sultan, Irawati Kandela, Marzena Lewandowska, Yi-Ping Wen, John Norton, Jin Sol Kang, Andrew Mazar, Wei Zhang, Jeffrey Aubé, Marc Ferrer, Udo Rudloff, Juan Jose Marugan, Sui Huang. Metarrestin effectively disassembles PNCs and inhibits metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5368. doi:10.1158/1538-7445.AM2015-5368
MALFORMATION OF THE OESOPHAGUS
Authors: F. Mason
Journal: BMJ (1855)

OUGNMAL XMN0A?IONB.l an 't y ibly prove of &icient interet for publica.T, e ough the practice recorded, that of leaving the g of the limb, to the patient's " feeling of animal con-; eiousne,s", after the fashion of Abernethy's monkey, be not in accordance with the " rules laid down by the warmest promoters of excision".P.S.-The case of "successful excision of the knee- joint", reported in the AssocIATIoir JOURNAL of August 4th, 1854, has been honoured by a far from complimentary cTitical notice in the Edinburgh Jfedica and Surical Journal of October 1854.It will not perhaps be uninter- esting to the authorities of that periodical to learn that t.heir predictions, as to permanency of cure, have not been realised; as the boy, now upwards of twenty months after the operation (as was reported in Mr. Butcher's excellent mono- graph in a recent number of the Dublin Quarterly Journal of Medical cience, continues in the enjoyment of better health, and has the use of a firmly anchylosed serviceable limb.The prospect of an operation of "settled inexpediency" triumphing over unmerited obloquy, and the admission of its right "'to a fair and properly conducted trial", must prove very gratifying to Mr. Jones and others, who have had as yet but to deal with " bare statements and pre- conceived opinions".
Abstract 1335: The {beta}-blocker Alprenolol Stimulates {beta}-arrestin Mediated Epidermal Growth Factor Receptor Transactivation
Authors: Il-Man Kim, Douglas G Tilley, Juhsien Chen, Natasha C Salazar, Erin J Whalen, Howard A Rockman
Journal: Circulation (2007)

The binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also G protein-coupled receptor kinase (GRK) and β-arrestin dependent signals. We recently identified a new signaling pathway in which β-arrestin mediates β 1 -adrenergic receptor (β 1 AR) transactivation of the epidermal growth factor receptor (EGFR). Activation of this β 1 AR-EGFR transactivation pathway provides cardioprotection  in vivo  under conditions of catecholamine toxicity. Recent observations suggest that binding of different β-adrenergic ligands stabilizes distinct receptor conformations, leading to specific signaling outcomes. To identify whether β-adrenergic ligands that do not activate G protein signaling can induce β-arrestin mediated EGFR transactivation, we screened 20 β-blockers using confocal microscopy in HEK 293 cells overexpressing β 1 AR and EGFR-GFP. We found that alprenolol consistently induced β-arrestin mediated β 1 AR transactivation of EGFR. Using mutants of the β 1 AR and siRNA directed against β-arrestin we show that alprenolol stimulated-EGFR transactivation requires both β 1 AR phosphorylation on the c-terminal tail and β-arrestin (see figure). Moreover, pharmacological inhibition of Src and EGFR blocked alprenolol-stimulated EGFR transactivation. Our findings suggest that alprenolol may represent a novel class of drugs that provide cardioprotection via β-arrestin mediated β 1 AR-EGFR transactivation as well as classical antagonistic action of G protein signaling.