tbuckley/cabot-search huggingface dataset:
Abstract 312: Selective Inhibition of Myocardial NADPH Oxidase Significantly Decreases Heart Size in Transgenic (Tg) Mice with Cardiac-Specific Overexpression of a Dominant-Negative (DN) Mutant of p67 <sup>phox</sup>
Authors: Qiong Zhao, Magdalena Ornatowska, Dalia Urboniene, Kristopher McGee, R J Solaro, Roberta Franks, John W Christman, Lei Xiao
Journal: Circulation (2008)

The role of NADPH oxidase (NOX) was recently suggested in cardiac diseases including hypertrophy. Overexpression of a DN mutant of p67 phox , a cytosolic subunit of NOX, DN-p67 with a V204A point mutation completely inhibited NOX enzymatic function of superoxide generation. We found that overexpression of DN-p67 in cultured adult rat cardiac myocytes attenuated α 1 -adrenoceptor-induced hypertrophy , we thus hypothesized that NOX/p67 phox plays a critical role in cardiac hypertrophy and remodeling in vivo . Accordingly, we recently generated a Tg mouse model in C57BL/6 strain with cardiac-specific overexpression of this DN-p67 mutant along with an IRES-initiated EGFP tag protein using the cardiac-specific α-MHC promoter. Hearts from 1.5-, 3- and 6-month (M) old heterozygous Tg mice and their Non-Tg (NTg) littermates were harvested and compared. The heart weight/body weight (HW/BW) ratio in Tg group was significantly smaller (overall: 14%↓; 1.5-M: 10%↓; 3-M: 16%↓; 6-M: 12%↓) vs. the NTg group ( p &lt; 0.01, n=23). This result was confirmed by 2D echocardiography (2D-echo) measuring the left ventricular myocardial area (LVMA) determined by subtracting endocardial area from epicardial area in short axis view at the end diastole. The LVMA (mm 2 ) in 3-M and 6-M mice was significantly ( p &lt; 0.05, n=21) smaller in Tg (0.44±0.02) than the NTg (0.50±0.02) with equal average BW in both groups. LV internal dimensions and systolic function were preserved without difference in Tg vs. NTg. The LV wall thickness is smaller in Tg vs. NTg by both 2D-echo and hematoxylin/eosin staining of LV cross-sections, but no change in fibrosis was detected in both groups by trichrome staining (n=4). Interestingly, the expression of NOX catalytic subunit gp91 phox in Tg hearts was significantly decreased (~3-fold↓, n=5) vs. NTg by Western blot, whereas the cardiac expression of other NOX subunits p47 phox and p22 phox remained the same in both groups. In summary, we have generated a viable Tg mouse model with cardiac-specific overexpression of a DN p67 phox , which shows significant reduction in both myocardial mass/size and gp91 phox expression with normal cardiac function and development. Our results first show the novel and critical role of NOX/p67 phox in normal cardiac growth and heart development. This research has received full or partial funding support from the American Heart Association, AHA National Center.
OPTICAL COHERENCE TOMOGRAPHY IN UNPROTECTED LEFT MAIN CORONARY ARTERY STENTING
Authors: Guido Parodi, Akiko Maehara, Gabriele Giuliani, Takashi Kubo, Gary Mintz, Ruben Vergara, Angela Migliorini, Renato Valenti, Nazario Carrabba, David Antoniucci
Journal: Journal of the American College of Cardiology (2010)
SIOP MMT 95: Intensified (6 drug) versus standard (IVA) chemotherapy for high risk non metastatic rhabdomyosarcoma (RMS)
Authors: M. Stevens, A. Rey, N. Bouvet, C. Ellershaw, J. Sanchez de Toledo, O. Oberlin
Journal: Journal of Clinical Oncology (2004)

8515 Background: MMT 95 was 3rd in a series of SIOP collaborations for children with non metastatic STS. Principal study objectives were: low and standard risk patients, to maintain excellent survival with limited chemotherapy and very selective use of local therapy.; high risk patients, to explore survival advantage for an intensified chemotherapy strategy in a randomised trial. Methods: Eligibility for randomisation included age ≥ 6 months ≤18 years, no distant metastases, diagnosis within previous 8 weeks without prior treatment except surgery, pathology available for central review, written consent according to institutional requirement. From July 1995 to July 2003, 456 high risk patients (incompletely resected embryonal RMS, undifferentiated sarcoma and soft tissue PNET at all sites except paratesticular, vagina and uterus, and all alveolar RMS) were randomised to receive IVA (ifosfamide, vincristine, actinomycin D) or a 6 drug combination (IVA + carboplatin, epirubicin, etoposide) both delivered over 27 weeks. Cumulative dose / m2 = ifosfamide 54g (both arms), epirubicin 450 mg, etoposide 1350 mg (6 drug). Delivery of radiotherapy was determined according to site and / or response to chemotherapy ± surgery. Non randomised exceptions were: orbital tumours (allocated IVA); SIOP stage III (node positive) and young (age < 3yr) parameningeal tumours (allocated 6 drugs). The study was powered to detect 10% difference in 3 year OS. Results: Data given only for randomised patients Toxicity was significantly greater (infection, myelosuppression, mucositis) for the 6 drug arm. Conclusions: Intensification of chemotherapy provides no overall advantage for non metastatic RMS / other chemosensitive STS, and adds toxicity. Further follow up is required to identify any benefit for patient subgroups. No significant financial relationships to disclose.
Restoration of Retinoid Sensitivity by MDR1 Ribozymes in Retinoic Acid–Resistant Myeloid Leukemic Cells
Authors: Hiromichi Matsushita, Masahiro Kizaki, Hiroyuki Kobayashi, Hironori Ueno, Akihiro Muto, Nobuyuki Takayama, Norihiro Awaya, Kentaro Kinjo, Yutaka Hattori, Yasuo Ikeda
Journal: Blood (1998)
Replication-Defective Canarypox (ALVAC) Vectors Effectively Activate Anti–Human Immunodeficiency Virus-1 Cytotoxic T Lymphocytes Present in Infected Patients: Implications for Antigen-Specific Immunotherapy
Authors: G. Ferrari, C. Berend, J. Ottinger, R. Dodge, J. Bartlett, J. Toso, D. Moody, J. Tartaglia, William I. Cox, E. Paoletti, K.J. Weinhold
Journal: Blood (1997)
Abstract 838: microRNA-210 Regulates Endothelial Cell Response to Hypoxia
Authors: Pasquale Fasanaro, Yuri D’Alessandra, Valeria Di Stefano, Roberta Melchionna, Sveva Romani, Giulio Pompilio, Maurizio C Capogrossi, Fabio Martelli
Journal: Circulation (2007)

Background . MicroRNAs (miRNAs) are small non-protein-coding RNAs that downregulate gene expression by inhibiting mRNA translation in mammalian cells. In this study, it was investigated miRNAs regulation and functional role in endothelial cell response to hypoxia. Methods and results. Human Umbelical Vein Endothelial Cells (HUVEC) were cultured either in normoxic conditions or in the presence of 1% oxygen for 8 – 48 hours. Then, a selection of 157 miRNAs was measured using a real-time PCR assay designed to quantify only mature miRNAs. The expression of miR-210 and miR-150 progressively increased upon exposure to hypoxia. At 48 hours, miR-210 and miR-150 were 35±5 and 14±4 fold more expressed than control (p&lt;0.001 and &lt;0.007, respectively). Both responses were independent of cell confluency and were not limited to vascular cells. In additional experiments it was characterized miR-210 regulation and its the role on HUVEC function. Neither acidification nor oxidative stress, two components of the cell response to hypoxia, modulated miR-210. Further, miR-210 overexpression in normoxic HUVEC stimulated the formation of capillary-like structures on Matrigel and VEGF-driven cell migration. Conversely, miR-210 blockade via LNA-antimiR transfection inhibited the formation of capillary-like structures stimulated by hypoxia and decreased cell migration in response to VEGF. miR-210 overexpression did not affect HUVEC growth in both normoxia and hypoxia. Conversely, antimiR-210 transfection inhibited cell growth both in normoxia (66%±8 of control; p&lt;0.003) and in hypoxia (50%±9 of control; p&lt;0.001). While DNA synthesis was not affected, miR-210 blockade induced apoptosis, as assessed by measuring cytoplasmic nucleosomal DNA. One relevant target of miR-210 in hypoxia was Ephrin-A3, since miR-210 was necessary to downmodulate its expression upon hypoxia. Moreover, miR-210 overexpression in normoxic condition was sufficient to inhibit Ephrin-A3 protein level. Finally, luciferase reporter assays showed that Ephrin-A3 was a direct target of miR-210. Conclusions . miR-210 upregulation is a crucial element of cell response to hypoxia, affecting cell survival, migration and differentiation. #
Abstract 17605: Gender Differences in Predictors of Risk of Retroperitoneal Bleeding
Authors: Bina Ahmed, Stefan Lischke, Faye Straight, Harold L Dauerman
Journal: Circulation (2011)

Background: Retroperitoneal bleeding (RPB) can be a serious complication related to cardiac catheterization via femoral approach. Despite improvement in procedural safety, women undergoing cardiac catheterization remain at a two-fold higher risk of access site bleeding including RPB compared to men. We sought to compare clinical and angiographic predictors of RPB among men and women undergoing cardiac catheterization. METHODS: Case-control study design was used to identify cases with documented RPB and matched using age, procedure and gender to define controls. Detailed clinical and femoral angiographic data was collected and analyzed. Safe zone arteriotomy (SZA) was defined as access below inferior epigastric artery and above femoral artery (CFA) bifurcation. Univariate comparisons were made between cases and controls in both genders. Multivariate analysis was performed to identify independent predictors of RPB after adjusting for baseline differences. RESULTS: There were significant differences in clinical variables such as BMI and femoral artery anatomy among women with and without RPB (Table). On the other hand among men, BMI or size of CFA was not relevant but non-SZA (high stick) was more likely in men with RPB. On multivariate analysis, BMI trended to be only independent predictor of RPB among women (OR 0.83, 95% CI 0.68-1.0, p=0.05) whereas in men, SZA strongly predicted RPB (OR 0.30, 95 % CI 0.1- 0.3, P&lt; 0.01). Conclusion: There are significant gender differences in mediators of RPB risk. The presence of non-modifiable risk factors such as smaller BMI and CFA vessel size in women may explain the persistent increased risk of RPB and access site complications seen in women.
Abstract 15714: Metabolic Modulation Of Vascular Distinctive P2X Receptors By Intracellular ATP In Rat Arterial Smooth Muscle
Authors: Hiromitsu Morita, Hisanori Umebayashi, Megumi Sugihara, Hiroshi Takeuchi, Kihachiro Abe, Masato Hirata, Yushi Ito
Journal: Circulation (2011)

Introduction:  It is broadly accepted that extracellular nucleotide sensitive P2 receptors are composed of two different groups, namely ionotropic P2X and metabotropic P2Y receptors. Therefore, it seems to be considered in general that P2X receptor lacks metabolic regulation site. However, we found that P2X1 and 5 receptors, which we identified as P2X receptors in vascular smooth muscle ( Circulation , 120: S1012 - S1013, 2009), are equipped with intracellular ATP binding site and its activation kinetics are modulated by cytosolic ATP.   Hypothesis:  Vascular smooth muscle type P2X1 and 5 subunits could be controlled by not only extracellular, but also intracellular ATP.   Methods:  We used male rats aged 10-11w, and recorded P2X receptor current from myocytes isolated from rat cerebral and mesenteric arteries, or aorta using whole-cell patch-clamp technique. We also performed tension recording by use of rat aorta ring preparation, western blot, immunoprecipitation and immunofluorescent analyses to detect the receptors in the smooth muscle.   Results:  We found that desensitization of α,β-methylene ATP(10μ M)-induced P2X receptor current is greatly suppressed by increasing intracellular ATP concentration through patch pipette solution (Initial desensitization rates were 52.4±6.0, 45.7±5.4 and 33.5±3.0% at 0, 2 and 5mM ATP, respectively: n=5-13). In contrast, ADP and AMP did not modulate the desensitization of the current at all. Similar effects were observed in rat cerebral and mesenteric artery myocytes. In addition, α,β-methylene ATP (10μ M)-induced contraction also showed desensitization similar to the results of patch-clamp experiment with 5mM ATP (Initial desensitization rate was 30.7±6.7%: n=5). Therefore, we searched ATP-binding motifs in P2X receptors, and found a putative ATP-binding motif, G-X-G-X-X-G, in intracellular domains of human P2X1 and 5 receptors. Expression of P2X1 and 5 receptor proteins and their co-localization were confirmed in each arterial tissue.   Conclusions:  Vascular distinctive P2X receptors, namely P2X1 and 5, are controlled by extracellular and intracellular ATP bi-directionally. These results suggest that P2X1 and 5 receptors may play important role under the pathophysiological condition including hypoxia.
Abstract 1770: Outcomes following ECMO use to aid Cardiopulmonary Resuscitation in Children
Authors: Ravi RThiagarajan, Peter CLaussen, PeterRycus, Susan LBratton
Journal: Circulation (2006)

Introduction: ECMO started during ongoing CPR (E-CPR) has been used to supplement cardiopulmonary resuscitation (CPR) in children. We describe outcomes, and factors associated with survival after E-CPR, using data reported to the Extracorporeal Life Support Organization Registry (ELSO). Methods: Patients receiving E-CPR during 1992 – 2005 were extracted from the ELSO registry database. Medical conditions leading to cardiac arrest were grouped by ICD-9 diagnosis codes into E-CPR indication groups: ‘cardiac’, ‘neonatal respiratory’, ‘pediatric respiratory’, ‘sepsis’, ‘trauma’ and ‘other disease’. Demographic, pre-ECMO and ECMO support data between patients surviving to hospital discharge and those who died were analyzed. Stepwise forward logistic regression models were used to evaluate factors associated with survival. Results: Six hundred and ninety E-CPR runs were reported in 682 patients during the study period. Overall survival was 38%. Median age was 3 months (range 0 – 215) and cardiac disease (74%) w...
Relation of serum valproate concentration to response in mania
Authors: C L Bowden, P G Janicak, P Orsulak, A C Swann, J M Davis, J R Calabrese, P Goodnick, J G Small, A J Rush, S E Kimmel, S C Risch, D D Morris
Journal: American Journal of Psychiatry (1996)

This study was designed to determine the relation of valproate serum levels to clinical improvement and development of adverse effects in hospitalized patients with acute mania. The initial fixed-dose escalation design, the monotherapy with divalproex, and the control of variables that is possible only with hospitalized patients reduced the confounding factors present in most outpatient studies of serum level-response relationships.Sixty-five hospitalized patients who met the Research Diagnostic Criteria for bipolar disorder with mania were treated with divalproex, 750 mg/day for 2 days and then 1,000 mg/day on days 3-5; the dosage was subsequently adjusted as clinically indicated for the remainder of the 21-day study. Manic symptoms were assessed with the Mania Rating Scale, which is derived from the Schedule for Affective Disorders and Schizophrenia.At day 5, patients with serum valproate levels > or = 45 micrograms/ml were two to seven times as likely as patients with levels < 45 micrograms/ml to show 20% or greater improvement in scores on the manic syndrome subscale, the behavior and ideation subscale, elevated mood, increased activity, motor hyperactivity, and psychosis. Endpoint analyses yielded similar results. Adverse experiences characteristic of divalproex treatment were disproportionately associated with serum levels > or = 125 micrograms/ml.Acutely manic patients treated with divalproex who have valproate serum levels between 45 and 100-125 micrograms/ml are much more likely to have efficacious and well-tolerated responses than patients with lower or higher levels of valproate.
Abstract 448: Platelets Contribute to Arterial and Venous Thrombosis in vivo
Authors: Maria Koellnberger, Marie-Luise von Bruehl, Wolfgang Bergmeier, Denisa Wagner, Nigel Mackman, Steffen Massberg
Journal: Circulation (2007)

Background: Arterial (AT) and venous thromboses (VT) are the major causes of morbidity in industrialized countries. While the critical contribution of platelets to AT has been recognized, the molecular and cellular mechanisms that trigger the development of VT are not yet fully understood. Methods: We established a novel model of VT, where thrombus formation occurs after venous stasis in the absence of mechanical endothelial injury. In contrast to published models, our approach closely resembles the triggers that lead to VT in humans. The molecular and cellular events in VT were assessed using intravital and electron microscopy. In particular, we evaluated the differential contribution of platelets (pts) and leukocytes (lcs) to AT and VT. Results: We found that in AT pts adhere rapidly, whereas only few lcs are recruited. The loss of platelet P-Selectin reduced lc accumulation during AT, was associated with thrombus destabilization, but had no effect on pt adhesion/aggregation. The loss of GPIIb led to a complete lack of pt adhesion/aggregation in AT. While AT largely depends on pts, lc adhesion was the prominent initial phenomenon during VT and involved both P-selectin and Mac-1. P-Selectin−/− as well as Mac-1−/− mice showed a massive reduction in lc accumulation. The lack of P-Selectin was accompanied by a reduction of the thrombus size 48 hours after stasis and was only marginally reduced in Mac 1−/− mice, indicating that lc rolling is sufficient to promote VT. The expression of tissue factor by lcs played a pivotal role for VT. Accordingly, mice with reduced TF expression showed a dramatic reduction in venous thrombus size. In addition to TF-bearing lcs, pts were recruited to the vessel wall early in VT. Pt accumulation involved both the fibrinogen and the vWF receptor and was virtually abolished in mice lacking GPIIb or GPIbα. To our surprise, we observed that pts do not accumulate during VT but play a functional role. Reduced pt adhesion in mice lacking either GPIIb, GPIbα, or VWF was associated with a significant reduction in venous thrombus size. Conclusion: Together, we show that VT, unlike AT depends on the concerted action of both lcs and pts. Hence, targeting pt activation and adhesion might provide a promising strategy in the prophylaxis and treatment of VT.
The Effect of 6-Mercaptopurine on the Duration of Steroid-induced Remissions in Acute Leukemia: A Model for Evaluation of Other Potentially Useful Therapy
Authors: EMIL J FREIREICH, EDMUND GEHAN, EMIL FREI, LESLIE R. SCHROEDER, IRVING J. WOLMAN, RACHAD ANBARI, E. OMAR BURGERT, STEPHEN D. MILLS, DONALD PINKEL, OLEG S. SELAWRY, JOHN H. MOON, B. R. GENDEL, CHARLES L. SPURR, ROBERT STORRS, FARID HAURANI, BARTH HOOGSTRATEN, STANLEY LEE
Journal: Blood (1963)
Irish poll indicates attitudes on abortion are changing
Authors: Doug Payne
Journal: BMJ (2001)

Irish attitudes towards abortion may gradually be changing judging from the results of a recent public poll released as a Dutch reproductive health clinic offering abortions, which is housed aboard a freighter, was due to reach Dublin.

The poll, done for the Abortion Reform lobby group in the Republic of Ireland by Lansdowne Market Research, indicates that 79% of respondents would now accept women having limited access to legal abortion. Nearly half (47%) supported abortion in cases of rape or incest, and 52% supported terminations when there was a physical threat to the mother's life. One in 6 …
Experiences of a paraplegic psychiatry resident on an inpatient psychiatric unit
Authors: B B Lawn
Journal: American Journal of Psychiatry (1989)

The author reviews the literature on disabled physicians and describes her own adjustment to paraplegia. While she was a medical student and practicing internist, she encountered few comments about her disability, but during her later psychiatry residency, hospitalized psychiatric patients discussed it frequently. The author presents examples and points out that patients' reactions often revealed much about their characteristic response patterns; reactions to her disability became a type of projective test. Her primary defenses against patients' remarks were intellectualization and isolation of affect. Supervisors who were able to discuss the impact of her disability on the doctor-patient relationship were considered most helpful.
Abstract 17204: Association Between Interarm Systolic Blood Pressure Differential and Peripheral Artery Disease: A Population Database of Over 3.6 Million Subjects
Authors: Vinay D Madan, Caron B Rockman, Yu Guo, Mark A Adelman, Thomas S Riles, Jeffrey S Berger
Journal: Circulation (2013)

Introduction: Assessment of blood pressure (BP) in both arms is part of clinical care and recommended by guidelines. Recent small studies suggest that an interarm blood pressure differential (IBPD) >10mmHg is associated with all-cause mortality, yet uncertainty remains around different IBPD thresholds and association with other vascular phenotypes. We sought to investigate the prevalence, different cut-offs, and association of IBPD with peripheral artery disease (PAD). Methods: We analyzed data on 3.6 million participants who underwent PAD screening in the Life Line Screening Program from 2003-2008. All subjects completed a medical and lifestyle questionnaire and were evaluated with bilateral ankle brachial indices (ABI). PAD was considered present with an ABI   10 mmHg, including 313,350 (9.7%) 11-15 mmHg, 124,870 (3.9%) 16-20 mmHg, and 17...
Phase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum- and erlotinib- resistant adenocarcinoma of the lung (NSCLA)
Authors: E. Massarelli, V. A. Miller, N. B. Leighl, P. J. Rosen, K. S. Albain, L. L. Hart, O. Melnyk, L. Sternas, J. Ackerman, R. S. Herbst
Journal: Journal of Clinical Oncology (2007)

7627 Background: AVE0005 (VEGF Trap) is a recombinant fusion molecule of the human VEGF receptor extracellular domains and the F c portion of human IgG 1 . Methods: This is an open-label, single arm, multi-center trial employing a Simon 2-stage design. A total of 94 pts are planned. Three responses in the first 37 evaluable pts are required to progress to the second stage. IV AVE0005 (VEGF Trap) 4.0 mg/kg is given every 2 weeks to pts with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Other eligibility requirements include prior treatment with at least two cancer drug regimens in the advanced disease treatment setting, measurable disease, and ECOG performance status (PS) =2. Exclusions include squamous-cell lung cancer, prior treatment with a VEGF or VEGF receptor inhibitor with the exception of bevacizumab, history of brain metastasis, significant bleeding diathesis. End points are objective response rate, safety profile, duration of response, progression-free survival, overall survival and quality of life. Results: The study is ongoing and response and safety data are available for 33 pts (median age=60; males/females=14/19; ECOG PS 0/1/2=6/26/1 pts). A total of 132 cycles have been administered (median=4). Most common reason for withdrawal was progressive disease. Grade 3–4 treatment emergent adverse events (TEAEs) included (pts/percent) dyspnea (5/15%), hypertension and non-cardiac chest pain (3 pts each/9 %) fatigue (2/6 %), and anxiety, epistaxis, nausea, bone pain, proteinuria, febrile neutropenia, pneumonia, pulmonary embolism, and renal pain (1 each/3%). No grade 3 or greater hemoptysis has occurred. Two partial responses (PRs) have been reported to date. Conclusions: AVE0005 (VEGF Trap) 4 mg/kg IV has shown to be generally well tolerated; no significant hemoptysis has been seen to date. Single agent activity has been observed in this heavily treated population; interim futility analysis is awaited. The safety and preliminary activity profile supports further investigation with other targeted agents and cytotoxic chemotherapy. [Table: see text]