tbuckley/cabot-search huggingface dataset:
Abstract 10462: Induction of Cardiomyogenic Differentiation in Human Mesenchymal Stem Cells is Mediated by Gap Junctional Coupling with Cultured Rat Cardiomyocytes
Authors: Arti A Ramkisoensing, Daniël A Pijnappels, Jim Swildens, Martin J Schalij, Antoine A de Vries, Douwe E Atsma
Journal: Circulation (2011)

Purpose  - Connexin43 (Cx43) expression is important for functional integration of therapeutic cells with host myocardium. However, the role of this gap junction protein in cardiomyogenic differentiation of such cells is still unclear. In this study, the role of Cx43 expression in cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs) was investigated.   Methods  - Knockdown of Cx43 (Cx43KD) was established by 2 short hairpins directed against Cx43 in fetal hMSCs. Dye transfer and whole-cell current-clamp recordings were used to determine functional coupling of neonatal rat cardiomyocytes (nrCMCs) with hMSCs. To study cardiomyogenic differentiation, control hMSCs transduced with a short hairpin directed against eGFP and Cx43KD-hMSCs were co-incubated with nrCMCs for 10 days. Differentiation was assessed by immunostaining and whole-cell current-clamp recordings. Cx45 overexpression was introduced in Cx43KD-hMSCs to establish whether the effects of Cx43KD could be restored.   Results  - A Cx43 knockdown of 80% was achieved in Cx43KD-hMSCs compared to control hMSCs. Dye transfer and patch clamp analysis showed diminished functional coupling between Cx43KD-hMSCs and nrCMCs compared to control hMSCs and nrCMCs. Ten days after co-incubation, not a single Cx43KD-hMSC expressed the cardiac protein α-actinin, while control hMSCs did (2.18±0.39%, n=5000). Furthermore, functional cardiomyogenic differentiation, based on action potential recordings after gap junctional uncoupling, was shown to occur in control hMSCs but not in Cx43KD-hMSCs. After overexpression of Cx45 in Cx43KD-hMSCs, functional gap junctions were formed with nrCMCs. The ability to undergo functional cardiomyogenic differentiation was restored in these cells. This was confirmed by expression of α-actinin (1.58±0.38%, n=5000) and the presence of intrinsic action potentials in these cells.   Conclusion  - Induction of cardiomyogenic differentiation in fetal hMSCs is mediated by gap junctional coupling with nrCMCs. Reduced expression of Cx43 in hMSCs inhibits cardiomyogenic differentiation, which can be rescued by concurrent overexpression of Cx45. These insights may improve our understanding of how the local environment influences stem cell differentiation.
Abstract 8293: Atrial Fibrillation and Stroke in the General Medicare Population: a Fifteen Year Perspective (1992-2007)
Authors: Charles A Herzog, Craig A Solid
Journal: Circulation (2011)

Introduction: Non-valvular atrial fibrillation (AF) is a major cause of stroke in the elderly, and anticoagulation is indicated in these pts. Due to changing demography of the US population (“graying of America”), AF prevalence and characteristics of AF pts may have changed over time. Temporal trends in warfarin therapy potentially reflect evolving evidence-based practice patterns and pt characteristics. Methods: We searched the 5% Medicare database (n ∼ 1.8 million pts/cohort yr) to identify AF pts (no ESRD, age 65+) in 1992-2007. We used Medicare claims to count ischemic and hemorrhagic strokes after the AF diagnosis. We used 3+ prothrombin time (PT/ INR) claims as a surrogate for warfarin use (a previously validated method). For each year's cohort, we calculated the rate of stroke events (per time at risk) and warfarin use within the cohort. CHADS2 risk scores and contra-indications to warfarin use were derived from diagnosis codes. Results: The prevalence of AF within the elderly Medicare population grew from 3% in 1992 (n= 40,094; 37% age 65-74, 44% 75-84, 20% 85+; 44.7% male, 94.1% white, 4.1% black) to 7% in 2007 (n= 72,615; 31% age 65-74, 45% 75-84, 24% 85+; 47.7% male, 93.7% white, 3.7% black). The percent of pts at “high” risk for stroke (CHADS2 score &gt;2) rose from 20% to 28%. Warfarin use progressively increased from 27% in 1992 to 63% in 2007, despite increase in warfarin contra-indications from 32 to 42%. The Figure details stroke rates and warfarin use over time. Conclusion: Progressively more elderly AF pts have received warfarin therapy from 1992 to 2007. The characteristics of AF pts receiving warfarin have changed over time, reflecting temporal changes in practice patterns. The 15 yr decline in ischemic strokes (with no change in hemorrhagic stroke) is temporally co-incident with increasing warfarin use. Newer oral anti-coagulants without PT/INR monitoring requirements may further increase the number of elderly AF pts receiving therapeutic anti-coagulation.
Abstract 14660: Severe Pulmonary Hypertension and Right Ventricular Dysfunction in Rats are Associated with Changes in Ubiquitin Proteasome System
Authors: Soban Umar, Shannamar Dewey Dewey, Andrea Iorga, Aldrin Gomes, Mansoureh Eghbali
Journal: Circulation (2011)

Introduction. Ubiquitin-proteasome system (UPS) is responsible for degradation of intracellular proteins. UPS maintains a dynamic equilibrium of proteins and prevents accumulation of damaged and mi...
Perioperative and bedside cerebral monitoring identifies cerebral injury after surgical correction of congenital aortic arch obstruction
Authors: Selma O. Algra, Antonius N. J. Schouten, Nicolaas J. G. Jansen, Wim van Oeveren, Felix Haas, Floris Groenendaal, Petra M. A. Lemmers, Ingrid C. van Haastert, Mona C. Toet, Linda S. de Vries
Journal: Intensive Care Medicine (2015)
Patients need more information
Authors: B O Adegbehingbe, C Williams, D L Easty
Journal: BMJ (1995)

Driving, glaucoma, and the law Regular checks on medical fitness to drive needed EDITOR,-Potamitis and colleagues draw attention to widespread ignorance about regulations con- cerning visual fields for driving.'Because drivers are required to pass a visual acuity test as part of their driving test, however, most are aware of visual acuity as a component of visual function and of its relevance to driving.This does not necessarily imply greater compliance with the regulation concerning visual acuity than with those concerning visual fields.We recorded visual acuity (with glasses if wom) in consecutive patients attending the accident and emergency service at Manchester Royal Eye Hospital.Over one month 1426 patients were tested, of whom 177 had a visual acuity insufficient for legal driving.Most of these patients did not drive, but 42 still drove a car.Of these 42, 21 were "borderline" failures (6/12 in the better eye) but the remaining 21 would definitely have failed a standard numberplate reading test.All these patients had evidence of chronic visual loss, which was correctable by refraction in only some cases.Clearly, patients with acute eye problems may have acute visual deterioration.Such deterioration, however, is almost invariably unilateral.For driving a car, acceptable vision is only required in one eye.There was no evidence to suggest that these data were invalidated by acute, temporary visual loss in these patients.Potamitis and colleagues rightly recommend that greater information should be made available to drivers, both from the Driver and Vehicle Licensing Agency and from ophthalmologists.The key role of optometrists should also be made clear.The authors comment that patients need more information and imply that this will in itself improve driving safety by resulting in voluntary withdrawal on the part of unfit drivers, but this is merely an assumption.Do we not need regular checks on medical aspects of fitness to drive, even for people under retirement age?
Abstract 4052: Women Differ from Men in the Contribution of Vascular Progenitor Cells to Endothelial Function and Cardiovascular Risk
Authors: Margaret F Lippincott, Andrea Carlow, Gloria Zalos, Maria E Rodrigo, Richard O Cannon
Journal: Circulation (2006)

Objective: Endothelial dysfunction has been implicated in the development of cardiovascular disease. Our group previously reported that in men without known cardiovascular disease, endothelial prog...
Abstract 17329: Myocardial-Specific Overexpression of a Dominant-Negative Mutant of NADPH Oxidase Subunit p67phox Attenuates Pressure-Overload-Induced Cardiac Hypertrophy in Adult Transgenic Mice
Authors: Qiong Zhao, Xianyao Xu, Guiqing Zhao, Chongxu Zhang, Jing Deng, John W Christman, Lei Xiao
Journal: Circulation (2011)

We had reported a transgenic (Tg) mouse model with cardiac-specific overexpression of a dominant-negative (DN) mutant (V204A) of NADPH oxidase (NOX) subunit p67phox that inhibits NOX activity. In o...
Four-Year (Yr) Follow-Up Of Patients (Pts) With Newly Diagnosed Chronic Myeloid Leukemia In Chronic Phase (CML-CP) Receiving Dasatinib Or Imatinib: Efficacy Based On Early Response
Authors: Jorge E. Cortes, Andreas Hochhaus, Dong-Wook Kim, Neil P. Shah, Jiri Mayer, Philip Rowlings, Hirohisa Nakamae, M. Brigid Bradley-Garelik, Hesham Mohamed, Hagop M. Kantarjian, Giuseppe Saglio
Journal: Blood (2013)
Primary Neuroendocrine Tumor in a Horseshoe Kidney With Positive 111In-Pentetreotide Somatostatin Receptor Scintigraphy and Negative 18F-DOPA PET/CT
Authors: Mathieu Gauthé, Astrid Lièvre, Jean-Louis Alberini
Journal: Clinical Nuclear Medicine (2015)

Primary renal neuroendocrine tumors (NETs) are low-grade tumors with neuroendocrine differentiation and have been reported to arise most commonly in renal abnormalities such as horseshoe kidney. We report a case of a 54-year-old woman with history of invasive ductal breast carcinoma presenting several liver lesions. Histological findings finally revealed liver locations of a well-differentiated NET. Imaging workup combining somatostatin receptor scintigraphy and F-DOPA PET/CT finally enable proper diagnosis of primary renal NET located on the isthmus of a horseshoe kidney.
Abstract 5771: Aortic Root Dilatation is a Phenotypic Manifestation of the Bicuspid Aortic Valve Disease Prevalent in Relatives with Normal Aortic Valve.
Authors: Simon Biner, Asim Rafique, Indraneil Ray, Olivera Cuk, Robert Siegel, Kirsten Tolstrup
Journal: Circulation (2008)

Background: Bicuspid aortic valve (BAV) and dilated ascending aorta frequently coexist. 10% of first degree relatives (FDRs) of probands with BAV inherit a valvular abnormality, however there is limited data concerning the occurrence of dilated aortic root in families of affected subjects. We evaluated the prevalence of aortic root dilatation among FDRs with a tricuspid aortic valve. Methods: Aortic root dimensions were measured by 2D echocardiography in BAV probands (n=48), their FDRs (n = 49) and controls without structural heart disease matched by age and gender (n=44). Aortic root was measured at: annulus, sinuses of Valsalva, sino-tubular junction and proximal ascending aorta. The dimensions were indexed by body surface area (BSA). Presence of dilatation was determined using published confidence intervals relating normal aortic diameters to BSA and age. Results: Five subjects (10%) in FDR group were found to have BAV, thus they were included in BAV group. Indexed aortic diameter was significantly different in 3 groups namely BAV&gt;FDR&gt;Control at annulus (2.0±0.3, 1.7±0.2, 1.6±0.1, p&lt;0.001) and sinuses of Valsalva (2.8±0.5, 2.4±0.4, 2.2±0.3, p&lt;0.001) Figure . BAV subjects showed significantly larger dimensions in the ascending aorta compared to FDRs and controls (p&lt;0.001). The prevalence of aortic root dilatation at all levels was 51% in BAV subjects, 25% in FDRs and 0% in controls (p&lt;0.001). Conclusions: There is high prevalence of aortic root dilatation in the FDRs of subjects with BAV despite having normal tricuspid aortic valve. This finding suggests that aortic root dilatation is another phenotypic manifestation of BAV disease that is inherited independent of BAV.
Abstract 1765: Immunosuppressive Potential of Ibp - A Novel Inhibitor of the Calcineurin/NF-AT Cascade
Authors: Claudia Gebhardt, Natalie Burkard, Martin Czolbe, Tatjana Williams, Franziska Panther, Oliver Ritter
Journal: Circulation (2008)

Background: The calcineurin (Cn)/NF-AT signaling cascade plays a crucial role during T-cell activation and development of myocardial hypertrophy. We previously demonstrated that, in addition to NF-AT, Cn is translocated to the nucleus. We also developed a synthetic peptide (IBP) which inhibited the nuclear import of Cn without affecting calcineurin phosphatase activity. The antihypertrophic effect of IBP on the rat myocardium was shown in vivo and in vitro . Here we extended our studies on a potential use of IBP in the prevention of transplant rejection. Methods and results: Coimmunoprecipitation experiments revealed that the synthetic IBP peptide, which is identical to the nuclear localization sequence of calcineurin, disrupts importin/calcineurin interaction. We further demonstrated that inhibition of the importin/calcineurin interaction by the small competitive peptide (IBP) is sufficient to inactivate the calcineurin/NF-AT signaling cascade. Inhibitory effects of IBP on T-cell activation were analyzed by [H 3 ]-thymidine incorporation (7135 ± 2503 vs. 2957 ± 1161 [%]) in activated T-cells in vitro (dentritic cells were used as antigen stimulation). To verify immunosuppressive effect of IBP in vitro , heterotopic heart transplantations were performed on rats. Following transplantation rats were treated with IBP (i.p. 130mg/kg/d) or peanut oil as control (i.p. 1 ml peanut oil/d) for 14 days. Time until transplant rejection was significantly prolonged in IBP treated animals compared to control group (15.2 ± 1.5 day vs. 4 ± 2.8 day; n = 8; p &lt; 0.05). Immunohistochemical studies from transplanted hearts demonstrated that the synthetic calcineurin inhibitory peptide IBP prevented calcineurin nuclear translocation in infiltrating T cells in the donor hearts. Conclusions: The synthetic inhibitory peptide IBP disrupts the calcineurin/NF-AT cascade by inhibition of Cn nuclear import. This suppresses T-cell activation in vitro and in vivo, thereby revealing a potential use of IBP as novel agent to protect donor organs from rejection.
Future of international health
Authors: F S Antezana, A. Haines
Journal: BMJ (1997)

Substantial progress has been made during the past 18 months within the World Health Organization (WHO) with regard to addressing the issues raised in the renewal of the Health for All process.  It is clear that WHO is taking a proactive role in advancing the health for all policy.  However Fiona Godlees editorial which focused upon internal and external debates failed to capture the full scope of the process.  Godlee did not note that those debates have been both formally and informally linked to the renewal process a process which WHO holds to be central to the future course of world health.  WHOs views are shared by its member states and governing bodies.  Policy renewal was discussed during the 50th World Health Assembly in May and during the subsequent session of the executive board.  Fundamental actions suggested during the board meeting include creating a universal Health for All value system which explicitly considers the pursuit of human rights and health security equity ethics and a gender perspective making health central to development.  The complexity of future health demands requires consideration of a broader agenda for global health action not one which is narrow and disease specific.
Abstract 37: The Impact Of Bodyweight On Early And Late Mortality And ICD Shocks In Ventricular Fibrillation Out-of-hospital Cardiac Arrest Survivors
Authors: T. J Bunch, Roger D White, Francisco Lopez-Jimenez, Randal J Thomas
Journal: Circulation (2007)

Background : Studies have shown an association between obesity and total mortality in patients with and without coronary artery disease. Less is known regarding the impact of obesity after cardiac arrest. Obese survivors of ventricular fibrillation (VF) out-of-hospital cardiac arrest (OHCA) may have worse outcomes than nonobese patients due to resuscitation challenges, long-term risks of cardiovascular disease, and other comorbidities. Methods : All patients who presented with a VF OHCA in Rochester Minnesota from November 1990-September 2006 were included. Patients were classified by weight (BMI &lt;25, 25–30, &gt;30). ICD shocks for VF/VT were determined by review of subsequent device interrogations. Results : 226 patients (age 63.7±13.5) were treated for VF OHCA with an average call-to-shock time of 6.3±1.8 minutes. 99 patients (44%) survived to hospital discharge with neurologic recovery. Data to calculate BMI were available in 213(95%). There was no difference between the relative distribution of body weight between the hospital survivors [&lt;25(32%), 25–30(37%), &gt;30(31%)] and nonsurvivors [&lt;25(32%), 25–30(44%), &gt;30(28%)], p=0.711. There was no difference in ICD implantation rates between weight groups (p=0.251). The patients were followed for an average of 5.8±4.4 years. The 5-year survival was 80±5%. 5-year survival was lower in underweight/normal patients [&lt;25, 71% (63–79) compared to heavier patients (25–30:88% (82–94), p=0.001]. The survival difference persisted after adjustment for age (p=0.02). Malignancy was the most common cause of death in the underweight group. The 5-year survival free of ICD shocks was 61±7% with no weight-based difference in shocks. Conclusion : There was no apparent weight-based influence on resuscitation survival after VF OHCA. Patients who are under to normal weight had a lower long-term survival and represent a high-risk population primarily due to noncardiac diseases.
A Phase I Study Of KB004, a Novel Non-Fucosylated humaneered® Antibody, Targeted Against The Receptor Tyrosine Kinase EphA3, In Advanced Hematologic Malignancies
Authors: Jeffrey E Lancet, Andrew H Wei, Simon TS Durrant, Mark S. Hertzberg, Ronan T. Swords, Ian D Lewis, Brian Jonas, Jorge E. Cortes, Geoffrey Yarranton, Jackie M. Walling
Journal: Blood (2013)
Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung
Authors: Hyo Sup Shim, Mari- Kenudson, Zongli Zheng, Matthew Liebers, Yoon Jin Cha, Quan Hoang Ho, Maristela Onozato, Long Phi Le, Rebecca S. Heist, A. John Iafrate
Journal: Journal of Thoracic Oncology (2015)
Abstract 15489: Postprandial Elevation of Granulocyte Inflammation Associated with Delayed Triglyceride-Rich Lipoprotein Clearance Contributes to Elevated Metabolic Risk in Apolipoprotein E2 Gene Replacement Mice
Authors: David G Kuhel, Joshua E Basford, Colleen T Goodin, Courtney McVey, Philip Howles, David Y Hui
Journal: Circulation (2011)

Although the e2 allele of the human APOE gene encoding apoE2 is typically associated with normal or reduced plasma lipid levels, prolonged postprandial hyperlipidemia is typical in e2 carriers. Sub...
Abstract 17993: Bystander-Initiated Cardiopulmonary Resuscitation Can Maintain Regional Cerebral Oxygen Saturation Levels on Hospital Arrival in Patients with Refractory Out-of-Hospital Cardiac Arrest
Authors: Noritoshi Ito, Shinsuke Nanto, Ken Nagao, Tetsuo Hatanaka, Kei Nishiyama, Yasuji Doi, Yuma Kurozumi, Tomoaki Natsukawa, Masaya Morita, Atsushi Kawata, Ayumu Tsuruoka, Hirotaka Sawano, Hiroyuki Shibata, Noriaki Yamada, Ken-ichiro Okada, Yasuyuki Hayashi, Tatsuro Kai, Toru Hayashi
Journal: Circulation (2011)

Background: Bystander-initiated cardiopulmonary resuscitation (B-CPR) plays a key role in the chain of survival for out-of-hospital cardiac arrest (OHCA) patients. We have previously reported that a low regional cerebral oxygen saturation (rSO2) level is a strong predictor of poor neurological outcome in OHCA patients. Objectives: To assess the association between B-CPR and rSO2 levels measured immediately on hospital arrival. Methods: This study was a prospective cohort study. Of 418 OHCA patients, 186 consecutive non-traumatic, cardiac arrest on arrival (CAOA) patients were prospectively registered. The rSO2 levels were measured with sensors placed on either side of their forehead using a near-infrared spectroscopy (NIRS) device (INVOS, Covidien, US) within 3 minutes after hospital arrival. We monitored rSO2 levels at least for more than one minute and used the lower of the 2 measured rSO2 levels for analysis. Clinical staff performed ordinary post-cardiac-arrest interventions (PCAIs) regardless of rSO2 levels. Primary outcome measure was good neurological outcome (CPC 1/2) at hospital discharge according to the “Utstein-style”. After dividing the eligible 186 patients into the two groups (B-CPR group (n=76) and no B-CPR group (n=110)), we compared the rSO2 levels on hospital arrival and the neurological outcome between the two groups. Results: Among 186 CAOA patients in PCAIs era, 18 patients (9.7%) had good neurological outcome. The B-CPR group patients had more maintained rSO2 levels on hospital arrival with a much higher proportion of good neurological outcome as compared with the no B-CPR group patients (33±20% vs. 22±13%, p=0.00003; 21% vs. 2%, p=0.00005, respectively). Conclusion: The findings suggest that B-CPR for CAOA patients after OHCA contributes to maintaining the rSO2 levels on hospital arrival and improving neurological outcome at hospital discharge even in the PCAIs era.
HoxC8 in cancer: Suppressor or progressor?
Authors: Carl C. Schimanski, Alfred Duehrssen, Anubha Kashyap, Arndt Weinmann, Martin R. Berger, Peter R. Galle, Susanne Strand, Dennis Strand
Journal: Cancer Research (2005)

2854  Introduction: Homebox genes encode transcription factors that play important roles during early developmental processes. Some are expressed in adulthood and alterations have been linked to cancers. Both proto-oncogenic and tumor suppressor functions have been described for homeobox genes. Dysregulation of HoxC8 in tumors has been correlated with tumor progression in prostate cancers. However, evidence for a tumor suppressor function for HoxC8 also exists. We have investigated the functional consequences of expressing HoxC8 in cell lines and compared HoxC8 expression in patients with colorectal cancer (CRC) to clinico-pathological paramenters. Experimental design: Ecdysone-inducible HoxC8 cell lines were established and applied in diverse functional assays. Putative HoxC8 target genes were identified by cDNA microarray analysis using these cell lines. To evaluate the impact of HoxC8 dysregulation in CRC, the transcription profile of HoxC8 was determined in colorectal cancer cell lines, colorectal mucosa, adenomas, colorectal cancer specimens and hepatic metastases by RT-PCR, respectively. Results: HoxC8 induction significantly decreased cell growth, colony formation and cell migration. Additionally, apoptosis induced by doxorubicin, bleomycin and CD95 increased when HoxC8 was induced. A number of the HoxC8 target genes we identified are regulators of the cell cycle and have tumor suppressor functions. Human colorectal cancer cell lines displayed variable intensities of HoxC8 transcription. In patient samples, no HoxC8 transcription was observed in colon mucosa (0/19) and polyps (0/10), but in 22% (15/69) of colorectal cancers and in 30% (3/10) of hepatic metastases. Interestingly, HoxC8 transcription was significantly associated with smaller tumors and with the absence of lymphatic invasion. Conclusion: Our results support a potential tumor suppressor function for HoxC8. We propose that upregulation of HoxC8 and its targets in certain contexts may be a compensentory response of the cell to counter transformation processes. Thus, de novo expression of tumor suppressor gene networks regulated by Hox genes may be an important mechanism operating in cells to eliminate or hinder tumor growt