tbuckley/cabot-search huggingface dataset:
Survival and Function of Bioengineered Cardiac Grafts
Authors: R.-K. Li, Z.-Q. Jia, R. D. Weisel, D. A. G. Mickle, A. Choi, T. M. Yau
Journal: Circulation (1999)

Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells derived from fetal rat ventricular muscle into a biodegradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft.A cardiomyocyte-enriched cell inoculum derived from fetal rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontario, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by constructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcutaneous tissue of adult rat legs or onto myocardial scar tissue in a cryoinjured rat heart. Five weeks later, the graft was studied histologically. The inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contracted regularly and spontaneously. When implanted onto myocardial scar tissue, the cells within the graft survived and formed junctions with the recipient heart cells.Fetal rat ventricular cells can grow 3-dimensionally in a gelatin mesh. The cells in the graft formed cardiac tissue and survived and contracted spontaneously both in tissue culture and after subcutaneous implantation. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects.
Effects of Inhibition of the <scp>l</scp> -Arginine/Nitric Oxide Pathway on Vasodilation Caused by β-Adrenergic Agonists in Human Forearm
Authors: Matthew Dawes, Philip J. Chowienczyk, James M. Ritter
Journal: Circulation (1997)

We examined whether vasodilator responses to beta-agonists in human forearm vasculature are mediated in part through the nitric oxide pathway.We measured forearm blood flow responses to brachial artery infusions of beta-adrenergic agonists in healthy men. Salbutamol was more than 100 times as potent as dobutamine. Cumulative doses of salbutamol (0.3 to 3.5 nmol.min-1) did not cause tachyphylaxis to an identical repeated infusion after a 24-minute recovery period. Vasodilators were infused with this sequence during coinfusion of saline and NG-monomethyl-L-arginine (L-NMMA, 4 mumol.min-1), an inhibitor of nitric oxide synthase. L-NMMA coinfusion inhibited responses (area under the dose-response curve) to isoproterenol (0.01 to 0.1 nmol.min-1) by 59 +/- 7% (n = 5) and inhibited those to salbutamol (0.3 to 3.5 nmol.min-1) by 52 +/- 6% (n = 8). L-NMMA had no significant effect on vasodilator responses to nitroprusside (2.7 to 11.0 nmol.min-1, n = 8), verapamil (20 to 80 nmol.min-1, n = 8), or prostacyclin (0.08 to 0.24 nmol.min-1, n = 8).These results suggest that beta-adrenergic vasodilator responses in human forearm vasculature are mediated predominantly through beta 2-adrenergic receptors and are dependent on nitric oxide synthesis.
Effects of Experimental Coarctation of the Aorta on the Blood Pressure of Sheep
Authors: F. R. MAGAREY, W. E. STEHBENS, ALAN SHARP
Journal: Circulation Research (1959)

Blood pressures have been taken from the carotid and femoral artery in sheep following experimental coarctation of the aorta at about the level of the ligamentum arteriosum. Systolic, diastolic, mean, and pulse pressures have been recorded at intervals of from 3 to 6 months over a period of as long as 3 years in some cases. Unoperated sheep have been used as controls. The main changes are a rise in all the carotid pressures and in the femoral diastolic, a fall in the femoral systolic and pulse pressures, and no significant change in the femoral mean pressure. These changes in hemodynamics resulting from coarctation may be adequately explained by the mechanical effects of the coarctation. Over a period of 3 years there is a slight rise of blood pressures in both the normal and the coarctated sheep.
Most C6 Cells Are Cancer Stem Cells: Evidence from Clonal and Population Analyses
Authors: Xuesheng Zheng, Gang Shen, Xiaofeng Yang, Weiguo Liu
Journal: Cancer Research (2007)

Abstract Cancer stem cells have been isolated from human gliomas and many other parenchymal tumors. It was previously assumed that many established malignant cell lines also contain a rare subpopulation of stem cells. This study was designed to investigate the fraction of cancer stem cells in the C6 glioma cell line using clonal and population analyses, rather than isolating methods, which are based on specific markers. Interestingly, in the serum-containing medium, each of the 67 single C6 cells plated per miniwell was able to generate a clone and subclones, which subsequently gave rise to a xenograft glioma in the BALB/C-nude mouse. The CD133− C6 cells also possessed clonogenic, self-renewal, and tumorigenic capacities. Moreover, our findings indicated that brief exposure to Hoechst 33342 was harmful to the clonogenicity and proliferation of individual C6 cells. Therefore, the non–side-population cells may be deprived of their stem cell features in the process of Hoechst 33342 staining as a step in isolating a Hoechst-negative side population with flow cytometry. Thus, we concluded that the C6 line was mainly composed of cancer stem cells, although many of them were neither CD133+ nor side population. [Cancer Res 2007;67(8):3691–7]
TCT-244 Baseline Thrombocytopenia: A Strong Predictor Of One-Year Adverse Ischemic Events In Patients With ACS Undergoing PCI: A Pooled analysis From ACUITY And HORIZONS-AMI Trials
Authors: Mayank Yadav, Philippe Genereux, Ajay J. Kirtane, Mahesh V. Madhavan, Ke Xu, Sorin Brener, Roxana Mehran, Gregg Stone
Journal: Journal of the American College of Cardiology (2013)
Docetaxel Combined With Trastuzumab Is an Active Regimen in HER-2 3+ Overexpressing and Fluorescent In Situ Hybridization–Positive Metastatic Breast Cancer: A Multi-Institutional Phase II Trial
Authors: K.L. Tedesco, A.D. Thor, D.H. Johnson, Y. Shyr, K.A. Blum, L.J. Goldstein, W.J. Gradishar, B.P. Nicholson, D.E. Merkel, D. Murrey, S. Edgerton, G.W. Sledge
Journal: Journal of Clinical Oncology (2004)

Purpose To determine the efficacy and safety of weekly docetaxel and trastuzumab as first- or second-line therapy in women with HER-2–overexpressing metastatic breast cancer and to correlate the efficacy of trastuzumab with HER-2 status as determined by immunohistochemistry assay and fluorescent in situ hybridization (FISH). Patients and Methods Twenty-six women with HER-2–positive (HercepTest [Dako Corp, Carpenteria, CA]2 to 3+) metastatic breast cancer were enrolled onto this study of trastuzumab (4 mg/kg load; 2 mg/kg/wk administered intravenously) and docetaxel (35 mg/m 2 /wk for 6 weeks). Results Using an intent-to-treat analysis, the overall response rate was 50% (13 of 26 patients). Eight patients (31%) had a period of stable disease posttherapy. Among HER-2 3+ patients, the overall response rate was 63% (12 of 19 patients) compared with a 14% response rate (one of seven patients) for HER-2 2+ patients (P = .07). Patients with FISH-positive tumors experienced an overall response rate of 64%. Median time to progression was 12.4 months for the entire cohort (HER-2 3+ tumors, 12.3 months; HER-2 2+ lesions, 9.5 months) and median survival was 22.1 months. All HER-2 3+ patients were FISH-positive; the only HER-2 2+ patient responding to treatment was also FISH-positive. Grade 4 toxicities occurred in four patients; most toxicities were mild. Conclusion Trastuzumab plus docetaxel is an active and well-tolerated regimen in women with HER-2 3+ overexpressing or FISH-positive metastatic breast cancer.
Extinction of the tumor necrosis factor locus, and of genes encoding the lipopolysaccharide signaling pathway.
Authors: V Kruys, P Thompson, B Beutler
Journal: The Journal of Experimental Medicine (1993)

The tumor necrosis factor (TNF-alpha or TNF) gene is activated by both lipopolysaccharide (LPS) and cycloheximide in RAW 264.7 macrophages, whereas neither stimulus activates the gene in 3T3 fibroblasts. Moreover, the pattern of CG methylation within the TNF gene is readily distinguishable in DNA derived from cells of these two types. These findings would suggest that the TNF gene has been rendered inaccessible to transcription in the 3T3 cell environment. When RAW 264.7 cells are fused with 3T3 cells, an immortal pentaploid hybrid results. In the hybrid cell, all three TNF genes contributed by the RAW 264.7 cell parent become highly methylated according to the pattern observed in the 3T3 cell parent. Permanently transfected chloramphenicol acetyl transferase (CAT) reporter constructs, bearing 2.2 kb of upstream sequence (including the entire TNF promoter and 5'-untranslated region [UTR]) as well as 1.0 kb of downstream sequence (including the entire TNF 3'-UTR and termination sequence), are accessible in both RAW 264.7 cells and 3T3 cells, but are silenced in transition from the RAW 264.7 cell to the hybrid cell environment. Moreover, the endotoxin signaling pathway is abrogated, as assessed by transient transfection of hybrid cells with LPS-responsive CAT reporter constructs. It would therefore appear that the fusion of 3T3 cells and RAW 264.7 cells activates a system that silences the TNF gene, as well as the LPS signaling pathway. This system may operate to determine TNF gene accessibility and LPS responsiveness in the course of cell differentiation. The DNA sequences targeted within the TNF gene are included in the CAT reporter construct; therefore, the silencing element has been circumscribed to a region of DNA 3.2 kb in length.
Plasma VEGF correlates with right ventricular function in pulmonary hypertension
Authors: Judit Pako, Andras Bikov, Kristof Karlocai, Gyorgyi Csosza, Dorottya Kovacs, Gyorgy Losonczy, Ildiko Horvath
Journal: European Respiratory Journal (2011)

Introduction:  Pulmonary hypertension (PH) is a severe, progressive condition of the small pulmonary vessels that leads to increased pulmonary vascular resistance, right ventricular failure and death. Previous studies suggest the role of VEGF (vascular endothelial growth factor) in the pathomechanism of PH by several pathways. Still, the relationship between airway VEGF and right ventricular function has not been investigated yet.   Aims:  We aimed to evaluate the exhaled breath condensate (EBC), as an airway sampling technique for VEGF detection in subjects with PH and to compare EBC and plasma VEGF with the best noninvasive clinical sign of advanced disease, by measuring right ventricular longitudinal function, tricuspid anular plane systolic excursion (TAPSE).   Methods:  10 PH patients (6 IPAH, 2 CTEPH, 1 scleroderma, 1 congenital heart disease, 58±17 years, mean pulmonary pressure 58±21 mmHg), and 9 healthy controls (50±13 year) participated in the study. Plasma and EBC (Rtube, Charlotteswille, US) were collected for VEGF measurements (Quantikine ELISA kit, R&D) and echocardiography was performed to assess TAPSE.   Results:  In EBC the VEGF concentration was under the limit of detection in both groups. The level of plasma VEGF was significantly higher in the patient group than in controls (130±98 pg/ml, 30±40 pg/ml, p=0,004). We found significant correlation between TAPSE and plasma VEGF level in PH patients (p=0,02, r=0,69).   Conclusion:  We suggest, that decrease of VEGF with advanced PAH disease can be a result of deterioration of right ventricular contractility accompanied with decreased pulmonary flow and wall stress. However, EBC is not applicable to assess airway VEGF levels in PH patients.
Effect of dry needling of gluteal muscles on straight leg raise: a randomised, placebo controlled, double blind trial
Authors: L Huguenin, P D Brukner, P McCrory, P Smith, H Wajswelner, K Bennell
Journal: British Journal of Sports Medicine (2005)

To use a randomised, double blind, placebo controlled trial to establish the effect on straight leg raise, hip internal rotation, and muscle pain of dry needling treatment to the gluteal muscles in athletes with posterior thigh pain referred from gluteal trigger points.A randomised, double blind, placebo controlled trial of 59 male runners was performed during the 2002 Australian Rules football season. Subjects were thoroughly screened and had magnetic resonance imaging of their hamstring muscles to exclude local pathology. The inclusion criterion was reproduction of recognisable posterior thigh pain with the application of digital pressure to the gluteal trigger points. Subjects randomly received either therapeutic or placebo needle treatment on one occasion at their gluteal trigger points. Range of motion and visual analogue scale data were collected immediately before, immediately after, 24 hours after, and 72 hours after the intervention. Range of motion was measured with passive straight leg raise and hip internal rotation. Visual analogue scales were completed for hamstring and gluteal pain and tightness at rest and during a running task.Magnetic resonance imaging scans revealed normal hamstring musculature in most subjects. Straight leg raise and hip internal rotation remained unchanged in both groups at all times. Visual analogue scale assessment of hamstring pain and tightness and gluteal tightness after running showed improvements immediately after the intervention in both groups (p = 0.001), which were maintained at 24 and 72 hours. The magnitude of this improvement was the same for therapeutic and placebo interventions. Resting muscle pain and tightness were unaffected.Neither dry needling nor placebo needling of the gluteal muscles resulted in any change in straight leg raise or hip internal rotation. Both interventions resulted in subjective improvement in activity related muscle pain and tightness. Despite being commonly used clinical tests in this situation, straight leg raise and hip internal rotation are not likely to help the therapist assess response to treatment. Patient reports of response to such treatment are better indicators of its success. The mechanisms by which these responses occur and the reasons for the success of the placebo needling treatment are areas for further investigation.
Reproductive risks of cocaine
Authors: B Rizk
Journal: Human Reproduction Update (1996)

Cocaine use during pregnancy in the USA has increased dramatically in the past decade, and has resulted in an associated increase in a variety of maternal and perinatal complications. However, a number of confounding factors make it difficult to determine the direct impact of perinatal cocaine use on maternal and fetal outcome. Many substance-abusing women use multiple drugs while pregnant, receive inadequate prenatal care and are predisposed to other health problems that impact on perinatal outcome. As a result of the rapid clearance of cocaine and limitations of available screening methods, the identification of individual users can be difficult. Furthermore, the determination of accurate prevalence rates of cocaine use during pregnancy has been frustrated by sampling bias. Cocaine has profound systemic and cardiovascular effects in both the mother and the fetus, and as a rsult a number of complications (i.e. fetal malformations, preterm labour, placental abruption) have been attributed to perinatal cocaine exposure. In addition, maternal cocaine use has been associated with a number of neonatal abnormalities, including cardio-pulmonary effects, somatic changes and neuro-behavioural sequelae. It is estimated that US $500 million dollars in additional health expenditure resulted from increased neonatal hospital costs and longer lengths of stay for cocaine-exposed neonates. This article reviews the reproductive risks associated with prenatal cocaine use. The pharmacology and physiology of cocaine in relation to pregnancy is discussed, and the impact of this substance on the growth and development of the fetus and infant is reviewed.
Puromycin Aminonucleoside Suppresses Integrin Expression in Cultured Glomerular Epithelial Cells
Authors: UMA KRISHNAMURTI, BING ZHOU, WEI-WEI FAN, EFFIE TSILIBARY, ELIZABETH WAYNER, YOUNGKI KIM, CLIFFORD E. KASHTAN, ALFRED MICHAEL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. Because PAN injection into rats results in retraction of glomerular epithelial cell foot processes and glomerular epithelial cell detachment, it was hypothesized that PAN might alter the contacts between these cells and the glomerular basement membrane. The major integrin expressed by glomerular epithelial cells is α3β1, which mediates attachment of these cells to extracellular matrix proteins including type IV collagen. T-SV 40 immortalized human glomerular epithelial cells were used to study PAN's effects on α3β1 expression, as well as that of podocalyxin and the slit diaphragm component ZO-1. Glomerular epithelial cells were seeded into plastic flasks and allowed to attach and proliferate for 48 h. The cells were then incubated for another 48 h in media containing 0, 0.5, or 5.0 μg/ml PAN. PAN exposure resulted in dose-dependent decreases in α3 and β1 expression, both at the protein level and at the mRNA level. This was accompanied by a significant decrease in the adhesion of glomerular epithelial cells to type IV collagen. PAN did not affect ZO-1 protein expression. Treatment with PAN increased the expression of podocalyxin at the protein and mRNA levels. Reduced glomerular epithelial cell expression of α3β1 integrins and impaired adhesion to type IV collagen may contribute to the glomerular epithelial cell detachment from glomerular basement membrane seen in the PAN nephrosis model.
Usefulness of Home Blood Pressure Measurement in the Morning in Type 1 Diabetic Patients
Authors: Kyuzi Kamoi, Youichi Imamura, Masashi Miyakoshi, Chiaki Kobayashi
Journal: Diabetes Care (2003)

Recently, we reported that home blood pressure (BP) measurement in the morning has a stronger predictive power for micro- and macrovascular complications in type 2 diabetic patients than casual/clinic BP measurement (1). Here we report the results examined in the study of type 1 diabetic patients.

We studied 53 type 1 diabetic patients who regularly visited our clinics. The number of female patients (36) was twice that of male patients (17). The subjects were aged 23–81 years (mean 54 ± 17) and had a diabetes duration of 2–47 years (mean 17 ± 10). Their mean BMI was 22 ± 3 kg/m2, HbA1c 7.0 ± 0.9%, triglycerides 94 ± 44 mg/dl, total cholesterol 201 ± 32 mg/dl, LDL 107 ± 25 mg/dl, and HDL 75 ± 18 mg/dl. Of 53 patients, 38 (72%) were treated by multiple daily insulin injections and the remaining (28%) received subcutaneous continuous insulin infusion for diabetes. Twenty-two patients (42%) were treated with antihypertensive drugs at the beginning of the study.

The study design and analysis are the same as previously reported (1). BP was measured at the clinic during the day and at home after waking. Clinic hypertension and morning hypertension were defined as systolic BP (SBP) 130 mmHg and/or diastolic BP (DBP) 85 mmHg, whereas clinic normotension and morning normotension were SBP …
Gemcitabine Pharmacogenomics: Cytidine Deaminase and Deoxycytidylate Deaminase Gene Resequencing and Functional Genomics
Authors: Judith A. Gilbert, Oreste E. Salavaggione, Yuan Ji, Linda L. Pelleymounter, Bruce W. Eckloff, Eric D. Wieben, Matthew M. Ames, Richard M. Weinshilboum
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Gemcitabine is a nucleoside analogue with activity against solid tumors. Gemcitabine metabolic inactivation is catalyzed by cytidine deaminase (CDA) or, after phosphorylation, by deoxycytidylate deaminase (DCTD). We set out to study the pharmacogenomics of CDA and DCTD. Experimental Design: The genes encoding CDA and DCTD were resequenced using DNA from 60 African American and 60 Caucasian American subjects. Expression constructs were created for nonsynonymous coding single nucleotide polymorphisms (cSNP) and reporter gene constructs were created for 5′-flanking region polymorphisms. Functional genomic studies were then conducted after the transfection of mammalian cells. Results: CDA resequencing revealed 17 polymorphisms, including one common nonsynonymous cSNP, 79 A&amp;gt;C (Lys27Gln). Recombinant Gln27 CDA had 66 ± 5.1% (mean ± SE) of the wild-type (WT) activity for gemcitabine but without a significant decrease in level of immunoreactive protein. The apparent Km (397 ± 40 μmol/L) for the Gln27 allozyme was significantly higher than that for the WT (289 ± 20 μmol/L; P &amp;lt; 0.025). CDA 5′-flanking region reporter gene studies showed significant differences among 5′-flanking region haplotypes in their ability to drive transcription. There were 29 SNPs in DCTD, including one nonsynonymous cSNP, 172 A&amp;gt;G (Asn58Asp), in Caucasian American DNA. Recombinant Asp58 DCTD had 11 ± 1.4% of WT activity for gemcitabine monophosphate with a significantly elevated level of immunoreactive protein. No DCTD polymorphisms were observed in the initial 500 bp of the 5′-flanking region. Conclusions: These results suggest that pharmacogenomic variation in the deamination of gemcitabine and its monophosphate might contribute to variation in therapeutic response to this antineoplastic agent.
High Burden of Kidney Disease in Youth-Onset Type 2 Diabetes
Authors: Allison B. Dart, Elizabeth A. Sellers, Patricia J. Martens, Claudio Rigatto, Marni D. Brownell, Heather J. Dean
Journal: Diabetes Care (2012)

To evaluate renal outcomes and survival in youth with type 2 diabetes (T2DM) versus type 1 diabetes (T1DM) versus nondiabetic control subjects.In total, 342 prevalent youth (aged 1-18 years) with T2DM, 1,011 youth with T1DM, and 1,710 control subjects identified from 1986 to 2007 were anonymously linked to health care records housed at the Manitoba Centre for Health Policy to assess long-term outcomes using ICD codes.Youth with T2DM were found to have a fourfold increased risk of renal failure versus youth with T1DM. Risk factors associated with renal failure were renin angiotensin aldosterone system inhibitor use and albuminuria in adolescence. Compared with control subjects (age, sex, and postal code matched), youth with T2DM had a 23-fold increased risk of renal failure and a 39-fold increased risk of dialysis. Kaplan-Meier survival at 10 years was 91.4% in the type 2 diabetic group versus 99.5% in the type 1 diabetic group (P < 0.0001). Renal survival was 100% at 10 years in both groups. It decreased to 92.0% at 15 years and 55.0% at 20 years in the type 2 diabetic group but remained stable in the type 1 diabetic group (P < 0.0001).Youth with T2DM are at high risk of adverse renal outcomes and death. Albuminuria and angiotensin aldosterone system inhibitor use, which may be a marker of severity of disease, are associated with poor outcomes in early adulthood.