tbuckley/cabot-search huggingface dataset:
Comparison of Real-Time and Intermittent Triggered Myocardial Contrast Echocardiography for Quantification of Coronary Stenosis Severity and Transmural Perfusion Gradient
Authors: Hisashi Masugata, Stephane Lafitte, Barry Peters, G. Monet Strachan, Anthony N. DeMaria
Journal: Circulation (2001)

Background Both intermittent triggered and real-time myocardial contrast echocardiography (MCE) have been proposed to detect impaired myocardial perfusion. We compared the ability of these 2 methods to quantify altered myocardial blood flow (MBF) and transmural distribution of MBF produced by graded coronary stenoses. Methods and Results In 8 open-chest dogs, we created 4 graded left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced adenosine hyperemia (non–flow-limiting at rest) and 1 grade of flow-limiting at rest. Real-time MCE was performed with SonoVue infusion using low-energy power pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI) was plotted versus time by real-time MCE and versus pulsing intervals by triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A) and the rate of SI rise (b). Visual detection of decreased opacification was equivalent by triggered and real-time MCE. Fluorescent microsphere–derived MBF ratio in LAD/left circumflex artery beds demonstrated close correlation with both real-time imaging (b, r =0.79; A×b, r =0.81) and triggered imaging (b, r =0.78; A×b, r =0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated closer correlation with the endocardial/epicardial ratios of b ( r =0.71) and A×b ( r =0.67) obtained by real-time than triggered imaging (b, r =0.42; A×b, r =0.52). Conclusions Real-time and triggered MCE are equivalent in their ability to identify coronary stenosis and quantify altered MBF.
SUMO-1 Modification of the Wilms’ Tumor Suppressor WT1
Authors: Gromoslaw A. Smolen, Maria T. Vassileva, Julie Wells, Michael J. Matunis, Daniel A. Haber
Journal: Cancer Research (2004)

SUMO-1 conjugation modulates numerous cellular functions, including the subnuclear localization of its target proteins. The WT1 tumor suppressor encodes a four-zinc finger protein with distinct splicing isoforms. WT1(-KTS), encoding uninterrupted zinc fingers, functions as a transcription factor and has a diffusely nuclear distribution; WT1(+KTS), with an insertion of three amino acids (KTS) between zinc fingers three and four, localizes to discrete nuclear speckles, the function of which is unknown. Because the SUMO-1 E2-conjugating enzyme, Ubc9, interacts with WT1, we tested whether sumoylation modulates the cellular localization of WT1. We find here that both WT1 isoforms are directly sumoylated on lysine residues 73 and 177. Although RNA interference-mediated Ubc9 depletion effectively suppresses WT1 nuclear speckles, a SUMO-1-deficient WT1(+KTS)(K73, 177R) double mutant retains localization to speckles. Thus, direct sumoylation of WT1 is not responsible for its cellular localization, and other sumoylated proteins may target WT1 to these nuclear structures. Identification of other components of WT1-associated speckles is likely to provide clues to their function.
Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy
Authors: Albrecht Bufe, Peter Eberle, Eivy Franke-Beckmann, Jürgen Funck, Martin Kimmig, Ludger Klimek, Roland Knecht, Volker Stephan, Bente Tholstrup, Christian Weißhaar, Friedrich Kaiser
Journal: Journal of Allergy and Clinical Immunology (2009)
Tissue Engineering Applications of Therapeutic Cloning
Authors: Anthony Atala, Chester J. Koh
Journal: Annual Review of Biomedical Engineering (2004)

Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.
Optical measurements of transmembrane potential changes during electric field stimulation of ventricular cells.
Authors: S B Knisley, T F Blitchington, B C Hill, A O Grant, W M Smith, T C Pilkington, R E Ideker
Journal: Circulation Research (1993)

We evaluated transmembrane potential changes at the ends of isolated rabbit ventricular myocytes during defibrillation-strength shocks given in the cellular refractory period. The myocytes were stimulated (S1 pulse) to produce an action potential. Then a constant-field shock (S2 pulse) with an electric field of 20 or 40 V/cm was given at an S1-S2 interval of 50 msec. The cells were stained with potentiometric dye (di-4-ANEPPS), and the cell end facing the S2 anode or cathode was illuminated with a laser while the fluorescence was recorded. During S2, the cell end facing the S2 cathode became more positive intracellularly, whereas the cell end facing the S2 anode became more negative intracellularly. The S2-induced transmembrane potential change at the cell end (delta Vm) was determined relative to the amplitude of the S1-induced action potential (APA) in each recording (i.e., delta Vm/APA). In Tyrode's solution containing 4.5 mM potassium, delta Vm/APA for 40-V/cm S2 was 1.36 +/- 0.34 at the cell end facing the S2 cathode and -1.65 +/- 0.61 at the cell end facing the S2 anode (n = 9). For the 20-V/cm S2, delta Vm/APA was 0.61 +/- 0.33 at the cell end facing the S2 cathode and -0.71 +/- 0.33 at the cell end facing the S2 anode (n = 6). The delta Vm/APA was not significantly influenced by 20 mM diacetyl monoxime. These results indicate that large delta Vm values occurred at the ends of the cells during S2. The calculated values of delta Vm, assuming a nominal APA of 130 mV, were 177 and -214 mV for the 40-V/cm S2 and 79 and -93 mV for the 20-V/cm S2. The delta Vm was correlated with cell size (r &gt; or = 0.95) and agreed with values predicted by the S2 electric field strength multiplied by half of the cell length to within 27%. When the potassium concentration was increased to 20 mM, delta Vm/APA for 40 V/cm S2 increased 85% and 67% at the cell ends facing the S2 cathode and anode, respectively (n = 9, p &lt; 0.005 versus 4.5 mM potassium), consistent with reduced APA. Thus, with normal or elevated extracellular potassium, transmembrane potential changes at the ends of cells during defibrillation-type stimulation are large enough to produce activation or recovery of voltage-dependent ion channels and may produce the effects responsible for defibrillation.
Isokinetic strength testing does not predict hamstring injury in Australian Rules footballers.
Authors: K Bennell, H Wajswelner, P Lew, A Schall-Riaucour, S Leslie, D Plant, J Cirone
Journal: British Journal of Sports Medicine (1998)

OBJECTIVE: To determine the relation of hamstring and quadriceps muscle strength and imbalance to hamstring injury using a prospective observational cohort study METHOD: A total of 102 senior male Australian Rules footballers aged 22.2 (3.6) years were tested at the start of a football season. Maximum voluntary concentric and eccentric torque of the hamstring and quadriceps muscles of both legs was assessed using a Kin-Com isokinetic dynamometer at angular velocities of 60 and 180 degrees/second. Twelve (11.8%) players sustained clinically diagnosed hamstring strains which caused them to miss one or more matches over the ensuing season. RESULTS: There were no significant differences for any of the isokinetic variables comparing the injured and non-injured legs in players with unilateral hamstring strains (n=9). Neither the injured nor the non-injured leg of injured players differed from the mean of left and right legs in non-injured players for any isokinetic variable. The hamstring to opposite hamstring ratios also did not differ between injured and non-injured players. A hamstring to opposite hamstring ratio of less than 0.90 and a hamstring to quadriceps ratio of less than 0.60 were not associated with an increased risk of hamstring injury. A significantly greater percentage of players who sustained a hamstring strain reported a history of hamstring strain compared with non-injured players (p=0.02). However, this was not related to muscle weakness or imbalance. CONCLUSIONS: Isokinetic muscle strength testing was not able to directly discriminate Australian Rules football players at risk for a hamstring injury.
Prospective Molecular Marker Analyses of <i>EGFR</i> and <i>KRAS</i> From a Randomized, Placebo-Controlled Study of Erlotinib Maintenance Therapy in Advanced Non–Small-Cell Lung Cancer
Authors: Wolfram Brugger, Nadja Triller, Maria Blasinska-Morawiec, Stefan Curescu, Raimundas Sakalauskas, Georgy Moiseevich Manikhas, Julien Mazieres, Renaud Whittom, Carol Ward, Karen Mayne, Kerstin Trunzer, Federico Cappuzzo
Journal: Journal of Clinical Oncology (2011)

The phase III, randomized, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study found that erlotinib maintenance therapy extended progression-free survival (PFS) and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) who had nonprogressive disease following first-line platinum-doublet chemotherapy. This study included prospective analysis of the prognostic and predictive value of several biomarkers.Mandatory diagnostic tumor specimens were collected before initiating first-line chemotherapy and were tested for epidermal growth factor receptor (EGFR) protein expression by using immunohistochemistry (IHC), EGFR gene copy number by using fluorescent in situ hybridization (FISH), and EGFR and KRAS mutations by using DNA sequencing. An EGFR CA simple sequence repeat in intron 1 (CA-SSR1) polymorphism was evaluated in blood.All 889 randomly assigned patients provided tumor samples. EGFR IHC, EGFR FISH, KRAS mutation, and EGFR CA-SSR1 repeat length status were not predictive for erlotinib efficacy. A profound predictive effect on PFS of erlotinib relative to placebo was observed in the EGFR mutation-positive subgroup (hazard ratio [HR], 0.10; P < .001). Significant PFS benefits were also observed with erlotinib in the wild-type EGFR subgroup (HR, 0.78; P = .0185). KRAS mutation status was a significant negative prognostic factor for PFS.This large prospective biomarker study found that patients with activating EGFR mutations derive the greatest PFS benefit from erlotinib maintenance therapy. No other biomarkers were predictive for outcomes with erlotinib, although the study was not powered for clinical outcomes in biomarker subgroups other than EGFR IHC-positive [corrected]. KRAS mutations were prognostic for reduced PFS. The study demonstrated the feasibility of prospective tissue collection for biomarker analyses in NSCLC.
Lp(a) lipoprotein levels as a predictor of risk for thrombogenic events in patients with Behcet's disease.
Authors: A Orem, O Deger, O Memis, S Bahadir, E Ovali, G Cimsit
Journal: Annals of the Rheumatic Diseases (1995)

To investigate whether plasma levels of Lp(a) lipoprotein (Lp(a)) are predictors of defective fibrinolytic activity, leading to thrombosis, in patients with Behçet's disease.Plasma Lp(a) was measured by enzyme linked immunosorbent assay, lipids and lipoproteins by enzymatic methods, and apolipoproteins A-I and B, fibrinogen (turbidimetric method), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and D-dimer levels by enzyme immunoassay. Their levels and interactions were evaluated in 33 patients with Behçet's disease (including five with thrombotic complications) and 30 healthy control subjects.Plasma Lp(a) concentration was significantly greater in the patients than in controls. Nine patients (27%) had levels > 0.30 microgram. There was no correlation between Lp(a) and other lipids and lipoproteins apart from apolipoprotein B. Lp(a) showed inverse correlation with t-PA (r = -0.34, p < 0.05) and D-dimer (r = 0.35, p < 0.05). Patients with thrombotic complications had significantly greater Lp(a) and PAI-1, and lower D-dimer concentrations than control subjects.Measurement of plasma Lp(a) levels in patients with Behçet's disease may provide useful information regarding the potential development of thrombotic events, because of its possible role in defective fibrinolysis.
Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors
Authors: Gillian M. Tozer, Simon Akerman, Neil A. Cross, Paul R. Barber, Meit A. Björndahl, Olga Greco, Sheila Harris, Sally A. Hill, Davina J. Honess, Christopher R. Ireson, Katie L. Pettyjohn, Vivien E. Prise, Constantino C. Reyes-Aldasoro, Christiana Ruhrberg, David T. Shima, Chryso Kanthou
Journal: Cancer Research (2008)

Abstract Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control. Once tumors were established, VEGF isoform expression did not affect growth or blood flow rate. However, VEGF188 was uniquely associated with tumor vascular maturity, resistance to hemorrhage, and resistance to CA-4-P. Pericyte staining was much greater in VEGF188 and control tumors than in VEGF120 and VEGF164 tumors. Vascular volume was highest in VEGF120 and control tumors (CD31 staining) but total vascular length was highest in VEGF188 tumors, reflecting very narrow vessels forming complex vascular networks. I.v. administered 40 kDa FITC-dextran leaked slowly from the vasculature of VEGF188 tumors compared with VEGF120 tumors. Intravital microscopy measurements of vascular length and RBC velocity showed that CA-4-P produced significantly more vascular damage in VEGF120 and VEGF164 tumors than in VEGF188 and control tumors. Importantly, this translated into a similar differential in therapeutic response, as determined by tumor growth delay. Results imply differences in signaling pathways between VEGF isoforms and suggest that VEGF isoforms might be useful in vascular-disrupting cancer therapy to predict tumor susceptibility to VDAs. [Cancer Res 2008;68(7):2301–11]
VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis
Authors: Seyedtaghi Takyar, Hema Vasavada, Jian-ge Zhang, Farida Ahangari, Naiqian Niu, Qing Liu, Chun Geun Lee, Lauren Cohn, Jack A. Elias
Journal: The Journal of Experimental Medicine (2013)

Asthma, the prototypic Th2-mediated inflammatory disorder of the lung, is an emergent disease worldwide. Vascular endothelial growth factor (VEGF) is a critical regulator of pulmonary Th2 inflammation, but the underlying mechanism and the roles of microRNAs (miRNAs) in this process have not been defined. Here we show that lung-specific overexpression of VEGF decreases miR-1 expression in the lung, most prominently in the endothelium, and a similar down-regulation occurs in lung endothelium in Th2 inflammation models. Intranasal delivery of miR-1 inhibited inflammatory responses to ovalbumin, house dust mite, and IL-13 overexpression. Blocking VEGF inhibited Th2-mediated lung inflammation, and this was restored by antagonizing miR-1. Using mRNA arrays, Argonaute pull-down assays, luciferase expression assays, and mutational analysis, we identified Mpl as a direct target of miR-1 and showed that VEGF controls the expression of endothelial Mpl during Th2 inflammation via the regulation of miR-1. In vivo knockdown of Mpl inhibited Th2 inflammation and indirectly inhibited the expression of P-selectin in lung endothelium. These experiments define a novel VEGF-miR-1-Mpl-P-selectin effector pathway in lung Th2 inflammation and herald the utility of miR-1 and Mpl as potential therapeutic targets for asthma.
Evolution by Recombination and Transspecies Polymorphism in the MHC Class I Gene of Xenopus laevis
Authors: David H. Bos, Bruce Waldman
Journal: Molecular Biology and Evolution (2005)

The patterns of major histocompatibility complex (MHC) evolution involve duplications, deletions, and independent divergence of loci during episodes punctuated by natural selection. Major differences in MHC evolution among taxa have previously been attributed to variation in linkage patterns of class I and class II MHC genes. Here we characterize patterns of evolution in the MHC class Ia gene of Xenopus laevis in terms of polymorphism, recombination, and extent of transspecies polymorphism. We also compare these patterns to see if a correlation exists with linkage or separation of the MHC class I and class II regions as seen in amphibians and teleost fishes. In X. laevis, we find high levels of polymorphism. Also, genetic exchange is relatively frequent and occurs in intron II, reshuffling allelic forms of exons 2 and 3. Evolutionary relationships among class I alleles show an intermingling of alleles from divergent Xenopus species rather than a species-specific clustering. Results indicate that the patterns of evolution are similar to those found in salmonid fishes and are different from the mode of evolution seen in primates. Similar patterns of class Ia evolution in salmonid fishes and X. laevis suggest that nonlinkage of class I and class II regions alone is insufficient to explain some patterns of MHC evolution in salmonids.
Quality of Diabetes Care and Management of General Physicians in Karachi, Pakistan
Authors: Jaweed Akhter
Journal: Diabetes Care (2007)

The recent article by Nagpal and Bhartia (1) from New Dehli, India, highlighted the wide gap between practice recommendations and delivery of care in a developing country like India. While standards of care (2) are continually emphasized, few individuals with diabetes actually receive even minimum standards of care. While many factors, including the level of public education, poverty, and poor state healthcare infrastructure, contribute to this in low-income groups, Nagpal and Bhartia (1) highlight deficiencies in quality of care administered …
Acute Effects of Peritoneal Dialysis with Dialysates Containing Dextrose or Dextrose and Amino Acids on Muscle Protein Turnover in Patients with Chronic Renal Failure
Authors: GIACOMO GARIBOTTO, ANTONELLA SOFIA, ALBERTO CANEPA, STEFANO SAFFIOTI, PAOLO SACCO, MARIA RITA SALA, LAURA DERTENOIS, NADIA PASTORINO, GIACOMO DEFERRARI, RODOLFO RUSSO
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Whether changes in substrate and insulin levels that occur during peritoneal dialysis (PD) have effects on muscle protein dynamics was evaluated by studying muscle protein synthesis (PS), breakdown (PB), and net protein balance (NB) by the forearm perfusion method associated with the kinetics of 3H-phenylalanine in acute, crossover studies in which PD patients served as their own controls. Studies were performed ( 1 ) in the basal state and during PD with dialysates that contained dextrose alone in different concentrations (protocol 1: eight patients), ( 2 ) during PD with dialysates that contained dextrose alone or dextrose and amino acids (AA) (protocol 2: five patients), and ( 3 ) in time controls (five patients). PD with dextrose alone induced ( 1 ) a two- to threefold increase in insulin, as well as a 20 to 25% decrease in AA, mainly BCAA, levels; ( 2 ) an insulin-related decline (-18%) in forearm PB ( P &lt;0.002); ( 3 ) a 20% decrease in muscle PS ( P &lt;0.04), which was related to arterial BCAA and K+ ( P &lt;0.02 to 0.05); ( 4 ) a persistent negative NB; and ( 5 ) a decrease in the efficiency of muscle protein turnover, expressed as the ratio NB/PB. PD with dextrose+AA versus PD with dextrose induced ( 1 ) similarly high insulin levels but with a significant increase in total arterial AA (+30 to 110%), mainly valine; ( 2 ) a reduced release of AA from muscle ( P &lt;0.05); and ( 3 ) a decrease in the negative NB observed during PD with dextrose, owing to an increase (approximately 20%) in muscle PS, without any further effect on muscle PB. This study indicates that in PD patients in the fasting state, the moderate hyperinsulinemia that occurs during PD with dextrose alone causes an antiproteolytic action that is obscured by a parallel decrease in AA availability for PS. Conversely, the combined use of dextrose and AA results in a cumulative effect, because of the suppression of endogenous muscle PB (induced by insulin) and the stimulation of muscle PS (induced by AA availability). The hypothesis, therefore, is that in patients who are treated with PD, when fasting or when nutrient intake is reduced, muscle mass could be maintained better by the combined use of dextrose and AA.
Changes in cyclic nucleotide levels and contractile force in the isolated hypoxic rat heart during perfusion with glucagon.
Authors: R W Busuttil, R J Paddock, J W Fisher, W J George
Journal: Circulation Research (1976)

Isolated rat hearts were perfused with hormonal concentrations of glucagon during a hypoxic perfusion to determine whether it would enhance recovery after reoxygenation. Rat hearts were divided into two groups: (1) those perfused with glucose-free Tyrode's solution and (2) those perfused with Tyrode's solution containing glucose. During 3 minutes of exposure to hypoxia both untreated hearts and hearts perfused with glucagon demonstrated a decrease in contractile force to 10-20% of control. When glucose was present in the perfusion medium, cardiac performance was better during both the periods of hypoxia and reoxygenation. During reoxygenation, recovery of contractile force was significantly better (P less than 0.05) in glucagon-perfused hearts than in untreated hearts; this improved recovery occurred regardless of whether glucose was included in the medium. The enhanced recovery of the glucagon-perfused hearts was associated with decreases in myocardial levels of guanosine, 3',5'-monophosphate (cyclic GMP) both during the periods of hypoxia and reoxygenation. At the end of the hypoxic period, cyclic GMP levels in the glucagon-perfused hearts were 20-64% of the levels in untreated hearts. Similarly, after 5 minutes of reoxygenation cyclic GMP levels in the glucagon-perfused hearts were 21% of the levels in the untreated hearts. The effect of glucagon on adenosine 3',5'-monophosphate (cyclic AMP) concentrations in untreated hearts and in hearts receiving glucagon was not significantly different either after 3 minutes of hypoxia or during reoxygenation. The rate of anaerobic glycolysis after 3 minutes of hypoxia was higher in untreated hearts than in glucagon-perfused hearts, as determined by the lactate content of coronary perfusates. These studies suggest that hormonal concentrations of glucagon exert a protective effect on the hypoxic rat heart which involves a modulation of cardiac cyclic GMP accumulation.