bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haplotype combination of the bovine INSIG1 gene sequence variants and association with growth traits in Nanyang cattle
Authors: Sun Jiajie , Gao Yuan , Liu Dong , Ma Wei , Xue Jing , Zhang Chunlei , Lan Xianyong , Lei Chuzhao , Chen Hong 
Published: June 2012

The insulin-induced gene 1 (INSIG1) gene encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose metabolism. However, similar research for the bovine INSIG1 gene is lacking. Therefore, in this study, polymorphisms of the bovine INSIG1 gene were detected in 643 individuals from four cattle breeds by DNA pooling, forced PCR–RFLP, PCR–SSCP, and DNA sequencing methods. Only 10 novel SNPs were identified, which included four mutations in the coding region and the others in the introns. In Nanyang individuals, seven common haplotypes were identified based on four coding region SNPs. The haplotype GACT, with a frequency of 75.4%, was the most prevalent haplotypes and SNPs formed two linkage disequilibrium blocks with strong multi-allelic D′ (D′ = 1). Additionally, association analysis between mutations of the bovine INSIG1 gene and growth traits in Nanyang cattle at 6, 12, 18, and 24 months old was performed, and the results indicated that the polymorphisms were not significantly associated with body mass.
Treatment with deferoxamine during ischemia improves functional and metabolic recovery and reduces reperfusion-induced oxygen radical generation in rabbit hearts.
Authors: Williams R E , Zweier J L , Flaherty J T 
Published: June 2012

BACKGROUND
Iron may play a central role in oxygen radical generation during myocardial ischemia and after reperfusion. Because conditions during ischemia may also liberate iron, we hypothesized that administration of the iron chelator deferoxamine during ischemia would result in improved functional and metabolic recovery after postischemic reperfusion.

METHODS AND RESULTS
Isolated, perfused rabbit hearts were studied by phosphorus-31 nuclear magnetic resonance spectroscopy. The hearts received one of three treatments: deferoxamine at the onset of 30 minutes of global ischemia (n = 9), deferoxamine as a bolus followed by a continuous 15-minute infusion begun at reflow (n = 9), or standard perfusate (n = 7). Hearts treated with deferoxamine during ischemia showed better recovery of developed pressure than did control hearts (63.2 +/- 7.5% versus 41.2 +/- 2.9% of baseline) (p = 0.02) and better recovery of myocardial phosphocreatine content (92.4 +/- 10.3% versus 68.2 +/- 4.5% of baseline, p less than 0.05). These functional and metabolic benefits were comparable to those obtained with deferoxamine treatment during early reperfusion. In 15 additional hearts, intraischemic treatment with deferoxamine resulted in no reduction in oxygen radical concentrations as measured on frozen tissue by electron paramagnetic resonance spectroscopy at end ischemia, but the treatment eliminated the reperfusion-induced increase of free radical generation observed in control hearts (2.9 +/- 0.01 versus 7.0 +/- 0.07 microM, p less than 0.001). The magnitude of reduction was similar to that when deferoxamine was given at the onset of reflow (2.4 +/- 0.02 microM, p less than 0.001 versus control).

CONCLUSIONS
These results demonstrate improved functional and metabolic recovery of myocardium treated with deferoxamine during ischemia, accompanied by a reduction in reperfusion-induced oxygen free-radical generation to the same degree as reflow treatment, confirming the importance of iron in the pathogenesis of myocardial reperfusion injury.
Left ventricular passive diastolic properties in chronic mitral regurgitation.
Authors: Corin W J , Murakami T , Monrad E S , Hess O M , Krayenbuehl H P 
Published: June 2012

BACKGROUND
In chronic mitral regurgitation, the myocardium responds to the increased filling volume by geometric alteration and eccentric hypertrophy. This study was designed to evaluate the effects of a pure volume overload on left ventricular diastolic chamber and myocardial properties and to assess the relation of passive diastolic function to systolic ejection performance.

METHODS AND RESULTS
By use of simultaneous cineangiography and left ventricular micromanometry, left ventricular passive diastolic stiffness was evaluated in nine normal controls (group 1), 14 patients with chronic mitral regurgitation and a normal ejection fraction (greater than or equal to 57%, group 2), and 13 patients with mitral regurgitation and a reduced ejection fraction (less than 57%, group 3). Passive diastolic function was evaluated by using a three-constant elastic model. Left ventricular chamber properties were represented by the relation of pressure to volume; myocardial properties were evaluated by relating myocardial midwall stress to midwall strain. The constant of left ventricular chamber stiffness was decreased in group 2 compared with controls (p less than 0.05) but it was normal in group 3. The constant of myocardial stiffness was increased in group 3 compared with groups 1 and 2 (p less than 0.01). Among patients with mitral regurgitation, there was a significant inverse relation between ejection fraction and the constant of myocardial stiffness (r = -0.83).

CONCLUSIONS
The chronic adaptation to volume overload in chronic mitral regurgitation tends to decrease left ventricular chamber stiffness. Patients with mitral regurgitation and a depressed ejection fraction demonstrated diastolic myocardial dysfunction. Compromised diastolic function in patients with chronic mitral regurgitation and reduced systolic performance may contribute to the clinical manifestations of congestive heart failure.
Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection.
Authors: Yun K L , Niczyporuk M A , Daughters G T , Ingels N B , Stinson E B , Alderman E L , Hansen D E , Miller D C 
Published: June 2012

BACKGROUND
Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle. The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation.

METHODS AND RESULTS
Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images. Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis. When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases. In systole, LV twist was linearly related to ejection of blood. In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred. During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change. In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values.

CONCLUSION
Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities. During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle.
Identification of acute myocardial infarction patients suitable for early hospital discharge after aggressive interventional therapy. Results from the Thrombolysis and Angioplasty in Acute Myocardial Infarction Registry.
Authors: Mark D B , Sigmon K , Topol E J , Kereiakes D J , Pryor D B , Candela R J , Califf R M 
Published: June 2012

BACKGROUND
Very early (day 4) hospital discharge has recently been proposed for selected patients with acute myocardial infarction (MI). The purpose of this study was to determine the most useful factors for identifying acute MI patients treated with aggressive interventional therapy who could be safely discharged on day 4.

METHODS AND RESULTS
We studied 708 patients enrolled in the Thrombolysis and Angioplasty in Acute Myocardial Infarction trials I-III. Patients dying in the first 3 days and those with early (days 1-3) emergency coronary artery bypass graft surgery (CABG), late elective CABG (greater than or equal to day 4), or urgent/emergency CABG resulting from a late elective coronary angioplasty were excluded. The remaining 580 patients were randomly divided into a training sample (group 1) that was used to build a logistic regression model for predicting the absence of a late major complication and a test sample (group 2) that was used to validate this model. For this study, patients were considered appropriate for day 4 hospital discharge if they did not experience any of the following for 30 days after MI: death, reinfarction, cardiogenic shock, pulmonary edema, sustained hypotension, sustained ventricular tachycardia, high-grade atrioventricular block, acute ventricular septal defect, and recurrent ischemia necessitating urgent CABG. In group 1, four variables were independent predictors of freedom from late major complications: absence of early sustained ventricular tachycardia or ventricular fibrillation, absence of early sustained hypotension or cardiogenic shock, fewer coronary arteries with significant (greater than or equal to 75%) stenosis, and a higher left ventricular ejection fraction. In group 2, 23% of patients had a logistic model prediction of a 3% or less chance of a late complication. These patients had no deaths or reinfarctions by day 30 and a 3% late major complication rate.

CONCLUSIONS
The results of early cardiac catheterization and the absence of selected early (days 1-3) major complications do allow identification of a low risk subgroup of acute MI patients that may be suitable for very early discharge.
Inhibition of dipyridamole-induced ischemia by antianginal therapy in humans. Correlation with exercise electrocardiography.
Authors: Lattanzi F , Picano E , Bolognese L , Piccinino C , Sarasso G , Orlandini A , L'Abbate A 
Published: June 2012

BACKGROUND
Dipyridamole echocardiography test (DET: two-dimensional echocardiographic monitoring with dipyridamole infusion up to 0.84 mg/kg in 10 minutes) is a useful tool for the noninvasive diagnosis of coronary artery disease. Aims of the present study were to assess the effects of antianginal drugs on dipyridamole-induced ischemia and to evaluate whether drug-induced changes in DET response may predict variations in exercise tolerance.

METHODS AND RESULTS
Fifty-seven patients with angiographically assessed significant coronary artery disease (greater than 70% lumen reduction in at least one major coronary vessel) performed a DET and an exercise electrocardiography test (EET) in random order both off treatment and on antianginal drugs (beta-blockers, calcium antagonists and nitrates, alone or in various combinations). The criterion for DET positivity was a transient dyssynergy of contraction absent or of a lesser degree in the baseline examination. In DET, two parameters were evaluated: the dipyridamole time (i.e., the time from onset of dipyridamole infusion to obvious dyssynergy) and the wall motion score index. DET sensitivity was 91% off therapy and fell to 65% under therapy (p less than 0.01). In the 37 patients who had a positive DET both off and on therapy, the dipyridamole time increased from 6 +/- 3 (off therapy) to 8 +/- 3 minutes (on therapy) (p less than 0.01). The wall motion score index at peak dipyridamole went from 1.38 +/- 0.14 to 1.31 +/- 0.14 (p less than 0.01). EET and DET yielded concordant (positive versus negative) results in 41 of 57 (71%) patients off and in 35 of 57 (61%) on therapy (p = NS). In the subgroup of 38 patients with both positive DET and EET without treatment, the therapy-induced variations in exercise time were significantly correlated with the variations in dipyridamole time (r = 0.5; p less than 0.01), not with variations in wall motion score index (r = 0.3; p = NS).

CONCLUSIONS
1) Antianginal therapy can protect from dipyridamole-induced ischemia and 2) the therapy-induced changes in DET response parallel variations in exercise tolerance and might be useful for the objective, exercise-independent assessment of the therapy efficacy.
Association between blood pressure and serum lipids in a population. The Tromsø Study.
Authors: Bønaa K H , Thelle D S 
Published: June 2012

BACKGROUND
High blood pressure has been associated with elevated atherogenic blood lipid fractions, but epidemiological surveys often give inconsistent results across population subgroups. A better understanding of the relation between blood pressure and blood lipids may provide insight into the mechanism(s) whereby hypertension is associated with increased risk of coronary heart disease.

METHODS AND RESULTS
We assessed the cross-sectional relations of serum total cholesterol, high density lipoprotein (HDL) cholesterol, non-HDL cholesterol (total minus HDL cholesterol), and triglyceride levels with blood pressure in a population of 8,081 men 20-54 years old and 7,663 women 20-49 years old. Stratified analyses and multivariable methods were used to control for potential confounding anthropometric and lifestyle variables. Total and non-HDL cholesterol levels increased significantly with increasing systolic or diastolic blood pressure in both sexes. Men 20-29 years old had steeper regression slopes for blood pressure by total cholesterol level than did women of similar age. In men, the association between blood pressure and total cholesterol level decreased with age, whereas in women, it increased with age. Body mass index modified the relation, whereas smoking, physical activity, and alcohol consumption had little influence on the association. Triglyceride levels increased with blood pressure, but this relation was weak in lean subjects. HDL cholesterol level correlated positively with blood pressure in population subgroups having a high alcohol consumption.

CONCLUSION
These results support the hypothesis that there are biological interrelations between blood pressure and blood lipids that may influence the mechanisms whereby blood pressure is associated with risk of coronary heart disease.
Release of nitrogen oxides from cultured bovine aortic endothelial cells is not impaired by calcium channel antagonists.
Authors: Mügge A , Peterson T , Harrison D G 
Published: June 2012

BACKGROUND
The endothelium-derived relaxing factor has been shown to be nitric oxide or a related nitroso compound, synthesized by the enzyme nitric oxide synthetase, which oxidizes the guanidono nitrogens of arginine. This enzyme is activated by increases in cytosolic calcium. The effect of the clinically used calcium channel antagonists on this process is controversial. The present study was performed to determine whether calcium channel blockade with these pharmacologic agents would alter the activity of nitric acid synthetase in intact endothelial cells.

METHODS AND RESULTS
A specific and sensitive chemiluminescence assay was used to measure the release of nitrogen oxides (nitric oxide and one-electron oxidation products of nitric oxide) from bovine aortic endothelial cells grown in culture. Under basal conditions, the release of nitrogen oxides was about 0.2 nmol/100 micrograms protein/hr. Bradykinin doubled this response. Removal of extracellular calcium abolished basal and bradykinin-stimulated release of nitrogen oxides. Neither diltiazem, verapamil, nor nifedipine in concentrations that are encountered clinically altered the release of nitrogen oxides.

CONCLUSIONS
These experiments show that although the production of nitrogen oxides is dependent on extracellular calcium, the clinically used calcium channel antagonists do not inhibit the release of the endothelium-derived relaxing factor.
Estimation of myocardial infarct size with ultrasonic tissue characterization.
Authors: Sagar K B , Pelc L R , Rhyne T L , Howard J , Warltier D C 
Published: June 2012

BACKGROUND
Ultrasonic tissue characterization (UTC) can distinguish normal from infarcted myocardium. Infarcted myocardium shows an increase in integrated backscatter and loss of cardiac cycle-dependent variation in backscatter. The cyclic variation of backscatter is closely related to regional myocardial contractile function; the latter is a marker of myocardial ischemia. The present study was designed to test the hypothesis that intramural cyclic variation of backscatter can map and estimate infarct size.

METHODS AND RESULTS
Transmural myocardial infarction was produced in 12 anesthetized, open-chest dogs by total occlusion of the left anterior descending coronary artery for 4 hours. A real-time ultrasonic tissue characterization instrument, which graphically displays integrated backscatter Rayleigh 5, cardiac cycle-dependent variation, and patterns of cyclic variation in backscatter, was used to map infarct size and area at risk of infarction. Staining with 2,3,4-triphenyltetrazolium chloride (TTC) and Patent Blue Dye was used to estimate infarct size and the area at risk, respectively. The ratio of infarct size to area at risk of infarction determined with UTC correlated well with that determined with TCC (r = 0.862, y = 23.7 +/- 0.792x). Correlation coefficients for infarct size and area at risk were also good (r = 0.736, y = 12.3 +/- 737x for infarct size and r = 0.714, y = 5.80 +/- 1.012x for area at risk). However, UTC underestimated both infarct size and area at risk.

CONCLUSIONS
Ultrasonic tissue characterization may provide a reliable, noninvasive method to estimate myocardial infarct size.
Induction of sustained patency after clot-selective coronary thrombolysis with Hybrid-B, a genetically engineered plasminogen activator with a prolonged biological half-life.
Authors: Weinheimer C J , James H L , Kalyan N K , Wilhelm J , Lee S G , Hung P P , Sobel B E , Bergmann S R 
Published: June 2012

BACKGROUND
Despite the utility of tissue-type plasminogen activator (t-PA) in eliciting coronary thrombolysis clinically, early reocclusion remains a problem, occurring despite anticoagulation in 5-30% of patients with initially successful recanalization. This study evaluated the utility of Hybrid-B, a molecular variant of t-PA with a prolonged half-life in the circulation, in eliciting coronary thrombolysis and maintaining patency in the presence of a continuing thrombogenic stimulus.

METHODS AND RESULTS
In intact, anesthetized dogs, either 18 mg Hybrid-B over 30 minutes (n = 15) or 50 mg t-PA (Activase) over 60 minutes (n = 8) was administered starting 60 minutes after left anterior descending coronary artery occlusion was induced with a thrombogenic copper coil. Time to lysis averaged 54 +/- 26 (means +/- SD) minutes and 64 +/- 34 minutes with Hybrid-B and t-PA, respectively (p = NS). When Hybrid-B was administered as a bolus (20 mg over 1 minute) to induce a high initial concentration in blood, time to lysis was shortened markedly and averaged 15 +/- 5 minutes. Dogs given Hybrid-B by either infusion or bolus exhibited prolonged time to reocclusion (337 +/- 192 minutes compared with 192 +/- 125 minutes in dogs given t-PA, p less than 0.03), reflecting maintenance of a subthrombolytic but persistently active concentration of activator in blood. Despite the persistence of Hybrid-B in blood, concentrations of fibrinogen and alpha 2-antiplasmin were not depleted markedly and remained at 77 +/- 25 and 56 +/- 24%, respectively, of control values.

CONCLUSIONS
Thus, Hybrid-B, a novel variant of t-PA with unique pharmacokinetic properties, elicits prompt, sustained, and clot-selective coronary thrombolysis.
Combined administration of aspirin and a specific thrombin inhibitor in man.
Authors: Clarke R J , Mayo G , FitzGerald G A , Fitzgerald D J 
Published: June 2012

BACKGROUND
Heparin is of limited value as an antithrombotic drug in the presence of platelet activation and residual thrombus. Greater anticoagulant activity can be achieved in vivo with more specific thrombin inhibitors. Heparin may also increase the risk of bleeding by an effect on platelets that is independent of its thrombin inhibitory activity.

METHODS AND RESULTS
The pharmacodynamic and pharmacokinetic effects of a novel thrombin inhibitor, argatroban, were examined alone and in combination with aspirin in normal male volunteers. Argatroban induced a dose-dependent prolongation of the thrombin time and the activated partial thromboplastin time (aPTT). aPTT had returned to its pretreatment value 1 hour after stopping the infusion of argatroban. Six male subjects received an infusion of 1 micrograms/kg/min argatroban after the administration of two doses of 162.5 mg aspirin or a matching placebo. At this dose, aspirin decreased serum thromboxane B2 by a mean of 99% and prolonged the bleeding time (230 +/- 52 versus 320 +/- 113 seconds, p less than 0.01). Argatroban given alone increased thrombin time by 454 +/- 18% and aPTT by 160 +/- 3%. Steady-state plasma concentrations were achieved at 1 hour and declined exponentially with an elimination half-life of 24 +/- 4 minutes. Neither the anticoagulant effects nor the plasma concentrations of argatroban were altered by aspirin. Furthermore, argatroban did not increase the bleeding time when given alone and did not further prolong the bleeding time when combined with aspirin.

CONCLUSION
The combination of aspirin and argatroban may prove to be an effective therapeutic strategy in the prevention of coronary thrombosis.