Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.

Although an increased risk of the skin cancer melanoma in people with Parkinson's Disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in the SK-MEL28 melanoma cell line, where it colocalizes with DNA damage markers and DSBs.

Determinants of maximal right ventricular function: role of septal shift.

Background: Right heart failure can occur after orthotopic heart transplantation and can complicate implantation of left ventricular assist devices. The functional codeterminants of right ventricular function are not fully understood. We investigated the effects of left ventricular preload and afterload, systemic pressure, and the contribution of the interventricular septum to right ventricular function.

Local relation between oxidative metabolism and perfusion in leg muscles of patients with heart failure studied by magnetic resonance imaging and spectroscopy.

Background: We studied the local relation of muscle perfusion and metabolism in patients with severe chronic heart failure. Alterations of skeletal muscle blood flow and oxidative capacity contribute to exercise intolerance in these patients. The interdependence of both parameters has often been questioned.

Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle.

Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With 31P-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography).

Contralateral shoe-lift: effect on oxygen cost of walking with an immobilized knee.

Objective: Evaluate the effect of a contralateral shoe-lift on the oxygen cost of walking with an artificially immobilized knee.

Design: A prospective quantitative evaluation of oxygen cost of walking under varying conditions. Subjects walked (1) normally (N), (2) with one knee immobilized (1), (3) with one knee immobilized and with a one-half-inch shoe-lift applied to the contralateral shoe (I1/2"L), and (4) with one knee immobilized and with a one-inch shoe-lift (I1"L).

Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging.

Muscle performance is markedly influenced by tissue perfusion. Techniques that allow quantification of microvascular flow are limited by the use of ionizing radiation. In this investigation, we apply an NMR model previously developed by Detre et al.

Measured versus predicted vertical displacement of the sacrum during gait as a tool to measure biomechanical gait performance.

The vertical displacement of the sacrum during walking is proposed as an estimation of the overall biomechanical performance of walking, independent of cardiopulmonary factors. Vertical sacral displacement during walking was measured using an optoelectronic motion analysis system in 10 normal volunteers at variable speeds. Oxygen consumption was simultaneously measured.

Microvascular capillaroscopic abnormalities in rheumatoid arthritis patients.

Microvascular circulation was investigated by nailfold capillaroscopy in 32 patients affected by rheumatoid arthritis (RA). In all the patients elongated and tiny capillaries as well as tortuousity were the main shape abnormalities of the capillary loops. Higher subpapilar venous plexus (SPVP) visibility was evidentiated in patients presenting antinuclear and anti-RANA antibodies.

Nitrous oxide does not depress left ventricular contractility in ischemic rat heart.

The direct effects of nitrous oxide on left ventricular contractility and myocardial oxygen consumption (MVO2) in the ischemic isolated rat heart were studied. The rat heart was isolated and perfused by a Langendorf technique. The aortic stump was cannulated and the heart was perfused with Kumpeis solution bubbled with 95% O2 and 5% CO2 (control phase).

Hemoglobin blood substitutes in extended preoperative autologous blood donation: an experimental study.

Background: The risks of homologous blood transfusion have stimulated interest in developing possible alternatives. In this study we examined the efficacy of using a hemoglobin-derived blood substitute to augment and extend preoperative autologous blood donation.

Methods: In an ovine model, two experimental groups (n = 6 each) of animals donated either 45% or 80% or more of calculated blood volume, which was replaced with a polymerized bovine hemoglobin solution.

Variables associated with a poor prognosis in patients with an ischemic thallium-201 exercise test.

To determine the exercise workload, ECG, and thallium-201 image parameters that are most closely associated with a poor prognosis from ischemic heart disease, the test results of 268 patients were reviewed. Only patients with unequivocal thallium-201 redistribution were selected. A multivariate analysis was performed to find the variables that were most strongly associated with the outcomes of coronary revascularization, myocardial infarction, and cardiac death during a follow-up period of 25 +/- 19 months.

Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation.

The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively.

Determinants of maximal right ventricular function.

After heart transplantation, right ventricular failure can occur because of increased afterload. Previous studies have suggested that the maximal pressure the right ventricle can develop is determined primarily by right ventricular perfusion pressure. However, the interaction of the left ventricle and the pericardium as functional co-determinants of maximal right ventricular function is unknown.

Silent versus symptomatic ischemia during a thallium-201 exercise test.

One hundred thirty-four patients with redistribution on a thallium-201 exercise test who did not experience angina (group 1) were compared with 134 patients also having redistribution who had angina during the test (group 2). The groups were matched by age, sex, and peak exercise heart rate. Although patients in both groups achieved an equivalent exercise level, patients in group 1 had less frequent (53 vs 71%, p less than 0.

Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction.

Low-level exercise thallium testing is useful in identifying the high-risk patient after acute myocardial infarction (AMI). To determine whether this use also applies to patients after thrombolytic treatment of AMI, 64 patients who underwent early thrombolytic therapy for AMI and 107 patients without acute intervention were evaluated. The ability of both the electrocardiogram and thallium tests to predict future events was compared in both groups.

Hemodynamic effects and oxygen transport properties of a new blood substitute in a model of massive blood replacement.

Recent concerns regarding the safety of the national blood supply have rekindled interest in the development of blood substitutes. Clinical studies have dampened the initial enthusiasm for fluorocarbon solutions as blood substitutes. The potential of hemoglobin solutions as blood substitutes has continued to stimulate investigations.

Complete heart block as the sole presentation of Lyme disease.

We report a case of Lyme myocarditis presenting solely as complete heart block in a previously healthy 32-year-old white man. Indium cardiac antimyosin scan showed diffuse uptake (2+, on a scale of 0 to 4+) during the acute phase of the illness. The electrocardiogram and the indium cardiac antimyosin scan were normal 6 weeks after completion of tetracycline and prednisone treatment.

Cardiac evaluation during physical rehabilitation of the complex medical patient.

Many rehabilitation patients have cardiovascular disease as a primary or secondary diagnosis. Such patients require careful evaluation before institution of vigorous therapeutic exercise and activity regimens. However, conventional exercise tests are often inappropriate due to orthopedic, neurologic, or functional limitations.

Thallium kinetics in rat cardiac transplant rejection.

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection.

Comparison of washed blood and oxygenator whole blood as vehicles for sanguinous multidose cardioplegia.

The effects of washed blood or oxygenator-traumatized whole blood as vehicles for sanguinous cardioplegia were studied utilizing the isolated blood-perfused dog heart preparation. Hearts were subjected to 2 hr of potassium-induced arrest at 27 degrees C followed by 90 min of normothermic reperfusion. Washed blood cardioplegia (n = 7) contained blood washed thrice with saline while oxygenator blood cardioplegia (n = 6) contained whole blood which had been exposed to an extracorporeal circuit for 30 to 45 min.

Myocardial temperature variation: effect on regional function and coronary flow in dogs.

Incremental changes in the temperature (28-42.5 degrees C) of the anterior left ventricular wall in a canine, working, beating right heart bypass preparation (constant preload, afterload, and heart rate) were produced to measure the effect of regional temperature on myocardial function and blood flow. Circumferential-axis segment lengths were measured with sonomicrometry in both the temperature-varied, left-anterior descending coronary artery (LAD)-supplied myocardium and the normothermic (38 degrees C) circumflex-supplied myocardium.

Effect of experimental cardiopulmonary bypass on systemic and transcardiac thromboxane B2 levels.

Systemic and cardiac metabolism of thromboxane was studied in a canine model (n = 13) of standard cardiopulmonary bypass and surgical cardioplegia. Sterile techniques were applied and no donor blood was used. Systemic samples (thoracic aorta) and transcardiac gradients (coronary sinus - aortic root) were obtained (1) 5 minutes after cannulation, (2) 20 minutes after the onset of partial bypass, (3) 5 seconds after the first administration of cardioplegic solution (CP-1), and (4) 5 seconds after the second administration of cardioplegic solution (CP-2).

Influence of coronary artery obstruction on cardiac prostaglandin metabolism during experimental cardioplegic arrest.

In order to test the influence of coronary artery obstruction on cardiac prostaglandin metabolism during surgically induced cardioplegia (CP), we have measured transcardiac veno-arterial gradients of prostacyclin and thromboxane A2 (TXA A2) during experimental canine cardiopulmonary bypass. Cardiac arrest was induced by infusion of 500 ml of hypothermic (8 degrees C), hyperkalemic (25 meq) crystalloid CP solution into the aortic root with (group I) and without (group II) occlusion of the left anterior descending artery (LAD). After 30 minutes of cardioplegic arrest the LAD occlusion in group I was released and a second set of CP infusion was applied in both groups.

Early detection of cardiac allograft rejection with proton nuclear magnetic resonance.

No reliable, noninvasive technique is currently available for the early detection of cardiac transplant rejection. In this study, pulse nuclear magnetic resonance (NMR) spectroscopy was used (20 MHz) to detect cardiac allograft rejection in rats. Proton spin-lattice relaxation time (T1), proton spin-spin relaxation time (T2), and water content were measured in both recipient and donor hearts at 2, 4, 6, and 8 days after transplantation.

Myocardial protection utilizing calcium containing and calcium free perfusates.

The effects of the presence or absence of calcium in the cardioplegic perfusate were studied utilizing the isolated blood perfused dog heart preparation. Hearts were subjected to two hours of arrest at 27 degrees C followed by 90 minutes of normothermic reperfusion. Perfusates with or without 2.