Role of nitric oxide in the vasodilator response to mental stress in normal subjects

Vascular production of nitric oxide (NO) plays an important role in a variety of physiologic processes. This study examines the contribution of NO to the vasodilator response to mental stress. The effects of mental arithmetic testing on forearm vascular dynamics were analyzed in 15 normal subjects (9 men; age 45 +/- 12 years) during intraarterial infusion of either saline or N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min for 15 minutes), an inhibitor of NO synthesis. The effect of L-NMMA on endothelium-independent vasodilation induced by intraarterial infusion of sodium nitroprusside was also studied in 11 of the 15 subjects. Forearm blood flow was measured by plethysmography. Mental stress increased forearm blood flow from 2.35 +/- 0.84 to 5.06 +/- 2.66 ml/min/dl (115%) during saline and from 1.72 +/- 0.59 to 2.81 +/- 0.99 ml/min/dl (63%) during L-NMMA infusion. The vasodilator effect of mental stress was significantly lower during L-NMMA infusion than during saline (1.1 +/- 0.65 vs 2.71 +/- 2.15 ml/min/dl; p = 0.01). L-NMMA administration did not significantly change mean arterial pressure and heart rate responses to mental stress. In contrast, the vasodilator effect of sodium nitroprusside (1.6 microg/min) was similar during infusion of L-NMMA and during saline (3.75 +/- 1.55 vs 2.85 +/- 1.38 ml/min/dl; p = 0.16). These findings indicate that local release of NO is involved in the forearm vasodilator response to mental stress.     

Improved specificity of transesophageal dobutamine stress echocardiography compared to standard tests for evaluation of coronary artery disease in women presenting with chest pain

The detection of coronary artery disease (CAD) by noninvasive methods has been hindered in women by the high rate of false-positive results. To determine the feasibility and accuracy of transesophageal dobutamine stress echocardiography for identification of CAD in women, we studied 84 patients (age 51 +/- 11 years) who underwent symptom-limited exercise treadmill testing, exercise thallium-201 scintigraphy, and coronary angiography for evaluation of anginal chest pain. Of the 84 patients, 62 had normal coronary arteries or nonsignificant coronary lesions, and 22 had significant stenosis of > or = 1 major coronary artery. During treadmill exercise, repolarization changes were observed in 16 of 21 patients with CAD and in 19 of 60 patients with normal coronary arteries. With thallium scintigraphy, a reversible defect was observed in 19 of 22 patients with CAD and in 12 of 60 patients with normal coronary arteries. Regional wall motion abnormalities during dobutamine infusion developed in 18 of 22 patients with CAD and in none of the 62 patients with normal coronary arteries. All 3 tests had similar sensitivity for detection of CAD (76% for exercise treadmill test, 86% for thallium scintigraphy, and 82% for transesophageal dobutamine stress echocardiography). However, transesophageal dobutamine stress echocardiography had significantly higher specificity than the other 2 tests (100% vs 68% for exercise treadmill test and 80% for thallium scintigraphy; p = 0.0001). Thus, transesophageal dobutamine stress echocardiography is accurate for evaluation of CAD among women presenting with chest pain; its use should be considered when more conventional tests are equivocal or technically suboptimal.     

Pluripotential melanoblastoma, a unifying concept on malignancies arising in congenital melanocytic nevi: report of two cases

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.     

The subunit structure of alpha-acetohydroxyacid isomeroreductase from Salmonella typhimurium

Alpha-Acetohydroxyacid isomeroreductase from Salmonella typhimurium has a native molecular weight of 220,000. The constituent polypeptide chains exhibit anomalous but unimodal electrophoretic migration on sodium dodecyl sulfate-urea polyacrylamide gels. The subunit molecular weight, determined by sedimentation equilibrium in 6 M guanidine hydrochloride, is 57,000. The apparent tetrameric nature of the native enzyme was confirmed by determining the types of oligomers formed upon cross-linking with dimethylsebacimidate. Analysis of tryptic peptides suggests that the polypeptide chains have an identical amino acid sequence. Carbohydrate analysis, ultraviolet absorption spectrum, and atomic absorption spectrum are consistent with the lack of cobalamine and cobalt. The Michaelis constants are as follows: alpha-acetolactate, 2.9 x 10-4 M; alpha-aceto-alpha-hydroxybutyrate, 7.8 x 10-4 M; NADPH, 1.5 x 10-5 M; Mg2+, 7.7 x 10-4 M. The catalytic constants (molecules of substrate catalyzed per min per molecules of enzyme) for alpha-acetolactate and alpha-aceto-alpha-hydroxybutyrate are 1,100 and 4,700, respectively. Comparative tryptic peptide analysis and immunological analysis show that alpha-acetohydroxyacid isomero-reductase and biosynthetic L-threonine deaminase bear no structural relationship and therefore rule out a "shared structure" hypothesis for the putative involvement of L-threonine deaminase in the synthesis of alpha-acetohydroxyacid isomeroreductase.