Dilated cardiomyopathy caused by acute myocarditis in pediatric patients: evolution of myocardial damage in a group of potential heart transplant candidates.

Dilated cardiomyopathy, frequently caused by acute myocarditis, is a common indication for heart transplantation in pediatric patients. The prognosis of children with acute myocarditis is not well known but is believed to be poor. We report the short-term follow-up in 20 pediatric patients (mean age 22 +/- 19 months) with acute myocarditis diagnosed by endomyocardial biopsy. All patients were treated by immunosuppression (cyclosporine and steroids). Endomyocardial biopsy was repeated after 6 months in all patients and after 1 year in patients with persistent acute myocarditis. To evaluate left ventricular function, two-dimensional echocardiography was performed at the time of each endomyocardial biopsy, and left ventricular end-diastolic volume index and ejection fraction were calculated. After 6 months, endomyocardial biopsy showed persistence of acute myocarditis in 13 of 20 patients. After 1 year, endomyocardial biopsy performed in 11 of 13 patients with persistent acute myocarditis showed ongoing acute myocarditis in 10 of 11 patients. On admission to the hospital, 16 of 20 patients had left ventricular dilation (end-diastolic volume index 122 +/- 19 ml/m2; normal values 63 +/- 17 ml/m2) and 20 of 20 had decreased contractility (ejection fraction 34% +/- 11%; normal values 66.1% +/- 5.2%). After 6 months, in all patients the end-diastolic volume index decreased to 73 +/- 23 ml/m2 (p < 0.001), and the ejection fraction increased to 56% +/- 8% (p < 0.000001).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose stimulates cAMP accumulation in the oral bacterium Actinomyces viscosus.

Actinomyces viscosus T14V, a Gram-positive bacterium found in the oral cavity, was found to be insensitive to glucose-mediated catabolite repression. Basal levels of beta-galactosidase (18-26 U) were observed at all phases of growth regardless of the culture conditions. Further, beta-galactosidase could not be induced with lactose, or with a known inducer of the enzyme, isopropyl-beta-D-thiogalactoside, or with dibutyryl cAMP. Glucose, on the other hand, stimulated cAMP accumulation in a concentration-dependent manner. Fructose and sucrose mimicked the effects of glucose on cAMP accumulation, whereas galactose, mannose and maltose had lesser stimulatory effects. Other carbon sources, i.e., lactose, alpha-methylglucoside, ribose, xylose and succinate were without effect. Glucose and alpha-methylglucoside were found to stimulate cAMP accumulation in toluene-permeabilized cells, in the presence of the phosphodiesterase inhibitor, theophylline. Glucose did not stimulate cAMP levels in other Gram-positive bacteria including Streptococcus mutans, S. sanguis and S. salivarius but did cause cAMP accumulation in other strains of A. viscosus. The results suggest that glucose effects on cAMP metabolism are independent of the induction of beta-galactosidase as presently defined for Escherichia coli, and that the effects appear to be selective to the A. viscosus bacteria. The results also suggest that glucose stimulates cAMP accumulation via activation of adenylate cyclase.

Identification and localization of G proteins in exocrine glands.

GTP-binding proteins were identified in rat parotid acinar plasma-enriched membranes (PM) by immunoblot analysis and localized immunohistochemically in the parotid gland as well as in other exocrine glands by using affinity-purified antisera specific for alpha subunits of the G proteins. Isolated rat parotid acinar PM immunoreacted strongly to antisera directed against Gs alpha, Gi alpha 1/alpha 2, Gi alpha 3, and Go alpha; the signal for Go alpha, however, was weak with crude Go antisera. Immunohistochemical studies to identify and localize Go in rat parotid tissue revealed that antisera to Go alpha immunoreacted with ductal cells. In addition, strong immunoreactivity to Go alpha antisera was noted in ductal cells of other salivary glands including rat submandibular, mouse parotid, and mouse submandibular glands. Light labeling of rat parotid and submandibular gland acinar cells was also noted. In contrast, in the rat and mouse pancreas, Go antisera immunoreacted primarily with islet cells. Ductal cells were negative, but there was light labeling of rat pancreatic acinar cells. The apparent ductal specificity of Go alpha staining was further verified by demonstrating that Go alpha antisera immunoreacted strongly with HSG-PA cells, a human transformed salivary ductal cell line. The results demonstrate that rat parotid acinar plasma membranes express a number of G proteins including Go and that Go appears to be selectively expressed in the ductal cells of rat parotid gland and other salivary glands. The selective enrichment of Go in ductal cells suggests that this G protein may play an important role in ductal cell physiology.

Inhibition of basal and calmodulin-activated Ca2+-pump ATPase by fractionated compound 48/80.

Compound 48/80 (48/80), a mixture of polycationic compounds was fractionated using affinity chromatography on calmodulin-Sepharose. Unfractionated 48/80 and various fractions were tested for their potential inhibitory effects on ATPase activities of isolated human red blood cell membranes. ATPase activities tested included: Mg2+-ATPase, the Na+/K+-pump ATPase, and the Ca2+-pump ATPase in both its basal (calmodulin-independent) and calmodulin-activated state. Neither 48/80 nor its various fractions were very potent or efficacious inhibitors of the Mg2+-ATPase or the Na+/K+-pump ATPase. In agreement with previous reports, 48/80 was found to be an inhibitor of the calmodulin-activated Ca2+-pump ATPase. By contrast, we found that unfractionated, as well as some fractionated, material inhibited both the basal (calmodulin-independent) and calmodulin-activated Ca2+-pump ATPase activity. A fraction designated as Fraction III bound to calmodulin-Sepharose in the presence of Ca2+ and low salt and was eluted in the absence of Ca2+ and 0.15 M NaCl. By gel filtration, Fraction III had an apparent average molecular weight of 2064 (1320 for unfractionated material). Fraction III was the most potent inhibitor of the Ca2+-pump ATPase with IC50 values for the basal and calmodulin-activated forms of the enzyme of 0.6 and 1.2 micrograms/ml, respectively. Inhibition by Fraction III was cooperative with n apparent values of 2.4 and 5.7, respectively, for the basal and calmodulin-activated forms of the enzyme. Thus, binding of 48/80 constituents to calmodulin can not fully account for the observed data. Direct interaction of 48/80 constituent(s) with the enzyme and/or the lipid portion of the membrane is suggested.