Ethanol Consumption Inhibits Fetal DNA Methylation in Mice: Implications for the Fetal Alcohol Syndrome

Acute ethanol administration (3 g/kg twice a day) to pregnant mice, from the 9th thru the 11th day of gestation, resulted in hypomethylation of fetal deoxyribonucleic acid (DNA). Nuclei isolated from the fetuses of the ethanol-treated mice had lower levels of methylase activity relative to controls even in the presence of excess S-adenosylmethionine, which serves as the methyl donor for the enzyme DNA methyltransferase. Acetaldehyde, at concentrations as low as 3 to 10 microM, inhibited DNA methyltransferase activity in vitro. Since DNA methylation is thought to play an important role in the regulation of gene expression during embryogenesis, ethanol-associated alterations in fetal DNA methylation may contribute to the developmental abnormalities seen in the fetal alcohol syndrome.     

Regulation of phospholipase Cbeta activity by muscarinic acetylcholine and 5-HT(2) receptors in crude and synaptosomal membranes from human cerebral cortex

Stimulation of phospholipase Cbeta by receptor agonists and G proteins has been characterized in crude cerebral membrane preparations, but little is known about their presynaptic localizations and little information is currently available for human brain tissue. The characteristics of phosphoplipase C transmembrane signaling were studied in crude and synaptosomal plasma membranes from postmortem human prefrontal cortex by measuring the hydrolysis of exogenous [(3)H]phosphatidylinositol4,5bisphosphate(PIP(2)) and the immunoreactive levels of phospholipase C (PLC) and G(alphaq/11) proteins. Regulation of PLC activity by Ca(2+) and the 5-HT(2) receptor agonist 5-methyltryptamine, but not by guanosine 5'-O-[3-thiotriphosphate] and the muscarinic acetylcholine receptor agonist carbachol were different between crude and synaptosomal membranes. KCl (20 mM) stimulation was absent in both preparations. Levels of G(alphaq/11)-protein subunits differed between preparations. The functional inhibition carried out with pirenzepine in crude membranes in order to reverse the carbachol-induced PLC stimulation indicates the existence of a component (53%) of the response that is activated by the M(1) muscarinic acetylcholine receptor subtype, and another component (47%) probably mediated by the M(3) muscarinic acetylcholine receptor subtype. In synaptosomal plasma membranes an increased inhibition of carbachol-induced PLC activation through M(1) was found. The PLC activation by 5-methyltryptamine (ketanserin-sensitive in crude membranes) was absent in synaptosomal plasma membranes suggesting the lack of activity mediated by 5-HT(2)-serotonin receptors.     

A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females

Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. The objective of this study is to compare the patient characteristics and survival of YST in males and females. Demographic and clinicopathologic information were obtained from the Surveillance, Epidemiology, and End Results Program from 1973 to 2003. Statistical analysis was performed using Independent-sample t-test, chi(2) test, Kaplan-Meier methods and Cox proportional hazards regression. Seven hundred eighty-eight patients were identified, 451 (57%) were males and 337 (43%) were females. The mean age at diagnosis was similar in males and females. The age at diagnosis showed a bimodal distribution with an increased incidence in the first 4 years of life and during the 2nd to 4th decade of life. The most common site of the primary tumor was gonadal, namely testis 336 (42.6%) and ovary 257 (32.6%). Among the extragonadal sites, tumor site of origin differed in males and females. The 5-year survival of extragonadal YST (66%) was worse than gonadal YST (86%) (p < 0.05). The overall median survival for the cohort was 87 months. This was similar in males (81 months) and females (91 months) (p > 0.05). As the year of diagnosis progressed from 1973 to 2003, survival of both males and females with YST consistently improved. The bimodal age distribution of YST generates the hypothesis that sex steroids may play a role in selected YST. Although the overall survival in all YST patients has improved over the past few decades, the primary sites of origin differ in males and females and impact prognosis.     

Light Microscopic Diagnosis of Microsporidiosis in Patients with AIDS

Objective: In the past, the diagnosis of chronic intestinal microsporidiosis, an important cause of diarrhea in patients with AIDS, relied upon transmission electron microscopy (TEM). In this study, the sensitivity and specificity of the light microscopic (LM) diagnosis of microsporidiosis was determined. Methods: Thirty-four consecutive jejunal biopsies from AIDS patients were evaluated at St. Luke's-Roosevelt and George Washington University Hospital Centers by several light microscopic stains, including hematoxylin and eosin. Gram stain, Giemsa stain, chromotrope 2R modified-trichrome stain, and Giemsa stain of mucosal touch preparations (TP). The results were compared to TEM, as the gold standard, and to estimates of parasite burden from plastic section light microscopy and TP. Results: Microsporidiosis was diagnosed by TEM in 15 cases. The diagnosis also was reached by light microscopy in most cases. The sensitivities and negative predictive values of the different techniques ranged from 57% to 88%, while the specificities and positive predictive values ranged from 94% to 100%. All stains gave concordant results in 23 of 34 cases. The parasite burden was lower by TEM ( p < 0.05) and TP in cases with discordant (false-negative) results than in those with concordant results, suggesting that a false-negative diagnosis is related to a low parasite burden. Conclusion: It should he possible to render the diagnosis of intestinal microsporidiosis hy LM in most cases. TEM may be needed for the minority of cases with low parasite burden.