Fetal alcohol syndrome: an international perspective.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Kenneth R. Warren and Faye J. Calhoun. The presentations were (1) Epidemiological research on fetal alcohol syndrome (FAS) in the United States, by Philip A. May; (2) An overview of fetal alcohol syndrome in the Western Cape Province of South Africa, by Denis L. Viljoen and Ting-Kai Li; (3) Diagnostic perspectives of fetal alcohol and tobacco syndromes, by Harumi Tanaka; (4) FAS among pupils of special boarding schools and orphanages in Moscow, Russia, by Galina S. Marinicheva and Luther K. Robinson; and (5) Research on FAS and FAE in Germany: Update and perspectives, by Goetz Mundle.

Alcohol-related birth defects--the past, present, and future.

In 1994 Alcohol Health & Research World (now titled Alcohol Research & Health) last devoted a full issue to the topic of fetal alcohol syndrome (FAS) and other alcohol-related birth defects (ARBD). This introductory article provides readers with information on how the field has advanced since then. In addition to tracing the development of the terminology used in the field, it describes the difficulties involved in determining the true prevalence of FAS and ARBD; the mechanisms that may play a role in alcohol-derived fetal injuries; approaches to preventing drinking during pregnancy; and strategies for assisting people who have been born with FAS and ARBD.

Alcohol-related birth defects: an update.

Historically, mankind has at least suspected that alcohol was somehow connected with undesirable effects on progeny. In the 18th century, physicians became aware that maternal alcohol consumption resulted in excess fetal and neonatal mortality, low birth weight, and many other deleterious effects. Perhaps as a response to the temperance and Prohibition periods, scientists lost sight of or interest in the effects of alcohol in pregnancy. In the late 1960s and early 1970s, the issue surfaced again, and scientists began systematic and in-depth studies of fetal alcohol syndrome (FAS) and alcohol-related birth defects (ARBD). Epidemiologic research now suggests that FAS has outranked Down's syndrome and spina bifida in prevalence and is now the leading known cause of mental retardation. Further, it is the only one of these three that is preventable. Because a safe limit of alcohol consumption in pregnancy is not defined, abstinence during pregnancy is the most prudent preventive measure. Factors such as race, beer drinking, maternal weight gain, and low socioeconomic status are associated with a statistical increase in the incidence of FAS. In families where one child has been diagnosed as having FAS, the incidence rate can be as much as 405-fold higher than the worldwide average. Neurobehavioral deficits can occur in the offspring of drinking mothers in the absence of a diagnosis of full FAS. The deficits differ with age and seem to persist into adulthood. Mental retardation or borderline mental retardation is a nearly ubiquitous neurological deficit in diagnosed FAS. In one study, it occurred in 75 percent of the non-FAS offspring of mothers who continued to drink heavily throughout their pregnancy.From the mid-1970s, having established that alcohol is a teratogen, scientists have been trying to uncover the mechanism by which alcohol exerts its embryotoxic effects. Recent promising neuroanatomical studies have demonstrated that alcohol has a deleterious effect on neuronal migration and hence on the development of the cerebral cortex. Other studies have shown that prenatal alcohol exposure,by adversely affecting hippocampal development,may be responsible for the learning deficits so frequently encountered in FAS children. Other research has implicated prostaglandins in the mechanism of alcohol-related dysmorphology.

Formaldehyde concentrations in workrooms resulting from off-gassing from sandpaper.

Formaldehyde was found to off-gas from flint sandpaper that contained an urea-formaldehyde resin as the minor component in a double glue system. Approximately 2000 sheets of sandpaper in a 115 m3 (4050 ft3) ship's storeroom with no mechanical ventilation produced a formaldehyde concentration of at least 4.5 ppm that was uniform throughout the compartment. A contributing factor was elevated compartment temperature due to high ambient temperature and the heating of the ship's steel hull by direct exposure to the sun.

Nonproliferating neoplastic cells in culture: behavior of the adenine nucleotides.

The intracellular concentrations of the adenine nucleotides were determined in suspension cultures of WRL-10A cells, a subline of the L-929 mouse fibroblasts, during the progression of the cells from exponential growth to high-density, nonproliferating populations. The development of the nonproliferating state was associated with a 50% reduction of the adenine nucleotide pool, whereas the energy charge remained at values above 0.90. This change was also observed in the early phase of starvation of low-density cultures and could be reproduced by selective simultaneous withdrawal of glucose and glutamine, which indicated interference with the de novo synthesis of purines. In this respect, therefore, nonproliferating populations of WRL-10A cells resemble purine-limited bacterial systems but not density-inhibited normal fibroblasts in which the size of the adenine nucleotide pool is known to remain unchanged. This difference in the physiologic state of nonproliferating normal and neoplastic cells is potentially significant for tumor chemotherapy.

The effects of N-hexyl-O-glucosyl sphingosine on normal cultured human fibroblasts: a chemical model for Gaucher's disease.

Normal human skin fibroblasts were grown in the presence of N-hexyl-O-glucosyl sphingosine (HGS), an inhibitor of aryl glucosidase and glucocerebrosidase. Tests of the cells with aryl glycosides showed that beta-glucosidase activity in the cells was drastically reduced while other enzyme activities (alpha-glucosidase, beta-galactosidase, and N-acetyl-beta-hexosaminidase) were normal or elevated. Exposure of cells to HGS for 28 days resulted in increased values for cell weight per plate, glucocerebroside concentration, and galactosyl-galactosylglucosyl ceramide concentration. The concentrations of total lipid, cholesterol, and protein were unchanged, as was the fatty acid distribution within the glycolipids. Chemically, the inhibitor-treated cells exhibited a model form of Gaucher's disease. Although many membranous cytoplasmic inclusions were induced by HGS, they were unlike the characteristic inclusions seen in individuals with the genetic disorder. Skin fibroblasts from a Gaucher patient showed no abnormalities in composition or appearance.

Uridine diphosphate glucose synthase from calf liver: determinants of enzyme activity in vitro.

The reaction catalyzed by calf liver uridine diphosphate glucose synthase (pyrophosphorylase) (EC 2.7.7.9; UTP + glucose 1-phosphate = UDP-glucose + PPi) is an example of an enzymic reaction in which a nucleoside triphosphate other than ATP is the immediate source of metabolic energy. Kinetic properties of the enzyme, acting in the direction of UCP-glucose formation were investigated in vitro. The reaction was inhibited by UDP-glucose (0.072), Pi (11), UDP (1.6), UDP-xylose (0.87), UDP-glucuronate (1.3), and UDP-galacturonate (0.95). The numbers in parentheses indicate the concentration (mM) required for half-maximal inhibition under the conditions used. Other compounds tested, including ATP, ADP, and AMP, had no effect. Over a range of concentrations of UTP (0.04-0.8 MM) and UDP-glucose (0.05-0.03 mM), the reaction rate was more dependent on the concentration ratio [UDP-glucose]/[UTP] than on the absolute concentration of either compound. Comparison of the kinetic properties in vitro with estimates of metabolite levels in vivo suggests that (1) the enzyme operates in a range far from its maximal rate, and (2) the concentrations of glucose 1-phosphate and Pi and the ratio [UDP-glucose]/[UTP] may be the most important determinants of UDP-glucose synthase activity.