g(m3)-ganglioside and Body-Weight

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GSD) causes a complete absence of GM3 and all downstream biosynthetic derivatives. The individuals affected by this disorder manifest severe irritability, intractable seizures and profound intellectual disability. However, we have found that most newborns seem symptom-free for a period of time after birth. In order to further understand the onset of the disease, we investigated the early growth and development of patients with this condition through this study. We compared 37 affected individuals with their normal siblings and revealed that all children with GSD had relatively normal intrauterine growth and development, as their weight, length and head circumference were similar to their normal siblings at birth. However, the disease progresses quickly after birth and causes significant constitutional impairments of growth and development by 6 months of age. Neither breastfeeding nor gastrostomy tube placement made significant difference on growth and development as all groups of patients showed the similar pattern. We conclude that GSD causes significant postnatal growth and developmental impairments and the amount of gangliosides in breast milk and general nutritional intervention do not seem to alter these outcomes.

Topics: Adolescent; Birth Weight; Body Weight; Child; Child, Preschool; Disease Progression; DNA Mutational Analysis; Epilepsy; Female; Fetal Development; G(M3) Ganglioside; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Male; Mutation; Sialyltransferases; Siblings

Patterns and contents of major acidic glycosphingolipids in the kidney of three marine mammalian species, the Steller sea lion (Pinnipedia), the rough-toothed dolphin and the broad-beaked dolphin (Odontoceti), were examined, and compared with those of terrestrial mesic mammals. The profile of major acidic glycosphingolipids was not significantly different between the terrestrial and marine mammals: predominant gangliosides were GM3 and GD3, and major sulfoglycolipids were SM4s and SM3. On the other hand, the total concentration (nmol/g wet tissue) of sulfoglycolipids was considerably higher in the marine mammals (2.3-3.0 times) than that in the terrestrial mesic mammals with comparable body weights. In contrast, there was no significant difference in the level of renal glycolipids-bound sialic acid between the marine and the terrestrial mammals. These results suggest that higher expression of renal sulfoglycolipids in marine mammals may contribute to the maintenance of osmotic balance of their body fluid against sea water.

Topics: Animals; Body Fluids; Body Weight; Cerebrosides; Dolphins; G(M3) Ganglioside; Gangliosides; Glycolipids; Kidney; Lactosylceramides; Mammals; Marine Biology; Molecular Structure; Sea Lions; Seawater; Species Specificity; Water-Electrolyte Balance

GM3 is a ganglioside that has been biochemically identified as dominating the cell surface of several human tumours, but is also found on human normal cells at much lower density. Since GM3 is widely distributed in essentially all types of animal cells, there is a conflict with the concepts of tumour-associated antigen, immunogen, and toxicity. We have designed a GM3-based cancer vaccine for the treatment of human breast and melanoma tumours. Prior to the Phase I clinical trial, we carried out a 12-month dose repeated toxicity study in five male Macaca fascicularis monkeys. Four male monkeys were treated with placebo in a similar way. During the study, no differences were observed between control and treated monkeys related to daily clinical observations (other than local damage) including rectal temperature, blood pressure, respiratory and cardiac rates, weight gain, biochemical and hematological parameters (with the exception of transitory pathological changes), and anti-DNA and anti-nuclear antibodies, although treated monkeys consistently developed both IgM- and IgG-specific anti-GM3 antibodies. Sixty per cent of treated monkeys developed moderate local reactions at the injection site, which disappeared without sequels. We concluded that this GM3 cancer vaccine overcame in monkeys the natural tolerance to GM3 ganglioside evidenced by a strong immune response, while the local reactions elicited-were transitory without apparent important systemic toxicity effects.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Neoplasm; Body Weight; Breast Neoplasms; Cancer Vaccines; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dogs; Drug Evaluation, Preclinical; G(M3) Ganglioside; Hematologic Tests; Immunoglobulin G; Immunoglobulin M; Kidney Function Tests; Liver Function Tests; Macaca fascicularis; Male; Melanoma; Proteolipids; Skin Neoplasms; Toxicity Tests