PubMed · 5970310
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A Carlsson. 1966. [Cerebral monoamines].. https://doi.org/10.3109/08039486609094786
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Infantile free sialic acid storage disease (ISSD), is an inherited metabolic disorder characterized by hyperexcretion of free sialic acid in the urine and by its storage in the lysosomes of different tissues. In order to obtain more reliable data on the amount of total and free sialic acid, we analyzed the urine, brain, cerebellum, liver, spleen, and kidneys from a 3-month-old baby who died with a diagnosis of ISSD. The lysosomal nature of the disease was confirmed by an electron microscopic study of cells in culture. No significant abnormalities were found involving cholesterol, total phospholipids, glycolipids, and gangliosides in the tissues examined. However, differences in the tissue distribution of individual glycolipids and gangliosides were observed. The amount of free and total sialic acid was markedly increased, due to the storage of free sialic acid accompanied by its hyperexcretion in the urine. These results demonstrate and confirm that only acid monosaccharide transport from the lysosome compartment is involved in the pathogenesis of ISSD.
Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocytochemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5' end containing both muscle and brain promoters. As the patient's mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent from the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin-positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5' end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed genotypic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation.
New chemical synthetic methods have permitted the synthesis of a spectrum of glycosphingolipid molecular species, some of which are not naturally occurring. Here we have studied a number of chemically synthesized gangliosides for immunosuppressive activity, using a human in vitro specific antigen (tetanus toxoid)-induced assay of the cellular immune response. Chemically synthesized GM3 and GM4 had the same high degree of immunosuppressive activity as did natural GM3 and GM4 gangliosides, verifying that inhibition is intrinsic to the ganglioside molecules and not caused by other molecules sometimes found in natural preparations (e.g., proteins). Studies of modified molecular species of GM3 and GM4, also prepared by chemical synthesis, have shown the influence of certain structural details upon the immunosuppressive activity of gangliosides: (i) the inverse relationship between fatty acyl chain length and immunosuppressive activity is extended to even shorter chain lengths, with the synthetic gangliosides d18:1-C2:0-GM3 and d18:1-C14:0-GM3 being more immunosuppressive than d18:1-C18:0-GM3 and d18:1-C24:0-GM3; (ii) hydroxylation of the fatty acyl group decreases immunosuppressive activity; (iii) substitution of an S-glycosidic bond for an O-glycosidic bond in the sialic acid ketosidic linkage in GM4 does not alter its activity; and (iv) modifications of the sialic acid group variably influence immunosuppressive activity, since KDN-GM3 and -GM4 ganglioside analogues, which contain a 3-deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid in place of N-acetylneuraminic acid, retain activity, while other modifications such as 8-epi-GM3, and to a lesser extent 9-deoxy-GM3, reduce immunosuppressive activity.(ABSTRACT TRUNCATED AT 250 WORDS)