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Infantile rhabdomyofibrosarcoma (IRMFS) is a rare soft tissue tumour affecting infants and young children. It occupies an intermediate position between infantile fibrosarcoma and spindle cell rhabdomyosarcoma in its clinical presentation, behaviour, morphology, immunohistochemical and ultrastructural features. This case is reported here to reiterate its occurrence as tumour with distinct morphological immunohistochemical and clinical behavioral patterns. [ABSTRACT FROM AUTHOR]

The established role of vitamin K in nutrition is as a cofactor in the post-translational conversion of specific glutamyl to gamma-carboxyglutamyl (Gla) residues in a limited number of proteins. Administration of the vitamin K antagonist warfarin has previously been shown to decrease brain sulfatide concentrations and decrease brain galactocerebroside sulfotransferase (GST) activity in young mice. A dietary deficiency of vitamin K has now been shown to decrease (P < 0.01) brain sulfatide concentrations of 30-d-old mice significantly (by 21%). Male 21-d-old rats fed an excess of vitamin K for 7 or 14 d had 26 and 31% (P < 0.05) greater GST activity and 15 and 18% (P < 0.05) greater brain sulfatide concentrations, respectively, than controls fed a vitamin K-deficient diet. Male 21-d-old rats fed a diet containing 500 mg of phylloquinone/kg diet had an intermediate response and were vitamin K sufficient by normal criteria. The vitamin K response was observed when either phylloquinone or menaquinone-4 was fed as a source of the vitamin. These data suggest that in addition to its recognized role in Gla synthesis, vitamin K status is important in the maintenance of normal complex lipid sulfatide metabolism in young rats and mice.

Galactosylceramide sulfotransferase (EC 2.8.2.11) catalyzes the biosynthesis of sulfatide from galactocerebroside and adenosine 3'-phosphate 5'-phosphosulfate (PAPS). This enzyme is developmentally controlled, reaching a maximum activity in the brains of mice corresponding to that of maximum myelination. The product, sulfatide, is an important component of myelin. This transferase from mouse brain has been purified 2600-fold using a combination of pyridoxal 5'-phosphate- and ATP-ligated columns. The purified enzyme yielded a single band following SDS-polyacrylamide gel electrophoresis with an apparent M(r) of 31,000. The entire purification procedure can be completed in 1 day. The pH optimum for the enzyme is 7.0. The Km for PAPS is 1.2 x 10(-6) M, and the Km for cerebroside is 2.6 x 10(-5) M. Cerebroside concentrations > 80 pmol/ml are inhibitory. Enzyme preparations were associated with several lipids. Vitamin K+P(i) activated purified preparations of the sulfotransferase and maintained enzyme activity during storage at -80 degrees C.

Previous work has shown that vitamin K regulates brain sulfotransferase activity. We now show that activity is lost after treatment with acid phosphatase and is restored with ATP. Orthophosphate activates sulfotransferase to a small degree (26%) with a maximum at 3 mM. Vitamin K1 (or menadione) + orthophosphate stimulates activity 400%; vitamin K alone is not active. ATP activates maximally at 10 mM; ATP + vitamin K increases activation 20%. Protein kinase inhibitors do not affect ATP or orthophosphate + vitamin K mediated activation. Sulfotransferase is inhibited by pyridoxal phosphate indicating modification of a lysyl residue.

We have shown previously that the administration of warfarin to 16-day-old mice results in a significant reduction in levels of sulfatides, and to a lesser degree a reduction of other sphingolipids in brain. Vitamin K stimulates biosynthesis of sulfatides in warfarin-treated mice. We now report that warfarin inhibits brain sulfotransferase activity. This inhibition is reversed by vitamin K. The treatment of normal mice with vitamin K stimulates the activities of sulfotransferase and arylsulfatase and the turnover rate of brain sulfatides. The ability of vitamin K to influence the activity of biosynthetic and catabolic enzymes and the turnover of sulfatides suggests a possible regulatory role for vitamin K in the maturing brain.

D- and L-cycloserine were shown to be irreversible inhibitors of the first enzyme of the sphingolipid pathway, 3-ketodihydrosphingosine synthetase, in a study using bacterial and brain microsomal enzymes. L-Cycloserine was shown to be 100 times more inhibitory than the D-isomer for the brain microsomal enzyme in vitro. In vivo, L-cycloserine caused a 70% inhibition of brain microsomal enzyme. Following one injection, enzyme activity recovered 80% of normal after 16 hours. Daily dosages of L-cycloserine on a regimen of intraperitoneal injection for 7 days caused a significant reduction in total brain ganglioside and cerebroside plus sulfatide levels.

Short-term experiments in which L-cycloserine, the inhibitor of 3-ketodihydrosphinogosine synthase, was injected subcutaneously in young mice have shown that cerebroside synthesis is inhibited specifically. Studies on the effect of long term L-cycloserine treatment on sphingolipid synthesis were performed to determine whether mice could tolerate continued cerebroside reduction and whether or not the synthesis of other sphingolipids would be inhibited. L-cycloserine, when injected at a low dose for a period of two months resulted in significantly reduced brain cerebroside level with little or no reduction in sulfatide, ganglioside, or sphingomyelin levels; liver and spleen glucocerebroside levels were also significantly reduced. The rate of cerebroside synthesis in brain was greatly reduced, whereas synthesis of sulfatides was much less affected by L-cycloserine indicating that a portion of newly synthesized galactocerebroside is shunted to synthesis of sulfatides.

L-cycloserine was found to significantly inhibit the activity of the first enzyme of the sphingolipid pathway when added to growing cultures of Bacteroides levii. The effect of cycloserine on the synthesis of the sphingolipids showed that ceramidephosphorylethanolamine was inhibited to a greater degree than ceramidephosphorylglycerol, although synthesis of both was significantly inhibited by cycloserine as determined by [32P] incorporation and phosphorus determination. In contrast, synthesis of phosphatidylethanolamine and phosphatidylglycerol was not inhibited by L-cycloserine at 100 micrograms/ml. Peturbation of sphingolipid synthesis by L-cycloserine may therefore provide a useful tool for the study of the function of these membrane lipids.

Uptake of radioactive tryptophan by Mycobacterium tuberculosis H(37)Rv grown in vitro and in vivo was investigated. K(m) values indicated low affinity, and sodium azide inhibited uptake. Rifampin at the minimal inhibitory concentration had no effect, whereas ethambutol inhibited uptake only in the bacilli grown under in vitro conditions. The significance of these results is discussed.