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A Frisch

Publications and source records attributed to A Frisch.

45 records · Page 3Linked to original sources
PubMed1982

Nonuniform deficiency of hexosaminidase A in tissues and fluids of two unrelated individuals.

Serum samples from two unrelated, clinically normal individuals lacked detectable hexosaminidase A by heat inactivation and electrophoretic analysis. In contrast, 15 and 17% of the hexosaminidase in their leukocytes and 23 and 26% of the hexosaminidase of their cultured fibroblasts had the heat stability and electrophoretic properties of the A form of this enzyme. An in vitro measurement of fibroblasts GM2 ganglioside-beta-galactosaminidase was in the range expected for Tay-Sachs disease (TSD) heterozygotes (2.5 and 3.1 versus a normal mean of 3.7). In contrast, fibroblasts from a patient with TSD, analyzed in an identical fashion, contained no detectable activity. Ten days after addition of labeled GM2 ganglioside to the medium of the cultured fibroblasts, 43 and 59% of the radioactivity taken up by the cells of these patients remained as unhydrolyzed ganglioside as compared with 94% in TSD fibroblasts and 42% in control cells. An analysis of sphingolipid composition by high performance liquid chromatography although the endogenous level of GM2 was elevated in TSD fibroblasts (0.39 nmoles/mg protein) there was no increase in the cells of these patients (0 and 0.12 versus control of 0.17 nmoles/mg protein). Finally, the synthesis of hexosaminidase was examined by an electrophoretic analysis of immunoprecipitates of the enzyme precursors that had been radiolabeled by culturing fibroblasts in medium containing [3H]-leucine. These studies revealed a normal pattern of biosynthesis, processing and secretion of the alpha and beta chains. The ratio of the alpha chain to the beta chain, however, was in the range expected for TSD heterozygotes.

Adult↗
PubMed1978

Inhibition of conjugation in Tetrahymena pyriformis by cerulenin. Possible requirement for de novo lipid synthesis.

Conjugation in Tetrahymena pyriformis is induced by the mixing of two starved complementary mating types. Addition of the antibiotic cerulenin, a specific inhibitor of de novo lipid synthesis, upon mixing of the mating types inhibited the conjugation process. The inhibition of conjugation was found to be reversible upon washing the cells. Cerulenin inhibited [14C]acetate incorporation into the lipid fraction of the cells, while it did not affect the incorporation of [3H]leucine into proteins. Analysis of the fatty acid composition of the whole cells revealed that during conjugation the ratio of saturated to unsaturated fatty acids is markedly changed. While the ratio of saturated:unsaturated fatty acids is 0.30 in unconjugated cells, it reached a value of 0.45 in conjugated cells.

Animals↗
PubMedDate not supplied

Adult-onset GM2 gangliosidosis diagnosed in a fetus.

Amniocentesis and subsequent tests are reported on a fetus conceived of a rare mating type: its mother has an intermediate level of beta hexosaminidase A (HEX A), characteristic of carriers of Tay-Sachs disease (TSD), while the father suffers from an adult-onset GM2 gangliosidosis (AOG) with severe HEX A deficiency. Activity of HEX A in the cultured fetal cells was very low when measured by the heat-inactivation method, thus showing the typical biochemical phenotype of TSD fetuses. However, upon separation of HEX isozymes by ion exchange chromatography, residual HEX A (17 per cent of total HEX) was demonstrated. Also in contrast to TSD fetuses, this fetus' fibroblasts were able to synthesize the precursor of alpha chains of HEX, and ultrastructural examination of its brain revealed few atypical lamellar bodies, unlike those found in TSD fetuses of the same gestational age. It is therefore concluded that the fetus was not affected with TSD, but rather with AOG.

Adult↗
PubMedDate not supplied

Lower frequency of Gaucher disease carriers among Tay-Sachs disease carriers.

The heterozygote frequency of Gaucher disease (GD) and Tay-Sachs disease (TSD) is distinctly high among Ashkenazi Jews (1:29 for TSD and 1:16 for GD). Two main theories have been suggested to explain this high occurrence: a founder effect with subsequent genetic drift, and a selective advantage of heterozygotes. We compared the frequency of the GD most common mutation (1226A-->G) among carriers of the common TSD mutation (+1277 TATC) with the frequency of this mutation in the general Ashkenazi population. The frequency of GD carriers among 308 TSD heterozygotes was 1:28 which is about half the expected (P = 0.03). These results indicate that carriers of both diseases do not possess additional evolutionary advantage over single mutation carriers. A reasonable interpretation of these findings is that one or both mutations have arisen relatively recently in different regions of Europe and have not yet reached genetic equilibrium.

DNA Mutational Analysis↗