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Biomedical subjects

G Bach

Publications and source records attributed to G Bach.

At least 109 records · Page 6Linked to original sources
PubMed1979

Intracellular localization of exogenous beta-glucuronidase in cultured skin fibroblasts.

The intracellular localization of exogenously supplied human platelet beta-glucuronidase in cultured skin fibroblasts derived from a beta-glucuronidase-deficient patient was studied. Four cellular fractions were obtained by differential speed centrifugation. Following two days of incubation, the exogenously supplied enzyme exhibited a distribution pattern identical to that of endogenous beta-hexosaminidase. Disruption of membranes by freezing and thawing caused a 35% increase of the enzyme activity, thus indicating a latent activity following the internalization. This indicated localization in the lysosomal fractions. Longer incubation periods led to an intracellular shift of the engulfed enzyme from the lighter lysosomal fraction to heavier particles. Once located in the heavier fraction, the enzyme was relatively stable, and participated in the catabolism of 35S-labeled mucopolysaccharides which had accumulated in the lysosomes of these fibroblasts. A marked reduction in the accumulated mucopolysaccharides of the lysosomal fraction was observed following addition of the enzyme. This was accompanied by the formation of smaller sized molecules.

Blood Platelets↗
PubMed1978

A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.

A partial deficiency of alpha-mannosidase was found in cultured skin fibroblasts, serum, and extracts of leukoytes in two siblings with mild mental retardation, delayed speech, a suggestion of coarse or full facies, and limited mobility of the large joints. All other lysosomal enzymes tested were within the normal range. Their father demonstrated intermediate alpha-mannosidase activity. The addition of 2 mM Zn++ caused a 40% increase of the alpha-mannosidase activity in cell extracts of both patients and control subjects. pH profiles and Cellogel electrophoresis of the patients' cells indicated 20% residual activity of the acidic alpha-mannosidase isoenzyme (pH optimum at 4.0), whereas the activity of the isozyme with pH optimum of 6.0 was normal. Increasing substrate concentration (1--10 mM) demonstrated a 4 to 5-fold increase in the apparent Km of the acidic alpha-mannosidase in the patients' fibroblasts. This residual activity, however, was apparently not sufficient for the normal catabolism of mannose-containing molecules, since electron microscopic examination of the cultured fibroblasts demonstrated numerous lysosomal storage bodies.

Arylsulfatases↗
PubMed1977

Prenatal diagnosis of mucolipidosis IV by electron microscopy.

Mucolipidosis IV, a recently recognized metabolic storage disease, is characterized clinically by corneal opacity in infancy, full facial features, and psychomotor retardation. Electron microscopy of cells from a 2-year-old affected girl revealed multiple cytoplasmic storage bodies. Cultured amniotic fluid cells, in two subsequent pregnancies, demonstrated similar abnormal storage bodies. Electron microscopic examination of various uncultured tissues from one abortus demonstrated abnormal inclusions in the cells of the brain, cornea, conjunctiva, and other epithelial tissues, thus confirming the prenatal diagnosis. This suggests that mucolipidosis IV is an autosomal recessive trait and demonstrates the efficacy of electron microscopy in the prenatal diagnosis of metabolic storage diseases whose biochemical defect is yet unknown.

Amniotic Fluid↗
PubMed1977

Mucopolysaccharide accumulation in cultured skin fibroblasts derived from patients with mucolipidosis IV.

Increased concentrations of total sulfated mucopolysaccharides (MPS), threefold, and hyaluronic acid (HA), 10-fold, were found in ML IV fibroblast extracts when compared to normal controls. Such accumulations altered the distribution of MPS:HA comprised 70% of total MPS in ML IV but only 30% in control cells. Intracellular sulfated MPS was observed accumulating almost linearly in ML IV fibroblasts. "Pulse-chase" experiments indicate that both HA and the sulfated MPS remain in the ML IV cells for long periods of time; in control cells, they are rapidly removed as low molecular weight, dialyzable fragments. These data suggest that the MPS accumulation in ML IV fibroblasts, is the consequence of a catabolic block, probably involving the lysosome.

Child, Preschool↗
PubMed1977

[Parallel determination of blood lead levels and clinical investigation of children with surgical diseases in an endangered area (author's transl)].

In an industrial area with heavy metal-processing industry investigations were made on 203 children with surgical diseases, questioning whether there is a correlation between blood lead level on one hand, and kind of disease, season of year, load by lead fall-out in the residence on the other hand. A correlation between blood lead level and amount of lead fall-out in the residence of the patients could not be proved.--Seasonal changes did not influence the height of the average blood lead level.--Stress situations like operations and serious diseases had no significant influence either. Parallel determination of 139 blood samples in two institutes showed essential differences in the individual results.--Conclusions of earlier investigators in the same industrial area could not be proved in essential items as mentioned above.

Abdomen↗
PubMed1977

Prenatal diagnosis of genetic disease. A report on 200 amniocenteses.

The results of 200 prenatal diagnoses following amniocentesis are summarized. The routine withdrawal of 40 to 45 ml amniotic fluid caused no increase in maternal morbidity, fetal loss, prematurity or congenital malformations. There were no culture failures and in all cases in which amniotic fluid was obtained the prenatal diagnosis was subsequently confirmed. Electron microscopy was used in the prenatal diagnosis of a newly described metabolic storage disease (mucolipidosis IV). Eleven abnormal fetuses and one male fetus at risk for hemophilia A were diagnosed and aborted.

Abortion, Induced↗
PubMed1976

Tay-Sachs disease in a Moroccan Jewish family: a possible new mutation.

The parents of a Jewish Moroccan family, in which a previous child had died of Tay-Sachs disease, both proved to be carriers of the mutant gene. Hexosaminidase A activity in the father was similar to that in Ashkenazic heterozygotes, while the mother showed extremely low hexosaminidase A activity in peripheral leukocytes. Amniocentesis was performed on the mother during a subsequent pregnancy; the fetus proved to be affected and the pregnancy was interrupted. Acrylamide isoelectrofocusing of fetal liver and leukocytes of additional family members revealed a variant mutation for Tay-Sachs disease.

Amniocentesis↗
PubMed1975

Heterogeneity of human hepatic H-acetyl-beta-D-hexosaminidose. A activity toward natural glycosphingolipid substrates.

A crude soluble preparation of human hepatic N-acetyl-beta-D-hexosaminidase was examined for its activities toward three natural glycosphingolipid substrates after fractionation by the isoelectric focusing procedure. Profiles of activities toward N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM2-ganglioside) and N-acetylgalactosaminyl-galactosyl-galactosyl-glucosylceramide (globoside) were always identical with that of nonspecific N-acetyl-beta-D-hexosaminidase as determined with artificial substrates. The Component A of the enzyme had the activity peak at an isoelectric point of 5.0 to 5.1. In contrast, hydrolytic activities toward N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl- glucosylceramide (GM2-ganglioside) were associated with only the most acidic subfraction of the hexosaminidase A component. The activity to hydrolyze GM2-ganglioside had its peak at an isoelectric point of 4.8 to 4.9. These findings might provide an explanation for the GM2-ganglioside accumulation in juvenile GM2-gangliosidosis (partial deficiency of hexosaminidase A) and in the so-called AB variant of GM2-gangliosidosis (apparently normal hexosaminidase A and B activity).

Autopsy↗
PubMed1973

The defect in the Hunter syndrome: deficiency of sulfoiduronate sulfatase.

Skin fibroblasts cultured from patients affected with the Hunter syndrome are deficient in the activity of a protein, named the "Hunter corrective factor," that is required for degradation of dermatan and heparan sulfates. We now show that this factor, purified from human urine, removes about 2% of the sulfate residues from [(35)S]mucopolysaccharide accumulated within Hunter fibroblasts; these groups are derived from "oversulfated" regions of the polymer. Acetone-powder extracts of fibroblasts derived from patients with the Hunter syndrome are deficient in this sulfatase, in contrast to similar extracts from fibroblasts of individuals of other genotype. Hunter corrective factor coupled to alpha-L-iduronidase (or alternatively, mixed extracts from Hurler and Hunter fibroblasts) release iduronic acid from 4-O-alpha-L-sulfoiduronosyl-D-sulfoanhydromannose. We conclude that the Hunter corrective factor is a sulfatase for sulfated iduronic acid residues.

Carbohydrate Metabolism, Inborn Errors↗