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Biomedical subjects

H Kresse

Publications and source records attributed to H Kresse.

At least 163 records · Page 9Linked to original sources
PubMed1976

Sanfilippo disease type B: presence of material cross reacting with antibodies against alpha-N-acetylglucosaminidase.

1. alpha-N-Acetylglucosaminidase, the enzyme deficient in Sanfilippo disease type B (mucopolysaccharidosis III B) was purified from normal human urine. An antiserum was raised in rabbits against the purified enzyme. Preincubation of the antiserum with crude alpha-N-acetylglucosaminidase from normal human urine, followed by centrifugation, led to a marked reduction of the enzyme activity in the supernatant. Formation of the antibody-enzyme complex had no influence on the activity. The thermal stability of the enzyme was markedly enhanced by complex formation with the antiserum. 2. In the urine from three patients with Sanfilippo disease type B the presence of cross-reacting material could be demonstrated by incubating the antiserum with alpha-N-acetylglucosaminidase in the presence of Sanfilippo B urine or by pretreatment of the antiserum with Sanfilippo B urine. 3. Immunodiffusion and immunoelectrophoresis of crude normal or Sanfilippo B urine gave rise to up to four precipitation lines, only one of which exhibited alpha-N-acetylglucosaminidase activity in the case of normal urine. Purified alpha-N-acetylglucosaminidase yielded only a single precipitation line. After adsorption with the purified enzyme the antiserum did not cross react with any of the urinary proteins. 4. On a quantitative determination of cross-reacting material using Sepharose immobilized antibodies in the urine from two Sanfilippo B patients the amount of cross-reacting material appeared to be less than one fourth of the amount of alpha-N-acetylglucosaminidase protein in an age-matched control urine. The cross-reacting material present in the urine of Sanfilippo B patients had a significant lower binding affinity for antibodies against alpha-N-acetylglucosaminidase than preparations from normal human urine. Taking into account this lower binding affinity, it can be calculated that the amount of cross-reacting material in the urine of Salfilippo B patients exceeds that of normal controls. 5. It is concluded that Sanfilippo disease type B is due to a mutation of a structural gene coding for alpha-N-acetylglucosaminidase. The mutation affects the catalytical and immunological properties of the enzyme protein.

Acetylglucosaminidase↗
PubMed1975

Morphological and biochemical findings in a case of mucopolysaccharidosis type III A (Sanfilippo's disease type A).

Morphological and biochemical autopsy findings of a 12 year old girl with mucopolysaccharidosis type III (Sanfilippo's syndrome). The clinically suspected diagnosis was biochemically ascertained before the patients death. The autopsy findings obtained by biochemical and by light and electron microscopic investigations of different organs are compared with the results of other authors.

Autopsy↗
PubMed1975

Metabolism of sulfated glycosaminoglycans in cultivated bovine arterial cells. I. Characterization of different pools of sulfated glycosaminoglycans.

"Fibroblast-like" cells from the intimal layer of bovine aorta were grown in culture. The formation, composition, molecular weight and turnover rate of different pools of glycosaminoglycans were investigated in cultures incubated in the presence [35S]sulfate or [14C]glucosamine. The newly synthesized glycosaminoglycans are distributed into an extracellular pool (37 - 58%), a cell-membrane associated or pericellular pool (23 - 33%), and an intracellular pool (19 - 30%), each pool exhibiting a characteristic distribution pattern of chondroitin sulfate, dermatan sulfate, heparan sulfate and hyaluronate. The distribution pattern of the extracellular glycosaminoglycans resembles closely that found in bovine aorta. A small subfraction of the pericellular pool - tentatively named "undercellular" pool--has been characterized by its high heparan sulfate content. The intracellular and pericellular [35S]glycosaminoglycan pools reach a constant radioactivity after 8-12 h and 24 h, respectively, whereas the extracellular [35S]glycosaminoglycans are secreted into the medium at a linear rate over a period of at least 6 days. The intracellular glycosaminoglycans are mainly in the process of degradation, as indicated by their low molecular weight and by their half-life of 7 h, but intracellular dermatan sulfate is degraded more rapidly (half-life 4-5 h) than intracellular chondroitin sulfate and heparan sulfate (half-life 7-8 h). Glycosaminoglycans leave the pericellular pool with a half-life of 12-14 h by 2 different routes: about 60% disappear as macromolecules into the culture medium, and the remainder is pinocytosed and degraded to a large extent. Extracellular and at least a part of the pericellular glycosaminoglycans are proteoglycans. Even under dissociative conditions (4M guanidinium chloride) their hydrodynamic volume is sufficient for partial exclusion from Sepharose 4B gel. The existence of topographically distinct glycosaminoglycan pools with varying metabolic characteristics and differing accessibility for degradation requiresa reconsideration and a more reserved interpretation of results concerning the turnover rates of glycosaminoglycans as determined in arterial tissue.

Animals↗
PubMed1975

Metabolism of sulfated glycosaminoglycans in cultivated bovine arterial cells. II. Quantitative studies on the uptake of 35SO4-labeled proteoglycans.

Cultured arterial fibroblasts were used for a quantitative study on adsorption, uptake and degradation of [35S]proteoglycans derived from secretions of cultured arterial or skin fibroblasts. The following results were obtained: 1) Proteoglycans added to the culture medium are integrated into the pool of cell membrane-associated (trypsin-removable) glycosaminoglycans by a saturable process, which depends on time and temperature. 2) Up to 17% of the added proteoglycans are taken up by the cells within 24 h. The uptake exhibits saturation kinetics, characteristic for adsorptive pinocytosis. Proteoglycan concentrations required for half-maximum uptake are higher than for half-maximum saturation of the glycosaminoglycan pool associated with the cell membrane. 3) After a lag phase, inorganic 35SO4 appears in the culture medium as a degradation product of the internalized proteoglycans. Pinocytosed proteoglycans are catabolized more rapidly than proteoglycans which remain inside the cell after their biosynthesis. 4) Pinocytosis exhibits specificity, the individual proteoglycans being internalized at different rates. The highest rate of uptake was measured for a dermatan-sulfate-rich proteoglycan. No competition of uptake between a dermatan-sulfate-rich and a heparan-sulfate-rich proteoglycan was observed. 5) Optimum pinocytosis requires an intact protein moiety and, presumably, undegraded carbohydrate chains of the proteoglycans.

Animals↗
PubMed1975

Serum alpha-N-acetylglucosaminidase: determination, characterization, and corrective activity in Sanifilippo B fibroblasts.

Assays for the determination of serum alpha-N-acetylglucosaminidase (EC 3.2.1.50) activity are described employing p-nitrophenyl-N-acetyl-alpha-D-glucosaminide, phenyl-N-acetyl-alpha-D-glucosaminide, and UDP-N-acetylglucosamine as substrates. A log normal distribution of the serum enzyme activity was found. The determination of serum alpha-N-acetylglucosaminidase activity proved to be a valuable tool for the recognition of homozygous and heterozygous carriers of the Sanfilippo B gene.

Acetylglucosaminidase↗
PubMed1975

Sandhoff disease: impaired catabolism of sulfated glycosaminoglycans in cultured fibroblasts.

Fibroblasts cultured from the skin of patients with Sandhoff disease accumulate excessive amounts of sulfated glycosaminoglycans because of degradative inadequacy. Only a slight such abnormality in the metabolism of sulfated glycosaminoglycans was seen in fibroblasts from patients with Tay-Sachs disease. The defective glycosaminoglycan catabolism in Sandhoff fibroblasts is specifically corrected by intracellular replacement of beta-N-acetyl-hexosaminidase. Both beta-N-acetyl-hexosaminidase A and B are effective in bringing about such correction, although there seem to be differences in specificity. Our findings suggest that in Sandhoff disease there is an impaired catabolism of glycosaminoglycans in addition to the defect in the degradation of glycosphingolipids.

Acetamides↗