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Biomedical subjects

H Kresse

Publications and source records attributed to H Kresse.

At least 127 records · Page 7Linked to original sources
PubMed1982

Impaired degradation of keratan sulphate by Morquio A fibroblasts.

Upon incubation of keratan [35S]sulphate with normal fibroblasts both [35S]sulphate and N-acetylglucosamine 6-[35S]sulphate are liberated. From the products obtained after digestion with various mutant fibroblasts and with purified N-acetylgalactosamine 6-sulphate sulphatase we suggest that (i) [35S]sulphate is released almost exclusively from galactose 6-sulphate residues; (ii) N-acetylgalactosamine 6-sulphate sulphatase exhibits galactose 6-sulphate sulphatase activity; (iii) both sulphatase activities are deficient in Morquio disease type A.

Cell Line↗
PubMed1982

[Heterogeneity of formes frustes of Morquio's disease].

Two children presenting with a mild form of Morquio's syndrome are reported. Clinically, there was a characteristic brevity of the trunk and slit lamp examination showed discrete corneal opacities. On X-ray films, generalized plastyspondylia was moderate but it was associated with hypoplasia of the odontoid process. Acetabula were enlarged with coxa valga; obliquity of inferior radio-cubital extremity was associated with a sharp pattern of the proximal end of metacarpi. Epiphyseal cartilage chondrocytes also looked like those of Morquio's syndrome: large cells containing numerous vacuoles, limited by a single smooth membrane. On the other hand, no keratosulfate was found in urines and N-acetylgalactosamine-6-sulfate-sulfatase and beta-galactosidase assays in fibroblasts were normal. Thus, this mild form is different from the so-called Morquio's syndromes types A and B.

Child↗
PubMed1981

Liberation of N-acetylglucosamine-6-sulfate by human beta-N-acetylhexosaminidase A.

The first step of the degradation of p-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside and of keratan sulfate-derived oligosaccharides bearing N-acetylglucosamine-6-sulfate residues at the nonreducing end was considered to be accomplished by the action of a specific sulfatase (Kresse, H., Paschke, E., von Figura, K., Gilberg, W., and Fuchs W. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 6822-6826). In purification from human placenta, however, this activity co-chromatographed with isoenzyme A of beta-N-acetylhexosaminidase and had the same electrophoretic mobility as the latter enzyme. The activity was precipitated by a specific antiserum against beta-N-acetylhexosaminidase. A pronounced enzyme deficiency was found in Tay-Sachs and Sandhoff fibroblasts. The purified enzyme released p-nitrophenol from the chromogenic substrate as well as a second product which contained equimolar amounts of hexosamine and sulfate. This product had the same electrophoretic and chromatographic behavior as sulfated N-acetylglucosamine. It could be degraded by periodate to a smaller charged fragment. Incubation of keratan sulfate-derived oligosaccharides with beta-N-acetylhexosaminidase A analogously resulted in the liberation of N-acetylglucosamine-6-sulfate. The enzyme showed the highest affinity towards a trisulfated tetrasaccharide and exhibited a similar Km for the sulfated and the unsulfated p-nitrophenyl derivative.

Acetylglucosamine↗
PubMed1981

The mucopolysaccharidoses: biochemistry and clinical symptoms.

The mucopolysaccharidoses are a group of genetic diseases which are characterized by an excessive intralysosomal accumulation of partially degraded mucopolysaccharides. This storage is caused by the inactivity of one of eleven enzymes that are required for the degradation of the different types of mucopolysaccharides. There is a rough correlation between phenotype and chemical nature of the storage material. Similar clinical pictures, however, may be caused by an inactivity of different enzymes. Conversely, different clinical expressions of the defect of a single enzyme may be attributed to allelic mutations. The recent development of specific assay procedures for the respective enzymes allows 1. an early genotype-specific diagnosis of affected patients, 2. prenatal diagnosis of the metabolic defect in families at risk, 3. to prognosticate the course of the disease at least in some instances, and 4. genetic counseling for members of affected families. At present, there is no specific therapy. Attempts of enzyme replacement therapy are still at an experimental stage.

Chemical Phenomena↗
PubMed1981

Degradation of keratan sulphate by beta-N-acetylhexosaminidases A and B.

Enzymic cleavage of beta-N-acetylglucosamine residues of keratan sulphate was studied in vitro by using substrate a [3H]glucosamine-labelled desulphated keratan sulphate with N-acetylglucosamine residues at the non-reducing end. Both lysosomal beta-N-acetylhexosaminidases A and B are proposed to participate in the degradation of keratan sulphate on the basis of the following observations. Homogenates of fibroblasts from patients with Sandhoff disease, but not those from patients with Tay--Sachs disease, were unable to release significant amounts of N-acetyl[3H]glucosamine. On isoelectric focusing of beta-N-acetylhexosaminidase from human liver the peaks of keratan sulphate-degrading activity coincided with the activity towards p-nitrophenyl beta-N-acetylglucosaminide. A monospecific antibody against the human enzyme reacted with both enzyme forms and precipitated the keratan sulphate-degrading activity. Both isoenzymes had the same apparent Km of 4mM, but the B form was approximately twice as active as the A form when compared with the activity towards a chromogenic substrate. Differences were noted in the pH--activity profiles of both isoenzymes. Thermal inactivation of isoenzyme B was less pronounced towards the polymeric substrate than towards the p-nitrophenyl derivative.

Cells, Cultured↗
PubMed1980

Morquio's disease type A: absence of material cross reacting with antibodies against N-acetylgalactosamine-6-sulfate sulfatase.

An antiserum was raised in guinea pigs against purified normal human N-acetylgalactosamine-6-sulfate sulfatase, the enzyme affecting in Morquio's disease type A. The antiserum precipitated most of N-acetylgalactosamine-6-sulfate sulfatase from a concentrate of normal human urine. The antigen-antibody complex was enzymatically active. Urine concentrates from five patients with Morquio's disease type A did not contain material competing with the normal enzyme for binding to soluble or Sepharose-bound antibodies. No precipitin arc was obtained on immunodiffusion of antiserum and urine from the single patient investigated by this method. From the sensitivity of the indirect immunoassay it was concluded that the urine of the five patients contained less than 5% of the normal amount of cross-reacting material.

Antibodies↗
PubMed1980

Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation.

Skin fibroblasts from two patients who had symptoms of the Sanfilippo syndrome (mucopolysaccharidosis III) accumulated excessive amounts of heparan sulfate and were unable to release sulfate from N-acetylglucosamine-6-sulfate linkages in heparan sulfate-derived oligosaccharides. Keratan sulfate-derived oligosaccharides bearing the same residue at the nonreducing end and p-nitrophenyl-6-sulfo-2-acetamido-2-deoxy-beta-D-glucopyranoside were degraded normally. Kinetic differences between th sulfatase activities of normal fibroblasts were found. These observations suggest that N-acetylglucosamine-6-sulfate sulfatase activities degrading heparan sulfate and keratan sulfate, respectively, can be distinguished. It is the activity directed toward heparan sulfate that is deficient in these patients; we propose that this deficiency causes Sanfilippo disease type D.

Glycosaminoglycans↗
PubMed1980

Morquio syndrome (mucopolysaccharidosis IV B) associated with beta-galactosidase deficiency. Report of two cases.

Two male patients, aged 6 and 25, both with normal intelligence and absence of neurological abnormalities, exhibited dysostosis multiplex, dwarfism, odontoid anomalies, cloudy corneas, exessive excretion of keratan sulfate, and abnormal urinary oligosaccharides. Leukocytes and fibroblasts of both patients were deficient in acid beta-galactosidase (beta-gal) and normal in N-acetylgalactosamine-6-sulfate sulfatase, the deficient enzyme in classical Morquio syndrome. The beta-gal deficiency was not due to an endogenous inhibitor, and the parents exhibited intermediate activities. Deficient beta-gal activity was observed toward p-nitrophenyl-beta-galactoside, 4-methylumbelliferyl-beta-galactoside (4 MU-beta-gal), lactose, GM1 ganglioside, keratan sulfate, and asialofetuin (ASF). Under standard assay conditions, the residual activity was similar for all substrates tested. Toward p-nitrophenyl-beta-glactoside, the mutant enzyme behaved as a Km variant.

Adult↗
PubMed1979

Multiple forms of 2-deoxy-D-glucoside-2-sulphamate sulphohydrolase from human placenta.

2-Deoxyglucoside-2-sulphamate sulphohydrolase was purified about 10 000-fold from the soluble extract of human placenta by using as substrate [N-sulpho-35S]heparin. Differently charged enzyme forms were observed on chromatography on DEAE-cellulose, all of which had an apparent mol.wt. of 110 000 as determined by gel filtration. By using immobilized heparan sulphate as affinity matrix the sulphamate sulphohydrolase could be separated into two forms, a minor one with low and a major one with high affinity for the adsorbent. When tested with [N-sulpho-35S]heparan sulphate the low-affinity form had a Km of 0.2 mM, and the high-affinity form a Km of 0.03 mM. Both forms exhibited the same Km of 10 microM towards [N-sulpho-35S]heparin and were equally well adsorbed to immobilized heparin. The two forms could be distinguished by their pH-optima and by the influence of KCl on heparan sulphate sulphohydrolase activity.

Chromatography, Affinity↗
PubMed1979

Purification and properties of N-acetylgalactosamine 6-sulphate sulphatase from human placenta.

1. N-Acetylgalactosamine 6-sulphate sulphatase was purified about 20000-fold from the soluble extract of human placenta with N-acetylgalactosamine 6-sulphate-glucuronic acid-N-acetyl[1-(3)H]galactosaminitol 6-sulphate as substrate in the activity assay. The enzyme appears to be a glycoprotein with a mol.wt. of about 100000 as determined by gel filtration. On gel electrophoresis in the presence of sodium dodecyl sulphate the major protein band had a mol.wt. of 78000. Variable charge heterogeneity was observed in several enzyme preparations. 2. The purified enzyme released up to one sulphate molecule from the disulphated trisaccharide. It was active towards N-acetylgalactosamine 6-sulphate and exhibited no measurable N-acetylglucosamine 6-sulphate sulphatase or any other known lysosomal sulphatase activity. Hydrolysis of [1-(3)H]galactitol 6-sulphate was achieved by incubation neither with a crude nor with a purified enzyme preparation. Chondroitin 6-sulphate and keratan sulphate, as well as heparin and heparan sulphate, served as competitive inhibitors of the enzyme. 3. Purified N-acetylgalactosamine 6-sulphate sulphatase activity was optimal at pH4.9 and 4.4 when assayed in 0.02m-sodium acetate buffer and at pH4.2 and 5.2 in 0.1m-sodium acetate buffer. A single pH-optimum at pH4.8 was observed for the crude enzyme and for the purified enzyme after mild periodate treatment. The sulphatase activity was inhibited by a variety of anions and cations and activated by thiol-specific and thiol reagents.

Chondroitinases and Chondroitin Lyases↗
PubMed1979

[Influence of glycosaminoglycan synthesis of cultured cornea stroma cells by variation of culture condition].

Cultured cells derived from bovine corneal stroma synthesize all types of sulfated glycosaminoglycans and distribute these macromolecules into topographically different compartments in a reproducible manner. Each compartment is characterized by a typical glycosaminoglycan distribution pattern. Corneal fibroblasts synthesize in vitro only small amounts of keratan sulfate in contrast to the in vivo conditions. We have, therefore, investigated the synthesis and topographical distribution of sulfated glycosaminoglycans as influenced by different culture conditions. The following results were obtained: 1) Cocultivation of epithelial and stromal fibroblasts from bovine cornea led to an increased incorporation of radiosulfate into sulfated glycosaminoglycans by about 50% as compared to the theoretical value. Glycosaminoglycan distribution of mixed cultures into different compartments showed no similarity compared with pure epithelial or stromal fibroblasts. 2) Addition of native or heat inactivated anterior chamber fluid to the culture medium was followed by a twofold increase of [35S]-sulfate incorporation and by an augmented intracellular and pericellular accumulation of labeled macromolecules. 3) Reduction of the incubation temperature led to a reduced synthesis of glycosaminoglycans without influencing their topographical distribution. Growth of stromal cells on type I collagen was accompanied by a reduced glycosaminoglycan synthesis of about 25%. Extracellular macromolecules reached only half of the normal value, while intracellularly their concentration was slightly increased. 4) None of the variations of the culture condition led to a significant change of the distribution pattern of sulfated glycosaminoglycans. Especially, no significant increase of keratan sulfate biosynthesis could be detected.

Animals↗
PubMed1979

Sanfilippo type C disease: clinical findings in four patients with a new variant of mucopolysaccharidosis III.

A new genetic variant of the Sanfilippo syndrome due to deficiency of acetyl CoA: alpha-glucosaminide N-acetyltransferase, was recently demonstrated in four patients. The clinical findings of these patients are reported here. Differential diagnosis from other types of the Sanfilippo syndrome on clinical and routine laboratory criteria is difficult and enzyme assay is necessary to reach the diagnosis. Since two of the patients reported are females and consanguinity was present in one case, autosomal recessive inheritance is most probable.

Adolescent↗