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Biomedical subjects

N Herschkowitz

Publications and source records attributed to N Herschkowitz.

At least 91 records · Page 5Linked to original sources
PubMed1979

Morphological observations in the nervous system of prenatal mucopolysaccharidosis II (M. Hunter).

Light and electron microscopic finding in the nervous system of a 23-week-old fetus are reported, in which MPS II was diagnosed prenatally. The degrees of myelination and neuronal differentiation were similar as in a normal fetus of the same age. A storage of mucopolysaccharides in typical vacuolar inclusion bodies was present throughout the peripheral and central nervous system, mainly in cells of mesenchymal origin. "Zebra" bodies and granulo-membranous bodies, which are thought to represent secondard ganglioside accumulation were only found in the well developed neurons of the spinal cord and spinal ganglia, but not in the poorly developed neurons of the cerebellar and cerebral cortex. Mucopolysaccharide storage in endothelial cells of cerebral bood vessels precedes the appearance of lipid storgae in cerebral neurons.

Brain↗
PubMed1978

Adrenoleukodystrophy. Preliminary report of a connatal case. Light- and electron microscopical, immunohistochemical and biochemical findings.

This is the first description of a connatal case of adrenoleukodystrophy. The clinical picture consisted of severe psychomotor retardation, convulsions and hypsarrhythmia, but no obvious signs of adrenal insufficiency. Pathologically, the adrenals were small. The entire cortex was largely replaced by large round cells. Ultrastructurally, some cells in the adrenal cortex contained inclusions with electron-lucent clefts surrounded by a membrane. The anterior pituitary lobe could be demonstrated to have produced ACTH. The central nervous system showed extensive zones of demyelination in the brainstem, the cerebellum and the right-sided capsula interna. In the demyelinated areas there was sudanophilic breakdown and an intense gliosis. Ongoing demyelination could also be demonstrated by the chemical analysis. In the gray matter there waere micropolygyria of the insular cortex and swollen nerve cells in the nucleus arcuatus. Ultrastructure revealed the type of inclusions in the microglia of the same type as in the adrenals, and a different type of inclusions in unidentifiable cells, possibly neurons. These latter inclusions consisted of loosely stacked lamellar material. The findings are interpreted as further evidence of storage taking place in this disease.

Adrenal Cortex↗
PubMed1978

Unusually mild course of beta-glucuronidase deficiency in two brothers (mucopolysaccharidosis VII).

Two brothers with oligosymptomatic mucopolysaccharidosis VII were observed from age 11 8/12 to 16 years, and 15 1/2 to 19 years, respectively. Asymptomatic thoracic kyphosis and mild scoliosis were the prominent clinical features. Herniae, hepatosplenomegaly, corneal clouding and shortness of stature were absent. Both had Alder type granulations in polymorphonuclear leukocytes and to a lesser degree in monocytes. Ultrastructural analysis of blood leukocytes revealed polymorphous inclusions of probably more than one class of organic substances. Radiological signs were mild, confined to the spine and consisted of irregularities of upper and lower vertebral plates, of vertebral flattening and some osteophytic changes. Both patients excreted excessive amounts of acid mucopolysaccharides in urine and also globoside. Cultured skin fibroblasts of both patients contained metachromatic granules, had only approx. 10% of normal beta-glucuronidase activity and degraded sulfated mucopolysaccharides at a slower than normal rate. Sera of the patients had none or minimal beta-glucuronidase activity, the mother's serum had subnormal and the father's serum low-normal activity. The older brother is the oldest known case of mucopolysaccharidosis VII. As this hereditary disorder may take a remarkably mild clinical course, beta-glucuronidase-deficient juveniles may exist undetected in the general population.

Adolescent↗
PubMed1977

Age-dependent modulation of 3'-phosphoadenosine-5'-phosphosulfate-galactosylceramide sulfotransferase by lipids extracted from the microsomal membranes and artificial lipid mixtures.

The 3'-phosphoadenosine-5'-phosphosulfate-galactosylceramide-sulfotransferase (cerebroside sulfotransferase) is microsomal enzyme, which shows a definite developmental activity pattern. This report gives evidence that the enzyme activity of partially delipidated microsomes is modulated by the cholesterol:phospholipid ratio of the extracted microsomal lipids in an age-dependent manner. These findings suggest that in vivo the enzyme activity is modulated by the lipid surrounding.

Adenosine Monophosphate↗
PubMed1977

Seitelberger's connatal form of Pelizaeus-Merzbacher Disease. Case report, clinical, pathological and biochemical findings.

A case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease is reported. He lived to the age of 13 and was able to recognize persons. Both is unusual in this disease. Some of the few myelin sheaths had two different periodicities (150 and 90 A). Intranuclear inclusions similar to Hirano's cytoplasmic eosinophilic rodlets were observed. The findings of connatal form of Pelizaeus-Merzbacher disease are compared with those of dysmyelinating mice (Jimpy and Quacking) and of manipulated myelinating tissue cultures. The possibility is considered, that the alterations in these dysmyelinating human and animal conditions are caused by extraneural circulating factors.

Adolescent↗
PubMed1977

Multiple abnormalities of ectoglycosyltransferases in cultured fibroblasts from patients with mucolipidosis II: Possible indication for abnormal plasma membrane glycoproteins.

Ectoglycosyltransferase activities were measured in cultured normal and mucolipidosis II fibroblasts using endogenous glycoproteins and glycolipids and whole cells. Nucleotide pyrophosphatase, known to interfere with glycosyltransferases, was completely inhibited with 6 mM 5' AMP. Since preliminary experiments have shown multiple abnormalities of ectoglycosyltransferases in mucolipidosis II fibroblasts (Di Donato, unpublished results), galactosyl (Gal)-and N-acetylglucosaminyl (GluNac)-transferase were studied in further detail in confluent and nonconfluent cultures of normal and patient fibroblasts. Activities of both transferases on glycoproteins were higher in nonconfluent cultures. A 50% reduced activity of Gal-transferase was measured in confluent mucolipidosis II cultures and of GluNac-transferase in nonconfluent mucolipidosis II cultures towards incorporation of sugar precursors into glycoproteins. Substrate saturation kinetics of both transferases in mucolipidosis II fibroblasts revealed an abnormal Km for Gal incorporation into endogenous glycoproteins. Glycosylation of glycolipids in mucolipidosis fibroblasts was normal.

Acetylglucosamine↗
PubMed1976

Generalized gangliosidosis: acid beta-galactosidase deficiency with early onset, rapid mental deterioration and minimal bone dysplasia.

This report concerns a 3-month-old girl with rapidly progressive psychomotor retardation, hepatomegaly, vacuolated lymphocytes, minimal bone dysplasia and normal excretion of acid mucopolysaccharides. A deficiency of acid beta-galactosidase was demonstrated in isolated leucocytes and in a liver biopsy. The diagnosis of generalized gangliosidosis due to deficiency of beta-galactosidase was also based on the absence of the enzyme activity from cultured fibroblasts. The diagnosis was confirmed on autopsy at 16 months by typical histology, electron microscopy and biochemistry of the organs. beta-galactosidase deficiency has been demonstrated in various clinical conditions ranging from generalized gangliosidosis with severe mental retardation to clinical pictures resembling Morquio's disease and normal intelligence. The heterogeneity of the clinical manifestations in beta-galactosidase deficiency could be explained by different residual activities of a structurally mutated enzyme towards its various substrates.

Bone Diseases, Developmental↗
PubMed1976

Spondyloepiphyseal dysplasia, corneal clouding, normal intelligence and acid beta-galactosidase deficiency.

A 14-year-old girl with a unique type of progressive spondyloepiphyseal dysplasia, corneal clouding, and no evidence of neurological abnormality, was found to have a remarkable deficiency of acid beta-galactosidase activity in cultured skin fibroblasts and in leucocyte preparations. In fibroblasts, ganglioside GM1 beta-galactosidase activity averaged 7% of the normal mean while asialofetuin beta-galactosidase and 4-methylumbe lifery-beta-galactosidase averaged 1.4% and 3.5%, respectively. Activities for all three substrates in leucocytes from both her parents were close to 50% of the normal mean indicating that the patient is homozygous for a mutation (or mutations) affecting GM1 beta-galactosidase.

Adolescent↗
PubMed1976

[Brain development: genetic and exogenous factors].

Growth disorders and differentiation of cerebral structures may be caused by mutations of exogenous noxae. The period of most active brain development is between the tenth week of pregnancy and the tenth year of life. In this period the brain is particularly sensitive to exogenous noxae. Basic research has revealed mechanisms that are responsible for normal development, and at the same time has led to the discovery of factors which may be associated with disturbance of these regulatory processess. Disorders of cerebral development may underlie minimal organic brain damage, though there is no proof of this as yet. Closer cooperation between basic and clinical research will be necessary to provide greater insight into the mechanisms of cerebral development. The knowledge thus obtained is one of the preconditions for the prevention, diagnosis and treatment of infantile minimal organic brain damage.

Animals↗
PubMed1975

Niemann-Pick's disease. Clinical, biochemical and ultrastructural findings in a case of the infantile form.

A diagnosis of Niemann-Pick disease type A was made in a 6-month-old boy on the grounds of progressive psychomotor retardation, hepatosplenomegaly, typical foam cells in the bone marrow and a deficiency of sphingomyelinase in a liver biopsy. Typical ultrastructural changes in lysosomes were found in hepatocytes and in Schwann cells. In spite of the absence of gross morphological changes in the axons and in the myelin sheath of the peripheral nerve biopsy, the nerve conduction velocity in the patient was greatly reduced. The ultrastructural aspect of the lysosomal inclusion suggested the storage of a phospholipid. Biochemical analysis of the liver biopsy demonstrated an increased content of total phospholipid of which sphingomyelin made up for more than 60%. The significance of these data are discussed.

Cholesterol↗
PubMed1975

Late infantile metachromatic leucodystrophy (MLD). Clinical and diagnostic evaluation in a typical case.

A typical case of late infantile MLD is presented with all available clinical, morphological and biochemical results. The diagnostical value of the different parameters is evaluated and the pathogenesis of the disorder discussed. In spite of successful experimental enzyme substitution in cultured MLD fibroblasts with restitution of function by added Arylsulfatase, the therapeutic possibilities for the fatal disease in the patients are extremely limited.

Age Factors↗