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Biomedical subjects

S W Eber

Publications and source records attributed to S W Eber.

44 records · Page 3Linked to original sources
PubMed1985

Generalised glucosephosphate isomerase (GPI) deficiency causing haemolytic anaemia, neuromuscular symptoms and impairment of granulocytic function: a new syndrome due to a new stable GPI variant with diminished specific activity (GPI Homburg).

A new glucosephosphate isomerase (GPI) variant is described which is characterised by very low specific activity in erythrocytes, granulocytes and muscle tissue, nearly normal stability, normal kinetic properties and a decreased electrophoretic mobility. The propositus suffers from a complex syndrome involving erythrocytes (congenital haemolytic anaemia), granulocytes (decreased production of superoxide anion and reduced bactericidal activity in vitro) and the neuromuscular system (myopathy, mental retardation). It is suggested that the clinical syndrome results from generalised GPI deficiency due to a decreased specific activity of the variant enzyme, which cannot be compensated by an increase of de-novo synthesis of GPI protein even in cells exhibiting active protein synthesis such as granulocytes and muscle cells.

Adolescent↗
PubMed1984

Prevalence of partial deficiency of red cell triosephosphate isomerase in Germany--a study of 3000 people.

During a heterozygote screening of nearly 3000 persons, triosephosphate isomerase (TPI) deficiencies in erythrocytes were discovered in 11 unrelated persons, showing a residual activity between 39 and 76% of normal activity. Extensive genealogic studies were performed to confirm that these persons with TPI deficiency were heterozygous carriers. The total heterozygote frequency of triosephosphate isomerase deficiencies was 3.7/1000. The persons with heterozygous deficiency could be divided into two categories. Subjects of category I had a mean residual activity of 49% of the expected normal activity and were represented by a frequency of 1.3/1000. Subjects of category II had a mean residual activity of 67% of the expected normal activity and were represented by a frequency of 2.4/1000. None of the heterozygous persons showed an electrophoretic variant. The immunologic specific activity was normal with one exception. Therefore, we assume that in many cases of our heterozygous TPI-deficiencies a TPI protein with a normal specific activity is synthesized to a diminished degree.

Carbohydrate Epimerases↗
PubMed1980

The isolation and characterization of the multiple forms of human skeletal muscle triosephosphate isomerase.

1. Human skeletal muscle triosephosphate isomeras (D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) was isolated and resolved by DEAE-cellulose chromatography into three major forms, A, B, and C, which comprise 97% of the total activity. The relative distribution was 25, 46 and 29% respectively. 2. The A and C forms are homodimers, alpha alpha and beta beta, and form B is the heterodimer, alpha beta. Reassociation studies from guanidinium chloride have indicated that A, B, and C are not conformers. Although these studies revealed the existence of two different chains, the amino acid analysis showed no significant variance. Since no differences were obsrved in Ouchterlony and Mancini tests or in immunotitration, the three fors are assumed to be immunologically identical. 3. The three forms have the same specific activity, Michaelis constants, pH optimum, activation energy, inhibition by metabolites and heat stability. Only with increasing ionic strength did the V and Km values differ. 4. The two poypeptide chains (alpha and beta) appear to be identical (amino acid composition, molecular weight and antigenity), and since the electrophoretic banding pattern changed with cell aging, it is concluded that the multiple forms of trisephosphate isomerase are the consequence of minor post-synthetic alteration(s) of form A.

Amino Acids↗
PubMed1980

Characterization of a phosphoglycerate kinase deficiency variants not associated with hemolytic anemia.

The properties of a variant phosphoglycerate kinase (PGK) found in a large German clan were examined. The normal and variant enzymes, isolated by affinity chromatography, have the same molecular weight, specific activity, substrate affinity, and nearly identical pH-optima. Using immunoinactivation and immunodiffusion, the same specific activity for both forms was again determined. Since the enzymatic activity in older and younger erythrocytes varied only slightly, and since the specific activity of the variant was normal, the variant seems to be stable in vivo. This suggests that the decreased enzyme content is due to a decreased synthesis rate. The variant PGK described here is distinctly different from the known PGK variants and has been designated as "PGK München."

Anemia, Hemolytic↗
PubMed1979

Hereditary deficiency of triosephosphate isomerase in four unrelated families.

Triosephosphate isomerase deficiencies in erythrocytes and leucocytes were discovered in three unrelated families by a heterozygote screening of 3000 blood samples. In addition, a family found by Schroter et al. [not published] was studied. In these four families, only heterozygote carriers were found. In the family described by Freycon et al. with hetero- and homozygote carriers of triosephosphate isomerase deficiency, the heterozygotes were reinvestigated. There was 51% of normal enzyme activity in three of the families. In the other two families the enzyme activity was 64% and 71% of normal. Two of the eleven heterozygotes, both children, were diseased, but it seems unlikely that the disorders resulted from the deficiencies. The activities of thirteen enzymes, the Km of triosephosphate isomerase for glyceraldehyde phosphate and the concentrations of metabolites were normal. Antibody titration showed normal specific activities in four families and 50% of normal in one family. No electrophoretic variant was detected. From the proved heredity, a heterozygous frequency of at least 1/1000 is indicated. A maximal frequency of 5/1000 is estimated by using further instances of triosephosphate isomerase deficiency where heredity has not yet been investigated. An explanation for the small number of known cases is that this enzyme is not routinely assayed.

Carbohydrate Epimerases↗
PubMedDate not supplied

[Disorders of the membrane skeleton of erythrocytes in hereditary spherocytosis and elliptocytosis: significance of the molecular defect for pathogenesis and clinical severity].

During recent years an increasing number of inherited variants of erythrocyte membrane proteins and defects of the membrane skeleton could be described. Mostly these defects explain the pathogenesis of hemolytic anemias due to erythrocyte membrane defects. For hereditary spherocytosis and elliptocytosis a close correlation between the clinical severity and the biochemical defect was found; thus biochemical characterization can give valuable information about the expected course of the disease and the need for splenectomy. The erythrocyte membrane skeleton stretches along the inner surface of the membrane; it provides the stability of the erythrocyte under circulatory shear stress. The membrane skeleton consists of spectrin, actin, band 4.1 and band 4.9. Spectrin is the major component. In the membrane mostly all spectrin self-associates to the tetrameric form: one tetramer is formed by two alpha and two beta-chains. By denaturing SDS polyacrylamide gelelectrophoresis the composition of the membrane proteins can be analysed. The portion of tetrameric and dimeric spectrin is determined on native agarose gel electrophoresis. The concentration of spectrin in the membrane can be measured by an enzyme linked immunosorbent assay using monoclonal antibodies against human spectrin. By polymerase chain reaction and DNA sequencing the moleculargenetic cause of singular membrane defects was clarified. Hereditary spherocytosis was mostly due to a more or less diminished concentration of spectrin. Based on hematological, clinical' and biochemical observations, a new classification of spherocytosis (mild, moderate and severe form) is proposed. In addition to routine hematologic determinations and osmotic fragility, erythrocyte spectrin content is taken into account. The disease severity correlates with the diminution of spectrin. In hereditary elliptocytosis the concentration of tetrameric spectrin is reduced in about 30% of the patients. Defects of the N-terminal alpha I 80,000 dalton peptide are predominantly found. The defective alpha chain can be further studied by analysis of "tryptic" peptides after limited tryptic digestion of the spectrin. According to the reduced molecular weight of the anomalous tryptic alpha I peptide the variant spectrin alpha chains are designed as Spectrin alpha I/46, Sp alpha I/50, Sp alpha I/65, Sp alpha I/74 and Sp alpha I/78. In most cases a single amino acid substitution of the alpha chain could be proven. Until now only singular patients with hereditary elliptocytosis due to a shortened spectrin beta chain have been described. The shortening of the beta chain is due to a loss of the C-terminal phosphorylated peptide. The molecular cause is a defect at the 3' end of the beta spectrin gen, resulting in a premature termination of the peptide chain-synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗
PubMedDate not supplied

Ultrastructural and histochemical abnormalities of skeletal muscle in a patient with a new variant (type Homburg) of glucosephosphate isomerase (GPI) deficiency.

Ultrastructural and enzyme histochemical muscle abnormalities are described in a case with a new variant (type Homburg) of glucosephosphate isomerase (GPI) deficiency, associated with congenital nonspherocytic hemolytic anemia and muscle weakness. The enzyme is thermostable in contrast to other described variants. The muscle fibers showed decreased GPI activity, ultrastructural abnormalities, including giant mitochondria, and a diffuse increase of glycogen. The functional alteration of muscle tissue is due to a stable enzyme protein with decreased specific activity.

Adolescent↗