Search PubMed⌕ Search

Biomedical subjects

S Miwa

Publications and source records attributed to S Miwa.

At least 325 records · Page 18Linked to original sources
PubMed1983

Hemoglobin saitama or beta 117 (G19) His leads to Pro, a new variant causing hemolytic disease.

An electrophoretically silent unstable hemoglobin was found in a 23-year-old Japanese woman suffering from hemolytic anemia and jaundice. The unstable beta subunit was precipitated with p-chloromercuribenzoic acid and the globin was further purified by urea CM-52 column chromatography. Results of amino acid analysis, tryptic fingerprinting and manual Edman degradation of the abnormal beta T12B established a substitution of proline for histidine beta 117 (G19). This new abnormal hemoglobin was absent in other members of the family.

Adult↗
PubMed1983

Lactate dehydrogenase A-subunit and B-subunit deficiencies: comparison of the physiological roles of LDH isozymes.

Different clinical features exist for lactate dehydrogenase A-subunit and B-subunit deficiencies. The metabolic basis for these clinical differences was elucidated by investigating carbohydrate metabolism in the affected tissues. Glycolysis was markedly retarded at the position of glyceraldehyde 3-phosphate dehydrogenase, and significant increases of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-diphosphate were observed. The physical and kinetic properties of glyceraldehyde 3-phosphate dehydrogenase prepared from human erythrocytes and skeletal muscle were almost identical, but the mode of inhibition of the enzyme was slightly different in erythrocytes and in skeletal muscle. In erythrocytes, impaired reoxidation of NADH followed by the deficiency of substrate NAD+ causes a reduction of glyceraldehyde 3-phosphate dehydrogenase activity. However, in skeletal muscle, the increased level of NADH markedly inhibits the enzyme under anaerobic conditions. A flux of triose phosphates from glycolysis occurred in skeletal muscle of a patient with A-subunit deficiency. This flux is attributable to the high cytosol alpha-glycerophosphate dehydrogenase activity in skeletal muscle. for these reasons the ATP production was significantly impaired in the patient and the damage to muscle cells brings about the release of cytosolic enzymes and muscle rigidity after hard exercise. In contrast in the erythrocytes, the level of alpha-glycerophosphate dehydrogenase is very low and another red cell-specific NADH reoxidizing system such as NADH-cytochrome b5 reductase (NADH-methemoglobin reductase) is operating. In this manner, the NAD+ level in erythrocytes is compensated for without the flux of triose phosphates derived from glucose. Therefore, the ATP production in erythrocytes is sufficiently maintained by glycolysis even in a patient with complete lactate dehydrogenase B-subunit deficiency. Thus, impaired ATP production in anaerobic stage is a condition which is specific for lactate dehydrogenase A-subunit deficiency but does not occur for B-subunit deficiency. The different clinical features of the A- and B-subunit deficiencies have been clearly elucidated.

Erythrocytes↗
PubMed1983

Decreased TCGF activity in the culture medium of PHA stimulated peripheral mononuclear cells from patients with metastatic cancer.

Activities of T cell growth factor (TCGF) of conditioned media from PHA stimulated cultures of peripheral mononuclear cells (PHA-MNC-CM) were compared among patients with cancer, patients with non-malignant disease and normal persons. In nine out of 10 cases of cancer with metastasis (including extensive infiltration to surrounding tissues), the activities were much lower than normal persons, whereas in four out of five cases of cancer without metastasis, the activities were almost the same as those of normal persons. The low activities of PHA-MNC-CM from patients with metastatic cancer were not due to the older age of patients, nor did it seem to be attributed to the malnutritional state of patients. When we examined the activity using non-adherent MNC instead of the whole MNC, the activities in patients with metastatic cancer rose up to almost the normal levels. In normal persons the decline of the activities after 3 days of culture were not observed after the removal of adherent cells. Our data indicate that the adherent cells have a suppressive effect on TCGF production in both normal persons and cancer patients, but that the effect may be exaggerated in patients with metastatic cancer.

Cell Adhesion↗
PubMed1983

Conversion of pyruvate kinase (PK) isozymes during development of normal and PK deficient erythroblasts.

Using immunofluorescent antibody techniques, conversion of pyruvate kinase (PK) isozymes during the maturation of erythroblasts was studied. In normal subjects, M2-type PK was clearly seen at the proerythroblast stage, then markedly declined with cell maturation, whereas L-type PK continued to increase. In classical type PK deficiency, M2-type PK was still clearly seen in orthochromatic erythroblasts, whereas L-type PK was scarcely detected during maturation. In other PK deficiency cases, change of L-type PK showed a similar pattern to that of normal while M2-type PK was still clearly seen at the later stage of maturation as in the classical type. In K-562 human leukemia cell line, M2-type PK declined and L-type PK increased in parallel with hemoglobin synthesis by addition of hemin, an inducer for differentiation into erythroblasts. Hemoglobin synthesis and L-type PK production appear to have interrelation during the differentiation and maturation of erythroblasts.

Erythroblasts↗
PubMed1982

A new glucose-6-phosphate dehydrogenase variant (G6PD Nagano) associated with congenital hemolytic anemia.

A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was reported. The patient, a 6-year-old Japanese male, was noticed to have hemolytic anemia soon after birth, and a diagnosis of G6PD deficiency was made at the age of 2. He had episodes of hemolytic crisis several times after upper respiratory infection. G6PD activity of the patient was 5.5% of normal. The enzymatic characteristics were examined when he was 5 years old, and his G6PD showed faster-than-normal electrophoretic mobility, low Km G6P, high Km NADP, low Ki NADPH, normal utilization of substrate analogues, heat instability, and a normal pH optimum curve. From these results, this was considered to be a new variant and was designated G6PD Nagano. Infection-induced hemolysis and chronic hemolytic anemia seem to be due to markedly impaired enzyme activity and thermal instability.

Anemia, Hemolytic, Congenital↗
PubMed1982

Overproduction of structurally normal enzyme in man: hereditary haemolytic anaemia with increased red cell adenosine deaminase activity.

The mechanism of red cell adenosine deaminase (ADA) accumulation in a case of hereditary haemolytic anaemia due to increased red cell ADA activity was investigated. ADA activity of the younger cells was twice that of the older cells. Rate of ADA synthesis in erythroid colony cells cultured from the patient's bone marrow cells was 11-fold greater than that from the normal. The accumulation of ADA in the patient seems to be due to the increased synthesis in precursors of red cells in spite of the increased degradation in peripheral blood.

Adenosine Deaminase↗
PubMed1982

The activities of noradrenergic and dopaminergic neuron systems in experimental hydrocephalus.

Experimental hydrocephalus was induced in rabbits by intracisternal injection of kaolin suspension, and the concentration of noradrenaline (NA), dopamine (DA), and their metabolites was determined in several brain regions. The NA concentration had decreased in the cerebellum, hypothalamus, and pons plus medulla oblongata, and increased in the caudate nucleus at 2 days after kaolin injection (the stage of early intracranial hypertension). At 1 week (the stage of progressive hydrocephalus), the NA content had returned to control levels in all brain regions studied, and it decreased again at 4 weeks (the stage of chronic hydrocephalus) in the pons plus medulla oblongata. The DA level was unchanged throughout the 4-week period after kaolin injection. The concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEG-SO4), the major metabolite of NA, was elevated in all brian regions except the caudate nucleus at all stages after kaolin injection. An increase in MOPEG-SO4 in the caudate nucleus was also observed 1 week after kaolin injection. The content of homovanillic acid (HVA), the major metabolite of DA in the rabbit brain, was decreased in the cerebral cortex at 2 days and at 1 week after kaolin injection, and in the caudate nucleus at 2 days and at 1 week, and 4 weeks. The level of HVA was increased in the hypothalamus at 2 days, in the cerebellum at 2 days and at 1 week, in the pons plus medulla oblongata at 2 days, 1 week, and 4 weeks, and in the midbrain at 4 weeks. These data suggest that, in experimental hydrocephalus in the rabbit, NA release is increased throughout the brain, while DA release is decreased in the cerebral cortex and caudate nucleus, and increased in the cerebellum, hypothalamus, midbrain, and pons plus medulla oblongata.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Hereditary disorders of enzymes in the Embden-Meyerhof pathway of glycolysis.

Recent advances in hereditary disorders of red cell enzymes in the Embden-Meyerhof pathway and the Rapoport-Luebering cycle are discussed with a stress on pyruvate kinase deficiency. Broad genetic heterogeneity exists in all the known erythroenzymopathies. The primary structure of normal human red cell phosphoglycerate kinase has been determined recently and single amino acid substitutions of four mutant phosphoglycerate kinases have been clarified. These studies allowed an analysis of the structure-function relationships at the molecular level more precisely than has been possible previously. It is the consensus of the investigators working in this field that the pathogenesis in three-quarters of the congenital nonspherocytic hemolytic anemia patients remains unknown even after adequate red cell enzyme studies and isopropanol test. This means that broad studies have to be carried out in this field.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1982

Alterations of polypeptide composition of mature granulocytes obtained from patients with chronic myelogenous leukemia.

In order to compare the polypeptide composition of the CML mature granulocytes with that of the normal whole cell lysates, mature granulocytes from four healthy volunteers and six CML patients were analyzed by two-dimensional gel electrophoresis. In the normal subjects, 60 major spots were commonly and reproducibly identified. In the CML, there were constant alterations in some of these major spots. Four spots were totally absent in all the CML samples, and another four spots were absent in five of the six samples. In addition, one spot was larger in CML than in normal cells, and another spot, which was only faintly visible or not detectable in the normal samples, was massively present in all the CML samples. Our data suggest specific changes in the polypeptide compositions of CML granulocytes. This method could be clinically applied for the analysis of granulocytic disorders.

Electrophoresis, Polyacrylamide Gel↗