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Biomedical subjects

S D Cederbaum

Publications and source records attributed to S D Cederbaum.

89 records · Page 5Linked to original sources
PubMed1977

Rapid diagnosis of pyruvate and ketoglutarate dehydrogenase deficiencies in platelet-enriched preparations from blood.

Radiochemical methods are described in detail to measure the activities of the pyruvate dehydrogenase complex and of the ketoglutarate dehydrogenase complex in platelet-enriched fractions. Determinations can be completed in one day with as little as 5 ml of venous blood. Activities are proportional to the length of the incubation and the amount of tissue protein added, show appropriate dependence on added cofactors, are stable for up to 2 days at -20 degrees C, and do not appear to be affected by diet. The pyruvate dehydrogenase complex appears to be fully activated (dephosphorylated) in these preparations. Activities were comparable in platelet-enriched fractions from 25 normal subjects and 25 patients with a variety of neurological and psychiatric diagnoses. Mean values (+/- S.E.M.) for these 50 individuals were 169+/-9 pmol/min per mg protein for the pyruvate dehydrogenase complex and 535+/-27 pmol/min per mg protein for the ketoglutarate dehydrogenase complex. These values are comparable to those found in cultured skin fibroblast with similar techniques. Deficient pyruvate dehydrogenase activity (19+/-6 and 11+/-4 pmol/min per mg protein) was demonstrated in platelet-enriched preparations from two brothers whose fibroblasts had previously been shown to be deficient in pyruvate dehydrogenase and who responed to a ketogenic diet. Experimental detail critical to obtaining reproducible results with these methods are stressed (notably the crucial importance of maintaining the purity of the radioactive substrates). These techniques allow identification of patients with pyruvate dehydrogenase deficiencies within one day without requiring liver or muscle biopsy.

Adolescent↗
PubMed1977

Hyperargininemia.

A 7 1/2-year-old boy had progressive psychomotor retardation, behavior disturbance, and spasticity, and had growth arrest from age three. Plasma arginine on a self-selected protein-poor diet was increased (4.05 mg/dl; nl 0.4 to 2.6), whereas urinary amino acid excretion was normal. Red blood cell arginase was less than 1% of normal in the patient and was half normal in both parents, in two normal siblings, and in his paternal grandfather. Three hours after a meal providing 2 gm protein/kg body weight, the plasma arginine value rose to 13.2 mg/dl, dibasic aminoaciduria was seen clearly for the only time, but blood ammonia concentration remained normal. We conclude that arginase deficiency in the red blood cells and probably in the liver is inherited in an autosomal recessive manner and is responsible for the clinical syndrome in this patient.

Amino Acid Metabolism, Inborn Errors↗
PubMed1976

Glucose 6-phosphate dehydrogenase in rainbow trout.

Electrophoretic analysis of glucose 6-phosphate dehydrogenase from liver and blood of rainbow trout revealed a complex series of bands, which could differ between fish. The partial interconvertible nature of these bands was demonstrated with enzyme that had been incompletely inactivated at pH 8.4. In a single population of 40 fish, a homozygote and a heterozygote for an electrophoretic variant allele were found. We suggest that G6PD in rainbow trout liver and blood is determinted by two alleles at a single locus, with posttranslational modification responsible for the complex electrophoretic patterns seen. The basis for this variation appears to be NADH binding to the protein molecule. Another variant and other properties of the enzyme are described.

Animals↗
PubMed1976

The chondro-osseous dysplasia of adenosine deaminase deficiency with severe combined immunodeficiency.

Three children, two of them siblings, with severe combined immunodeficiency and adenosine deaminase deficiency died within the first six months of life from the complications of acute bacterial infections. Subtle radiographic abnormalities were seen at the costochondral junctions, at the apophysis of the iliac bones, and in the vertebral bodies. At autopsy, the thymus showed evidence of early differentiation and, in one instance, aborted Hassall's corpuscles. Histologic study of the bone disclosed lack of organized cartilage columnar formation, large lacuni containing hypertrophied cells, and lack of trabecular formation with uninterrupted areas of calcified cartilage. These changes are distinctly different from those observed in the metaphyseal chondrodysplasias or in other chondrodystrophies.

Adenosine Deaminase↗
PubMed1976

Sensitivity to carbohydrate in a patient with familial intermittent lactic acidosis and pyruvate dehydrogenase deficiency.

A 9-year old boy with severe mental and growth retardation and diffuse neurologic damage had minimal elevation of blood pyruvate (0.21 mM) and lactate (2.1 mM) on a normal diet but developed life-threatening lactic acidosis (pH 7.14; lactate 21.0 MM) on a diet containing 65% carbohydrate and 15% fat. Subsequently, blood pyruvate levels rose significantly higher than in 16 control subjects during a glucose tolerance test whereas the glucose levels were normal. Two sisters died with spontaneous lactic acidosis and an otherwise similar clinical course...

Acidosis↗
PubMed1976

Ketonic diet in the management of pyruvate dehydrogenase deficiency.

Two brothers, aged 11 years 6 months and 2 years 3 months, with psychomotor and growth retardation, episodes of weakness, ataxia, ophthalmoplegia, and elevated levels of blood pyruvate were shown to have a deficiency in the pyruvate dehydrogenase complex (PDH). When they ate a diet high enough in fats to cause ketonemia but not acidosis, there was a fall in blood pyruvate levels, a decrease in the frequency and severity of the episodes of neurological deterioration, an increased rate of growth and development in the younger brother, and increased strength and endurance in the older one. The possibility of dietary treatment makes the early diagnosis of PDH deficiency more important. Determination of blood pyruvate and lactate levels following a standard glucose meal (glucose-pyruvate test) appears to be the most reliable screening test for this condition.

Alanine↗
PubMed1975

Familial poliodystrophy, mitochondrial myopathy, and lactate acidemia.

In two siblings with limb-girdle muscle weakness and episodic headaches and vomiting from early childhood, progressive neurologic degeneration later developed, and both children died. In one child, corticosteroids induced improvement in both cerebral and muscular symptoms that lasted 1 year. This patient had elevated blood, urine, and spinal fluid lactate levels, together with increased cardiac output and oxygen consumption at rest. Several muscle fibers were characterized by a "ragged red" appearance with the trichrome stain. Subsarcolemmal and intermyofibrillar excess of mitochondrial oxidative enzyme reaction product was correlated with abnormal mitochondrial aggregates by electron microscopy. The brain revealed focal areas of cortical degeneration and necrosis with adjacent gliosis or edema. Ferrocalcific deposits were prominent in the globus pallidus. The other sibling had similar changes in the brain at autopsy. This familial multisystem disorder especially involving the brain, skeletal muscle, and heart appears to represent a defect in some mitochondrial oxidative mechanism.

Adolescent↗
PubMed1975

T-cell reconstitution by thymus transplantation and transfer factor in severe combined immunodeficiency.

Reconstitution of cell-mediated immunity was achieved in a 5-month old female infant with severe combined immunodeficiency by fetal thymus transplant given simultaneously with two units of transfer factor. Thymus was obtained from a 15-week gestational age male fetus, and the two units of transfer factor from the lymphocytes of 500 ml of peripheral blood. Three weeks after transplantation, two nel HL-A antigens were detected on the infant's lymphocytes, one of which was present in the mother of the thymus donor; at the same time, some of the infant's own HL-A antigens disappeared. Thereafter, the percent of rosette-forming cells (T-cells) increased and the in vitro response to phytohemagglutinin and allogeneic lymphocytes became normal, and delayed skin tests became positive. Karyotyping of peripheral blood lymphocytes posttransplantation reveals an XY (male) pattern. These results suggest lymphocyte re-population as a result of the thymus-transfer factor therapy. Five months after transplantation, the patient has normal cellular immunity but persistent hypogammaglobulinemia. She is free of infection and growing normally on gammaglobulin injections.

Female↗
PubMed1974

Combined immunodeficiency presenting as the Letterer-Siwe syndrome.

Four infants with skin rash, hepatosplenomegaly, lymphocytosis, eosinophilis, and histiocytic infiltration of the lymph nodes and skin are described; in each of these infants an initial diagnosis of the Letterer-Siwe syndrome was made. Postmortem findings of thymic dysplasia and poorly differentiated, lymphopenic peripheral lympoid tissue in each of the four infants, as well as antimortem clinical findings in one, established a diagnosis of severe combined immunodeficiency. From these and similar cases in the literature, we postulate that the Letterer-Siwe syndrome may not be an unusual presentation of combined immunodeficiency. Appropriate immunologic studies will help to differentiate the two disorders.

Autopsy↗
PubMed1972

Tetrazolium oxidase polymorphism in rainbow trout.

Tetrazolium oxidase from the blood and liver of rainbow trout was found to be genetically polymorphic. The inheritance pattern of the liver enzyme was compatible only with a one locus-two allele hypothesis. The enzymes in the blood while having an electrophoretically identical polymorphism could differ genotypically from that of the liver in a given fish. The significance of these findings to the understanding of the evolution of the salmonid genome is discussed.

Alleles↗