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Biomedical subjects

U Wendel

Publications and source records attributed to U Wendel.

At least 127 records · Page 7Linked to original sources
PubMed1988

Transamination and oxidative decarboxylation rates of branched-chain 2-oxo acids in cultured human skin fibroblasts.

Transamination and oxidative decarboxylation of branched-chain L-amino acid derived 2-oxo acids in cultured human skin fibroblasts from normal subjects and from a patient with maple syrup urine disease (variant form) were comparatively studied in incubations with 1-14C-labeled substrates (1 mmol/liter). With normal cells, 14CO2 release ranged from about 11 to 3 nmol/90 min/mg of cell protein in the order 3-methyl-2-oxo[14C]butanoate greater than (S)-3-methyl-2-oxo[14C]pentanoate greater than 4-methyl-2-oxo[14C]pentanoate greater than (R)-3-methyl-2-oxo[14C]pentanoate. Formation of the corresponding branched-chain amino[14C] acids was substantially higher than 14CO2 production (around 10-fold) and similar with L-valine, L-isoleucine, and L-leucine. L-Allo-isoleucine production [from (R)-3-methyl-2-oxopentanoate] was significantly lower. With maple syrup urine disease fibroblasts, comparable transamination rates were observed. Related to the findings with normal cells, 14CO2 release from each substrate was differently reduced and apparent residual branched-chain 2-oxo acid dehydrogenase complex activity with 3-methyl-2-oxobutanoate, 4-methyl-2-oxopentanoate, (S)-, and (R)-3-methyl-2-oxopentanoate amounted to 12, 13, 22, and 50%, respectively.

Amination↗
PubMed1988

Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency.

We previously described demyelination in the brain and subacute combined degeneration of the spinal cord in a patient with 5,10-methylenetetrahydrofolate reductase deficiency. To assess the role of methionine, S-adenosylmethionine, folate, and neurotransmitter amine metabolism in the demyelination process, we measured these metabolites in CSF from this patient; the findings are compared with those obtained from three patients in whom neurologic deterioration had been halted by the administration of betaine. Folate concentrations were low, and amine and biopterin metabolism were abnormal in all patients. Methionine and S-adenosylmethionine concentrations were undetectable in the first patient. In those receiving betaine, methionine concentrations were proportional to the dose administered and S-adenosylmethionine concentrations were near normal. The results provide the first evidence for an association between defective S-adenosylmethionine metabolism and demyelination in humans.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1988

[Diagnostic procedures in pediatric hypoglycemias].

Depending on its etiology hypoglycemia appears after short or prolonged periods of fasting and shows different metabolite and hormonal patterns. In children it is caused by a disturbed homoeostasis of blood glucose (hormonal disorders, decreased activity of glycogenolysis or gluconeogenesis), by a primarily decreased ketogenic activity, or by a deranged adjustment of ketogenesis and carbohydrate metabolism. For the diagnostic procedure the age at manifestation, periods of fasting as well as signs and symptoms (f.e. hepatomegaly, growth retardation, somnolence) have to be carefully evaluated. Based on the extent of ketonemia the hypoglycemic syndromes can be classified into ketotic and hypoketotic forms. Hyperinsulinism, defects in fatty acid oxydation, glycogen storage disease I and postprandial hypoglycemias belong to the second category. In diagnosing hypoglycemia analysis of metabolite (glucose, lactate, beta-hydroxybutyrate, free fatty acids, carnitine) and hormonal (insulin, cortisol, growth hormone) patterns during hypoglycemic episodes is of outstanding importance. Urine has to be analysed for abnormal organic acids in order to demonstrate disturbed fatty acid oxydation. Rarely, loading tests with intermediates of carbohydrate metabolism are necessary. Suspected enzyme deficiencies have to be demonstrated in appropriate tissues (liver biopsy, erythrocytes, fibroblasts).

Child↗
PubMed1987

Comparison of the catabolism of branched-chain L-amino acids in cultured human skin fibroblasts.

Using 1-14C-labeled substrates, the metabolism of naturally occurring branched-chain L-amino acids was studied in incubations with cultured human skin fibroblasts derived from normal subjects and from a patient with maple syrup urine disease (variant form). Practically saturating conditions were reached at 1 mmol/liter of substrate and metabolic rates remained essentially constant up to 120 min. In control fibroblasts, the transamination of 14C-labeled leucine, valine, isoleucine, and allo-isoleucine (1 mmol/liter) was about 26, 13, 12, and 5 nmol/90 min/mg of cell protein, respectively. The portion of transamination products undergoing oxidative decarboxylation within the cells was about 17, 43, 34, and 23%, respectively. With the maple syrup urine disease cell line, comparable transamination rates were found. As compared to the findings with normal cells, however, 14CO2 production from the above mentioned substrates was reduced and amounted to 14, 11, 25, and 45%, respectively. Thus it appeared that residual branched-chain 2-oxo acid dehydrogenase activity was differently reduced towards the four 2-oxo acid substrates.

Amino Acids, Branched-Chain↗
PubMed1986

Increased manganese content and reduced arginase activity in erythrocytes of a patient with prolidase deficiency (iminodipeptiduria).

Manganese was measured in blood of a patient with prolidase deficiency by neutron activation analysis. The manganese content of packed blood cells was 48.9 ng/g wet weight (controls 18.4 +/- 4.3 ng/g wet weight). It was proportionately increased in whole blood, whereas the serum manganese concentration was unchanged. The erythrocyte arginase activity was reduced to 46% of the mean control value. The reduced activities of two manganese-dependent enzymes, prolidase and arginase in erythrocytes in combination with an increased manganese content cannot be explained at the moment and leads to the speculation that manganese is inaccessible for enzyme activation.

Adult↗
PubMed1986

[Cranial computed tomography in maple syrup urine disease].

Cranial computed tomography in the initial stage of the intermediate phenotype of maple syrup urine disease (MSUD) demonstrates diffuse, symmetric hypodensities in white and grey matter, which show a complete return to normal after early introduction of an adequate protein-restrictive diet. If diagnosis of this disease is missed or delayed, progressive global (end-stage) atrophy will take place over several years. A decrease in density values correlates well with the total cerebral lipid and water content (closely related to myelinisation), whereas progression and grade of atrophy show a relationship with the severity of pathological white and grey matter changes that are not demonstrable with computed tomography but can be proven histologically. Analysis of both morphological parameters corresponds well with clinical-neurological outcome and therapeutic success.

Brain↗
PubMed1986

[Type I glycogenosis: extending therapy with uncooked cornstarch].

Normal or slightly elevated blood lactate levels and normal to slightly elevated lactate-/creatinine-ratios in 24-h-urine were found in 12 patients (0.9 to 16 years) with glycogenosis type I under conventional treatment with nocturnal gastric drip feeding with maltodextrine combined with frequent daytime feedings. Replacing the nocturnal gastric drip feeding by two doses of uncooked cornstarch suspended in water (single dose 1.4-2.0 g/kg body weight) 4 patients at the ages of 10 to 16 years obtained similar metabolic control. A 7-year old patient with glycogenosis type Ib showing an extremely low fasting tolerance attained stable blood glucose levels by eating two doses of uncooked cornstarch in the morning, so that she was able to attend school. A 2-year old patient received 2-3 g cornstarch/kg body weight every 6 h resulting in constant blood glucose levels, so that she was able to emigrate to Turkey. The therapy with uncooked cornstarch is suitable to augment the therapy of some patients with glycogenosis type I.

Adolescent↗
PubMed1985

3-Methylglutaconic and 3-methylglutaric aciduria in a patient with suspected 3-methylglutaconyl-CoA hydratase deficiency.

A girl suffering from marked muscular hypotonia, severe statomotor and mental retardation, bilateral optic atrophy with chorioretinal degeneration, convulsions and a moderate compensated metabolic acidosis is described. Screening for metabolic disorders revealed massive 3-methylglutaconic with 3-methylglutaric aciduria leading to the tentative diagnosis of 3-methylglutaconyl-CoA hydratase deficiency. Metabolite excretion was correlated with variation of leucine intake. 3-methyl-3-hydroxyglutaryl-CoA lyase activity in cultured fibroblasts was normal. The suspected metabolic defect was not demonstrable in cultured skin fibroblasts, however.

Acidosis↗
PubMed1985

[Somatostatin in the emergency treatment of persistent hypoglycemias caused by hyperinsulinism (nesidioblastosis of the pancreas)].

11 infants with persisting hypoglycemia due to hyperinsulinism (nesidioblastosis of the pancreas) were treated with somatostatin. Somatostatin administration in a relatively high dosage (initially 145 micrograms/m2 body surface as bolus followed by a continuous infusion of the same dose per hour) resulted in a suppression of the circulating insulin concentration leading to a less abrupt fall of the postprandial plasma glucose level. By somatostatin infusion we were able to keep two patients with intractable neonatal hypoglycemia in a normoglycemic state until subtotal pancreatectomy. Infants suffering from nesidioblastosis require 1.0-4.5 micrograms/kg/h somatostatin and a concomitant carbohydrate supply of 0.3-0.48 g/kg/h in order to maintain normoglycemia. An initial somatostatin bolus can be omitted. Somatostatin is very reliable in the treatment of neonatal hypoglycemia due to hyperinsulinism for a limited period of time until subtotal pancreatectomy is performed. In most cases of nesidioblastosis this operative measure seems to be inevitable for the control of hyperinsulinism.

Combined Modality Therapy↗
PubMed1984

Betaine in the treatment of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.

In a 3-year-old mentally retarded girl with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency among different therapeutic approaches only treatment with betaine (15-20 g/day) resulted in a satisfactory biochemical response. Betaine improved homocysteine remethylation and thus lowered plasma homocystine to trace amounts and normalized the previously very low plasma methionine concentration. This biochemical response was associated with a clinical improvement although she remained mentally retarded.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed1984

Intracellular levels and metabolism of leucine and alpha-ketoisocaproate in normal and maple syrup urine disease fibroblasts.

The interdependence of intra- and extracellular leucine and KICA concentration was studied in cultured MSUD and control fibroblasts. Intracellular KICA levels were measurable only after leucine load and were 1/20th to 1/40th that of leucine. In cells exposed to high KICA concentrations (2 mmole/liter) KICA accumulation followed linear kinetics, finally overwhelming the transamination capacity. Transamination of KICA to leucine became saturated at 2-6 mmole/liter of extracellular KICA. MSUD and control fibroblasts differed slightly in intracellular KICA concentrations, and only at high concentrations of leucine in medium. Release of KICA into the medium after leucine loading was found to be slightly increased in MSUD fibroblasts.

Amino Acids, Branched-Chain↗