Search PubMed⌕ Search

Biomedical subjects

U Langenbeck

Publications and source records attributed to U Langenbeck.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1984

Serum branched-chain amino and keto acid response to a protein-rich meal in man.

In 8 healthy volunteers blood levels of branched-chain amino (BCAA) and keto acids (BCKA) were determined in response to a protein-rich meal. Serum concentrations of leucine, isoleucine, valine, alpha-ketoisocaproic acid and alpha-keto-beta-methyl-n-valeric acid increased within 30 min and continued to rise throughout the observation. Only the keto analog of valine remained unaffected. As the BCAA increased significantly more percentagewise than their keto analogs, the ratios between amino and keto acids became augmented. It is suggested that (1) augmentation of keto acids may reflect transamination of amino acids rather than intestinal uptake; (2) the overall capacity of the organism for decarboxylation of ketovaline is greater than for the other keto acids, and (3) augmentation of the ratio between BCAA and BCKA may favor the storage of amino acids from the protein load into the body's protein stores.

Adult↗
PubMed1984

Oral administration of alpha-ketoisovaleric acid or valine in humans: blood kinetics and biochemical effects.

alpha-Ketoisovaleric acid levels increase from 10.6 +/- 0.8 to 121 +/- 20 mumol/L, and valine levels increase from 175 +/- 14 to 940 +/- 50 mumol/L after oral administration of an isomolar (62.5 mg/kg) bolus of alpha-ketoisovaleric acid or valine to healthy human subjects. alpha-Ketoisovaleric acid levels have a different time course relative to valine. alpha-Ketoisovaleric acid and valine affect various other amino and keto acids, and some of these effects are qualitatively different. alpha-Ketoisovaleric acid enhances alpha-ketoisocaproic acid and alpha-keto-beta-methyl-n-valeric acid, but diminishes the corresponding amino acids, and causes an early decline of ornithine along with a late augmentation of plasma arginine. Valine does the opposite. The data suggest that in humans, overall capacity for alpha-ketoisovaleric acid decarboxylation appears greater than the capacity for valine transamination, and that all branched-chain amino acids and branched-chain keto acids seem to be interconvertible by reversible transaminations.

Administration, Oral↗
PubMed1983

Quantitative gas chromatographic mass spectrometric determination of mandelic acid in blood plasma. Comparison of deuterated and homologous internal standards.

Quantitative gas chromatography/mass spectrometry/selected ion monitoring of mandelic acid in plasma in the lower micromolar range has been investigated using both the deuterated compound and a homologue, 2-phenyllactic acid, as internal standards. On chromatography of the TMSi-ester ethers, the latter is less stable than the former. The chromatographic isotope effect observed for deuterated mandelic acid does not suggest a carrier function for this compound. Normal plasma levels of mandelic acid are about 0.5 microM. Only a minor portion of phenyramidol is metabolized to mandelic acid. Preliminary in vivo data indicate the presence of a stereoselective transport system for D(-)-mandelic acid in gastrointestinal tract and possibly kidney.

Adult↗
PubMed1983

Influence of insulin on blood levels of branched chain keto and amino acids in man.

Branched chain keto acids, their corresponding amino acids, glucose, glucagon, growth hormone, C-peptide and gastric inhibitory polypeptide were determined in 8 healthy subjects after an intravenous bolus injection of 0.1 U/kg insulin. Branched chain keto acids declined within 60 min, the corresponding amino acids within 20 min or later. Amino acids tended to return towards normal earlier than their keto acids. Blood glucose levels were normal 2 hr after insulin injection while keto and amino acids remained diminished for more than 3 hr. In 8 healthy controls, given physiological saline instead of insulin, the branched chain keto acids did not decline throughout the test. It is suggested that insulin diminishes blood levels of branched chain keto acids, that the intraorgan flux of branched chain keto acids is different from the flux of branched chain amino acids and that branched chain keto acids may serve to correct for hypoglycemia.

Adult↗
PubMed1982

A familial progressive neurodegenerative disease with 2-oxoglutaric aciduria.

A boy and a girl born to a consanguineous Tunisian couple are suffering from a slowly progressive nervous disorder. Initially they both had normal psychomotor development with acquisition of gait and speech. First symptoms in the boy were athetoid movements during the second year of life. He later lost all motor and language skills and developed muscular rigidity and intention tremor. At the age of five years, he was completely bedridden while he appeared mentally much less affected. His younger sister followed a similar course. The major specific abnormality detected was a strikingly elevated excretion of 2-oxoglutaric acid, which was identified by gas liquid chromatography, mass spectrometry, and enzymatic analysis. 2-oxoglutarate dehydrogenase activity in homogenates of cultured skin fibroblasts was reduced to about 25% of control values in both children. Although the pathogenetic mechanisms leading to brain damage remain obscure, the finding strongly suggest an autosomal recessive neurometabolic disease with predominant involvement of the extrapyramidal system.

Basal Ganglia Diseases↗
PubMed1982

Exchange transfusion in acute episodes of maple syrup urine disease. Studies on branched-chain amino and keto acids.

Two neonates with maple syrup urine disease were treated by exchange transfusion. Within 15 h blood leucine and KICA concentrations were lowered from 2.6 mM to 1.1 mM using 570 to 620 ml blood per kg body weight. The other branched-chain amino acid/keto acid pairs fell to normal. During exchange transfusion the patient's nitrogen balance seems to be negative. Further exchange transfusion was useless. More importantly the patient should be forced into an anabolic state by high caloric supply or insulin plus glucose treatment. More KICA than leucine was eliminated, however, KICA blood levels remained slightly higher than that of leucine indicating different leucine/KICA equilibria in extravascular compartments than in blood. In a given time interval exchange transfusion was more effective than peritoneal dialysis, probably due to a lack of an additional (peritoneal) membrane. Renal excretion of branched-chain amino and keto acids was very inefficient. The allegedly most toxic metabolite, KICA, had the lowest renal clearance of the branched-chain keto acids.

Amino Acids↗
PubMed1982

Maple syrup urine disease--therapeutic use of insulin in catabolic states.

High and neurotoxic blood levels of leucine and its ketoanalogue develop in catabolic patients with maple syrup urine disease. The use of relatively high doses of insulin and additional glucose had a more pronounced effect on lowering leucine (and alpha-ketoisocaproate) blood levels than dietary elimination of leucine alone. This is demonstrated in 2 neonates after blood exchange transfusion and in one 4-months old patient suffering from febrile diarrhea.

Glucose↗
PubMed1982

Biochemical and therapeutical studies in a case of atrophia gyrata.

A thirty-six years old man from an inbred family with the typical clinical picture of Atrophia gyrata chorioideae et retinae was found to have hyperornithinemia and a partial deficiency of ornithin-ketoacid-transaminase activity. The residual activity was stimulated in vitro by high concentrations of pyridoxal phosphate. We have initiated a therapeutic study with vitamin B6 per os accordingly. Comparitively low doses may be sufficient for long term treatment. The necessity to start therapy early in life is emphazised. Possible mechanisms of the pathogenesis of Atrophia gyrata are discussed.

Adult↗
PubMed1981

Blood levels of branched-chain alpha-keto acids in uremia: effect of an oral glucose tolerance test.

The effect of an oral glucose tolerance test (oGTT) on serum levels of branched-chain keto acids (BCKA), i.e. alpha-keto-isocaproic acid (KICA), alpha-keto-isovaleric acid (KIVA) and alpha-keto-beta methyl-n-valeric acid (KMVA) as well as on serum insulin, C-peptide and blood glucose levels was determined in uremic patients and in healthy control subjects. In controls, blood levels of KICA, KMVA and KIVA declined significantly following oral administration of 100 glucose. In uremic patients no decline of KICA was observed. The fall of KMVA was diminished, while suppression of KIVA blood levels in response to the oGGT remained unimpaired. Although serum insulin and C-peptide levels in uremic patients were not significantly different from the controls before and throughout the oGTT, six out of eight displayed abnormal glucose tolerance. It is suggested that the response of blood BCKA levels to an oGTT is altered in uremia, an abnormality restricted primarily to KICA and possibly explained by insulin antagonism and/or by insufficient insulin secretion.

Adult↗
PubMed1981

The dup(3q) syndrome: report of eight cases and review of the literature.

Clinical and cytogenetic examinations were performed on eight unrelated infants with duplication of part of the long arm of chromosome 3. A review of published cases shows a clinical syndrome characterized by statomotoric retardation, shortened life span, and a multiple congenital anomalies (MCA) syndrome of abnormal head configuration, hypertrichosis, hypertelorism, ocular anomalies, anteverted nostrils, long philtrum, maxillary prognathia, down-turned corners of the mouth, highly arched or cleft plate, micrognathia, malformed auricles, short, webbed neck, clinodactyly, simian crease, talipes, and congenital heart disease. The dup(3q) syndrome is a clinically easily recognizable entity.

Abnormalities, Multiple↗
PubMed1981

Renal transport of aromatic acids in patients with phenylketonuria.

Renal clearance of phenylpyruvic acid is maximal at a plasma concentration of 40-60 mumol/l. This concentration is obtained with plasma phenylalanine concentrations of 1.0-1.2 mmol/l, the threshold for separating classical phenylketonuria from phenylketonuria variants.

Child↗
PubMed1981

[Oculo-cerebral dysplasia: aplasia of the optic nerve with familial microphthalmos and cryptophthalmus. Clinical and computer tomography study].

The authors report on two siblings with severe malformations of the eyes. The 16-year-old girl has bilateral microphthalmus with aplasia of the right optic nerve and a Dandy-Walker cyst of the cerebellum. The right eye has no optic disk or retinal vessels. Her 13-year-old brother has unilateral aplasia of the optic nerve with cryptophthalmus and contralateral microphthalmus. In a computer tomography examination no optic nerve could be demonstrated on the left. The presence of an oculocerebral dysplasia in a brother and sister with healthy parents suggest an autosomal-recessive mode of inheritance of the aplasia of the optic nerve with microphthalmus and/or cryptophthalmus.

Adolescent↗
PubMed1980

Characterization of experimental phenylketonuria. Augmentation of hyperphenylalaninemia with alpha-methylphenylalanine and p-chlorophenylalanine.

Phenylalanine in conjunction with p-chlorophenylalanine or alpha-methylphenylalanine was administered to suckling rats to induce hyperphenylalaninemia reminiscent of untreated phenylketonuria, and developmental parameters were monitored. The experimental model utilizing p-chlorophenylalanine was found to be unsatisfactory, in that the drug had general deleterious effects on growth, numerous side effects including increased mortality, and affected brain levels of biogenic monoamine neurotransmitters. The model utilizing alpha-methylphenylalanine was relatively free from nonspecific effects and thus, changes observed in the animals were attributable to experimental phenylketonuria. The latter animals had slightly decreased body and brain weights, and exhibited grossly elevated serum phenylalanine and urinary excretion of phenylketone metabolites. Hyperphenylalaninemia produced greatly disrupted brain amino acids at 10 days of age (prior to the formalization of the blood-brain barrier and specific transport systems) which was limited by 30 days of age to changes in glycine, gamma-aminobutyric acid and the aliphatic and aromatic amino acids which compete for uptake in the brain by a common carrier. These animals also exhibited a myelin deficit and changes in proteins from isolated nerve cell preparations. Mature animals which had daily treatment up to 60 days of age exhibited a long-term learning impairment. These observations are consistent with many aspects of the clinical picture of untreated phenylketonuric patients, and suggest that this animal model will be beneficial in studying the disease.

Age Factors↗