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Biomedical subjects

E Christensen

Publications and source records attributed to E Christensen.

At least 145 records · Page 8Linked to original sources
PubMed1991

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Aged↗
PubMed1991

[Macrocephaly and dystonic cerebral palsy in a child with type I glutaric aciduria].

In a male infant with macrocephaly and dystonic cerebral palsy glutaric aciduria type I was detected by analysis of urine for organic acids. Glutaric aciduria type I is an inherited metabolic disorder of organic acids due to a defect of glutaryl-CoA-dehydrogenase in the intermediate metabolic step of lysine and tryptophan degradation. In the urine glutaric acid is usually accompanied by 3-hydroxy-glutaric acid in abnormal quantities. The enzyme defect in our patient was proved in cultured fibroblasts. In the cerebral computer tomography marked atrophy of bilateral frontotemporal regions could be demonstrated. The amount of urinary glutarat excretion decreased after protein but especially after lysine and tryptophan restriction in the diet. The administration of carnitine improved carnitine levels in blood and urine. Although the progression of neurological impairment could be stopped, dystonia and dyskinesis remained nearly unaltered. In spite of severe motor retardation, recognition and vocalisation were established. In the two year old patient mental retardation is relatively mild comparing with motor retardation. The administration of 100 or 200 mg Riboflavin/day was stopped, as it did not alter clinical symptoms or excretion of glutarat. Baclofen, an analogue of gamma-amino-butyric acid, was orally given (2 mg/kg/day) and improved dystonia, but did not influence organic aciduria. The neurological manifestations may be due in part to inhibition of neuronal glutamat decarboxylase by glutaric acid with decreased gamma-amino-butyric acid biosynthesis. The characteristic clinical symptoms with macrocephaly and dystonia and the very typical pattern of organic acids in urine are a challenge for rapid diagnosis and therapy.

Amino Acid Metabolism, Inborn Errors↗
PubMed1991

Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy.

Clinical course, diagnostic and therapeutic management, and neurodevelopmental outcome were evaluated in 11 patients with glutaryl-coenzyme A dehydrogenase deficiency. In 9 patients macrocephalus was present at or shortly after birth and preceded the neurological disease. In 7 children an acute illness resembling encephalitis appeared after a period of normal development; 2 had developmental delay and progressive "dystonic cerebral palsy." Later, all 9 displayed typical signs of a disorder of the basal ganglia. In 1 patient with macrocephalus the disorder was diagnosed before the onset of neurological disease; in another it was diagnosed prenatally. Computed tomography and magnetic resonance imaging scans revealed severe generalized cerebral atrophy, most striking in the frontal and temporal lobes in 10 patients. Further deterioration was halted after initiation of treatment consisting of low-protein diets, special formulas low in lysine and tryptophan, and supplements of riboflavin and L-carnitine. Only 1 patient showed a slight clinical improvement. Later, dietary therapy was discontinued in 2 older patients and relaxed in a third without observed adverse effects. Two patients in whom treatment could be initiated before the onset of neurological symptoms have developed normally. However, duration of follow-up (6 and 29 months) does not yet allow classification of glutaryl-coenzyme A dehydrogenase deficiency as a treatable disorder. Total body production of glutaric acid, reflected in the daily urinary output, was efficiently reduced by therapeutic measures. Levels of glutaric acid in plasma and cerebrospinal fluid remained unchanged, which may in part explain the overall unsatisfactory outcome. All patients presented with a severe secondary deficiency of carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

The Zellweger syndrome: deficient conversion of docosahexaenoic acid (22:6(n-3)) to eicosapentaenoic acid (20:5(n-3)) and normal delta 4-desaturase activity in cultured skin fibroblasts.

The metabolism of docosahexaenoic acid (22:6(n-3)) and adrenic acid (22:4(n-6)) was studied in cultured fibroblasts from patients with the Zellweger syndrome, X-linked adrenoleukodystrophy (X-ALD) and normal controls. It was shown that [4,5- 3H]22:6(n-3) is retroconverted to labelled eicosapentaenoic acid (20:5(n-3)) in normal and X-ALD fibroblasts, while this conversion is deficient in Zellweger fibroblasts. [U- 14C]Eicosapentaenoic acid (20:5(n-3)) is elongated to docosapentaenoic acid (22:5(n-3)) in all three cell lines. With [U- 14C]20:5(n-3) as the substrate, shorter fatty acids were not detected. With [4,5- 3H]22:6(n-3) as the substrate, labelled fatty acids were esterified in the phospholipid- and triacylglycerol-fraction to approximately the same extent in all three cell lines. [2- 14C]Adrenic acid (22:4(n-6)) was desaturated to 22:5(n-6) and elongated to 24:4(n-6) in all three cell lines and to the largest extent in the Zellweger fibroblasts. This agrees with the view that the delta 4-desaturase is not a peroxisomal enzyme. The observation that the retroconversion of 22:6(n-3) to 20:5(n-3) is deficient in Zellweger fibroblasts strongly suggest that the beta-oxidation step in the retroconversion is a peroxisomal function. Peroxisomal very-long-chain (lignoceroyl) CoA ligase is probably not required for the activation of 22:6(n-3), since the retroconversion to 20:5(n-3) is normal in X-ALD fibroblasts.

Adrenoleukodystrophy↗
PubMed1990

Recurrent, familial Reye-like syndrome with a new complex amino and organic aciduria.

Five of 13 siblings from a Jewish-Ashkenazi family suffered from recurrent Reye-like episodes. During attacks, these patients excreted alpha-keto-adipic, alpha-hydroxy-adipic, and alpha-aminoadipic acids, branched-chain keto acids and saccharopine in addition to lactic, pyruvic, and dicarboxylic acids characteristic of Reye syndrome. The serum concentrations of citrulline and alpha-amino-adipic acid were elevated and carnitine was at the upper limit of the normal range. Serum acetoacetate level was 4-5 times the beta-hydroxybutyrate level, but the pyruvate/lactate ratio was normal. Notably, plasma ketone bodies were lower than expected from the degree of catabolism. When the patients were symptom-free, no abnormal amino or organic acids in serum or urine were detected. These findings might be interpreted as a functional impairment at three different biochemical sites: fatty acid beta-oxidation, dehydrogenase complexes of the pyruvic, alpha-ketoglutaric, alpha-ketoadipic, and branched-chain keto acids, and pyruvate carboxylase. We suggest that in this hereditary disorder a toxic substance, exogenously or endogenously derived, interfered at multiple sites in different metabolic pathways.

Adipates↗
PubMed1990

[Ultrasound, computed tomography and magnetic resonance tomography in a child with macrocephaly and glutaric aciduria type I].

The rare case of glutaric aciduria type I (GA Type I) is described. Its characteristics are discussed and compared with cases in the literature. This disease is basically due to a lack of glutaryl-CoA-dehydrogenase with increased excretion of glutaric acid. Most authors describe frontotemporal cerebral atrophy. In the majority of cases macrocephaly is also present. This sign was also seen in our case and was the reason for performing an ultrasound examination, CT and MR. Ultrasound and CT showed a large insular cistern with incomplete formation of the opercula and frontal atrophy. In addition MR revealed hyperintensity of the basal ganglia and the periventricular white matter. To our knowledge this is the first publication of radiological findings in GA Type I in the German language.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

Beta-oxidation of medium chain (C8-C14) fatty acids studied in isolated liver cells.

The beta-oxidation and esterification of medium-chain fatty acids were studied in hepatocytes from fasted, fed and fructose-refed rats. The beta-oxidation of lauric acid (12:0) was less inhibited by fructose refeeding and by (+)-decanoyl-carnitine than the oxidation of oleic acid was, suggesting a peroxisomal beta-oxidation of lauric acid. Little lauric acid was esterified in triacylglycerol fraction, except at high substrate concentrations or in the fructose-refed state. With [1-14C]myristic acid (14:0), [1-14C]lauric acid (12:0), [1-14C]octanoic acid (8:0) and [2-14C]adrenic acid (22:4(n - 6] as substrate for hepatocytes from carbohydrate-refed rats, a large fraction of the 14C-labelled esterified fatty acids consisted of newly synthesized palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) while intact [1-14C]oleic acid substrate was esterified directly. With [9,10-3H]myristic acid as the substrate, small amounts of shortened 3H-labelled beta-oxidation intermediates were found. With [U-14C]palmitic acid, no shortened fatty acids were detected. It was concluded that when the mitochondrial fatty acid oxidation is down-regulated such as in the carbohydrate-refed state, medium-chain fatty acids can partly be retailored to long-chain fatty acids by peroxisomal beta-oxidation followed by synthesis of C16 and C16 fatty acids which can then stored as triacylglycerol.

Animals↗
PubMed1989

The effect of dietary alpha-bromopalmitate on blood lipids in the rat.

When alpha-bromopalmitate was fed to rats for 9-30 days, the level of serum triacylglycerol increased up to 2-fold over the concentration of controls. alpha-Bromopalmitate treatment had no effect on concentration of complex lipids in liver, while the triacylglycerol level in heart was significantly enhanced. From metabolic studies using isolated hepatocytes and liver microsomes, it is suggested that the increased serum triacylglycerol level after alpha-bromopalmitate feeding is mainly due to reduced fatty acid oxidation in both liver and peripheral tissues, and to a lesser extent, to inhibited fatty acid uptake and esterification.

Animals↗
PubMed1989

Adrenoleukodystrophy. The chain shortening of erucic acid (22:1(n-9)) and adrenic acid (22:4(n-6)) is deficient in neonatal adrenoleukodystrophy and normal in X-linked adrenoleukodistrophy skin fibroblasts.

The metabolism of long chain unsaturated fatty acids was studied in cultured fibroblasts from patients with X-linked adrenoleukodystrophy (ALD) and with neonatal ALD. By using [14-14C] erucic acid (22:1(n-9)) as substrate it was shown that the peroxisomal beta-oxidation, measured as chain shortening, was impaired in cells from patients with neonatal ALD. The beta-oxidation of adrenic acid (22:4(n-6)), measured as acid-soluble products, was also reduced in the neonatal ALD cells. The peroxisomal beta-oxidation of [14-14C]erucic acid (22:1(n-9)) and [2-14C]adrenic acid (22:4(n-6)) was normal in cells from X-ALD patients. The beta-oxidation, esterification and chain elongation of [1-14C]arachidonic acid (20:4(n-6)) and [1-14C]eicosapentaenoic acid (20:5(n-3)) was normal in both X-linked ALD and in neonatal ALD. Previous studies suggest that the activation of very long chain fatty acids by a lignoceryl (24:0)-CoA ligase is deficient in X-linked ALD, while the peroxisomal beta-oxidation enzymes are deficient in neonatal ALD. The present results suggest that the peroxisomal very long-chain acyl-CoA ligase is not required for activation of unsaturated C20 and C22 fatty acids and that these fatty acids can be efficiently activated by the long chain acyl-(palmityl)-CoA ligase.

Adrenoleukodystrophy↗