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Biomedical subjects

E Christensen

Publications and source records attributed to E Christensen.

At least 235 records · Page 13Linked to original sources
PubMed1980

Inhibition of the glycine cleavage system: hyperglycinemia and hyperglycinuria caused by valproic acid.

Elevated amounts of glycine in serum and urine were demonstrated in patients and rats receiving the antiepileptic drug valproic acid. The hyperglycinuria in the patients was correlated to the dose of the anticonvulsant. The activity of the glycine cleavage system, the major catabolic pathway of glycine, in liver homogenates from rats treated with valproic acid was clearly reduced. Further in vitro studies on intact rat liver mitochondria and the solubilized glycine cleavage system showed that valproic acid and valproyl-CoA significantly inhibited the glycine cleavage enzyme complex. It was concluded that the hyperglycinemia and hyperglycinuria seen in patients and rats during the administration of valproic acid are due to the inhibition of the glycine cleavage system, most probably by valproic acid and/or valproyl-CoA.

Animals↗
PubMed1980

Studies of the glycine metabolism in a patient with D-glyceric acidemia and hyperglycinemia.

A mentally retarded boy exhibiting both hyper-D-glyceric acidemia and hyperglycinemia and in whom a deficiency of D-glycerate dehydrogenase had previously been demonstrated was investigated to elucidate the ethiology of the glycine accumulation and its relationship to the D-glyceric acid accumulation. It was found that a positive correlation existed between excretion of D-glyceric acid and glycine (coefficient of correlation: r = 0.62, P < 0.001), that part of the IV injected [14C]glycine was metabolized to D-glyceric acid whereas no [14C]glyceric acid was metabolized to glycine, and that the in vivo degradation of IV injected [14C]glycine to 14CO2 was diminished. Measurement of glycine cleavage activity in autoptic liver tissue from the patient showed only 10% of normal activity. It is argued that this diminished activity could be caused by an endogenous inhibitor. D-glyceric acid is demonstrated not to possess such an inhibitory effect. Based on the finding of increased urinary excretion of both free and conjugated isobutyric acid, 2-methylbutyric acid, and isovaleric acid, it is hypothesized that the diminished glycine cleavage activity might be due, at least partially, to inhibition by 2-methylbutyryl-CoA and isobutyryl-CoA, two compounds that are known to inhibit the glycine cleavage system.

Amino Acid Metabolism, Inborn Errors↗
PubMed1980

Acquired zinc deficiency in alcoholic liver cirrhosis: report of two cases.

Acquired zinc deficiency in two patients suffering from alcoholic liver cirrhosis is reported. Skin changes included bullae and erosions on the heels, desquamating dermatitis on feet, hands and shins, and localized alopecia. Following oral zinc therapy the skin changes disappeared and Beau lines were later seen on the finger nails. Concomitantly with the rise in the depressed plasma zinc levels, serum alkaline phosphatase and prothrombin levels rose and serum bilirubin decreased. The observations are in agreement with earlier reports dealing with congenital and conditioned zinc deficiency and oral zinc therapy in alcoholic liver cirrhosis.

Humans↗
PubMed1980

Primary biliary cirrhosis: the prevalence of hypothyroidism and its relationship to thyroid autoantibodies and sicca syndrome.

A survey of thyroid function in 95 patients with primary biliary cirrhosis revealed the presence of thyroid antibodies in 24 females and 1 male. Thirteen (52%) of this thyroid antibody positive group (all female) had biochemical evidence of thyroid disease: 8 (32%) were hypothyroid (7 of whom showed signs of myxedema), 2 had elevated thyroid stimulating hormone (TSH) levels, and 3 had abnormal responses to stimulation with thyrotropin releasing hormone (TRH). In contrast, only 3 (4%) of the thyroid antibody negative patients had reduced serum thyroxine (T4) levels and none were clinically hypothyroid. Evidence of an increase in thyroid hormone binding, as reported by other workers, was not found, and both the resin uptake of radioactive triiodothyronine and the free thyroxine indices were normal in both groups. The presence of thyroid antibodies showed a highly significant association with lacrimal gland dysfunction but not with liver histologic staging or liver function tests.

Adult↗
PubMed1980

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗
PubMed1980

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗
PubMed1979

Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria). Experience with diet, riboflavin, and GABA analogue.

The autosomal recessive inherited disorder glutaryl-CoA dehydrogenase deficiency (glutaric aciduria) runs a progressive course with severe choreoathetosis and dystonia, eventually leading to total helplessness and early death. Theree patients were observed during therapeutic trials with a protein-low diet, riboflavin and GABA analogue. Diet and riboflavin had a slight-to-moderate effect on the clinical symptoms; the excretion of glutaric acid and 2-amino-adipic acid decreased considerably during treatment. Regression of neurologic symptoms was observed during treatment with GABA analogue. It is concluded that the patients should be treated as early as possible with protein-low diet, riboflavin, and GABA analogue.

2-Aminoadipic Acid↗
PubMed1979

Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial.

A double-blind clinical trial with zinc sulfate, 0.2 g three times daily, and a placebo was performed in 30 patients with biopsy-proven alcoholic liver cirrhosis. The disease was in a stable phase, and none of the patients showed evidence of a decompensated liver function. Parameters of liver function, taste acuity, dark adaptation and of zinc and vitamin A metabolism were followed for six weeks. In the zinc-treated group of 16 patients, serum zinc rose from a normal mean value of 13.3 to 17.4 mumol/l, whereas the mean serum vitamin A level remained practically unaltered within the normal range, 1.89 at the entry and 1.83 mumol/l at the end of the study. Plasma prothrombin and serum alkaline phosphatase levels of the zinc group increased and serum bilirubin and serum carotene decreased significantly. The dark adaptation did not change, but the taste function was significantly improved during zinc treatment. The results indicate that zinc supplementation causes alleviation of certain abnormalities of cirrhotics, which deserves further attention.

Aged↗
PubMed1979

Prenatal diagnosis of galactosaemia in six pregnancies -- possible complications with rare alleles of the galactose 1-phosphate uridyl transferase locus.

We describe our experience in prenatal diagnosis of six foetuses at risk for galactosaemia. In one family the parents were both shown to be double heterozygotes at the galactose 1-phosphate uridyl transferase (Gal-PUT) locus, the mother having a Duarte/Los Angeles and the father a Duarte/galactosaemia genotype. The foetus (and an older brother previously thought to have classical galactosaemia) was also a Duarte/galactosaemia double heterozygote. In the other five families, the parents and three foetuses were heterozygous carriers of the galactosaemia gene, one of the foetuses had galactosaemia, and one was homozygous for the normal gene. It is concluded that by a combination of family studies and assay of cultured amniotic cell Gal-PUT, accurate prediction of the foetal Gal-PUT genotype is now possible.

Alleles↗
PubMed1979

Nonketotic hyperglycinemia. Clinical, biochemical and therapeutic aspects.

A patient exhibiting progressive cerebral depression from the first days of life is described. The diagnosis of nonketotic hyperglycinemia was established on the typical clinical presentation, elevated glycine concentrations in body fluids and diminished glycine cleavage activity in liver tissue. A series of therapeutic trials, including strychnine treatment, was tried on this patient without apparent effect on the clinical course.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

Studies on glutaryl-CoA dehydrogenase in leucocytes, fibroblasts and amniotic fluid cells. The normal enzyme and the mutant form in patients with glutaric aciduria.

Three patients with glutaric aciduria have been shown to possess a partial but severe defect of the enzyme glutaryl-CoA dehydrogenase in isolated leucocytes and cultured skin fibroblasts. They could readily be distinguished from heterozygotes by measuring the activity of this enzyme, as shown in a study of the two families involved. The activity of glutaryl-CoA dehydrogenase in normal cultured amniotic fluid cells was comparable to the activity in normal cultured skin fibroblasts indicating the possibility of prenatal diagnosis. Without flavin adenine dinucleotide added to the assay mixture, the activity of glutaryl-CoA dehydrogenase in fibroblasts from normal individuals was very much reduced and similar to the activity in the patients, but after addition of flavin adenine dinucleotide to saturation the activity increased 20-fold in normal subjects while only a very slight increase could be demonstrated in the patients. The Michaelis constant for the substrate glutaryl-CoA was similar for both normal and patient cell lines. The optimum assay conditions for the enzyme in cultured fibroblasts from normal individuals have been established. In contrast to our patients, we found no activity in a fibroblast cell line from a patient with glutaric aciduria diagnosed elsewhere.

Amniotic Fluid↗
PubMed1978

Prenatal and postnatal diagnostic difficulties in a family with rare alleles of the galactose-1-phosphate uridyl transferase locus.

Whole-blood galactose-1-phosphate uridyl transferase (Gal-PUT) (EC 2.7.7.12) activity was absent in a newborn boy with galactosaemic symptoms. The symptoms disappeared on a galactose free diet. In the next pregnancy prenatal diagnosis was performed. Gal-PUT activity was measured by isotope technique and Gal-PUT genotype was determined by gel electrophoresis. The mother was shown to be heterozygous Duarte/heterozygous Los Angeles, the father heterozygous Duarte/heterozygous galactosaemia. The fetus had the same genotype as the father. A normal girl without galactosaemic symptoms was born. Reinvestigation of the index case showed that he was also heterozygous Duarte/heterozygous galactosaemia. It is concluded that the activity of Gal-PUT should always be measured by isotope technique to prove the diagnosis of heteditary galactosaemia. Furthermore, Gal-PUT-genotyping in families with rare alleles is essential for safe prenatal diagnosis.

Alleles↗
PubMed1978

Stimulation of amniotic fluid cells by fibroblast growth factor.

Amniotic fluid cells were grown in modified Dulbecco's medium with and without the following additives in different combinations: fibroblast growth factor (FGF), dexamethasone (DME), insulin and cyclic GMP under controlled conditions. Experiments were also conducted with varying amounts of foetal calf serum and FGF to establish optimum levels. Comparative growth, determined by measuring 3H-thymidine uptake, showed that the combination of FGF, DME and insulin in medium with 20% foetal calf serum produced the highest growth rate. These experiments indicate that the culture time of amniotic fluid cells for chromosome studies could be reduced by 25%. FGF did not have any deleterious effect on the chromosomes.

Amniotic Fluid↗