Free amino acid pattern of cerebrospinal fluid in amyotrophic lateral sclerosis.

The concentrations of 23 amino acids (AA) were measured in CSF of patients with Amyotrophic Lateral Sclerosis (ALS). A micro-method with picomole sensitivity was used. Compared with healthy controls no significant alterations of single or total AA concentrations were found. These results contrast with data published in a previous study and will be discussed in detail.

Free amino acid pattern of cerebrospinal fluid in meningeal pathology.

Free amino acid concentrations of CSF were measured in bacterial meningitis, aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth, multiple sclerosis, carcinomatous meningitis, and controls. Almost all CSF amino acids were highly elevated in bacterial but not in aseptic meningitis, meningoradiculitis Garin-Bujadoux-Bannwarth or carcinomatous meningitis thus providing a laboratory tool for their differential diagnosis. In carcinomatous meningitis the amino acid pattern indicates metabolic activity of tumor cells. Minimal alterations were found in multiple sclerosis which have no diagnostic value.

Lysosomal protein degradation in experimental hyperphenylalaninaemia.

The influence of alpha-methylphenylalanine-induced hyperphenylalaninaemia (HYP) on the lysosomal protein degradation system in brain and liver of suckling rats was investigated. In both tissues cathepsin D and L activities, measured at 5, 10 and 15 days post partum (p.p.), exhibited no differences between experimental and control animals. N-Acetyl-beta-D-glucosaminidase (NAGase) activity in brain, measured at 10 and 15 days p.p., was not affected by HYP either. The release of valine and lysine from liver and brain homogenates respectively, serving as a measure for the lysosomal content of degradable proteins, was not influenced by HYP. Lysosomal integrity during incubation of homogenate was monitored by the recovery of NAGase activity in the cytosolic supernatant, and by the relative NAGase activity in total homogenates in the absence of the lysosome disrupting detergent Triton X-100. In conclusion, experimental HYP appears unlikely to influence the lysosomal protein degradation system in brain and liver of suckling rats.

On the role of branched-chain amino acids in protein turnover of skeletal muscle. Studies in vivo with L-norleucine.

The effect of L-norleucine, an isomer of leucine, on protein metabolism in vivo was studied in suckling rats. Rats were injected subcutaneously with various doses of L-norleucine (0.5 and 5.0 mumol/g body wt.) every 12 h from 3 to 15 days post partum. Protein concentration, amino acid concentrations, and incorporation of [3H]tyrosine into protein were analyzed in liver, muscles of thigh and small intestine. Amino acid concentrations and insulin levels in serum were also measured. At 5 days of age, norleucine induced an increase in protein concentration of skeletal muscle with an increased incorporation of [3H]tyrosine into protein indicating an accelerated protein synthesis. Changes in protein metabolism were paralleled by alterations in the amino acid pattern of this tissue. When protein concentration and protein synthesis were increased in skeletal muscle, protein concentration of small intestine was decreased, accompanied by elevated levels of amino acids in tissue. Protein synthesis of small intestine was not altered by the norleucine treatment. The results suggest a close interrelationship between skeletal muscle and small intestine with respect to protein turnover. The effects of norleucine were less pronounced at 10 and 15 days of age, which indicates a metabolic adaptation to the treatment. Alterations in amino acid concentrations of tissue due to changes in protein metabolism were not uniform but tissue-specific. Current concepts for explaining the effects of branched-chain amino acids (BCAA) on protein turnover in skeletal muscle are based on the assumption that the BCAA or leucine alone might become rate-limiting for protein synthesis in muscle under catabolic conditions. The amino acid analogue norleucine, however, cannot replace any of the BCAA in protein. Additionally, norleucine affected protein metabolism in highly anabolic organisms. Therefore, the present thoughts on this issue appear to be incomplete.

[Studies on the effect of the neurolathyrogenic substance beta,beta'-iminodipropionitrile on the branchiopode Artemia salina (author's transl)]. / Untersuchungen über die Wirkung der "neurolathyrogenen" Substanz beta,beta'-Iminodipropionitril auf den Salzkrebs Artermia salina.

beta,beta'-Iminodipropionitrile (IDPN) is a neurotoxic substance, which induces choreiform movements for life in rats and mice. As for the phenotype this seems to be a suitable animal model for the comparison with Huntington's chorea in man. In our experiments we have tested the effect of IDPN on different developmental stages of the branchiopode artermia salina. One-day old nauplii show the strongest reaction to the substance. As little as 10(-5) g IDPN/l culture medium induces in one-day old nauplii a characteristically altered swimming behavior. This behavioral response of the one-day old nauplii may possibly serve as a basis for a simple qualitative biological assay for the detection of IDPN or its effective metabolite, respectively.