Human salivary arginase and its deficiency in argininaemia.

Arginase from normal human mixed saliva was characterized. The enzyme was completely activated after a preincubation of 20 min at 55 degrees C and a Mn2+ final concentration of 5 mmol/l. The pH optimum was 9.

[CNS tumors with the clinical picture of meningitis].

Incidentally CNS tumours may simulate acute bacterial or viral meningitis, cerebral abscess, and tuberculous or luetic basal meningitis. 64 cases from the literature are analysed together with 2 personal observations. This form of presentation is found most frequently in high-grade malignancy, i.

[Congenital hypophosphatasia].

Hypophosphatasia represents an inborn enzymatic deficiency characterized by a reduced activity of alkaline phosphatase in serum and tissue and an increased urinary excretion of phosphoethanolamine. 278 cases have been described until the end of 1980. Based on the age of manifestation and the predominant clinical findings the following classification is possible: The prenatal form (49 cases) with caput membranaceum, skeletal deformities and respiratory distress has a mortality of 100%.

Hyperargininemia: the rat as a model for the human disease and the comparative response to enzyme replacement therapy with free arginase and arginase-loaded erythrocytes in vivo.

Rat erythrocytes lack arginase as do the erythrocytes of human homozygote patients with hyperargininemia due to arginase deficiency. The rat has physiological liver arginase activity and plasma arginine and ornithine levels between the homozygotes and the heterozygotes with hyperargininemia. In rats, one injection of free arginase induces a transient exogenous arginase effect which is abolished after 24 hr.

Measurement of arginine transport in human erythrocytes using their intrinsic arginase activity: implications for the treatment of familial hyperargininemia.

A procedure making use of the intracellular arginase activity has been developed for measuring the transport of arginine across the human erythrocyte membrane. (1) The arginine translocation is carrier mediated with simple Michaelis-Menten kinetics, showing one high affinity, low capacity transport system characterized by a half saturation constant KT of 0.177 +/- 0.

Isolation and identification of 2-oxo-5-guanidinovaleric acid in urine of patients with hyperargininaemia by chromatography and gas chromatography/mass spectrometry.

An unknown guanidino-positive peak has been identified in urines of three sisters affected with hyperargininaemia. Identification was made on the basis of its similarity with the liquid and thin-layer chromatographic characteristics of enzymatically synthesized 2-oxo-5-guanidinovaleric acid. Identification was also made by combined gas chromatography-mass spectrometry of the unknown compound peak.

Excretion of alpha-keto-delta-guanidinovaleric acid and its cyclic form in patients with hyperargininemia.

alpha-Keto-delta-guanidinovaleric acid, in equilibrium with its cyclic form, has been identified in the urines of three sisters affected with hyperargininemia. Identification was achieved on the basis of its similarity with the enzymatically synthesized compounds.

Arginase and free amino acids in hyperargininemia: leukocyte arginine as a diagnostic parameter for heterozygotes.

Arginase activity and free amino acids were measured in plasma, erythrocytes and leukocytes of patients with hyperargininemia and in controls. There is no arginase activity in the leukocytes and erythrocytes of homozygous patients; in heterozygotes it is normal to low. The activity is 50 to 100 times higher in leukocytes than in erythrocytes.

Acute bone marrow necrosis caused by streptococcal infection.

An 8 year old boy with a furuncle on the dorsum of the right foot, high fever, severe pain in the right knee joint, slight hepatosplenomegaly, leukopenia and thrombocytopenia was admitted with the working diagnosis of acute leukemia. However, an abundance of necrotic cells, together with clusters of streptococci, could be demonstrated in the bone marrow aspirate. After antibiotic therapy the boy recovered completely.

[Non-leukemic disease of the central nervous system in children with acute lymphoblastic leukemia. III. Subacute sclerosing panencephalitis (author's transl)].

Diseases of the central nervous system (CNS) occurring during treatment of acute lymphoblastic leukemia (ALL) may be of leukemic or nonleukemic origin. Well known examples for CNS disease of nonleukemic origin are somnolence following prophylactic CNS irradiation, methotrexate-induced encephalopathy and acute infections caused by bacteria, viruses and toxoplasma gondii. Less known is the fact that also subacute CNS infections may occur in patients undergoing cytostatic therapy.

[Non-leukemic disease of the central nervous system in children with acute lymphoblastic leukemia. I. Somnolence syndrome (author's transl)].

Prophylactic irradiation of the skull and intrathecal application of methotrexate has proven to be highly effective in preventing central nervous system disease in acute lymphoblastic leukemia or non-Hodgkin-lymphoma. Prophylactic treatment may be complicated by a somnolence syndrome occuring 4--8 weaks after the end of irradiation. The main features of this clinical entity are somnolence, lethargy, dullness, anorexia, headache, and vomiting.

Extracerebrospinal metastases in glioblastoma. Case report and review of the literature.

A malignant glioblastoma adherent to the dura mater was removed from the parieto-occipital lobe in a 12-year-old boy. The site of the tumor was subsequently irridiated by 4000 rads of Cobalt-60. Five months later the boy was readmitted complaining of pains in the pelvis an in both thighs.

Intravenous loading with arginine-hydrochloride and ornithine-aspartate in siblings of two families, presenting a familial neurological syndrome associated with cystinuria.

1. Arginine-hydrochloride and ornithine-aspartate solutions have been infused intravenously to children of two families. Three children of the WOL.

Use of enzyme-loaded erythrocytes in in-vitro correction of arginase-deficient erythrocytes in familial hyperargininemia.

The capacity of arginase-deficient erythrocytes of patients with familial hyperargininemia to produce urea and to catabolize arginine can be increased in vitro by introducing human liver arginase into their erythrocytes. The results of this study on a specific human model show that it is possible to change the metabolic function of a genetically defective erythrocyte by incorporating exogenous human enzyme. The in vivo application of enzyme-loaded erythrocytes for enzyme replacement therapy of inborn metabolic errors in humans must await in vivo studies on animal models.

Excretion of guanidino-derivates in urine of hyperargininemic patients.

Quantitative determinations were made for seven guanidino-derivates in urine of patients affected with hyperargininemia, lysine cystinuria, healthy children and adults, goats and monkey. The amount of all seven guanidino-derivates excreted in the urine with the exception of guanidino-succinic acid was large in the case of hyperargininemic patients. Guanidino-succinic acid is found in traces in the urine of these patients, even after arginine loading tests.

Familial hyperargininaemia.

A third case of hyperargininaemia occurring in one family was studied from birth. In cord blood serum arginine concentration was only slightly raised, but arginase activity in red blood cell haemolysates was very low. In the urine on day 2 a typical cystinuria pattern was present.

[The "juvenile" type of chronic myelogenous leukemia (author's transl)].

The juvenile type of chronic myelogenous leukemia (CML) is characterized by hemorrhagic diathesis, hepatosplenomegaly, generalized enlargement of lymph nodes, reduced erythro- and thrombopoiesis, leukemic infiltration of bone marrow, and decreased activity of leukocyte alkaline phosphatase. The disorder differs from the adult type by the early manifestation of anemia and thrombocytopenia, the minor degree of leucocytosis, the failure to demonstrate the Philadelphia chromosome, and the presence of fetal markers in the patients' erythrocytes. The persistence of fetal markers in erythrocytes and the clinical manifestation in infancy and early childhood suggest that the disease is congenital in origin.

Unsuccessful trial of gene replacement in arginase deficiency.

The Shope virus following cutaneous inoculation produces skin papillomas in rabbits and induces a virus-coded arginase in the squameous epithelium of these papillomas. The only discernible effect of the virus inoculated intravenously in rabbits and other animals was a decrease of the serum arginine concentration. Intravenous injection in 3 hyperargininemic patients, however, did not influence the underlying metabolic disease.

Induction of arginase activity with the Shope papilloma virus in tissue culture cells from an argininemic patient.

Inoculation of the Shope virus in tissue cultures of human fibroblasts from a patient with a deficiency of the enzyme arginase results in an induction of arginase activity, apparently virus coded.