The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

Aims: To clarify the underlying causes of corneal opacification in Tangier disease.

Methods: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry.

Results: Membranous inclusions in the stroma were seen on transmission electron microscopy.

Lesch-Nyhan syndrome and its pathogenesis: normal nicotinamide-adenine dinucleotide but reduced ATP concentrations that correlate with reduced poly(ADP-ribose) synthetase activity in HPRT-deficient lymphoblasts.

In hypoxanthine (guanine) phosphoribosyltransferase- (HPRT; EC 2.4.2.

The pathogenesis of the Lesch-Nyhan syndrome: ATP use is positively related to hypoxanthine supply to hypoxanthine guanine phosphoribosyltransferase.

In order to explain features of severe hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency, the Lesch-Nyhan syndrome, a continuous supply of substrate, hypoxanthine, for the enzyme must be generated. This supply must be increased in association with increased ATP turnover. We have shown that ATP turnover continuously supplies hypoxanthine for recycling by the enzyme HPRT and that this supply increases curvilinearly with increasing ATP turnover.

Hypoxanthine phosphoribosyltransferase activity in tissues and hypoxanthine concentrations in plasma and CSF of the horse in comparison with other species.

1. Plasma hypoxanthine and xanthine concentrations are very low in the horse and low in rat, mouse and greyhound compared to concentrations in beagles, man, sheep and rabbit. 2.

Cerebrospinal fluid nucleotide metabolites following non-convulsive status epilepticus.

The authors studied specific and sensitive indicators of neuronal adenosine triphosphate (ATP) depletion--hypoxanthine, xanthine and uridine levels--in the cerebrospinal fluid (CSF) of nine children during non-convulsive status epilepticus. No evidence of ATP depletion was found and CSF pH and creatine kinase levels were similar to those of controls. Hypoxanthine, xanthine and uridine had a tendency to be low, but this was significant only for xanthine.

Cerebrospinal fluid nucleotide metabolites following short febrile convulsions.

Cerebrospinal fluid (CSF) markers of cerebral energy depletion were measured in 32 infants and children following short (less than 10 minutes) febrile convulsions, and in 19 controls. Specific and sensitive indices of high-energy phosphate compound depletion (hypoxanthine, xanthine and uridine) showed no marked changes. Values for patients and febrile controls were significantly higher than for afebrile controls, which is consistent with increased cerebral metabolism in febrile patients.

Lesch-Nyhan syndrome and its pathogenesis: purine concentrations in plasma and urine with metabolite profiles in CSF.

Purine metabolism in the Lesch-Nyhan syndrome has been re-examined in 10 patients. Hypoxanthine and xanthine concentrations in plasma and CSF and urinary excretion have been studied, on and off allopurinol treatment, using high performance liquid chromatographic methods. Accumulation of the substrate, hypoxanthine, of the missing hypoxanthine guanine phosphoribosyltransferase (HPRT) enzyme, is more marked in urine and in CSF than in plasma.

The metabolism of high intakes of tryptophan, nicotinamide and nicotinic acid in the rat.

1. The metabolic fate of high dietary intakes of nicotinamide, nicotinic acid and tryptophan, and of acute doses of nicotinamide and nicotinic acid, has been studied in the rat. A new high-pressure liquid chromatography method for measurement of the principal urinary metabolites of niacin is described.

Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts.

A new hereditary defect of tryptophan metabolism is described in a Sudanese family with a high degree of consanguinity. It has an autosomal recessive pattern of inheritance. The condition manifests as a pellagra-like skin rash within 8 weeks after birth, with signs of cerebellar ataxia and developmental retardation.

The role of catabolism in controlling tissue concentrations of nicotinamide nucleotide coenzymes.

A previous report from this laboratory (Bender, D.A., Magboul, B.

The preferred route of kynurenine metabolism in the rat.

It has been suggested (Ueda, T., Otsuka, H. and Goda, K.