Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy.

The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of [2H] glucosamine and [35S] sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of [3H] glucosamine into HA, CS + DS, and HS and [35S] sulfate into CS + DS and HS were not significantly different between the three groups.

Tetrahydrobiopterin and Parkinson's disease.

Two patients with Parkinson's disease were treated with 1 g tetrahydrobiopterin (BH4) for 5 days. Clinical improvement was not observed. In the cerebrospinal fluid (CSF) a 4-8 fold increase in the concentration of homovanillic acid (HVA), and a 3-fold increase in the concentration of 5-hydroxyindole acetic acid (5-HIAA) was measured.

Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine.

Seven phenylketonuria (PKU) patients aged 15-24 years were allowed unrestricted diet for 3 weeks. Three of these patients performed well on unrestricted diet according to visual reaction time variability (RTv 50-100 ms) and did not show significant changes when returning to the phenylalanine-restricted diet (RTv 70-100 ms). Neither did the concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) change significantly.

Increased vigilance and dopamine synthesis by large doses of tyrosine or phenylalanine restriction in phenylketonuria.

In a group of 9 patients with classical phenylketonuria (PKU) aged 15-24 years we examined the effect of phenylalanine restricted diet on vigilance, as judged by the continuous visual reaction times, and neurotransmitter synthesis, as judged by cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) levels. HVA and 5-HIAA levels decreased significantly with increase in plasma phenylalanine concentration on free diet (p less than 0.01 and p less than 0.