SUMMARY There is a defect in tetrahydrobiopterin metabolism in brains from subjects with senile dementia of Alzheimer type compared to age-matched controls. This defect results in lowered total biopterin concentrations in brain. Brains from subjects with senile dementia of Alzheimer type retain their ability to synthesis neopterin and have normal dihydropteridine reductase activity, indicating a specific loss of ability to convert dihydroneopterin triphosphate to tetrahydrobiopterin.The synthesis of dopamine and noradrenaline in the brain is dependent upon the activity of tyrosine hydroxylase, and this in tum is regulated by the concentration of the hydroxylase cofactor, 5,6, 7, Protein was measured by the biuret method. Each brain sample was assayed for dihydropteridine reductase, BH4 synthesis activity, total neopterin and total biopterin.

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Sixteen patients with chronic idiopathic urticaria were skin tested with their own serum, IO with autologous plasma and five with serum that had been heated to 56 degrees C to inactivate complement. Eight showed a weal and flare response to whole serum, four to plasma and five to heat-treated serum. All serum-positive patients showed the same response to their own plasma and to heated serum, indicating that the mediator concerned is not generated by clotting and is not dependent on a functioning complement pathway. Three control subjects were negative to autologous serum, plasma and heated serum. Local tachyphylaxis was demonstrated in five serum-positive patients on reinjection of the same site with autologous serum on 3 consecutive days. This raises the possibility that the serological mediator may be acting by mast cell degranulation or directly on receptors in blood vessels and that repeated injections could induce a change in the number of receptors. Passage of whole autologous serum from four serum-positive patients through ultrafiltration membranes showed that fractions with a molecular weight of less than 30,000 daltons were still able to produce a positive skin test response, but those less than 1000 daltons were not. All serum fractions from two serum-negative patients and three normal controls were negative. Whole autologous serum from five serum-positive patients and two control subjects were separated by column chromatography. On skin testing with pooled fractions, the greatest response was produced by fractions of 10,000-15,000 daltons in the serum-positive patients, but there was no response in the controls.

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