The biochemical features of two families with purine nucleoside phosphorylase deficiency are compared. Laboratory studies and an evaluation of kinetic and physical properties of erythrocyte purine nucleoside phosphorylase give evidence that a) the degree of abnormality in uric acid and nucleoside concentrations in plasma and urine reflect the severity of the enzymatic deficiency and b) structural alterations of the mutant enzymes result from structural gene mutations and demonstrate genetic heterogeneity in the disease purine nucleoside phosphorylase deficiency.Purine nucleotide degradation is an intricately regulated enzymatic sequence. The relevance of these enzyme reactions to clinical disorders of immune function was first noted when adenosine deaminase deficiency was found associated with combined B-and T-cell dysfunction (1). The observations that purine nucleoside phosphorylase deficiency occurs with cellular immune dysfunction (2-8) and ecto-5'-nucleotidase Submitted for publication November 2, 1978; accepted January 9, 1979. deficiency occurs with agammaglobulinemia (9) further emphasized this relationship.Purine nucleoside phosphorylase is an integral part of the nucleotide degradation pathway. A deficiency of this enzyme blocks this reaction sequence and results in an immune disorder (2-8). The enzyme deficiency and the concomitant clinical syndrome may result from structural gene mutations (10,ll). We have examined the clinical features and biochemical properties of the enzyme from 3 patients in two families with purine nucleoside phosphorylase deficiency. The data indicate that the laboratory changes observed in the patients reflect the degree of enzyme deficiency and that altered properties of the deficient enzymes provide evidence for a structural gene alteration and genetic heterogeneity in the disease purine nucleoside phosphorylase deficiency.
Purine and pyrimidine metabolism was compared in erythrocytes from three patients from two families with purine nucleoside phosphorylase deficiency and T-cell immunodeficiency, one heterozygote subject for this enzyme deficiency, one patient with a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase, and two normal subjects. The erythrocytes from the heterozygote subject were indistinguishable from the normal erythrocytes. The purine nucleoside phosphorylase deficient erythrocytes had a block in the conversion of inosine to hypoxanthine. The erythrocytes with 0.07% of normal purine nucleoside phosphorylase activity resembled erythrocytes with hypoxanthine-guanine phosphoribosyltransferase deficiency by having an elevated intracellular concentration of PP-ribose-P, increased synthesis of PP-ribose-P, and an elevated rate of carbon dioxide release from orotic acid during its conversion to UMP. Two hypotheses to account for the associated immunodeficiency--that the enzyme deficiency leads to a block of PP-ribose-P synthesis or inhibition of pyrimidine synthesis--could not be supported by observations in erythrocytes from both enzyme-deficient families.
In 1989, the authors surveyed all general psychiatry residency programs to assess the availability, extent, and emphasis of administrative teaching currently being offered during residency training. With a return rate of 74.5%, the results reveal that 69.5% of the respondents presently include administrative training within their curricula and 56% offer didactic teaching about administrative issues. These results are compared with a similar survey performed 10 years previously in which 85% of the respondents reported offering some administrative training but only 39% offered didactic instruction in this area. An analysis of these data and a review of proposed curricula for training in administration are provided.
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