Mapping the active-site tyrosine of vaccinia virus DNA topoisomerase I.

Site-directed mutagenesis of the vaccinia virus gene encoding a type I DNA topoisomerase implicates Tyr-274 as the active-site residue that forms a covalent adduct with DNA during cycles of DNA-strand breakage and reunion. Replacement of Tyr-274 by phenylalanine results in loss of the ability of the enzyme to relax negatively supercoiled DNA as well as to form the covalent DNA-protein intermediate. Substitution of phenylalanine for tyrosine at nine other sites in the protein has no apparent effect on enzyme activity. Amino acid sequence alignment reveals Tyr-274 to be homologous to Tyr-727 and Tyr-771, respectively, of the type I topoisomerases from Saccharomyces cerevisiae and Saccharomyces pombe; Tyr-727 and Tyr-771 have been shown to represent the active-site tyrosines of those enzymes. Sequence comparison of the active-site regions defines a motif Ser-Lys-Xaa-Xaa-Tyr common to the viral and cellular type I topoisomerases, including the human enzyme.     

Primary hyperparathyroidism and monoclonal gammopathy

Coexistent primary hyperparathyroidism and monoclonal gammopathy, although rare, has been reported previously by a number of investigators. We report four patients with such an occurrence who were seen between 1976 and 1988. Another patient with primary hyperparathyroidism also had multiple myeloma and was in remission for 12 years. These patients represent approximately 1% of the 386 patients with primary hyperparathyroidism seen during the same 12-year period. Although several mechanisms have been proposed to explain this concurrence, we believe it is the result of a chance occurrence. A review of the literature, an estimate of the chance occurrence of coincidental monoclonal gammopathy, benign or malignant, in patients with primary hyperparathyroidism, and some practical implications of this interesting coexistence are presented.     

Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis.

BACKGROUND AND OBJECTIVE: The adverse effects of untreated seasonal allergic rhinitis (AR) on performance in the workplace, school, and home are poorly understood. To delineate more clearly the impact and consequences of the disease on performance, the effect of symptomatic AR on vigilance and a wide range of cognitive functions was investigated. METHODS: A battery of automated neuropsychological tests was administered to asymptomatic adult subjects with histories of AR. Subjects were randomized to either a symptomatic or to an asymptomatic group. Subjects in the symptomatic group were exposed to ragweed pollen in a controlled exposure setting until they demonstrated predetermined severities of AR symptoms. Subjects in the asymptomatic group were not exposed to ragweed pollen in the environmental unit and retained a minimum symptom profile. The battery of cognitive measures was re-administered to both groups. RESULTS: AR had major adverse impacts on measures of vigilance. Further, AR adversely affected a broad range of cognitive functions. Specifically, subjects with AR symptoms demonstrated longer response times and decreased efficiency on measures of working memory, psychomotor speed, reasoning/computation, and divided attention as compared with asymptomatic subjects. CONCLUSIONS: In addition to decreased vigilance, AR was associated with decrements in speed and efficiency across several cognitive domains. This is similar to findings in research on medications and medical conditions that cause sedation. Findings may represent a link between AR and poor productivity/personal safety among AR sufferers. This suggests that these results have implications with regard to public health.