Continuous spectrophotometric assay of human lysosomal cathepsin A/protective protein in normal and galactosialidosis cells.

We describe a method to determine the substrate specificity of human lysosomal carboxypeptidase, cathepsin A/protective protein, using furylacryloyl (FA)-Phe-X dipeptides as substrates. These dipeptides contain a chromophore which allows continuous spectrophotometric assay at wavelengths above 324 nm with little interference from protein absorbance. The results obtained with cathepsin A purified from human placenta demonstrate that the enzyme has the highest affinity for substrates with large hydrophobic (Phe, Leu) or positively charged (Arg) amino acid residues in P1' position. The three substrates (FA-Phe-Phe, FA-Phe-Leu, and FA-Phe-Ala) which demonstrated the highest specificity (kcat/Km) for the purified enzyme were then used to assay cathepsin A activity in cultured skin fibroblasts from patients affected with galactosialidosis, an inherited lysosomal storage disease caused by the genetic deficiency of cathepsin A. Residual cathepsin A activity in galactosialidosis fibroblasts was lower than 6% of controls, indicating the high specificity of the assay method.

Potential gains in life expectancy of Kuwaiti nationals through partial and complete elimination of infectious and parasitic disease mortality.

This study attempts to estimate potential gains in life expectancy in 1984 through partial and complete elimination of infectious and parasitic diseases among Kuwaiti nationals. For deriving these estimates, a multiple decrement life table approach was applied. The results of the study show that complete elimination of infectious and parasitic disease mortality would further add 0.45 years to the life expectancy at birth of Kuwaiti males and 0.54 yr to that of Kuwaiti females. A partial reduction by 50% would result in gains of just one-half of the years gained through complete elimination of these causes. Also, as partial reduction is increased from 10% to 90%, the gains in life expectancy at birth would go up from 0.04 yr to 0.40 yr in the case of Kuwaiti males and 0.06 to 0.48 yr for Kuwaiti females.