Selective induction of human heat shock gene transcription by the adenovirus E1A gene products, including the 12S E1A product.

We have previously shown that the human 70-kilodalton heat shock protein gene (hsp70) is induced by the adenovirus E1A gene product and during the S-G2 phase of the cell cycle. In this study, we investigated the effect of E1A on the expression of other human hsp genes. A gene encoding one form of the hsp89 protein (hsp89 alpha) was activated during an adenovirus infection with kinetics similar to those of activation of hsp70. The induction required a functional E1A gene. However, the hsp89 transcript was not cell cycle regulated. Genes encoding another form of hsp89 and the hsp27 protein were not induced by E1A or during the cell cycle. Further examination of hsp70 expression revealed a greater complexity than previously seen. S1 nuclease analysis using an hsp70 cDNA as well as a distinct hsp70 genomic clone demonstrated three related hsp70 transcripts; two were induced by E1A, and one was not. Both of the E1A-inducible genes were regulated during the cell cycle. All three were induced by heat shock. These results suggest common aspects of control among certain members of this family of cellular genes distinct from heat shock control. Finally, using viruses that express the individual E1A proteins, we found that the hsp70 gene is induced by the 12S and the 13S E1A products. The efficiency of induction by the 12S product was somewhat less than that by the 13S product but only by a factor of less than 2. This is in contrast to the induction of early viral genes, for which the 13S product is considerably more efficient than the 12S product.

An iron-containing superoxide dismutase in Tritrichomonas foetus.

Dialysed extracts of Tritrichomonas foetus were found to have superoxide dismutase at substantially higher levels than those found in trypanosomatids and mouse red blood cells. The activity was sensitive to inhibition by H2O2 but not by cyanide, suggesting that this organism has iron-containing superoxide dismutase(s). Three isozymes were seen by isoelectric focusing which appeared to be sensitive to inhibition by H2O2.

Trypanosomatid iron-superoxide dismutase inhibitors. Selectivity and mechanism of N1,N6-bis(2,3-dihydroxybenzoyl)-1,6-diaminohexane.

Crithidia, like trypanosomes and leishmania, has an iron-containing superoxide dismutase. The iron chelator N1,N6-bis (dihydroxybenzoyl)-1,6-diaminohexane proved to be a potent inhibitor of this enzyme. Inhibition of the crithidial superoxide dismutase by this compound was dependent on the presence of oxygen and associated with the formation of a complex which could not be dissociated by gel-filtration chromatography. We propose that this biscatecholic inhibitor is first oxidized to a quinone which then covalently modifies a nucleophilic residue on the enzyme. This compound was less effective as an inhibitor of a mammalian copper- and zinc-containing superoxide dismutase. Thus, this inhibitor could serve as a prototype for the design of antiparasitic agents.

Iron-containing superoxide dismutase from Crithidia fasciculata. Purification, characterization, and similarity to Leishmanial and trypanosomal enzymes.

Leishmania tropica, Trypanosoma brucei, Trypanosoma cruzi, and Crithidia fasciculata have superoxide dismutases which are insensitive to cyanide and sensitive to peroxide and azide, properties characteristic of iron-containing superoxide dismutase. Studies on the superoxide dismutase of C. fasciculata have revealed that: 1) the enzyme is located in the cytosol; 2) isozymes exist; 3) the major superoxide dismutase isozyme (superoxide dismutase 2) has Mr approximately equal to 43,000 and consists of two equal-sized subunits, each of which contains 1.4 atoms of iron. Comparisons of the amino acid content of this crithidial superoxide dismutase with those of superoxide dismutases from other sources suggests that the crithidial enzyme is closely related to bacterial Fe-containing superoxide dismutases, and only distantly related to human Mn- and Cu,Zn-containing superoxide dismutases and to Euglena Fe-containing superoxide dismutase. Attempts are now underway to develop specific inhibitors of the trypanosomatid superoxide dismutase which may be of use in the treatment of leishmaniasis or trypanosomiasis.

A longitudinal study of moral and ego development in young adults.

The purpose of this study was to investigate the longitudinal changes in moral judgment and ego development in a young adult sample when a concurrent measure of verbal ability was used as a statistical control. Sixty-one late adolescents and young adults, representing three educational groups, were tested in 1977 and 1979 on the Defining Issues Tests, a measure of moral judgment (Rest), the Sentence Completion Test of Ego Development (Loevinger and Wessler) and Terman's Concept Mastery Test, a measure of verbal ability. No group or time differences were found in ego development. A significant increase was found between the 1977 and 1979 moral judgment scores,p<0.05, and between groups at both testing,p<0.001. Sex differences were found,p<0.01, with females scoring higher than males, which were statistically accounted for by verbal ability. These findings suggest that moral development continues into the young adult years and that verbal ability may moderate sex differences in moral judgment.