Conserved exon-intron organization in two different caerulein precursor genes of Xenopus laevis. Additional detection of an exon potentially coding for a new peptide

From a genomic library of Xenopus laevis, two genes coding for different preprocaeruleins have been isolated and sequenced. These correspond to the type I and type III precursors analyzed previously at the cDNA level [Richter, K., Egger, R. and Kreil, G. (1986) J. Biol. Chem. 261, 3676-3680]. The type III gene comprises eight exons; the type I apparently contains eight exons as well, of which six have been sequenced. The genetic information for the dekapeptide caerulein is present on small exons of 45 base pairs. The two genes are highly homologous in their 5'-flanking region, the exon/intron boundaries, and long stretches of intron sequences. A possible scheme for the evolution of this small family of genes through exon and gene duplications is presented. In the type I gene, in place of one of the caerulein exons, a potential exon with conserved splice sites was discovered. If expressed in some frog cells, this exon would code for a new peptide 60% homologous to caerulein.     

The analysis of the joint effect of substances on reversion systems and the assessment of antimutagenicity.

The statistical methods for the analysis of mutagenicity and carcinogenicity underwent considerable theoretical-practical development following the need for assessing the mutagenic and carcinogenic potential of substances. Antimutagenicity is investigated through the analysis of respondents in dose-response assays, when two different molecules are administered separately and as a mixture to a respondent system. When the number of respondent units is high, and doses are orthogonal, it is possible to apply simple models such as analysis of variance. This is not always possible or common, and alternative approaches have been developed, based on multiple regression and on tables of proportions. In this work, some of the most frequently used methods for the assessment of joint responses are reviewed, particularly those based on multiple regression, such as the method of Shaeffer et al. and the method of Hass et al. In order to illustrate these methods, joint responses of perylene and cyclopentapyrene, of N-acetylcysteine and dinitropyrene, and of N-acetylcysteine and extracts from diesel exhausts were analyzed. An antagonistic effect of perylene on the action of CPP was detected by the algorithm of Shaeffer et al. The effect is not multiplicative, i.e., it is not proportional to the product of doses. The antimutagenic effect of N-acetylcysteine on dinitropyrene is multiplicative, as detected by the method of Hass et al. The latter reveals that the inhibition by N-acetylcysteine on the mutagenic effect of extracts from diesel exhausts is also multiplicative.     

The wrong way to think about gene conversion?

Summary The sex circle model for crossing over and gene conversion proposed by Stahl has a number of properties which are in conflict with a considerable body of recombination data in fungi. The model is unable to explain the observed frequencies of gene conversion and postmeiotic segregation for particular mutants in several species. It does not provide an explanation for fine structure map expansion, nor does it account satisfactorily for the polarised distribution of outside markers amongst allelic recombinants.     

Endogenous CD8+ T cell expansion during regression of monoclonal EBV-associated posttransplant lymphoproliferative disorder.

There are experimental data which suggest that the primary immune effector cell responsible for maintaining immune surveillance against the outgrowth of EBV-transformed B cells in humans is the CTL, but in vivo proof of this is lacking. In this study we perform a series of cellular and molecular assays to characterize an autologous, endogenous immune response against a transplantation-associated, monoclonal, EBV+ posttransplant lymphoproliferative disorder (PTLD). Following allogeneic bone marrow transplantation, a patient developed a monoclonal PTLD of donor B cell origin. With a decrease in immune suppression, we document the emergence of endogenous, donor-derived CD3+CD8+ CTLs, followed by regression of the PTLD. The TCR Vbeta repertoire went from a polyclonal pattern prior to the development of PTLD to a restricted TCR Vbeta pattern during the outgrowth and regression of PTLD. Donor-derived CD3+CD8+ T lymphocytes displayed MHC class I-restricted cytolytic activity against the autologous EBV+ B cells ex vivo without additional in vitro sensitization. The striking temporal relationship between the endogenous expansion of a TCR Vbeta-restricted, CD3+CD8+ population of MHC class I-restricted CTL, and the regression of an autologous monoclonal PTLD, provides direct evidence in humans that endogenous CD3+CD8+ CTLs can be responsible for effective immune surveillance against malignant transformation of EBV+ B cells.