5-Hydroxymethyluracil excretion, plasma tbars and plasma antioxidant vitamins in adriamycin-treated patients

The thymine oxidative lesion-5-hydroxymethyluracil (HMUra)—was measured in urine collected from cancer patients. These patients all received chemotherapy using Adriamycin. Adriamycin (ADR) intercalates DNA coils and interferes with normal cell metabolism through diverse biochemical mechanisms that may explain its different actions. The anticancer action of ADR could derive from its interaction with topoisomerase II, resulting in DNA nicking followed by DNA fragmentation and apoptosis. Side effects of ADR—mainly its cardiotoxicity—may derive from the fact that ADR generates superoxide and hydroxyl radicals in two ways: redox-cycling and a Haber-Weiss type reaction due to Fe-ADR complexes. The oxygen free radicals, particularly 'OH, are thought to be produced by ADR directly in genomic material and attack all its components. 5-Hydroxymethyluracil is a thymine lesion provoked by these attacks, and it has been proposed as a marker of DNA alterations. In this article, we report the results of a study involving 14 cancer patients treated with ADR. We found that urine HMUra is significantly increased by the anticancer therapy (HMUra (nmol/24 h): 74.4 9.46 vs. 96.3 8.74; p < .01), this increase reveals a higher risk of mutagenesis. Our study is the first to show an in vivo alteration of DNA by ADR. Results also show that thiobarbituric acid reactants increase significantly, and that the vitamin levels for retinol and a-tocopherol, which are antioxidant vitamins, are lower at the end of chemotherapy. We suggest to supplement these patients with vitamins A and E, and selenium to reduce the side effects of ADR.     

Temperature-dependent gonadal differentiation in the turtle Emys orbicularis: concordance between sexual phenotype and serological H-Y antigen expression at threshold temperature

As in many other turtles, the sexual differentiation of gonads in embryos of Emys orbicularis is temperature-sensitive, 100% phenotypic males being obtained below 27.5 degrees C and 100% phenotypic females above 29.5 degrees C. The expression of the serologically defined H-Y (SD-H-Y) antigen at both low and high temperatures has been shown to be different in gonads and in blood : in gonads, it is closely associated with ovarian structure, whereas in blood it is independent of sexual phenotype and appears to indicate sexual genotype. Both sexes differentiate at 28.5 degrees C, suggesting that at this intermediate (threshold) temperature, sexual differentiation of gonads conforms with sexual genotype. To test this hypothesis, the expression of SD-H-Y antigen has been carried out in blood cells of Emys individuals raised from eggs incubated at the threshold temperature (28.5 degrees C). All phenotypic males typed SD-H-Y negative, whereas most phenotypic females typed SD-H-Y positive. From this concordance between sexual phenotype of gonads and SD-H-Y phenotype of blood, we postulate that a ZZ male/ZW female mechanism of genotypic sex determination is revealed at the threshold temperature for gonad differentiation in Emys.     

Genetic analysis of uxuR and exuR genes: evidence for ExuR and UxuR monomer repressors interactions

Summary The uxuAB operon is under the dual control of uxuR- and exuR-encoded repressors whereas the exu regulon genes are regulated by the sole ExuR repressor. Mutations affecting the two exuR and uxuR regulatory genes were selected to investigate the relationship between the two repressors. The isolation of exuR and uxuR negative dominant mutations on a multicopy plasmid indicated that the active form of the two repressors was multimeric.The introduction of a uxuR negative dominant allele into a wild-type strain resulted in a significant increase in exu gene expression. This unexpected effect may have been the consequence of the formation of hybrid repressor molecules. This protein must be composed of native ExuR⁺ subunits aggregated with altered UxuR subunits. The same interference was observed for the exuR negative dominant allele on uxu gene derepression. The hypothesis given here implies that the two regions of the ExuR and UxuR repressors involved in the subunit aggregation present enough homologies to allow the formation of hybrid repressor molecules.     

Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus

 By the use of a newly developed technique of ultrathin-layer electrophoresis, class I and class II alcohol dehydrogenase activity could be demonstrated in microdissected samples of the periportal, intermediate, and perivenous zones of the liver acinus in men and women. It could be demonstrated that both classes exhibit low activity in the periportal zone. From there, a rising gradient in the direction of the perivenous end was apparent. This increase, however, was found to be significant only in women. The analysis of class I alcohol dehydrogenase isoenzymes showed that the expression of α-, β-, and γ-containing isoforms did not differ in relation to the intraacinar position. The constant proportions of the isoenzymes to the maxima and minima of the total alcohol dehydrogenase activity support the view that the adult liver-specific isoenzyme pattern is determined during postnatal development. Accepted: 1 February 1999     

Increased tritiated thymidine-labeling index of bone marrow myeloblasts following BCG administration in man

Summary The in vitro (³H)thymidine-labeling index of bone marrow myeloblasts was determined in eight hematologically normal individuals before and after the administration of Bacillus Calmette-Guérin twice weekly for 2 weeks. The mean labeling indexes of myeloblasts were 30.5 and 45.2% respectively (P<0.004).Further characterization of this stimulation of proliferation of bone marrow myeloblasts could provide some rationale for combining cytotoxic drugs and immunotherapy in cancer patients.The present work was supported by the Fonds Cancérologique de la Caisse Générale d'Epargne et de Retraite de Belgique and by Euratom Grant No. 161-76-1. B 10B and by the NCI Grant No. 2R 10CA 11488-07     

The distribution and abundance of boring species of polychaetes and sipunculans in coral substrates in French Polynesia

The distribution and abundance of the dominant initial macroborers of dead coral substrate, sipunculans and polychaetes were investigated over time at seven sites within French Polynesia. Sites were located in the lagoon of high islands and atolls, and varied from highly eutrophic to oligotrophic. Significant differences occurred between sites and patterns of recruitment varied over time and between sites. With increasing exposure, the densities of polychaetes increased but not the number of species present, whereas both the densities and number of species of sipunculans increased. The atoll sites tended to be dominated by suspension feeding polychaetes and the high island sites by deposit feeding polychaetes. Sipunculans tended to dominate the high island sites in comparison to the atoll sites and they all fed by scraping algae and detritus from the substrate. We suggest that this distribution of feeding types is related to water quality and to land run off. In the atolls, the lagoonal waters are oligotrophic and little land run off occurs, whereas at the high island sites, high rates of land run off occur during the wet season with high levels of suspended material in the water column.These variations in densities of boring species, affect rates of bioerosion and have the potential to alter the equilibrium between reef growth and reef destruction. We suggest that it is critical for reef managers to try to maintain water quality and limit land-based terrestrial run off and associated nutrients into coastal waters. This is especially important if the reefs have been affected by bleaching events or Crown of Thorns plagues, resulting in extensive death of coral colonies and with it, the potential for a massive increase in the rate of bioerosion. The long-term maintenance of the reef structure is critical if coral recruitment and recovery of the reef are to occur.     

The immunolysis,isolation, and properties of subpopulations of mammalian brain synaptosomes

Five subpopulations of mammalian brain synaptosomes can be selectively damaged by complement-mediated immunolysis employing antibodies to specific surface markers for each subpopulation. This allows the size of these subpopulations to be estimated. Employing antibodies alone, it has proved possible to isolate three of these subpopulations in very pure preparations which are metabolically viable. The immunoaffinity technique involved (immunomagnetophoresis) uses magnetic microspheres and produces mg (protein) quantities of synaptosomes.Special issue dedicated to Dr. Elling Kvamme.     

Absence congenitale des canaux deferents: Phenotype genital de la mucoviscidose?

Because spermatogenesis is typically normal in men with bilateral agenesis of the vas deferens, epididymal sperm recovery for subsequent use in in-vitro fertilization (IVF) has recently been proposed for such patients. The discovery of the presence of mutations in the cystic fibrosis gene in such patients has indicated that this disease might constitute a genital phenotypie concomitant of cystic fibrosis, and has profound genetic implications if the spouse is heterozygous. Testing for mutations of the cystic fibrosis gene, and the provision of genetic counselling as appropriate, should be performed in patients, and their partners, when IVF is being considered for such couples presenting with infertility. The main characteristics of the cystic fibrosis gene and its mutations are discussed, with particular reference to problems in identifying mutations among the 27 exons encoding the gene’s product