PubMed HealthSearch

Biomedical subjects

R C Richmond

Publications and source records attributed to R C Richmond.

14 recordsLinked to original sources

Studies of esterase 6 in Drosophila melanogaster. I. The genetics of a posttranslational modification.

A locus has been found, an allele of which causes a modification of some allozymes of the enzyme esterase 6 in Drosophila melanogaster. There are two alleles of this locus, one of which is dominant to the other and results in increased electrophoretic mobility of affected allozymes. The locus responsible has been mapped to 3-56.7 on the standard genetic map (Est-6 is at 3-36.8). Of 13 other enzyme systems analyzed, only leucine aminopeptidase is affected by the modifier locus. Neuraminidase incubations of homogenates altered the electrophoretic mobility of esterase 6 allozymes, but the mobility differences found are not large enough to conclude that esterase 6 is sialylated.

Alleles

Genetic basis of aristal morphology in Drosophila melanogaster and its correlation with behavior: selection for increased and decreased aristal branching.

The aristae of Drosophila have been shown to play a role in mating behavior and geotaxis. Two populations of D. melanogaster were selected for increased and decreased numbers of major aristal branches. Selection was successful and resulted in two lines differing by an average of six aristal branches. Hybridization analyses of selected lines revealed that genes influencing aristal branching are located on both the X chromosome and the autosomes. Polygenic control of aristal morphology is indicated by a gradual response to selection and low realized heritabilities. When selection was relaxed for 19 generations, the number of aristal branches did not revert to the number in the control line. Changes in aristal branching did not appear to have a consistent influence on geotaxis, although there was a tendency for flies with fewer aristal branches to be geonegative. Neither mating speed nor ethological isolation between the two populations was affected by selection. It is concluded that the number of aristal branches in Drosophila is a neutral trait (i.e., not subject to natural selection) under laboratory conditions. Correlations between aristal morphology and behavior found in other selection experiments by previous investigators were likely due to linkage disequilibria.

Animals

Oviposition site preference in Drosophila.

Comparative studies of oviposition site preference (OSP) in Drosophila suggest that choice of oviposition site is an important adaptive behavior which influences individual fitness and the potential of populations for speciation. OSP has been investigated under conditions which provided females with a choice of standard medium or medium containing ethanol for oviposition. OSP is an extremely labile behavior in the laboratory, but a technique has been developed which minimizes variation between replicates and allows the detection of OPS differences between semispecies of a single species. An analysis of the OSP of 14 Drosophila species shows that this behavior is not correlated with phylogenetic relationships. OSP with respect to ethanol may be correlated with the presence of ethanol in the environment and the activity of alcohol dehydrogenase in the species tested.

Animals

Studies of esterase-6 in Drosophila melanogaster. II. The genetics and frequency distributions of naturally occurring variants studied by electrophoretic and heat stability criteria.

Measurements of the electrophoretic mobility and thermostability of esterase-6 allozymes have been used to determine the amount of allelic variation at the esterase-6 locus in Drosophila melanogaster. We studied 398 homozygous lines obtained from four natural populations. Use of a spectrophotometric assay for esterase-6 activity has allowed precise quantitation of heat-stability variants. Using these methods, eight putative alleles were detected within the two most common electrophoretic classes. Analyses of F1 and F2 progeny show that the behavior of stability variants is consistent with the hypothesis that this variation is due to allelic variation at the Est-6 locus. Analyses of the gene-frequency distributions within and between populations show (1) that observed allele-frequency distributions do not deviate significantly from those expected for neutral variants, and (2) that there is little evidence for an increase in apparent divergence of the different populations at the genotypic or phenotypic levels when the additional variation detected is considered. These findings suggest that gene-frequency analysis alone is unlikely to resolve the question of the selective significance of allozyme variation.

Alleles

Effect of radiation on cis-dichlorodiammineplatinum (II) and DNA in aqueous solution.

The radiolysis of cis-dichlorodiammineplatinum (II) (cis-PDD) was studied in order to better understand the mechanisms by which it acts as a radiation sensitizer. The Pt(I) intermediate formed by e- aq reduction of cis-PDD loses both chlorides rapidly, interacts with O2 to form a Pt-oxygen adduct, reacts with the hydroxyl radical adduct of thymine and the peroxy radical of t-butanol, and disproportionates to platinum metal and trans-PDD. The Pt (III) intermediate formed by OH oxidation of cis-PDD likely disproportionates to cis-PDD and Pt(IV) complexes. In a biological model, radiation-induced 3H-thymine base residue release from DNA is found to be inhibited by cis-PDD.

Cisplatin

Platinum complexes as radiosensitizers of hypoxic mammalian cells.

Cis-dichlorodiammineplatinum (II), or cis-PDD, has recently been shown to be a potent radiosensitizer of bacteria, particularly under conditions of acute hypoxia. This study extends this observation to include the radiosensitization of mammalian cell (V-79) by low concentrations of cis-PDD, cis-dichlorobis(aziridine) platinum (II), and the trans-isomer of PDD as measured from survival curve analysis. This radiosensitization was obtained at concentrations of 10 micrometer, 60 micrometer, and 100 micrometer for the cis-PDD, aziridine-platinum, and trans-isomer respectively. The corresponding drug toxicity survival levels were 8, 40 and 50%. Dose modification factors of around 1.3 to 1.4 were observed.

Aziridines

Platinum levels and clinical responses of tumours treated by cisplatin with and without concurrent hyperthermia: a case study.

The heterogeneity of platinum distributed within tissue after clinical administration of cisplatin was evaluated for the first time. Platinum levels were correlated with the observed clinical responses of separate superficial histiocytic sarcomas located in the forearm of a 74-year-old male patient. One of four lesions received four weekly treatments with hyperthermia administered concurrently with 30 mg/m2 cisplatin, while three lesions were treated with cisplatin alone. The lesion receiving hyperthermia concurrently with cisplatin had a solid partial response during a 6-week period following this therapy, whereas two other tumours receiving cisplatin alone progressed. One lesion could not be clinically evaluated. Platinum levels were determined in multiple samplings from three of the four lesions and normal tissue in order to evaluate the validity of taking a single tumour sample of 100 mg or less for the analysis of platinum content. Such a small single sample might provide a value significantly different from the true average because of sampling error. The range in platinum distribution encompassed an average of three-fold difference within eight separate sample groups, with a factor of six being the greatest difference in a single sample group. This degree of heterogeneity is great enough to suggest that conclusions made from the analysis of small and single random tissue samples could be sufficiently in error to misdirect investigative or medical decisions.

Aged