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Biomedical subjects

R D Snyder

Publications and source records attributed to R D Snyder.

At least 91 records · Page 5Linked to original sources
PubMed1982

Studies on the inhibition of repair of ultraviolet- and methyl methanesulfonate-induced damage in the DNA of human fibroblasts by novobiocin.

The antibiotic novobiocin is shown to alter the sedimentation properties of human cellular DNA in alkaline sucrose. This alteration is at least partially due to increased DNA-protein binding in the cell in the presence of novobiocin. Pyrimidine dimer analysis and repair replication studies support previous reports that novobiocin inhibits repair of UV damage in human cells but we find this block to be shortlived. It is also shown that novobiocin is ineffective at blocking "long-patch" repair induced by methyl methanesulfonate as measured both by CsCl density centrifugation and the ara-C inhibition technique. However, the accumulation of breaks in MMS-treated cellular DNA in the presence of novobiocin suggests that some "short-patch" alkylation repair may be inhibited by the antibiotic. These findings are discussed in light of the proposal that novobiocin may inhibit a DNA gyrase-like activity in human as in bacterial cells.

Cell Line↗
PubMed1982

Differential responses of log and stationary phase human fibroblasts to inhibition of DNA repair by aphidicolin.

The tetracyclic diterpenoid, aphidicolin, is an effective inhibitor of DNA repair in human cells following ultraviolet irradiation. This inhibition is very efficient in confluent resting cells but not in rapidly cycling cells as measured by (1) analysis of DNA single-strand breaks by alkaline sucrose sedimentation, (2) chromatographic analysis of pyrimidine-dimer removal, and (3) repair replication using CsCl density centrifugation. The inhibition is reversed by deoxycytidine or thymidine but not by deoxyadenosine or deoxyguanosine during the repair period. The data suggest that differences in deoxynucleoside triphosphate pools between cycling and confluent resting cells determine the different efficacies of the agent in these two situations.

Aphidicolin↗
PubMed1982

Drug trial of superoxide dismutase in Duchenne's muscular dystrophy.

A multicenter, randomized, double-blind, placebo-controlled drug trial in Duchenne's muscular dystrophy, evaluating a superoxide dismutase in 51 ambulatory patients for 18 months was conducted. Fourteen aspects of muscle strength and five of functional ability, as well as serum creatine phosphokinase (CPK) level were studied. The total change in strength, function, and CPK level did not differ significantly in the two groups. The testing method used was reliable in assessing the natural history of Duchenne's dystrophy and would, therefore, be useful in future multicenter drug trials.

Child, Preschool↗
PubMed1982

Mutagen sensitivity of Drosophila melanogaster. V. Identification of second chromosomal mutagen sensitive strains.

Six recessive second chromosomal mutants of Drosophila melanogaster exhibiting larval hypersensitivity to methyl methanesulfonate have been identified and assigned to six complementation groups. The strains have been analyzed for their sensitivities to UV, X-ray, nitrogen mustard and formaldehyde. Two classes of mutants not previously observed in Drosophila have been identified. The mus 204A1 and mus 205A1 mutants exhibit sensitivity to MMS and UV but not X-ray or nitrogen mustard, while the mus 206A1 and mus 207A1 mutants display sensitivity to MMS, UV, and nitrogen mustard. Four of the seven strains exhibit poor female fertility and two of these are shown to have a weak meiotic disjunctional defect. Biochemical studies of the mus 205A1 mutant suggest a defect in DNA synthetic ability associated with excision and postreplication repair performed on UV and alkylation-damaged templates (Boyd and Harris 1981; Brown and Boyd 1981 b; R.L. Dusenbery, manuscript in preparation).

Animals↗
PubMed1982

DNA repair in normal human and xeroderma pigmentosum group A fibroblasts following treatment with various methanesulfonates and the demonstration of a long-patch (u.v.-like) repair component.

Excision repair of DNA in normal and xeroderma pigmentosum complementation group A fibroblasts were examined following treatment with methyl-, ethyl-, and isopropyl methanesulfonate. Studies utilizing repair synthesis methods and inhibition with arabinofuranosyl cytosine revealed two distinct phases of repair; one commencing and terminating within the first 3-5 h after the treatment, and a second much longer phase extending from 9-35 h post-treatment. Both phases of repair have a long-patch (u.v.-like) component, which establishes for the first time the existence of this mode of repair in response to alkane sulfonate damage. While xeroderma cells display somewhat fewer alkaline labile sites in their DNA following alkylation treatment than do their normal counterparts (consistent with earlier observations suggesting a deficiency in a glycosylase or apurinic endonuclease), we are unable to demonstrate a deficiency of these cells in either of the two phases of repair.

Alkylating Agents↗
PubMed1982

Identification of a second locus in Drosophila melanogaster required for excision repair.

The mus(2)201 locus in Drosophila is defined by two mutant alleles that render homozygous larvae hypersensitive to mutagens. Both alleles confer strong in vivo somatic sensitivity to treatment by methyl methanesulfonate, nitrogen mustard and ultraviolet radiation but only weak hypersensitivity to X-irradiation. Unlike the excision-defective mei-9 mutants identified in previous studies, the mus(2)201 mutants do not affect female fertility and do not appear to influence recombination proficiency or chromosome segregation in female meiocytes.--Three independent biochemical assays reveal that cell cultures derived from embryos homozygous for the mus(2)D1 allele are devoid of detectable excision repair. 1. Such cells quantitatively retain pyrimidine dimers in their DNA for 24 hr following UV exposure. 2. No measurable unscheduled DNA synthesis is induced in mutant cultures by UV treatment. 3. Single-strand DNA breaks, which are associated with normal excision repair after treatment with either UV or N-acetoxy-N-acetyl-2-aminofluorene, are much reduced in these cultures. Mutant cells possess a normal capacity for postreplication repair and the repair of single-strand breaks induced by X-rays.

Alleles↗
PubMed1981

Combination therapy for advanced malignant melanoma with BCNU, pseudomonas vaccine, and heparin.

A study was undertaken to investigate the addition of heparin and pseudomonas vaccine to BCNU in the treatment of patients with progressive malignant melanoma refractory to front-line therapeutic regimens containing DTIC. Out of 27 evaluable patients, there was one partial remission (4%), and an additional ten patients (41%) had at least stable disease with a median survival time of 39 weeks compared to 15 weeks for those with progressive disease. The therapy was well tolerated. A schedule of pseudomonas vaccine that seemed to be tolerated has been established.

Adult↗
PubMed1981

Classification of chemical agents as to their ability to induce long- or short-patch DNA repair in human cells.

33 chemical agents and UV- and gamma-irradiation were tested for their comparative ability to induce long-patch or short-patch repair using the 5-bromodeoxy-uridine photolysis assay. For 11 chemical agents repair was long-patch in nature as determined by calculated patch size and response of xeroderma pigmentosum cells relative to normal human cells. Typical patch sizes as measured by this assay were about 90 nucleotides for UV repair, a range of 30 to 70 nucleotides for a variety of known and suspected UV-mimetic chemicals, and 3-4 nucleotides for gamma-radiation. Alkylating agents previously shown to induce short-patch repair were shown also to induce long-patch repair.

Cell Line↗
PubMed1981

Application of arabinofuranosyl cytosine in the kinetic analysis and quantitation of DNA repair in human cells after ultraviolet irradiation.

We have developed a technique whereby 3-h pulses of arabinofuranosyl cytosine (ara-C) and hydroxyurea (HU) are used to analyze the kinetics of repair with time after ultraviolet irradiation in human fibroblasts. We demonstrate that this technique offers a significant improvement over existing repair assays in its ability to visualize between 57 and 100% of all sites undergoing repair in a given period of time. In addition, kinetic analyses of repair are more easily made and yield more information than techniques such as repair replication or unscheduled DNA synthesis. We have also examined the nature of the inhibition event by ara-C and have determined that repair breaks accumulate in the presence of ara-C and HU only up to a certain time beyond which no further breaks appear. The time needed to reach this saturation point depends on the number of sites undergoing repair during the treatment time. This observation is discussed with respect to a possible mechanism of excision repair inhibition by ara-C and HU.

Cells, Cultured↗
PubMed1981

Suppressors of mutations in the rII gene of bacteriophage T4 affect promoter utilization.

Homyk, Rodriguez and Weil (1976) have described T4 mutants, called sip, that partially suppress the inability of T4rII mutants to grow in lambda lysogens. We have found that mutants sip1 and sip2 are resistant to folate analogs and overproduce FH2 reductase. The results of recombination and complementation studies indicate that sip mutations are in the mot gene. Like other mot mutations (Mattson, Richardson and Goodin 1974; Chace and Hall 1975; Sauerbier, Hercules and Hall 1976), the sip2 mutation affects the expression of many genes and appears to affect promoter utilization. The mot gene function is not required for T4 growth on most hosts, but we have found that it is required for good growth on E. coli CTr5X. Homyk, Rodriguez and Weil (1976) also described L mutations that reverse the effects of sip mutations. L2 decreases the folate analog resistant and the inability of sip2 to grow on CTr5X. L2 itself is partially resistant to a folate analog, and appears to reverse the effects of sip2 on gene expression. These results suggest that L2 affects another regulatory gene related to the mot gene.

Gene Expression Regulation↗
PubMed1981

Cerebral infarction in childhood bacterial meningitis.

Forty-nine children with complicated bacterial meningitis were studied. Thirteen had abnormalities on computed tomography compatible with the diagnosis of brain infarction; one had a brain biopsy with the histological appearance of infarction. Factors exist in childhood bacterial meningitis which are associated with the development of brain infraction.

Biopsy↗