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Biomedical subjects

R Waters

Publications and source records attributed to R Waters.

At least 91 records · Page 5Linked to original sources
PubMed1983

N-methyl-N'-nitro-N-nitrosoguanidine induced genetic change during the meiotic cell cycle in Saccharomyces cerevisiae: an absence of S-phase specificity.

In the yeast Saccharomyces cerevisiae enhanced nuclear mutagenesis was found during meiotic DNA synthesis after treatment with N-methyl-N'-nitrosoguanidine (MNNG), but not during meiotic DNA synthesis. Further experiments found no significant variation in the mol. wt. of DNA from control or MNNG-treated samples during meiosis after alkaline sucrose gradient analysis. Using tritiated MNNG no variation in uptake of MNNG by meiotic cells was found, but enhanced binding of label from [3H]MNNG to mitochondrial DNA was detected during meiotic DNA synthesis when mitochondrial DNA synthesis occurred. In contrast, no enhanced binding of label from [3H]MNNG to the nuclear DNA during meiotic DNA synthesis was found.

DNA Replication↗
PubMed1983

Double-blind evaluation of plasmapheresis in schizophrenic patients: a pilot study.

Interest in the effects and possible mechanisms of hemodialysis on schizophrenic patients has led to a double-blind evaluation of the effects of plasmapheresis on symptoms of schizophrenia. Also, plasmapheresis was felt to be an invaluable tool for investigating the autoimmune theory of schizophrenia. Patients (n = 10) in the study fulfilled Research Diagnostic Criteria for schizophrenia and were randomly assigned to either sham or active plasmapheresis. They were blindly assessed by staff psychiatrists and nurses. Evaluation of the behavioral ratings revealed no significant decrease in psychosis for either the active or sham group. Also, no individual responding patient was identified. This finding complements our group's early negative results of a hemodialysis experiment and casts doubt on a simple autoimmune hypothesis of schizophrenia.

Adolescent↗
PubMed1982

The inhibition of DNA repair by aphidicolin or cytosine arabinoside in X-irradiated normal and xeroderma pigmentosum fibroblasts.

Normal and excision-deficient xeroderma pigmentosum fibroblasts were X-irradiated and the influence on DNA repair of either the repair inhibitor cytosine arabinoside or the specific inhibitor of Dna polymerase alpha, aphidicolin, investigated. The data indicated that the repair of a certain fraction of X-ray-induced lesions can be inhibited in both cell lines by both compounds. Thus, as aphidicolin blocks the operation of polymerase alpha, this enzyme must be involved in an excision repair pathway operating in both normal and excision-deficient xeroderma pigmentosum cells.

Aphidicolin↗
PubMed1982

Excision repair in Cockayne syndrome.

Cockayne syndrome (CS) is a genetic disorder showing cellular sensitivity to the lethal effects of UV-irradiation. No defects in unscheduled DNA synthesis or in daughter-strand repair have been detected after UV-irradiation of CS cells. We have studied several aspects of excision repair, particularly at early times after UV-irradiation, and with one exception, we have not been able to detect any difference in the response of normal and CS cells to UV-irradiation, by measuring: (1) the rate of formation of incision breaks in the presence of 1-beta-D-arabinofuranosylcytosine (araC); (2) the amount of repair replication as measured by equilibrium centrifugation; (3) the ligation of repaired DNA to pre-existing DNA; (4) the digestibility of repaired DNA after treatment of nuclei with micrococcal nuclease. The single exception was a pair of CS strains from sibling donors in which the rate of uncoupled incision due to the presence of either araC or the specific inhibitor of DNA polymerase alpha, aphidicolin, was slightly faster than in other cells studied. This effect was absent in the heterozygous parents. However, since this was not seen in two other CS strains in the same genetic complementation group, we can not attribute this increased rate of incision to the defective CS gene. We conclude that, within the limits of resolution of these techniques, CS cells do not have a detectable defect in excision repair.

Cells, Cultured↗
PubMed1982

The use of a yeast strain with a temperature-sensitive DNA ligase to estimate DNA repair after exposure to mutagens.

The yeast strain cdc9 which possesses a temperature-sensitive DNA ligase, was used to estimate DNA repair after mutagen exposure. Following low UV fluences, single-strand breaks in DNA were detected after an incubation at the restrictive temperature but were absent at the permissive temperature. These DNA breaks were shown to be equal to the number of pyrimidine dimers induced in DNA as measured by the presence of UV-endonuclease sensitive sites. Similarly, after exposure to the chemical mutagen 4-chloromethyl-biphenyl (4CMB) single-strand breaks accumulated at the restrictive temperature. Hence the technique described should be applicable for the estimation of the early steps of repair of a wide range of different types of DNA damage induced in yeast by exposure to either physical or chemical mutagens.

DNA Ligases↗
PubMed1982

3-Aminobenzamide, an inhibitor of poly ADP-ribose polymerase, decreases the frequency of alkaline labile lesions and increases growth in human fibroblasts exposed to 3-methyl 4-nitroquinoline 1-oxide.

Normal human fibroblasts exposed to the mutagen 3-methyl 4-nitroquinoline 1-oxide (3me4NQO) were additionally incubated with or without the inhibitor of poly ADP-ribose polymerase, 3 aminobenzamide (3AB) either during or after mutagen treatment. The number of single strand DNA breaks detectable by alkaline sucrose sedimentation at any given time after exposure to this mutagen was reduced by the prior addition of 3AB, regardless of whether this drug was present during or after mutagen exposure. Furthermore, this effect is reversible upon 3AB removal. Finally, cell survival as analysed by cell growth was increased if cells were treated for one hour with 3AB directly following a 30 min exposure to 3-me4NQO. The data presented suggest an additional role for poly ADP ribose polymerase in DNA repair other than that of inhibiting the increase in ligase II, which occurs after exposure to monofunctional alkylating agents.

4-Nitroquinoline-1-oxide↗
PubMed1981

DNA damage and its repair in human normal or xeroderma pigmentosum fibroblasts treated with 4-nitroquinoline 1-oxide or its 3-methyl derivative.

Normal human or excision deficient xeroderma pigmentosum (XP) fibroblasts were exposed to either the potent carcinogen 4-nitroquinoline 1-oxide (4NQO) or the weaker acting 3 methyl derivative of this compound. The inhibition of cell growth, DNA damage and DNA repair were then monitored in these cells. The data indicate that the modification of 4NQO by methylation actually changes the type and amount of DNA damage induced by this carcinogen. More specifically, the methylation of 4NQO at the three position prevented the formation of 4NQO induced DNA adducts manifesting themselves as alkaline stable lesions whose repair was cytosine arabinoside inhibitable in normal cells, but defective in excision deficient XP cells. Alkaline labile lesions induced by 4NQO which are repairable in the above XP cells were still induced by the 3 methyl derivative but a lower frequency on an equimolar basis.

4-Nitroquinoline-1-oxide↗
PubMed1981

Aphidicolin: an inhibitor of DNA repair in human fibroblasts.

Aphidicolin is a specific inhibitor of DNA polymerase alpha. Its influence of DNA repair has been studied in both normal and excision deficient xeroderma pigmentosum cells exposed to u.v. irradiation at 254 nm. Single strand DNA breaks accumulated in u.v. irradiated normal cells when the inhibitor was present. Such breaks were absent in both unirradiated normal cells and in u.v. irradiated excision efficient cells incubated with the compound. The data therefore indicate that aphidicolin prevents the rejoining of single strand breaks formed during the excision repair process and imply that DNA polymerase alpha is involved in the repair of DNA in human cells.

Aphidicolin↗
PubMed1980

Repair of human DNA in molecules that replicate or remain unreplicated following ultraviolet irradiation.

The extent of DNA replication, the incidence of UV induced pyrimidine dimers and the repair replication observed after their excision was monitored in human fibroblasts UV irradiated with single or split UV doses. The excision repair processes were measured in molecules that remained unreplicated or in those that replicated after the latter UV irradiation. Less DNA replication was observed after a split as opposed to single UV irradiation. Furthermore, a split dose did not modify the excision parameters measured after a single irradiation, regardless of whether the DNA had replicated or not.

DNA↗
PubMed1980

Walking and wheelchair energetics in persons with paraplegia.

The energetics of walking with orthoses and wheelchair propulsion at free velocity were tested in 10 adults with low-level spinal cord injuries. Eight were subjects who customarily used wheelchairs as their primary mode of locomotion; the other two used orthoses and had discontinued use of their wheelchairs. All required bilateral knee-ankle-foot orthoses to walk. A third habitual walker also was tested during walking only. Patients walked or propelled their wheelchairs around a 60.5-meter outdoor cement track. Heart rate, respiratory rate, and step frequency were recorded and transmitted by radiotelemetry. Expired air was collected for gas analysis in a polyethylene bag during the activity after a three-minute warm-up. During wheelchair propulsion all subjects demonstrated physiological responses within normal limits. Walking was significantly more difficult to perform than wheelchair propulsion (p < .005). Subjects who customarily used orthoses walked at a mean velocity of 59 +/- 5 m/min; those who primarily used wheelchairs had a mean walking velocity of 22 +/- 13 m/min. Oxygen uptake per minute was similar for both groups. These data suggest that the wheelchair will be the primary mode of locomotion for persons with spinal cord injury who need two knee-ankle-foot orthoses to walk, unless they are willing to work under anaerobic conditions and can walk at a velocity of 54 m/min or better.

Adult↗
PubMed1979

Energy cost of walking of below-knee amputees having no vascular disease.

Fifteen unilateral below-knee amputees with no preexisting vascular disease were studied during free velocity walking to determine energy expenditure with and without a prosthesis. Expired air was collected, and heart rate and respiratory rate data were telemetered. Mean velocity for the unrestrained walking was 71 m/min, both during ambulation with a prosthesis and during crutch walking (without a prosthesis). Heart rates were within normal ranges during prosthetic walking (106 beats/min), but rose significantly to 135 beats/min for crutch walking. Energy cost also rose significantly from a mean of 15.5 ml O2/kg/min with a prosthesis of 22.3 ml O2/kg/min with crutches. The oxygen uptake measured in units of ml O2/kg/m increased when the subjects walked faster or slower than their free cadence. We concluded that the use of the prosthesis should be encouraged and that the amputee should be allowed to choose his natural velocity of walking.

Adult↗
PubMed1979

Overlapping pathways for repair of damage from ultraviolet light and chemical carcinogens in human fibroblasts.

DNA excision repair was measured in cultured human fibroblasts after single or dual treatments with ultraviolet radiation, 4-nitroquinoline 1-oxide, or N-acetoxy-2-acetylaminofluorene. Three approaches were used to monitor repair: unscheduled DNA synthesis, measured by autoradiography; repair replication, measured by the incorporation of a density-labeled DNA precursor into repaired regions; and excision of ultraviolet endonuclease-sensitive sites. When a single repair- saturating dose of one of the three carcinogens was administered, little stimulation of unscheduled DNA synthesis or repair replication could be observed by additional treatment with one of the other carcinogens. In no instance was total additivity of repair observed. These observations were confirmed by showing that the excision of endonuclease-sensitive sites produced by ultraviolet damage (i.e., pyrimidine dimers) was inhibited by exposure to 4-nitroquinoline 1-oxide and N-acetoxy-2-acetylaminofluorene. The data indicate that the repair of lesions induced by these substances may have common rate-limiting steps, a conclusion previously indicated by the repair deficiency in xeroderma pigmentosum cells in which a single mutation eliminates the repair of damage caused by each of these agents.

4-Nitroquinoline-1-oxide↗
PubMed1978

Postreplication repair of DNA in human fibroblasts after UV irradiation or treatment with metabolites of benzo(a)pyrene.

We have examined the ability of normal fibroblasts and of excision-deficient xeroderma pigmentosum (XP) and XP variant fibroblasts to perform postreplication DNA repair after increasing doses of either ultraviolet (UV) irradiation or mutagenic benzo(a)pyrene derivatives. XP cells defective in the excision of both UV-induced pyrimidine dimers and guanine adducts induced by treatment with the 7,8-diol-9,10-epoxides of benzo(a)pyrene were partially defective in their ability to synthesize high molecular weight DNA after the induction of both classes of DNA lesions. This defect was more marked in XP variant cells, despite their ability to remove by excision repair both pyrimidine dimers and the diol epoxide-induced lesions to the same degree as observed in normal cells. The benzo(a)pyrene 9,10-oxide had no effect in any of the 3 cell lines. The response of the excision and postreplication DNA repair mechanisms operating in human fibroblasts treated with benzo(a)pyrene 7,8-diol-9,10-epoxides, therefore, appears to resemble closely that seen after the induction of pyrimidine dimers by UV irradiation.

Benzopyrenes↗
PubMed1978

Pyrimidine dimer excision in human cells and skin cancer.

We compared three methods for estimating the induction and removal of UV-induced pyrimidine dimers from the DNA of human fibroblasts. Results indicate that after UV doses of 5-20 J/m2, 50% of the dimers are removed by 24 hours. Almost complete excision can be observed if the cells are incubated for periods not less than 72 hours after a dose of 5 J/m2. After higher doses, it probably takes even longer for such complete removal to doses, it probably takes even longer for such complete removal to be seen.

Animals↗
PubMed1977

Partial inhibition of postreplication repair and enhanced frequency of chemical transformation in rat cells infected with leukemia virus.

Postreplication repair of DNA and chemical transformation with the carcinogen 4-nitroquinoline-1-oxide were studied in rat cell lines either uninfected or infected with Rauscher leukemia virus. The results indicate that equivalent amounts of carcinogen are bound to the DNA initially and removed during excision repair. However, the lines differ in that the infected line alone exhibits both sensitivity to nitroquinoline-oxide-induced transformation and a partial inhibition of the postreplication repair process after notroquinoline oxide or UV treatment.

4-Nitroquinoline-1-oxide↗
PubMed1977

Influence of floor surface on the energy cost of wheelchair propulsion.

Carpeting of the type commonly used in hospitals imposed a burden upon normal and patient wheelchair users propelling a wheelchair as reflected in increased energy cost per unit of distance traveled. Wheelchair propulsion also tended to produce high heart rates compared to values reported for normal walking. Pneumatic tires offered no advantage over hard rubber tires on the type of carpet used in this study. Wheelchair propulsion required more energy expenditure per minute than values reported for normal ambulation at the same velocity.

Adult↗