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Biomedical subjects

R Waters

Publications and source records attributed to R Waters.

At least 19 recordsLinked to original sources
PubMed1992

The repair of large DNA adducts in mammalian cells.

This paper describes experiments involving the measurement of DNA damage and repair after treatment with 4-nitroquinoline 1-oxide (4NQO) or aflatoxin B1 (AFB1) epoxide in a number of mammalian cell cultures primarily associated with defects in the excision repair of UV-induced DNA damage. The results with transformed derivatives of XP cells belonging to different complementation groups showed that the extent of repair of 4NQO adducts at the N2 or C8 of guanosine did not correlate to the extent of repair reported by others after UV-irradiation. An examination of 4NQO repair in rodent UV-sensitive cell lines from different ERCC groups indicated that again there was little correlation between the extent of 4NQO and UV repair. However, regardless of complementation group those mutants that were defective in the repair of pyrimidine dimers and 6,4-photoproducts did exhibit a reduced ability to repair the 4NQO N2 guanosine adduct, whereas those mutants defective in pyrimidine dimer repair alone were able to repair this lesion as normal. In all of these cell lines there was a normal capacity to repair the 4NQO C8 guanosine adduct. Less extensive experiments involving AFB1 epoxide showed an XPC-transformed cell line was able to repair 40% of lesions after 6 h, whereas only 20% of repair is seen after UV. The rodent mutant V-C4 which belongs to the same ionising radiation group as irs2, was partially defective in repairing AFB1-induced damage. These experiments highlight the fact that although there are many commonalities between the repair of UV damages and lesions classed as large DNA adducts differences clearly exist, the most striking example here being the repair of the C8 guanosine 4NQO adduct which rarely correlates with a defect in UV repair.

4-Nitroquinoline-1-oxide↗
PubMed1992

Sensitivity and single-strand DNA break repair in Chinese hamster mutants exposed to the carcinogen aflatoxin B1 epoxide and its dichloride model.

Aflatoxin B1 (AFB1) is a potent carcinogen and mutagen. It requires metabolic activation to be converted to the DNA-binding product aflatoxin B1 epoxide (AFB1-epoxide). A model of this epoxide is aflatoxin B1 dichloride (AFB1Cl2). Both react at the N7 position of guanine to form large adducts. The major adduct formed can either be rapidly removed to leave an apurinic site or can undergo ring opening of the imidazole ring to form a chemically stable adduct. A number of Chinese hamster DNA repair-deficient mutants have been screened for their sensitivity to AFB1-epoxide and AFB1Cl2. Some of the mutants screened belong to different UV complementation groups. Human genes involved in nucleotide excision-repair correct deficiencies found in these complementation groups. The mutants which were found to be most sensitive to AFB1 (V-C4 and V-H1) were further investigated. Alkaline elution was used to measure AFB1-induced DNA single-strand break repair in the mutants. V-H1 repaired completely in 24 h whereas V-C4 displayed only partial repair.

Aflatoxin B1↗
PubMed1992

Radical axillary dissection in the staging and treatment of breast cancer.

The results of 237 radical axillary dissections undertaken by one surgeon in patients with breast cancer were reviewed to evaluate the role of this procedure in staging and treatment. The accuracy of physical examination in detecting axillary metastases was 68%. With a policy of enforced shoulder immobilisation for 10 days postoperatively, the incidence of postoperative wound complications was 8%. There have been three axillary recurrences during a median follow-up period of 44 months (range 6-97 months). Late complications were assessed in 50 patients followed up for greater than 12 months. While eight patients complained of constant swelling of the arm, only three had a difference in arm circumference of greater than 3 cm and only one had persistent limitation of shoulder abduction. Radical axillary dissection ensures accurate clinical staging and provides excellent local control with few complications and without the need for axillary irradiation.

Axilla↗
PubMed1991

32P-postlabelling analysis and micronuclei induction in primary Chinese hamster lung cells exposed to tobacco particulate matter.

The genotoxicity of tobacco particulate matter (TPM) derived from a low-tar, low-nicotine cigarette has been examined by measuring micronucleus induction in a primary pulmonary cell line, both in the absence and presence of an exogenous source of metabolic activation. In an attempt to correlate the cytogenetic damage observed with DNA adduct formation, DNA extracted from TPM-treated cells has been analysed with two different modifications of the 32P-postlabelling assay. The results from the 32P-postlabelling analysis taken together with the pattern of micronucleus induction provide strong evidence that bioreactivated aromatic carcinogens, such as benzo[a]pyrene, are unlikely to be responsible for the TPM-induced cytogenetic damage observed in cultured mammalian cells.

Animals↗
PubMed1991

The repair of 4-nitroquinoline-1-oxide induced DNA adducts in hypersensitive Chinese hamster mutants: lack of repair of UV induced (6-4) photoproduct correlates with reduced repair of adducts at the N2 of guanosine.

UV sensitive Chinese hamster mutants belonging to ERCC groups 1, 2 and 6 together with one cross-link- and one X-ray-sensitive mutant have been examined for sensitivity to 4-nitroquinoline-1-oxide (4NQO) and the ability to repair 4NQO adducts at the N2 and C8 of guanosine. Despite the fact that all of the mutants examined were hyper-sensitive to 4NQO there was little difference between the mutants V-H1, V-H4, V-C4 and UV61 and the parental cell lines as regards the ability to remove these lesions from bulk DNA. The UV5 and UV20 mutants were both defective in the ability to remove N2 guanosine adducts yet repaired the C8 guanine adduct as normal. The fact that the mutants V-H1, V-H4, V-C4 and UV61 are 4NQO sensitive but repair the above adducts suggests that either some other lesion(s) is responsible for increased toxicity in these mutants, or that some regions of the genome may not be repaired as effectively as bulk DNA in these mutants, or that the quality of the repair is less than in the parental cells. Clearly the inability to remove UV induced pyrimidine dimers and the (6-4) photoproduct associated with the UV5 and UV20 mutants correlates with the inability to repair 4NQO-N2 guanosine adducts. However, mutants capable of (6-4) photoproduct repair but not dimer repair (VH-1 and UV61) can repair this lesion. Hence it is possible that the same domains in these repair proteins are required for the recognition of (6-4) photoproduct repair and 4NQO-N2 guanosine adducts.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Nitroquinoline-1-oxide↗
PubMed1991

Spinal cord injury from civilian gunshot wounds: the Rancho experience 1980-88.

We performed a retrospective review of the medical records of 316 patients with spinal cord injury (SCI) secondary to gunshot wounds (GSW) admitted to Rancho Los Amigos Medical Center for rehabilitation between 1980 and 1988. There were 289 male and 27 female patients whose mean age was 25.9 years (range, 11-56 years). Of these, 238 were paraplegic (103 incomplete, 135 complete), and 78 were quadriplegic (45 incomplete, 33 complete). Forty were shot by handguns of known caliber and four by shotguns; in 272 cases, the type of weapon was unknown. A total of 230 cases sustained a single bullet wound, and 86 had multiple bullet wounds. The length of acute hospitalization, but not rehabilitation hospital stay, increased with the number of associated injuries. Rehabilitation and, hence, total length of stay was significantly less (mean, 100 and 130 days, respectively) for SCI/GSW victims than for SCI victims of motor vehicle accidents, falls, or diving accidents. The methods of calculating costs for admission were based upon Rancho Los Amigos Medical Center financial statistics. This hospital has charged for a daily occupancy fee. The fee is based upon an average of all charges for all patients. No additional fees are charged for special tests or procedures. In 1980, the average daily admission hospitalization charge was $785. In 1990, the last quoted hospital charge was $1,125. This is for the basic spinal cord injury rehabilitative stay. In general, at Rancho Los Amigos, patients are admitted for rehabilitation when all acute medical and surgical problems have been cleared and the patient is ready to participate in rehabilitation evaluation and therapy programs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Differential repair of UV damage in Saccharomyces cerevisiae is cell cycle dependent.

In the yeast Saccharomyces cerevisiae the transcriptionally active MAT alpha locus is repaired preferentially to the inactive HML alpha locus after UV irradiation. Here we analysed the repair of both loci after irradiating yeast cells at different stages of the mitotic cell cycle. In all stages repair of the active MAT alpha locus occurs at a rate of 30% removal of dimers per hour after a UV dose of 60 J/m2. The inactive HML alpha is repaired as efficiently as MAT alpha following irradiation in G2 whereas repair of HML alpha is less efficient in the other stages. Thus differential repair is observed in G1 and S but not in G2. Apparently, in G2 a chromatin structure exists in which repair does not discriminate between transcriptionally active and inactive DNA or, alternatively, an additional repair mechanism might exist which is only operational during G2.

Blotting, Southern↗
PubMed1990

Formal axillary dissection.

Formal axillary dissection is a precise anatomical procedure by which the lymphatic contents of the axilla are removed en bloc. It is used as both a staging and a therapeutic procedure for carcinoma of the breast, and as a therapeutic or palliative procedure for established axillary metastases.

Axilla↗
PubMed1990

DNA alkylations and mutation after exposure to ethyl methanesulphonate in mammalian cell lines routinely used in mutagenicity testing.

DNA ethylations were measured in four mammalian cell lines, Chinese hamster ovary CHO, mouse lymphoma L5178Y t k+/-, human lymphoblastoid TK6 and Chinese hamster V79, following exposure to [3H]ethyl methanesulphonate. Concurrent estimates of cytotoxicity and gene mutation were also carried out. Total DNA-binding and relative levels of ethylation at N-7 guanine (N-7G), O6 guanine (O6G) and N-3 adenine (N-3A) were essentially the same in all four cell lines. Differences in response to EMS between the cell lines, namely the greater cytotoxicity in TK6 cells, would therefore appear to reflect subsequent handling of the DNA lesions, rather than different levels of DNA ethylation in the cell lines.

Adenine↗
PubMed1990

Transfer of the pronator teres tendon to the tendons of the flexor digitorum profundus in tetraplegia.

In eleven patients who had traumatic tetraplegia, the pronator teres tendon was transferred to the flexor digitorum profundus tendons to restore active flexion of the fingers. At the same time, in ten of these patients the tendon of the brachioradialis was transferred to the tendon of the flexor pollicis longus, and in the eleventh patient the brachioradialis tendon was transferred to the tendon of the flexor digitorum superficialis of the small finger, to restore pinch. The average time between injury and operation was thirty-four months. The average length of follow-up after operation was thirty-four months. Ten patients gained functional active flexion of the fingers, and they reported improved performance of activities of daily living. When the wrist was in 30 degrees of extension, the average active grasp strength was twenty-one millimeters of mercury and the average key-pinch strength was 2.2 kilograms. The average active flexion of the fingers from the resting position, measured from the tip of the finger to the distal palmar crease, was 1.5 centimeters. Only one patient did not gain active flexion of the fingers. Of the entire group, this patient had the least function of the hand on preoperative evaluation; retrospectively, he seemed to be a poor candidate for operation, since the strength of the pronator teres muscle and the sensibility of the hand were insufficient for useful function. We concluded that, in selected tetraplegic patients, transfer of the pronator teres tendon to the flexor digitorum profundus tendons provides useful active flexion of the fingers.

Adult↗
PubMed1989

The repair of identified large DNA adducts induced by 4-nitroquinoline-1-oxide in normal or xeroderma pigmentosum group A human fibroblasts, and the role of DNA polymerases alpha or delta.

4-Nitroquinoline-1-oxide (4NQO) reacts with DNA primarily at the N2 and C8 of guanosine, with a small percent of reaction at the N6 of adenosine. In human cells it has been unclear whether or not all 4NQO-induced adducts are removed by a nucleotide excision repair mechanism. In this paper we demonstrate that the inhibitor of DNA polymerases alpha and delta, aphidicolin, blocks the repair of all 4NQO adducts. Hence excision repair must operate on all of these lesions. After 4NQO the residual excision repair seen in a xeroderma pigmentosum group A cell line virtually totally defective in UV repair was 40-60% of that in normal cells. Therefore there must be some differences between the excision repair operating on UV as opposed to 4NQO-induced DNA damage.

4-Nitroquinoline-1-oxide↗
PubMed1989

Orofacial infection of athymic mice with defined mixtures of acyclovir-susceptible and acyclovir-resistant herpes simplex virus type 1.

Infection of athymic mice with defined populations of acyclovir-susceptible (thymidine kinase [TK]-positive) and acyclovir-resistant (TK-deficient or TK-altered) herpes simplex virus type 1 strains was used to simulate herpetic skin disease of the immunocompromised host. In vitro characterization of the defined virus mixtures revealed that the dye uptake method was quite sensitive in the detection of small amounts (3 to 9%) of acylovir-resistant virus. Mice infected with homogeneous virus populations exhibited a good correlation between clinical response and the in vitro drug susceptibility of the infecting virus. Animals infected with defined mixtures of viruses exhibited varied patterns of infection and responses to acyclovir treatment. However, disease severity was useful in predicting the TK phenotype of virus recovered from lesions. Pathogenic, TK-altered virus was responsible for progressive disease in animals receiving low-dose (0.25-mg/ml) prophylactic acyclovir or high-dose (1.25-mg/ml) delayed therapy. Although this mutant was recovered infrequently, it was responsible for clinically significant disease in the animals from which it was isolated.

Acyclovir↗
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↗