PubMed Health⌕ Search

Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 19 recordsLinked to original sources
PubMed1992

Herbicide resistance due to amplification of a mutant acetohydroxyacid synthase gene.

We have selected a tobacco cell line, SU-27D5, that is highly resistant to sulfonylurea and imidazolinone herbicides. This line was developed by selection first on a lethal concentration of cinosulfuron and then on increasing concentrations of primisulfuron, both sulfonylurea herbicides. SU-27D5 was tested against five sulfonylureas and one imidazolinone herbicide and was shown, in every case, to be two to three orders of magnitude more resistant than wild-type cells. The acetohydroxyacid synthase (AHAS) of SU-27D5 was 50- to 780-fold less sensitive than that of wild-type cells to herbicide inhibition. The specific activity of AHAS in the SU-27D5 cell lysate was 6 to 7 times greater than that in wild-type cells. Using Southern analysis, we showed that cell line SU-27D5 had amplified its SuRB AHAS gene about 20-fold while maintaining a normal diploid complement of the SuRA AHAS gene. Genomic clones of both AHAS genes were isolated and used to transform wild-type tobacco protoplasts. SuRB clones gave rise to herbicide-resistant transformants, whereas SuRA clones did not. DNA sequencing showed that all SuRB clones contained a point mutation at nucleotide 588 that converted amino acid 196 of AHAS from proline to serine. In contrast, no mutations were found in the SuRA clones. The stability of SuRB gene amplification was variable in the absence of selection. In one experiment, the withdrawal of selection reduced the copy number of the amplified SuRB gene to the normal level within 30 days. In another experiment, amplification remained stable after extended cultivation on herbicide-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetolactate Synthase↗
PubMed1992

Alterations in quantitative distribution of Na,K-ATPase activity along crypt-villus axis in animal model of malabsorption characterized by hyperproliferative crypt cytokinetics.

The distribution of sodium- and potassium-stimulated ATPase (Na,K-ATPase) along the crypt-villus axis and crypt cytokinetics were examined in an infective model of celiac disease produced by infection of the rat with the nematode Nippostrongylus brasiliensis. In controls, levels of enzyme activity remained stable during enterocyte migration to the villous apex. In the jejunum of infected rats, the structural lesion of villous atrophy and crypt hyperplasia, observed at day 10 of infection, was associated with a three-dimensional expansion of the crypts. Cell cycle time was shortened and this resulted in a markedly increased crypt cell production rate. Enterocytes emerged from the crypts at a faster rate, and this functional immaturity was paralleled by decreased Na,K-ATPase activity. Further decreases in enzyme levels were observed during enterocyte migration along the villi. This may reflect enterocyte damage or increased enzyme turnover. In the ileum of these animals, enterocyte maturation was prolonged and enzyme activity was increased at the level of the crypt villus junction with further increases noted during enterocyte transit. These changes in ileal Na,K-ATPase appear to be adaptive.

Animals↗
PubMed1992

Radiosensitization of cultured human colon adenocarcinoma cells by 5-fluorouracil: effects on cell survival, DNA repair, and cell recovery.

Although 5-fluorouracil (5-FU) is commonly used in conjunction with radiotherapy to treat gastrointestinal malignancies, the molecular mechanisms underlying the clinically observed therapeutic advantage of this combination of agents have not been clearly established. The present in vitro studies addressed the possibility that the radiosensitization of log-phase cultured human colon adenocarcinoma cells by postirradiation administration of 5-FU was accompanied by an interference either with the rejoining of radiation-induced DNA double-strand breaks (DSB's) or with recovery from potentially lethal damage (PLD). Significantly more killing was observed in cells exposed to gamma-rays (1-6 Gy) and then treated with 5-FU (100 micrograms/mL; 0.77 mM) for 1 hr at 37 degrees C than in cells given gamma-rays but not 5-FU; essentially, the survival curve shoulder was removed. DSB rejoining measured using the neutral filter elution method after exposure to 25 Gy was identical regardless of whether 5-FU (100 micrograms/mL) was present during the repair period; thus, radiosensitization by this high-concentration postirradiation 5-FU protocol does not appear to be a result of interference with the overall rate of ligation of gamma-ray-induced DSB's. The effect of 5-FU on the ability of log-phase cells to recover from that sector of PLD that can be expressed by postirradiation incubation with hypertonic (0.5 M) salt solution (HSS) was also examined. When irradiated cells were treated with 5-FU during their recovery period and then incubated with HSS, no clonogenic cells survived. Therefore, although it was not possible to assess the actual kinetics of recovery from gamma-ray-induced PLD in 5-FU-treated cells, the drug clearly altered the metabolism or structure of the cells such that their susceptibility to HSS was markedly enhanced.

Adenocarcinoma↗
PubMed1992

Relationships between DNA damage and the survival of radiosensitive mutant Chinese hamster cell lines exposed to gamma-radiation. Part 1: Intrinsic radiosensitivity.

In this study we used the neutral elution technique (at pH 9.6) to compare the efficiency of DNA double-strand break (dsb) induction and cell killing in two radiosensitive Chinese hamster ovary cell lines, EM9 and NM2, and their parent cell line, AA8, after exposure to low doses (2.5-12 Gy) of 137Cs gamma-radiation. The survival curves indicated that at all radiation doses examined EM9 cells were the most radiosensitive and AA8 cells were the least radiosensitive. We found significant differences among the three cell lines in the neutral elution assay. While NM2 cells showed the same immediate postirradiation dose response for DNA damage as the parent cell line, EM9 cells showed a two-fold greater elution rate than AA8 cells per unit dose. Either the dsb induction efficiency was greater in EM9 than in AA8 cells, or the same frequency of dsb in EM9 and AA8 cells gave rise to a different DNA elution rate, perhaps because of differences in their chromatin structure. We also used a mitotic selection technique to examine the duration of the gamma-ray-induced mitotic delay in the three cell lines. Mitotic delay was less severe in NM2 cells than in AA8 cells, but was significantly longer in EM9 cells than in AA8 cells. Thus the measurements obtained using both neutral elution and mitotic selection suggest that the underlying molecular bases of the radiosensitivity of EM9 and NM2 cells are very different.

Animals↗
PubMed1992

Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly.

OBJECTIVE: To compare clinical status of elderly institutionalized subjects with asymptomatic bacteriuria and normal urinary antibody to those with elevated urinary antibody to the major outer membrane of Escherichia coli. DESIGN: Retrospective review. SETTING: Long term facility for the elderly. PARTICIPANTS: Convenience sample of 63 elderly subjects, 26% of those resident in the institution, aged 78.8 +/- 8.4 years with urine specimens collected and stored in 1987. MAIN OUTCOME MEASURES: Differences in clinical or functional status, demographic features, and outcome during 3-years follow-up between bacteriuric subjects with normal and elevated urine antibody. RESULTS: Thirteen subjects had no bacteriuria, and 12 had infrequent, intermittent bacteriuria; 38 (60%) had persistent bacteriuria, including four with frequent, intermittent infections. In the persistently bacteriuric group, 18 (47%) had persistently elevated urine antibody. There was no significant differences between bacteriuric residents with normal vs elevated urine antibody in clinical or functional status, age, duration of residence, or infecting organisms. However, 11 of 20 in the cohort with normal urine antibody were alive at 3 years compared to 3 of 18 with elevated urine antibody (P = 0.014). CONCLUSIONS: Elderly institutionalized subjects with persistent bacteriuria and elevated urine antibody have decreased survival compared to those with normal urine antibody. No differences in underlying illness or clinical course to explain this survival difference were identified.

Aged↗
PubMed1992

Social care services for patients with HIV at a London teaching hospital; an evaluation.

OBJECTIVE: To investigate outpatients' use of, and satisfaction with social care services in an HIV unit. DESIGN: Survey of patients with HIV infection using self administered questionnaire. SETTING: Outpatient HIV clinics at the Royal Free Hospital, London, March-April 1991. MAIN OUTCOME MEASURES: Patients' social circumstances, use or intended use of social care services and satisfaction with social care services. RESULTS: The greatest demand was for counselling about coping with HIV (38% of respondents), available medical treatment (24%), counselling for the HIV test (33%), psychological support for emotional (24%) or relationship problems (16%), advice about housing (24%) and financial matters (20%). In general, the use of social care services by men and women was similar. Twice as many men, however, sought help with payment of domestic bills, compared with women. Women were more likely to seek advice about financial benefits, obtaining sterile injecting equipment and discuss sleep and relationship problems. Thirty eight percent of patients were unemployed. Overall, 84% thought the service was good or excellent. Although less than 40% of patients currently used any one service, 60% thought they would use these services in the future. CONCLUSION: The greatest demand for social care services was for coping with HIV, housing and financial matters, and HIV test counselling. More than half the patients stated that they would probably need social care services in future.

Adaptation, Psychological↗
PubMed1992

Alveolar damage due to inhalation of amitrole-containing herbicide.

Amitrole-containing herbicides are commonly used by home and cottage owners for spraying grass. They are manufactured and distributed in the United States, Canada and throughout the world by several pharmaceutical/chemical industries under many different trade names, such as Amitrole-T, Amizol, Azolan, Cytrol and Weedazol. They have not been previously associated with pulmonary toxicity in man or laboratory animals. We describe the first case in which inhalation of amitrole herbicide resulted in diffuse, asymmetric, severe alveolar damage, which was reversed after treatment with high-dose corticosteroids.

Aged↗
PubMed1992

The distribution of immunoreactive interferon-gamma-containing cells in normal human tissues.

An immunohistochemical technique has been used to study the distribution of lymphocytes expressing interferon-gamma in normal adult tissues. The greatest concentrations of these cells were seen in mucosal sites exposed to a resident microflora. It is proposed that such organisms, by eliciting immune responses, provide the stimulus for the production of 'physiological' interferon-gamma. This in turn may act to preserve the 'tone' or readiness of the immune system.

Adult↗
PubMed1991

RJR Nabisco's cartoon camel promotes camel cigarettes to children.

OBJECTIVES: To determine if RJR Nabisco's cartoon-theme advertising is more effective in promoting Camel cigarettes to children or to adults. To determine if children see, remember, and are influenced by cigarette advertising. DESIGN: Use of four standard marketing measures to compare the effects of Camel's Old Joe cartoon advertising on children and adults. SUBJECTS: High school students, grades 9 through 12, from five regions of the United States, and adults, aged 21 years and over, from Massachusetts. OUTCOME MEASURES: Recognition of Camel's Old Joe cartoon character, product and brand name recall, brand preference, appeal of advertising themes. RESULTS: Children were more likely to report prior exposure to the Old Joe cartoon character (97.7% vs 72.2%; P less than .0001). Children were better able to identify the type of product being advertised (97.5% vs 67.0%; P less than .0001) and the the Camel cigarette brand name (93.6% vs 57.7%; P less than .0001). Children also found the Camel cigarette advertisements more appealing (P less than .0001). Camel's share of the illegal children's cigarette market segment has increased from 0.5% to 32.8%, representing sales estimated at $476 million per year. CONCLUSION: Old Joe Camel cartoon advertisements are far more successful at marketing Camel cigarettes to children than to adults. This finding is consistent with tobacco industry documents that indicate that a major function of tobacco advertising is to promote and maintain tobacco addiction among children.

Adolescent↗
PubMed1991

Effect of thiols on micronucleus frequency in gamma-irradiated mammalian cells.

The effects of the thiols cysteamine, WR-1065, and WR-255591 on radiation-induced micronucleus (MN) frequency and cell killing were compared in cultured Chinese hamster ovary cells. MN were measured using the cytochalasin B assay of Fenech and Morley (1985), which minimizes the effect of cytokinetic perturbations on MN expression. The dose-response curves for MN induction were curvilinear both for control cells at doses between 1.5 and 4.5 Gy and for thiol-treated cells at doses between 3 and 9 Gy. Protection against MN induction by each thiol was independent of radiation dose. Furthermore, there was a close correlation between the degree of modification of MN induction and cell survival by each thiol, i.e., the MN frequency closely predicted the survival level regardless of the presence of absence of the thiols. A similar predictive relationship has also been reported by us for cell survival and DNA double-strand break (DSB) induction in this cell line following treatment with these same thiols. Collectively, these data support the hypothesis that, for DNA-repair-proficient mammalian cells treated with radiomodifying agents that do not alter DNA-repair processes, MN and DSB induction are predictive of the level of radiation lethality and of each other.

Animals↗
PubMed1991

Isolation and characterization of nitrogen mustard-sensitive mutants of Chinese hamster ovary cells.

Three nitrogen mustard-sensitive lines of Chinese hamster ovary cells were isolated from mutagenized cultures using the procedure of Thompson et al. (1980). The lines, designated NM1, NM2 and NM3, were 2.1-, 17- and 6.8-fold more sensitive to nitrogen mustard, respectively, than their parent, wild-type, line as determined by the dose required to kill 90% of the cells, IC90. Patterns of cross-sensitivity to other DNA-damaging agents including ultraviolet light, cis-diamminedichloroplatinum, and other alkylating agents were determined for each line. Analysis of these results suggests that the phenotypes of the mutant lines are different from those lines reported previously.

Aminacrine↗
PubMed1991

Counselling patients with HIV infection about laboratory tests with predictive values.

Laboratory tests, including CD4 counts, p24 antigen, raised levels of B2 microglobulin, neopterin and CMV antibodies, have been established as important predictive markers of disease progression in patients with HIV infection. As HIV antibody testing becomes more accepted in medical practice, counselling about these laboratory predictors of progression can help patients and doctors plan together the patients' care and treatment. Addressing patients' main concerns at each stage of investigation and illness may help them to plan ahead of crises, reduce stress, and enhance communication between patients and health care providers.

Adult↗
PubMed1991

Changing patterns in the workload of a district HIV/AIDS counselling unit 1987-90.

OBJECTIVES: To describe the changing workload of an HIV/AIDS counselling unit between 1987 and 1990. DESIGN: Retrospective examination of data collected by the HIV/AIDS counselling unit between 1987-90 on the number of counselling sessions with patients, family members and staff. SETTING: An HIV/AIDS counselling unit established in 1987 in a London teaching hospital. MAIN OUTCOME MEASURES: Number of new referrals to the HIV/AIDS counselling unit and the number of follow-up sessions. Number of counselling sessions with family members, hospital staff and people making telephone contact with the unit. RESULTS: New referrals to the HIV/AIDS counselling unit increased from 117 (1987-88) to 926 (1989-90). Follow-up appointments increased from 403 to 2016 in the same period. Telephone counselling sessions increased five-fold, and counselling sessions with family members nearly ten-fold over the three year period. Staff consultations doubled. CONCLUSION: The increase in the HIV/AIDS counselling unit's workload may be partly attributable to the rising incidence of AIDS in the community, reflecting earlier patterns of HIV infection. In addition, new HIV/AIDS services were developed in the hospital between 1987 and 1990. These included the establishment of a same-day HIV test and result clinic; integrated management of patients with HIV/AIDS, with an emphasis on early intervention in HIV infection; specialist services for families, antenatal clinic attenders and others affected by HIV; and the appointment of a designated HIV/AIDS consultant. New approaches to counselling and training health care providers in counselling skills will assume increasing importance in meeting future demand for HIV/AIDS counselling.

AIDS Serodiagnosis↗