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Biomedical subjects

D Murray

Publications and source records attributed to D Murray.

At least 199 records · Page 11Linked to original sources

A controlled study of the onset, duration and prevalence of postnatal depression.

In a two-stage screening procedure using the Edinburgh Postnatal Depression Scale and Goldberg's Standardised Psychiatric Interview, 232 women six months after delivery were compared with control women individually matched for age, marital status and number of children, obtained from general practitioner lists, who were not pregnant nor had had a baby in the previous 12 months. No significant difference in the point prevalence of depression at six months was found between the postnatal (9.1%) and control women (8.2%) nor in the six-month period prevalence (13.8% postnatal, 13.4% controls), but a threefold higher rate of onset of depression was found within five weeks of childbirth. The possible explanations relate to the long duration of depression in women with young children, and the stressful effect of childbirth and its psychosocial sequelae.

Adolescent↗

The significance of spinal cord compression as the initial manifestation of lymphoma.

Eighteen patients with spinal cord compression caused by previously undiagnosed lymphoma were treated at our institution between 1976 and 1991. There were 14 male and 4 female patients (mean age, 58.2 years). The absence of bony involvement on radiographic images was a feature in 16 of the cases. All patients underwent laminectomy for decompression and tissue diagnosis, after which 5 underwent radiotherapy, 3 underwent chemotherapy, and 10 underwent combined-modality treatment. The functional outcome was improvement in 8 patients and no change in 10; no patient worsened after surgery. Eleven had advanced disease at diagnosis, while seven had limited disease, including three patients with localized extradural lymphoma. There were 16 cases of non-Hodgkin's lymphoma and 2 of Hodgkin's disease. Two patients had T-cell lymphoma and were among the longest survivors. DNA flow cytometry identified the low-grade tumors as diploid with very low proliferative indices, while the high-grade tumors all had high indices. At a mean observation time of 41.7 months, five patients have died of their disease, and seven remain in complete remission. Survival is markedly better than that reported for other malignant extradural tumors; however, even limited stage lymphoma can behave aggressively. Similarities in age, sex distribution, histological features, and the results of flow cytometry suggest behavior similar to extranodal lymphoma at other sites. Surgery to provide a tissue diagnosis, followed by combined radiotherapy and chemotherapy, is indicated for all cases.

Adult↗

Detection of false DNA aneuploidy and false DNA multiploidy in flow cytometric DNA analysis.

Although false DNA aneuploid peaks have previously been described in normal tissue, criteria for distinguishing them from 'true' near-diploid peaks have not been established. Normal thyroid (n = 4) and kidney (n = 1) tissue were allowed to autolyze over a fixed period of time and DNA content was analyzed by flow cytometry (FCM). Autolysis was associated with the development of distinct separate G0/G1 peaks which had low DNA indices (1.09-1.18) and showed decreased forward light scatter (FSC) when compared to fresh tissue. Using DNA content and FSC measurements similar false DNA aneuploid peaks were identified in 29/94 surgical specimens. These cases included both benign and malignant lesions from thyroid (n = 63) with the remaining 31 neoplastic cases being from breast (16), lymphoma (8), sarcoma (4), lung (2) and uterine (1) tissue. In addition, false DNA multiploidy was identified. None of these cases showed histological evidence of necrosis. In a parallel comparison study using image cytometry (ICM) on the thyroid nodules, the presence of false DNA aneuploidy was supported. Investigators should routinely employ quality control criteria to identify possible cases of false DNA aneuploidy when measuring DNA content using FCM.

Adolescent↗

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↗

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↗

Radiation protection against early and late effects of ionizing irradiation by the prostaglandin inhibitor indomethacin.

Protective effects of indomethacin, a prototype prostaglandin-inhibiting agent, against early and late sequelae of radiation injury (after X-rays or gamma rays) in mice were investigated. The following tissues or organs were examined: hematopoietic tissue, esophagus, jejunum, colon, lung, hair follicles, and tissues involved in the development of radiation-induced leg contractures. In addition, the effect of indomethacin was tested against radiation-induced carcinogenesis. In all experiments, the radiation was delivered as a single dose. Indomethacin led to significant protection of hematopoietic tissue, by a factor of 1.3. There was also some protection against radiation-induced pneumonitis and against radiation-induced carcinogenesis (protection factor of 1.2). The other tissues tested showed no change in their radioresponse after being treated with indomethacin. Thus, indomethacin can act as a radioprotective agent against both early and late sequelae of radiation, but its effect is dependent on the tissue tested. This protection is smaller than that observed with WR-2721. However, indomethacin combined with WR-2721 produced a radioprotective effect greater than the radioprotection achieved by individual treatments.

Amifostine↗

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↗

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↗

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↗

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↗

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↗

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↗