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Biomedical subjects

D Young

Publications and source records attributed to D Young.

At least 487 records · Page 27Linked to original sources
PubMed1984

Single mutations at many sites within the DNA polymerase locus of herpes simplex viruses can confer hypersensitivity to aphidicolin and resistance to phosphonoacetic acid.

Aphidicolin, a tetracyclic diterpenoid which inhibits the DNA polymerase-alpha activities of many eukaryotic cells, inhibited herpes simplex virus growth and DNA synthesis in infected cultures and the activity of the virus DNA polymerase in vitro. A wide range of stable aphidicolin sensitivities was represented amongst a collection of virus strains with no prior exposure to this drug, but viruses with polymerase mutations selected for resistance to phosphonoacetic acid (PAA) or to acycloguanosine typically showed increased sensitivity to aphidicolin. Of 16 unrelated PAA-resistant variants, 7 were hypersensitive to aphidicolin. A number of mutants with temperature-sensitive (ts) lesions in the polymerase gene also showed increased aphidicolin sensitivity (e.g. HSV-1[mP17]tsH) or aphidicolin hypersensitivity (e.g. HSV-1[KOS]tsD9, tsC4). Resistance or hypersensitivity of virus growth and DNA synthesis in vivo were correlated with resistance or hypersensitivity of virus DNA polymerase reactions in vitro. Resistance phenotypes were closely linked to the polymerase gene during recombination with outside markers. Moreover, the selection of aphidicolin-resistant mutants from hypersensitive variants with independent PAA resistance or ts mutations in the polymerase gene could result in co-selection for PAA-sensitive and ts+ phenotypes. Confirmation that multiple independent mutations could determine aphidicolin hypersensitivity was obtained by studies of recombination between independent hypersensitive variants. Aphidicolin-resistant recombinant progeny were formed with recombination frequencies (0.4 to 2.6%) compatible with intragenic events. With parental hypersensitive variants which were products of limited PAA selection, or with the ts polymerase mutations, aphidicolin-resistant recombinants were PAA-sensitive and/or ts+. The segregation of other markers (ts, plaque morphology) amongst recombinant progeny permitted the orientation of multiple determinants of PAA resistance and aphidicolin hypersensitivity with respect to other markers in the polymerase gene and in other genes. The nature of residues determined at any one of a constellation of separate sites within the polymerase locus can determine resistance or sensitivity to antiviral drugs and aphidicolin hypersensitivity associated with changes at the polymerase locus facilitates high resolution genetic analysis of this locus.

Antiviral Agents↗
PubMed1984

A randomized trial of metoclopramide and a combination of dexamethasone and lorazepam for prevention of chemotherapy-induced vomiting.

In a randomized, crossover design the antiemetic activity of one of the most active single agents, metoclopramide was compared with a combination of dexamethasone and lorazepam. Both regimens were effective, but dexamethasone-lorazepam was significantly better than metoclopramide in preventing (26% versus 13%) or limiting (44% versus 23%) vomiting. Although side effects were more frequent with lorazepam-dexamethasone, the patients generally judged them desirable and overall patient preference was strong (70% versus 12%) for the lorazepam-dexamethasone combination. Patients required supervision and assistance due to lorazepam-induced drowsiness.

Adolescent↗
PubMed1984

Interferon-alpha therapy of renal cancer.

Thirty-three patients with renal cancer began treatment with human lymphoblastoid interferon (Wellferon) between August 1982 and February 1983. Interferon was administered as an i.m. injection at a dose of 5 X 10(6) units/sq m 3 times per week. Treatments were continued for at least 24 weeks in the absence of rapid disease progression or intolerable toxicity. Five patients demonstrated partial responses, which continued in two patients with durations of 239+ and 300+ days. Prolonged therapy was often required with a mean time to response of 99 days (22 to 190 days). Toxicity was substantial. Fever, chills, arthralgias, and myalgias occurred following most doses, but usually were well tolerated. Leukopenia and hepatic enzyme elevations were usually modest and always reversible. Dose-limiting side effects were progressive fatigue and anorexia which reversed within approximately 4 to 6 weeks after cessation of interferon therapy. There was no correlation between interferon levels, clinical toxicities, and response in this group of patients. We conclude that interferon has definite antitumor activity in renal cancer when given by this dose and schedule.

Clinical Trials as Topic↗
PubMed1984

A comparative trial of mitoxantrone and doxorubicin in patients with minimally pretreated breast cancer.

A randomized trial began in 1980 comparing the efficacy and toxicity of mitoxantrone and doxorubicin. Patients with metastatic breast cancer unresponsive to cyclophosphamide-methotrexate-5-fluorouracil with or without tamoxifen were randomized to either mitoxantrone, 12 mg/m2, or doxorubicin, 60 mg/m2, every 3 weeks. Patients were crossed over to the alternative treatment if they progressed after two courses or fail to respond after four courses. Fifty-nine patients have been randomized at the present time, and most of these have a performance status near to normal. During initial therapy, partial responses were obtained in 10 of 25 patients receiving doxorubicin, and a further 12 showed stable disease; 3 showed progressive disease. Of the 26 patients who received mitoxantrone as initial therapy, 7 achieved a partial response, 14 had stable disease, and 5 progressive disease. Twenty-seven patients received doxorubicin or mitoxantrone as secondary therapy; two patients each responded to these drugs, suggesting a lack of cross-resistance. The median time to response was 48 days for doxorubicin and 57 days for mitoxantrone. The duration of partial responses measured from the onset of response was similar for both drugs, being 84 days for doxorubicin and 96 days for mitoxantrone. Hematologic toxicity, vomiting, alopecia, and fatigue tended to be less frequent and less severe with mitoxantrone than with doxorubicin. Mitoxantrone appears to be an effective and well-tolerated agent for breast cancer. Definitive comparisons will be available at the completion of this study.

Adult↗
PubMed1984

Double suicides: four modal cases.

Double suicides, or suicide pacts, are relatively rare and usually involve older married couples. Histories of four such couples are reviewed. The participants were similar to other (nonpact) suicides with regard to recent visits to physicians, alcohol use, and communication of intent. They differ from other suicides in that they are more likely to have a first-degree relative who died by suicide. Similar DSM-III diagnoses were found in both members of each couple, and there was a complementary quality in their personal and family histories.

Age Factors↗
PubMed1983

Comparison of natural and synthetic prostaglandin E2 tablets in labour induction.

A multicentre, randomized, double-blind trial compared the efficacy and safety of and tolerance to natural and synthetically produced prostaglandin E2 tablets in the induction of labour in 202 women. The compounds were similarly effective, inducing labour in approximately 66% of patients. The total dose required and the interval between induction and delivery were similar in the two groups, as were the Apgar scores at 1 and 5 minutes and the incidence of maternal and fetal side effects.

Abortifacient Agents↗
PubMed1983

Age-related morphologic differences in the rat cerebral cortex and hippocampus: male-female; right-left.

This paper is one of a series presenting right-left differences in the morphology of the rat forebrain, but this presentation differs from the previous ones by offering age-related changes in both sexes. Long-Evans rats were housed with the dam prior to weaning at 21 days of age and three to a cage thereafter. The ages of the animals studied were 6 to 7, 14, 21, 90, 180 to 185, 390 to 400, and 870 to 876 days. The thicknesses of the cerebral cortex and of the hippocampus were measured on microslide-projected images of thionin-stained sections. We learned that the cerebral cortex of the male rat was thicker on the right side than on the left at all ages in 41 of 42 measures, being statistically significant in 30 of 42 measures. Areas 10, 3 and 17 showed the most marked differences at all ages. In the female rat, laterality was not so well defined, but, in general, the left cerebral cortex was thicker than the right in 33 of 54 measures, but in only 5 of the 54 were statistically significant differences found. The right-left differences in the hippocampus followed the pattern of the cortical differences in the male and female rats. The right male hippocampus was thicker than the left at all ages, with greater differences noted in the younger than in the older groups. The female left hippocampus was thicker than the right, but only in the 90-day group was the difference significant.

Age Factors↗
PubMed1983

Regular arrangement of nucleosomes on 5S rRNA genes in Xenopus laevis.

The chromatin structure of the oocyte-type 5S RNA genes in Xenopus laevis was investigated. Blot hybridization analysis of DNA from micrococcal nuclease digests of erythrocyte nuclei showed that 5S DNA has the same average nucleosome repeat length, 192 +/- 4 base pairs, as two Xenopus satellite DNAs and bulk erythrocyte chromatin. The positions of nuclease-sensitive regions in the 5S DNA repeats of purified DNA and chromatin from erythrocytes were mapped by using an indirect end-labeling technique. Although most of the sites cleaved in purified DNA were also cleaved in chromatin, the patterns of intensities were strikingly different in the two cases. In 5S chromatin, three nuclease-sensitive regions were spaced approximately a nucleosome length apart, suggesting a single, regular arrangement of nucleosomes on most of the 5S DNA repeats. The observed nucleosome locations are discussed with respect to nucleotide sequences known to be important for expression of 5S RNA. Because the preferred locations appear to be reestablished in each repeating unit, despite spacer length heterogeneity, we suggest that the regular chromatin structure reflects the presence of a sequence-specific DNA-binding component on inactive 5S RNA genes.

Animals↗