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D Anderson

Publications and source records attributed to D Anderson.

At least 469 records · Page 26Linked to original sources
PubMed1988

Studies of the 'adaptive' repair response in human lymphocytes and V79 cells after treatment with MNNG and MNU.

In bacteria, there is evidence that a damage inducible repair response system known as the adaptive response exists since pretreatment with low doses of a simple monofunctional alkylating agent leads to a decrease in both the lethal and mutagenic effects of a subsequent challenge dose of the agent. The evidence for an analogous system in mammalian cells has proved to be inconsistent to date. The induction of chromosome repair mechanisms in human cells by low-dose radiation from tritiated thymidine has been shown to make the cells refractory to the induction of chromosome aberrations by X-rays. The present communication investigates the induction of an adaptive response in human lymphocytes from four donors and V79 cells using SCE and mutation as endpoints and MNNG and MNU for the adapting and challenging treatment. It is clear that a reproducible model of the adaptive response in human lymphocytes is difficult to establish because of the variability between different donors and different culture times. In V79 cells, assays with much larger cell numbers are required to detect a reproducible response with such small changes in mutant frequency. To demonstrate an adaptive response conclusively in mammalian cells will probably require the use of more sensitive experimental protocols and alternative methods of administration of adaptive doses of mutagen.

Animals↗
PubMed1988

Human interleukin-3 and granulocyte-macrophage colony stimulating factor: site-specific mutagenesis and expression in yeast.

The two human colony stimulating factors, interleukin-3 and granulocyte-macrophage colony stimulating factor, have been molecularly cloned and expressed as secreted proteins in yeast. In both cases, non-glycosylated and glycosylated forms of the molecules were produced. Removal of N-linked glycosylation sites from the genes by site-directed mutagenesis prevented addition of most of the sugar residues, but revealed a low level of residual O-linked glycosylation on a portion of the molecules. No difference in specific biological activity was found between the different forms of the proteins. It was found that a significant proportion of human granulocyte-macrophage colony stimulating factor was degraded by the yeast KEX2 protease that was cleaving after the dibasic sequence Arg-Arg at positions 23-24 of the mature protein. Site-specific mutagenesis was employed to change this sequence to Leu-Arg, and this change resulted in greatly increased expression levels of full length protein and biological activity.

Bone Marrow↗
PubMed1988

Human macrophage colony stimulating factor (M-CSF): alternate RNA splicing generates three different proteins that are expressed on the cell surface and secreted.

Human macrophage colony stimulating factor (M-CSF) cDNA clones were isolated from a pancreatic carcinoma cell line. Three different classes of M-CSF precursor protein (256, 554 and 438 amino acids in length) were predicted to be encoded by these cDNAs. Two of these, that we designate M-CSF alpha and M-CSF beta have already been described. The third, M-CSF gamma represents a novel class of M-CSF cDNA. All three precursors share a 32 amino acid signal sequence and the first 149 amino acids of the mature protein. At this position, M-CSF beta and gamma have insertions of 298 and 182 amino acids relative to M-CSF alpha. The first 182 amino acids of these insertions are shared between M-CSF beta and gamma. All three precursors share the C-terminal 75 amino acids that encode the transmembrane and cytoplasmic domains. Expression of all three cDNAs in COS-7 monkey kidney cells gave rise to soluble M-CSF activity, associated with proteins of subunit molecular weight 44 Kda (beta and gamma) or 28 Kda (alpha). In addition, M-CSF proteins could be detected on the surface of the transfected cells by indirect immunofluorescence. When the transmembrane and cytoplasmic domains of M-CSF alpha were removed by introducing a stop codon after amino acid 190, no membrane-bound M-CSF could be detected, but the truncated protein was secreted efficiently and was biologically active. This suggests that all three forms of M-CSF can exist as cell surface proteins, anchored by their hydrophobic transmembrane domains, and can be processed to soluble forms by proteolytic digestion. Although all soluble forms of M-CSF were biologically active in murine bone marrow colony and proliferation assays, they showed greatly reduced or no activity in similar assays using human bone marrow.

Amino Acid Sequence↗
PubMed1987

Initiation events in in-vitro packaging of bacteriophage phi 29 DNA-gp3.

Initiation events in the packaging of bacteriophage phi 29 DNA-gp3 (DNA-gene product 3 complex) were studied in a completely defined in-vitro system that included purified proheads, DNA-gp3 and the DNA packaging protein gp16. In the sequential interactions, gp16 first bound to, and was modified by, the prohead. The prohead-gp16 complex then bound to DNA-gp3, resulting in a second modification of gp16 that permitted binding of ATP. DNA-gp3 aggregates were produced, and the hydrolysis of ATP accompanied DNA-gp3 packaging. Binding and hydrolysis of ATP by gp16 was both prohead- and DNA-gp3-dependent. Interruption of packaging by DNase I addition revealed filled heads but few particles containing partial lengths of DNA, suggesting that following a rate-limiting initiation, the translocation of DNA-gp3 into the prohead was much faster in the defined in-vitro system than in extracts.

Adenosine Triphosphate↗
PubMed1987

Prohead and DNA-gp3-dependent ATPase activity of the DNA packaging protein gp16 of bacteriophage phi 29.

The ATPase activity of the DNA packaging protein gp16 (gene product 16) of bacteriophage phi 29 was studied in the completely defined in-vitro assembly system. ATP was hydrolyzed to ADP and Pi in the packaging reaction that included purified proheads, DNA-gp3 and gp16. Approximately one molecule of ATP was used in the packaging of 2 base-pairs of phi 29 DNA, or 9 X 10(3) ATP molecules per virion. The hydrolysis of ATP by gp16 was both prohead and DNA-gp3 dependent. gp16 contained both the "A-type" and the "B-type" ATP-binding consensus sequences (Walker et al., 1982) and the predicted secondary structure for ATP binding. The A-type sequence of gp16 was "basic-hydrophobic region-G-X2-G-X-G-K-S-X7-hydrophobic", and similar sequences were found in the phage DNA packaging proteins gpA of lambda, gp19 of T7 and gp17 of T4. Having both the ATP-binding and potential magnesium-binding domains, all of these proteins probably function as ATPases and may have common prohead-binding capabilities. The phi 29 protein gp3, covalently bound to the DNA, may be analogous in function to proteins gpNul of lambda and gpl of phi 21 that bind the DNA.

Adenosine Triphosphatases↗
PubMed1987

Local therapy in stage I clear cell adenocarcinoma of the vagina.

Of the 219 cases of Stage I vaginal clear cell adenocarcinoma reviewed, 176 had conventional therapy and 43 underwent local therapy. The two groups appear to be similar with respect to symptoms, stage, location of the lesion in the vagina, greatest tumor diameter, surface area, depth of invasion, predominant histologic pattern, grade, and number of mitoses; nonetheless, firm conclusions cannot be drawn because of missing data. Actuarial survival rates at 5 and 10 years for the local therapy group (92% and 88%, respectively) were essentially equivalent to those for the conventional therapy group (92% and 90%, respectively), however, the recurrence experience after local therapy was less favorable. Local therapy consisted of vaginectomy in nine cases, local excision alone in 17 cases, and local irradiation (with or without local excision) in 17 cases. The subgroup of patients receiving local irradiation had a recurrence experience as favorable as that of the conventional therapy group and more favorable than that of either the subgroup treated with vaginectomy or local excision alone. The data suggest that when employed, local therapy should include local irradiation.

Adenocarcinoma↗
PubMed1987

Characterization of the small RNA of the bacteriophage phi 29 DNA packaging machine.

The prohead connector of the bacteriophage luminal diameter 29 DNA packaging machine was reconstructed with the small RNA that regulates DNA packaging in vitro. The complete sequence of the 120 nucleotide RNA proved its origination from the promoter PE1(A1) of the left early region of phi 29 DNA, the end packaged first during assembly. The prohead RNA was clearly distinct from eubacterial 5S rRNA in sequence and composition.

Bacillus subtilis↗
PubMed1987

A small viral RNA is required for in vitro packaging of bacteriophage phi 29 DNA.

A small RNA of Bacillus subtilis bacteriophage phi 29 is shown to have a novel and essential role in viral DNA packaging in vitro. This requirement for RNA in the encapsidation of viral DNA provides a new dimension of complexity to the attendant protein-DNA interactions. The RNA is a constituent of the viral precursor shell of the DNA-packaging machine but is not a component of the mature virion. Studies of the sequential interactions involving this RNA molecule are likely to provide new insight into the structural and possible catalytic roles of small RNA molecules. The phi 29 assembly in extracts and phi 29 DNA packaging in the defined in vitro system were strongly inhibited by treatment with the ribonucleases A or T1. However, phage assembly occurred normally in the presence of ribonuclease A that had been treated with a ribonuclease inhibitor. An RNA of approximately 120 nucleotides co-purified with the phi 29 precursor protein shell (prohead), and this particle was the target of ribonuclease action. Removal of RNA from the prohead by ribonuclease rendered it inactive for DNA packaging. By RNA-DNA hybridization analysis, the RNA was shown to originate from a viral DNA segment very near the left end of the genome, the end packaged first during in vitro assembly.

Bacillus subtilis↗
PubMed1987

Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. An update.

We reviewed 519 cases of clear-cell adenocarcinoma of the vagina and cervix identified by the Registry for Research on Hormonal Transplacental Carcinogenesis of the University of Chicago through June 30, 1985. In 60 percent of all cases the patient's mother had received diethylstilbestrol during pregnancy. An additional 12 percent of all mothers had been treated with another hormone or with an unidentified medication. Ninety-one percent of the cases in diethylstilbestrol-exposed women were diagnosed when the patient was between the ages of 15 and 27. The median age at diagnosis was 19.0 years. The risk that clear-cell adenocarcinoma will develop in an exposed female from birth through age 34 is 1 case per 1000 women. The temporal pattern of occurrence of clear-cell adenocarcinoma corresponds closely with that of the use of diethylstilbestrol for pregnancy support in the United States. The rarity of this tumor among exposed women suggests that diethylstilbestrol is not a complete carcinogen and that some other factor is also involved in the pathogenesis of clear-cell adenocarcinoma of the vagina and cervix.

Adenocarcinoma↗
PubMed1987

The comparative validities of six MMPI repression scales.

The validities of six MMPI repression scales were compared using each of the other five and an independent measure as criteria (N = 190). The data gave little support to the Eichman, Welsh, and Haan Repression scales as operational definitions of this construct. The results for the Little-Fisher Denial, Byrne et al. R-S, and Haan Denial scales showed more promise.

Adult↗
PubMed1987

Effect of ethylene glycol monomethyl ether on spermatogenesis, dominant lethality, and F1 abnormalities in the rat and the mouse after treatment of F0 males.

Adult male CD rats and CD-1 mice were given a single oral dose of ethylene glycol monomethyl ether (EGM) at 0, 500, 750, 1,000, or 1500 mg/kg. Groups of 10 were killed at weekly intervals after dosing for analysis of sperm counts and morphology or testicular histology; further groups of 10 were sequentially mated to pairs of virgin females to test for dominant lethality or gross foetal malformations in the F1 generation (F1 abnormalities). EGM was found to deplete the spermatocytes of both species severely, principally pachytene cells, but with other stages affected with increasing dose. A delay in the progression of spermatogenesis may account for a discrepancy between the apparent stage-specificity of damage deduced from lowered sperm counts and that observed histologically. In the rat, morphological abnormalities were observed in sperm that had been exposed as spermatocytes; in the mouse, however, the sensitive cells were the late spermatocytes and early spermatids. In all these parameters there was an indication of a dose-response relationship in both rats and mice. In the mating studies EGM induced a dose-related decrease in fertility 5 weeks after dosing in the rat, but complete sterility in all but the lowest dose after 6 weeks. In contrast, EGM had no effect on the reproductive capacity of the mouse. There was no statistically significant evidence for the induction of dominant lethal mutations or F1 abnormalities in either species. A single oral dose of cyclophosphamide (CTX) at 100 mg/kg induced a significant increase in dominant lethality in both species. CTX reduced the number of total implants in the rat and induced a nonsignificant increase in the number of abnormal offspring sired by treated male mice.

Abnormalities, Drug-Induced↗
PubMed1987

Quinpirole hydrochloride, a potential anti-parkinsonism drug.

Quinpirole hydrochloride, a putative dopamine agonist, was investigated in animal models of central dopaminergic activity, to evaluate its possible role in the treatment of Parkinson's disease. The drug induced stereotyped sniffing in rats but, unlike apomorphine, did not produce a maximal behavioural response (stereotyped gnawing). Pretreatment with neuroleptics blocked the stereotypy induced by quinpirole. Quinpirole reversed the effects of reserpine and alpha-methyl-paratyrosine, caused dose-dependent contralateral rotations in rats with unilateral lesions of the substantia nigra induced by 6-hydroxydopamine and induced vomiting in dogs. Small doses of quinpirole decreased locomotor activity, an effect presumably mediated by pre-synaptic autoreceptors. Quinpirole bound to D2 dopamine receptors in the striatum of the rat. The chronic injection of both subthreshold and suprathreshold doses, failed to induce behavioral supersensitivity. These data indicate that quinpirole can stimulate central dopaminergic receptors, and that it is a partial agonist with direct-acting properties. Quinpirole differs from other dopaminergic drugs and may be useful for the therapy of Parkinson's disease.

Animals↗
PubMed1987

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC Working Paper No. 15/1. Genetic effects of ethanol.

Alcoholics have a higher frequency of chromosomal aberrations and sister-chromatid exchanges (SCEs) in their peripheral lymphocytes. In human and mammalian cells in vitro, ethanol generally does not induce genetic damage, but it induces SCEs in the presence of an exogenous metabolic system. In human lymphocytes in vitro, ethanol induces SCEs in the presence of alcohol dehydrogenase. In animals in vivo, ethanol induces a variety of genetic effects, including SCEs, micronuclei, dominant lethal mutations and aneuploidy in mouse eggs. There is some indication that ethanol may lead to genetic damage in sperm. In bacteria, ethanol is at best marginally active. Ethanol leads to anomalous chromosome segregation in Aspergillus, to mutations in yeast, to chromosomal aberrations and SCEs in plant root tips and to disturbances of meiosis and micronuclei in tetrads in Zea and Tradescantia respectively. The first metabolite of ethanol, acetaldehyde is mutagenic in a variety of test systems. The mutagenic activity of acetaldehyde in bacteria is questionable, but there is no doubt of its mutagenic activity in a variety of eukaryotic test systems in vitro as well as in vivo.

Animals↗
PubMed1987

The use of a battery of strains of mice in a factorial design to study the induction of dominant lethal mutations.

The induction of dominant lethality following oral dosing of males with 200 mg/kg of cyclophosphamide was investigated using a factorial experimental design. Males from 3 genotypes, BALB/c, CBA/Ca and CBA/Ca X C57BL/6JF1 hybrid (CBB6F1) were mated to 6 females of the same genotype as the males over 3 weeks. Cyclophosphamide reduced the mating frequency of the BALB/c and CBA/Ca males. The total number of implants/female was reduced in all 3 genotypes with the greatest effect in the first 2 weeks after the males were treated. The proportion of early deaths/litter was significantly increased in CBA/Ca and CBB6F1 but the increase was smaller and non-significant with BALB/c. There was a high incidence (29.8%) of early deaths in the control BALB/c females. Statistical analysis of the ratio of early deaths to total implants in a litter using either the Freeman-Tukey binomial or the arc-sine transformation gave similar and satisfactory results. Analysis of early death data rather then the ratio of early deaths: total implants would have led to misleading conclusions. The implications of the use of a factorial design in dominant lethal assays for the detection of strain variation in mutagenic response without an increase in animal usage is discussed.

Animals↗