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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 217 records · Page 12Linked to original sources
PubMed1982

The effects of methylated thymidines upon cultures of V79 cells and the mechanism of incorporation of O4-methylthymidine into their DNA.

High concentrations of O2-methylthymidine, 3-methylthymidine and O4-methylthymidine (O4-MedT) have little effect on the colony forming ability of cultured Chinese hamster (V79) cells. However, the methylated derivatives enhance the toxic effects of thymidine (dT) at concentrations at which the modified nucleosides alone show no toxicity. O4-MedT was the only modified nucleoside which is incorporated into V79 cell DNA at a detectable level. In the presence of added dT there is an increase in the amount of O4-MedT incorporated. O4-MedT did not induce mutation, either forward or reverse, in V79 cells. The results indicate that O4-MedT is incorporated into DNA as an analogue of deoxycytidine and once incorporated behaves as cytidine during DNA synthesis, in contrast to O4-MedT produced in cellular DNA synthesis, in contrast to O4-MedT produced in cellular DNA by methylating carcinogens which is miscoding and potentially mutagenic.

Animals↗
PubMed1982

Trisomy 18 mosaicism: clues to the diagnosis.

Karyotypes of blood and skin fibroblasts at ages 3 and 8.5 years had shown non-mosaic trisomy 18 in a male now of age 19. Because of his prolonged survival and an atypical phenotype, skin fibroblast cultures from a new biopsy were established at age 18, and only normal 46,XY cells were observed, while peripheral blood lymphocytes still demonstrated 47,XY, + 18. This patient and six others with trisomy 18 mosaicism illustrate the advisability of looking for such a pattern in individuals whose phenotype in early life is not fully consistent with the trisomy 18 syndrome. Additional clues to the presence of trisomy 18 mosaicism are male sex, survival beyond 2 years and lack of fingertip arches.

Adult↗
PubMed1982

Natural killer cell activity and response to phytohaemagglutinin compared with the histological diagnosis of patients with transitional cell carcinoma of the bladder.

In vitro tests of immune reactivity in patients with transitional cell carcinoma (TCC) of the urinary bladder were compared with the clinical and histological diagnosis. Response of peripheral blood lymphocytes to the mitogen phytohaemagglutinin (PHA) tended to be reduced in patients with more advanced disease, although the difference between patients with advanced disease and those with early disease or controls was not statistically significant (P greater than 0.05). Assessment of natural killer (NK) cell activity in the same patients showed no change in levels of reactivity at any stage of the disease. There was no difference between the NK cell activity of patients with TCC of the bladder and normal controls.

Aged↗
PubMed1982

Custom made C18 columns for the hydrophobic chromatography of cephalosporin C derivatives.

"Hydrophobic chromatography", which is a variation of reverse phase chromatography, is applicable to the analysis of cephalosporin C derivatives, especially in fermentation broths. Unfortunately, there are no commercial C18 columns which are entirely suitable for this class of compounds. For this reason C18 columns were prepared by an in-situ bonding technique and were optimally designed for cephalosporin C derivatives. Mono-, di- and trifunctional octadecyl bonding agents were used with 10 microns silica of both 60 A and 100 A pore diameter. The best results were obtained with the difunctional agent, methyloctadecyldichlorosilane, and 100 A silica. "Endcapping" of residual silanol groups with a trimethylsilylation agent was optional, since good results were obtained with both a plain C18 column and one that was "endcapped".

Cephalosporins↗
PubMed1981

Effects of metabolic inhibitors on cell lethality and mutation induction in Chinese hamster cells. I. Inhibitors of de novo purine synthesis and a comparison with the effects of caffeine.

The effect of pre- and posttreatment incubation of UV-irradiated and ethyl methanesulphonate (EMS) treated cells with non-toxic concentrations of inhibitors of de novo purine synthesis (dnPS) on expression of potentially lethal and premutational damage at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 cells has been examined. The concentrations of inhibitors used were shown to profoundly perturb de novo DNA synthesis, by measurements of [14C]formate uptake, and cell cycle progression by flow cytofluorimetry. Postincubation in 6-methyl mercapto-purine ribonucleoside (MMPR) usually but not invariably potentiated the cytotoxic effect of UV and EMS but azaserine (AZS) and methotrexate (MTX) were without effect. No effects on mutant frequencies were observed on posttreatment with any of these agents. Caffeine produced the least effect on dnPS, but invariably potentiated lethal damage. This potentiation of lethal damage is not mediated by dnPS inhibition as has been suggested for Chinese hamster ovary (CHO) cells.

Animals↗
PubMed1981

Effects of metabolic inhibitors on cel lethality and mutation induction in Chinese hamster cells. II. The effect of posttreatment with non-toxic concentrations of thymidine.

The ability of posttreatment exposure to non-toxic concentrations of thymidine (TdR) to enhance the lethal effects of a number of alkylating agents, X-rays and UV and the lethal and mutagenic effects of N'-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) has been examined in V79 cell lines. TdR posttreatment enhanced the cytotoxic effects of ethyl methanesulphonate (EMS), MNU and ENU but not of UV or X-rays and increased both the spontaneous and MNU- and ENU-induced frequencies of azaguanine resistant (AZR) mutants. No significant effect of TdR on the spontaneous frequency of thioguanine resistant (TGR) mutants was demonstrated but the frequency of MNU-induced mutants to TGR premutagenic was enhanced. The effects on expression of both potentially lethal and premutagenic damage were reversed by addition of an equimolar concentration of deoxycytidine (dCdR). The enhancement in spontaneous and induced mutant frequency (IMF) at the HGPRT locus appears to be due to an alteration in the selective efficiency of urine analogous due to alteration in growth kinetics of cells exposed to TdR or treated with alkylated agents or posttreated with thymidine after alkylation damage and not to an alteration in the miscoding potential of alkylated bases.

Animals↗
PubMed1981

Mechanism of cytotoxic action of azaguanine and thioguanine in wild-type V79 cell lines and their relative efficiency in selection of structural gene mutants.

The cytotoxic effects of azaguanine and thioguanine have been compared in two wild-type V79 cells. To achieve equitoxic effects in both cell lines a 10-20-fold higher concentration of azaguanine than thioguanine was required. Affinity of HGPRT for azaguanine was 10-fold lower than for hypoxanthine in both cell lines and was similar to that for thioguanine in V79S cells. Affinity for thioguanine differed by a factor of 3 in the two cell lines. The rate of cell kill by azaguanine was markedly slower than by thioguanine in both cell lines. Reduction of whole cell uptake of [14C]hypoxanthine incorporation by unlabelled azaguanine was only demonstrable after prolonged incubation periods as was incorporation of [14C]azaguanine into acid-insoluble material. Experiments with cell-free extracts indicated that hypoxanthine acts as a non-competitive inhibitor of the enzyme. The slow rate of dissociation of the HGPRT-azaguanine complex is reflected in the slow rate of killing of wild-type cells. Clones resistant to the cytotoxic effects of these analogues have been selected from both cell lines and have been shown to possess HGPRT with altered kinetic properties. Our data suggest that azaguanine and thioguanine may select for mutations at different sites on the HGPRT molecule in V79 cells and provide possible explanations for the differences in effectiveness of these two agents reported in other cell lines.

Animals↗
PubMed1981

Efficiency of isolation of revertible 6-thioguanine resistant clones is dependent on the concentration of thioguanine used for selection.

The availability of a number of well characterised mammalian cell mutants which revert at measurable frequencies when exposed to specific chemical mutagens would considerably aid analysis of mechanisms of mutagenesis in mammalian cells, might ultimately provide the mammalian cell equivalent of the "Ames' tester strains and could aid the understanding of the spectrum of mutations produced by different carcinogens. As an approach to this goal we have analysed the phenotypes and revertibility of a considerable number of 6-thioguanine resistant (6TGR) mutants isolated from V79 cells and have determined the 6TG concentration which yields the optimum number of revertible cell lines.

Animals↗
PubMed1981

Transferral of malignancy as a complication of organ transplantation: an insuperable problem?

A case of inadvertent transplantation of malignancy is presented in detail. The donor was a 36-year-old woman with an unsuspected disseminated carcinoma of lung, and the renal and tumour transplant recipient a 53-year-old man. The transplanted tumour remained clinically "silent" and was discovered only a necropsy after the recipient's death from ischaemic heart disease. The phenomena of de novo primary and transferred (donor) malignancy in organ recipients, along with related immunological considerations, are briefly reviewed. Finally, with regard to the increasing frequency and variability of organ transplants, the routine clinical practice required to minimise the risk of these complications is re-emphasised, with additional recommendations.

Adenocarcinoma↗
PubMed1981

Prostatectomy in patients of 70 and over.

The management and results of a series of 200 consecutive patients, aged 70 years and over, who were treated by prostatectomy are reported. The mean age was 76 years. Significant cardiovascular and pulmonary disease was present in 51%. Transurethral prostatectomy was performed in 58%, the others being treated by open methods. In spite of the old age and associated problems and a rejection rate for operation of 5.5%, mortality within 1 month of surgery was only 2.5%. But as expected, there was post-operative morbidity particularly from pulmonary and cerebrovascular causes. However, most patients stayed in hospital for between 6 and 10 days only, with an average of 7.3 days after transurethral surgery. Management is discussed in relation to the general condition, size of the gland and the care in a specialised urology unit adapted to the treatment of this type of patient.

Age Factors↗