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Biomedical subjects

N G Harding

Publications and source records attributed to N G Harding.

At least 19 recordsLinked to original sources
PubMed1985

Reversibility of cyclosporin nephrotoxicity after three months' treatment.

86 renal allograft recipients were randomly assigned to cyclosporin (Cy) for 90 days followed by azathioprine and prednisolone (Aza and P), or to Aza and P from day 0, as part of the second Oxford trial of short-term Cy use. All 62 patients whose grafts functioned for at least 120 days were included in this study. Serum creatinine was significantly higher in Cy-treated patients than in control patients from day 28 to day 90. Serum uric acid was also significantly higher in Cy-treated patients over the same period. Both creatinine and uric acid fell to the level of the control group after conversion to Aza and P. Serum uric acid was significantly higher for a given level of creatinine during Cy treatment than in either the control patients or the Cy-treated patients after their treatment had been changed to Aza and P. These data imply that Cy affects both the glomerular filtration rate and renal tubular function but that these effects are largely reversible.

Azathioprine↗
PubMed1982

Molecular biology and the clinician.

Molecular biology has uncovered informational processes which broadly apply in medicine. The points of attack range from diagnosis at the most fundamental level of information flow to the production of therapeutic agents. This is promoting movement from serendipitous strategies of advance to those of predictive rational clinical design. Specific examples show how three principal types of molecular probe are benefiting a wide range of clinical disciplines and thereby blurring interdisciplinary boundaries. There are signs that current medical training is not making the best use of contemporary molecular biology. The identification of areas in which molecular biology can be usefully applied to medicine requires medical practitioners to be aware of its diagnostic and prognostic potential. Equally, advances are delayed by gaps between laboratory workers and their clinical colleagues. The dilemma is that by creating a specialist discipline of clinical molecular biology we risk it becoming isolated and delay the impact of molecular biology in medicine as a whole. An alternative is to find a means for raising molecular consciousness throughout all disciplines in medicine.

Cloning, Molecular↗
PubMed1979

The development of resistance to methotrexate in a mouse melanoma cell line. I. Characterisation of the dihydrofolate reductases and chromosomes in sensitive and resistant cells.

PG19T3 mouse melanoma cells were selected for resistance to methotrexate. Nine sub-lines that are resistant to concentrations of methotrexate ranging from 1.27 x 10(-7) M, to 1 x 10(-4) M methotrexate were selected and characterised in terms of their content of dihydrofolate reductase activity and their chromosomes. The intracellular level of dihydrofolate reductase activity increases with increasing resistance such that at the highest level of resistance PG19T3:MTXR10(-4)M cells contain approximately 1,000 fold more enzyme activity than the parental PG19T3 cells. It is shown that the enhanced activity is due to an increase in the amount of the enzyme rather than any structural change to the enzyme in resistant cells. Comparisons of pH activity profiles, profiles under different activating conditions and titrations with methotrexate suggest that the sensitive and resistant cells contain identical dihydrofolate reductases. Analysis of the chromosomes of resistant cells shows the presence of up to 5 large marker chromosomes which contain homogeneously staining regions after G-banding. These same regions stain intensely after C-banding and fluoresce brightly after staining with Hoechst 33258. The size of homogeneously staining regions increases throughout the process of selection. For one marker chromosome this increase may have been mediated via a ring chromosome.

Animals↗
PubMed1977

Reduction of oxidised folates by dihydrofolate reductase from methotrexate-resistant Lactobacillus casei.

The use of alternative substrates by dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) was investigated as a possible mechanism for the resistance of Lactobacillus casei to the cytotoxic drug methotrexate. The reduction of folic acid and 10-formylfolic acid by homogeneous enzyme was compared to that of the normal substrate, dihydrofolic acid. The three substrates have different pH optima and Km values. In addition, it was found that the reduction of 10-formylfolic acid was markedly stimulated by the presence of ions. Although the reduction was sensitive to methotrexate in all cases, the ion activation may be of importance in partially inhibited systems.

Drug Resistance, Microbial↗