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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 181 records · Page 10Linked to original sources
PubMed1986

Renal neoplasia and acquired cystic kidney disease in patients receiving long-term dialysis.

Acquired cystic disease (ACD) is a recently described phenomenon occurring in the native kidneys of patients treated with long-term dialysis. Renal cell carcinoma is being diagnosed with increasing frequency in patients with chronic renal failure. In most, but not all, instances the cancers develop in association with ACD. Careful microscopic examination of end-stage kidneys undergoing dialysis discloses cysts lined with hyperplastic cells. Papillary hyperplasia of cyst epithelium is recorded in virtually every detailed pathology report of tumors arising in ACD and is the likely pathogenetic basis for the development of renal tumors in cystic kidneys undergoing dialysis. The pathology of ACD and its related neoplasms is reviewed. An estimate is made of the incidence of ACD and renal cell carcinoma in patients receiving dialysis by tabulating data from studies published in medical journals. Acquired cystic disease is found in approximately 35% of patients treated by long-term hemodialysis. Renal cell carcinoma occurs in approximately 5.8% of cases of ACD. Most of the cancers are found incidentally at autopsy or by examination of kidneys from bilateral nephrectomies and are of little clinical significance, but occasional cases present aggressive neoplasms that metastasize and cause the deaths of patients.

Age Factors↗
PubMed1985

The effects of pyrimidine nucleotides on alkylating agent induced cytotoxicity and spontaneous and induced mutation to purine analog resistance in V79 cells.

Exposure of three V79 cell lines to dT after treatment with monofunctional alkylating agents resulted in potentiation of alkylation induced cytotoxicity. The degree of potentiation achieved was dependent on the concentration and duration of exposure to dT and was reversed by equimolar concentrations of dCyd. Exposure to dT after UV or X-irradiation or treatment with HN2 or MMC did not affect the cytotoxic response. dT exposure at non-cytotoxic concentrations did not affect DNA synthesis as measured by [3H]-dT incorporation when allowance was made for reductions in specific activity of labelled thymidine. However, dT post treatment reversed the alkylation induced inhibition of DNA synthesis. Toxic concentrations of dT caused an increase in frequency of TGR colonies but this increase was shown to be due to effects of dT on cell growth rate, and differential sensitivity ot HGPRT- and HGPRT+ cells. The frequency of spontaneous and alkylation induced AZR and to a lesser extent TGR colonies was also increased by non-toxic dT concentrations. Evidence was obtained which suggests that this increase is more likely to be due to alterations in the selective efficiency of the purine analogs than alterations in coding fidelity due to altered dNTP pools.

Alkylating Agents↗
PubMed1985

A family with three independent autosomal translocations associated with 7q32----7qter syndrome.

Two persons within the same family were discovered to be trisomic for the segment 7qter. However, several features differed from those described in other patients with this syndrome, for example, normal birth weight and neck size, cleft palate, and beaked nose. In addition to the phenotypic variation, there were three independently segregating autosomal translocations in the pedigree: t(1;7)(q43;q32), t(1;6) (p22.3;q14.1), and t(3;10)(q26.1;p11.21). This is a finding that, to our knowledge, has not been previously reported.

Adult↗
PubMed1984

A microsurgical technique for simultaneous pancreas and renal transplantation in the rat.

A successful technique of simultaneous pancreatico-renal transplantation into the streptozotocin-induced diabetic rat is described employing a sutureless cuff technique for three of four vascular anastomoses. Reversal of the diabetic state was uniformly observed within 24 hours postoperatively and near-normal renal function was evidenced by 50 days postoperatively. The technique is reliable and reproducible and represents the first report of successful combined transplantation into the diabetic rat.

Animals↗
PubMed1984

Modulation of enzyme activity in azaguanine-resistant V79 cells selected by chronic drug exposure.

Exposure of V79 cells to azaguanine (7-21 microM for 2-7 weeks) had little effect on growth or plating efficiency but resulted in gradual acquisition of resistance to 8-azaguanine (AZ) and 6-thioguanine (TG) and loss of ability to grow in HAT. The rate of evolution of the resistant phenotype was dependent on the concentration and duration of exposure to AZ. The increase in proportion of resistant cells was paralleled by a rise in phosphatase activity (pH optimum 7.0-7.5) expressed by intact cells and this preceded the fall in HGPRT activity. Elevated phosphatase activity and a resistant phenotype were stably expressed in clones isolated and cultured in the absence of AZ. Hypoxanthine guanine phosphoribosyl transferase (HGPRT) activity in cell extracts of three resistant clones ranged from 18 to 43% of wild-type levels but was unaltered with respect to substrate affinity and electrophoretic mobility. Mg2+-dependent activity dephosphorylated inosine 5'monophosphate (IMP), guanine 5'monophosphate (GMP), adenosine-5-monophosphate (AMP) and p-nitrophenylphosphate (PNPP) and was also elevated with respect to wild-type levels in resistant cell extracts. Purine nucleoside phosphorylase levels were similar in sensitive and resistant cell extracts. Cross-sensitivity studies with other purine analogues suggest that the elevated phosphatase activity does not contribute to the resistant phenotype. No karyotypic changes were observed in the resistant cell lines.

Animals↗
PubMed1984

Use of a reversion assay HGPRT- to HGPRT+ to demonstrate mutagenic adaptation in V79 Chinese hamster cells.

A reverse mutation assay HGPRT- to HGPRT+ has been used to demonstrate adaptation to the mutagenic effects of monofunctional alkylating agents. HGPRT- cells exposed to single doses of methylating or ethylating agents show maximum revertant frequencies immediately after treatment and these subsequently decline exponentially. Cells pre-treated with MNNG (1.0 microM) or MMS (0.27 mM) then challenged 6-168 h later with MNNG or EMS showed a consistent reduction in revertant frequencies. Pretreatment with EMS did not result in any reduction in EMS-induced reversion frequency. In parallel experiments no modifications in survival kinetics were observed. V79 cells do not remove O6-methylguanine and totally lack O6-methylguanine transferase activity, therefore other lesions and repair enzymes must be involved in the mutagenic adaptation observed.

Adaptation, Physiological↗
PubMed1984

Maternal and neonatal blood glucose after crystalloid loading for epidural caesarean section.

Serial blood glucose estimations were made in 30 women undergoing elective Caesarean section under epidural anaesthesia, 2 litres of Hartmann's solution having been rapidly infused as a circulatory preload Neonatal blood glucose estimations were made of cord blood at birth and 1 and 2 hours post delivery. A small rise in maternal blood glucose occurred during the period of preloading and time before delivery, which was not statistically significant (p greater than 0.05). There was no biochemical or clinical evidence of neonatal hypoglycaemia. We conclude that despite rapid infusion of non-dextrose crystalloid solution there is neither danger of a relative maternal hypoglycaemia in fasted mothers nor neonatal hypoglycaemia, and offer an argument that even small amounts of dextrose contained in any preloading mixture are unnecessary.

Acid-Base Equilibrium↗
PubMed1984

Azathioprine metabolism in kidney transplant recipients.

Azathioprine metabolite concentrations were studied in 54 kidney transplant recipients. Thirty-seven of these patients were studied over a 6 month period to investigate the intrapatient variation in metabolite concentrations. All patients had stable functioning grafts and normal peripheral white blood cell counts. The metabolites measured were plasma 6-mercaptopurine and red blood cell 6-thioguanine nucleotide. There was no correlation between azathioprine dose and plasma 6-mercaptopurine concentration but there was a significant correlation between dose and red blood cell 6-thioguanine nucleotide concentration (rs = 0.41, P less than 0.005). The individual transplant recipient showed little variation in metabolite concentrations over several months. Using this group as a control we studied metabolite concentrations in patients with kidney transplants who developed leucopenia. Our preliminary findings indicate that elevated red cell 6-thioguanine nucleotide concentrations, above the control range, can be associated with bone marrow depression.

Adult↗
PubMed1984

Splenic siderosis and parenteral iron dextran in maintenance haemodialysis patients.

The histological features of 40 spleens surgically removed from maintenance haemodialysis patients are reported. Twenty-four of the 40 (60%) showed massive iron loading and a significant direct correlation was found between iron loading and the amount of intravenous iron dextran administered. Since parenteral iron dextran appears to be a major factor in causing iron overload in haemodialysis patients its use as a method of iron replacement in these patients would appear inappropriate.

Blood Transfusion↗
PubMed1984

Effect of 12-O-tetradecanoylphorbol-13-acetate on selection of drug-resistant phenotypes in rodent cells.

The effect of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the selection of drug-resistant phenotypes in hamster and mouse cells has been studied. TPA increased considerably the incidence of methotrexate (MTX)-, N-(phosphonacetyl)-L-aspartate- and cadmium-resistant 3T6 and 3T3 mouse cell clones, but it had little effect on V79 and CHO hamster cells. The MTX-resistant V79 hamster cell clones, selected with or without TPA, lost their resistance within 15 cell cycles, however, 50% of the 3T6 mouse cell clones selected and maintained in the presence of TPA preserved their resistance for more than 15 cell cycles. A number of the MTX-resistant 3T6 clones overproduced dihydrofolate reductase enzyme; however, their frequency was lower among the clones selected in the presence of TPA.

Animals↗