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Biomedical subjects

M Fox

Publications and source records attributed to M Fox.

At least 73 records · Page 4Linked to original sources
PubMed1989

Pseudomembranous trigonitis of the bladder: hormonal aetiology.

Fourteen formalin fixed and paraffin wax embedded biopsy specimens from 10 women (age range 34-68) presenting with pseudomembranous trigonitis were studied using a combination of anti-oestrogen receptor monoclonal antibodies in an avidin-biotin immunoperoxidase technique. All epithelial areas showing vaginal metaplasia exhibited staining confined to the nucleus in the basal and parabasal layers of the squamous epithelium while no staining was encountered in adjacent trigonal transitional epithelium included in nine of the biopsy specimens. The selective expression of nuclear oestrogen receptor in trigonal epithelium affected by vaginal metaplasia in a distribution similar to that reported in vaginal epithelium by other workers lends further support to oestrogen mediated aetiology in this condition and is consistent with an embryological derivation of the trigone, distinct from that of the rest of the bladder.

Adult↗
PubMed1989

The in-vitro inhibition of rat alloantigen presentation by immunotoxins--implications for allografting.

The removal of graft interstitial dendritic cells (IDC) prior to transplantation into a recipient has been shown to improve graft survival in a number of experimental studies. We report the in-vitro properties of two immunotoxins (IT) which could be used to deplete graft IDC when administered ex vivo by hypothermic perfusion in an experimental rat transplantation model. Ricin A chain (RAC) IT targeted at either class II major histocompatibility complex (MHC) molecules or leukocyte common antigens (LCA) were prepared. These IT had similar equilibrium constants, binding kinetics and inhibiting activity of cell-free protein synthesis. IT cytotoxicity was assessed by inhibition of alloantigen presentation by targeted low density spleen cells (LDSC) in a one way mixed lymphocyte culture (MLC). When LDSC were hypothermically incubated for 2 h with IT only the anti class II MHC IT inhibited the MLC and the maximum inhibition depended on the cell allotypes. The inhibition was increased to almost 100% when chloroquine was incorporated throughout the culture period.

Animals↗
PubMed1989

N-ras mutation in chemically induced rat brain tumour.

Rat brain tumour was induced by treatment with N-ethyl-nitrosourea. Using Southern blot analysis, restriction fragment length polymorphism of N-ras gene was identified. Comparative studies showed that new restriction site did not occur in the DNA of DMN induced renal and liver tumours. The data suggest that the mutation occurring may be specific to the "target" cell or to the structure of carcinogens.

Animals↗
PubMed1989

Validity of self-estimated and weighed dietary data for assessment of military rations.

Validity of food intake values, self-estimated by subjects and weighed by researchers, was evaluated during the assessment of a new military ration. As an addition to food intake measured by the two methods, a third set of intake values was generated by combining food intakes from the self-estimated and weighted data. This combined method is proposed as another reference for assessing validity. The new ration, Meal-Ready-to-Eat (MRE), was the sole source of food for an experimental group of 27 soldiers engaged in a 34-day field exercise. A control group of 30 soldiers ate a freshly prepared (A ration) breakfast and dinner and an MRE lunch. Agreement of mean nutrient intake values from self-estimated and weighed data was high among both experimental and control groups (average coefficients of correlation for 16 nutrients, 0.948 and 0.884, respectively). Paired t-tests yielded no significant differences between self-estimated and weighed means for nutrient intake but were significantly different from the means obtained by the combined method (p less than .0001). Mean nutrient intakes determined by both the self-estimated and weighed methods approached 90% of the intakes found by the combined method.

Adult↗
PubMed1988

TPA enhancement of the recovery of methotrexate and N-phosphonacetyl L-aspartate resistant mouse 3T6 cell clones is associated with transient alterations of cell cycle progression.

The effects of methotrexate (MTX) and N-phosphonacetyl L-aspartate (PALA) with and without 12-O-tetradecanoylphorbol-13-acetate (TPA) have been tested on the cell-cycle traverse of mouse 3T6 and Chinese hamster V79 cell lines. MTX, whether administered with or without TPA, had very little effect on the cell cycle of the V79 Chinese hamster cell line. However, low MTX concentrations produced a significant G1 accumulation in the mouse 3T6 cell line after 24 hr, and this was accentuated by TPA treatment. These findings parallel previous observations that TPA enhances the recovery of MTX- and PALA-resistant mouse 3T6 cell clones but has little or no effect on drug-resistant colony recovery in the V79 Chinese hamster cell line. The possibility that the increase in accumulation of cells in G1 might permit the rescue of an increased proportion of cells due to the release of purines and pyrimidines from dying cells is discussed. Such rescue should occur irrespective of whether or not the cell line has the ability to amplify its target genes.

Animals↗
PubMed1988

Phenotypic resistance to methotrexate and N-phosphonacetyl L-aspartate is induced by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA).

Three different 3T6 mouse fibroblast cell clones with intrinsically different sensitivities to methotrexate (MTX) have been isolated from an originally heterogeneous population. When these 3 different clones were exposed to MTX in the presence of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) the degree of enhancement of recovery of methotrexate resistant (MTXR) colonies was greatest in the most sensitive clone. MTXR colonies isolated and cultured in the presence and absence of MTX and TPA were analysed for dihydrofolic acid reductase (dhfr) levels by flow cytometry after binding of fluorescent methotrexate. None of the 58 clones showed major changes in dhfr levels. Dot-blot analysis of 12 clones indicated no increases in dhfr gene copy number or mRNA levels consistent with gene amplification. Southern analysis of 6 further clones indicated that only 1 clone isolated by multi-step selection had amplified dhfr sequences. TPA-enhanced mouse 3T6 N-phosphonacetyl-L-aspartate (PALA)-resistant colony recovery and mouse 3T3 MTXR colony recovery were also shown, by dot-blot analysis, not to be due to gene amplification. The data indicate that TPA can have a profound effect on drug-resistant colony recovery by mechanisms other than induction of gene amplification.

Animals↗
PubMed1988

Assignment of ecto-5'-nucleotidase to human chromosome 6.

Ecto-5'-nucleotidase activity (5NT) was measured on whole cells of 26 human x Chinese hamster hybrids. Concordance analysis showed 100% correlation between enzyme activity and inheritance of human chromosome 6. This observation was confirmed by a segregation analysis in which cells of a hybrid containing chromosome 6 were stained by indirect immunofluorescence for HLA Class 1 antigen and sorted by a fluorescence-activated cell sorter (FACS). Cells in the HLA- compartment were cloned and expression of HLA and 5NT was determined. Of nine clones, three were HLA-, 5NT- and six were HLA+, 5NT+, supporting the linkage of 5NT to chromosome 6.

5'-Nucleotidase↗
PubMed1988

Different mechanisms of reversion of HPRT-deficient V79 Chinese hamster cells.

The revertibility of three spontaneous hypoxanthine phosphoribosyl transferase (HPRT)-deficient V79 cell lines has been determined after exposure to a number of alkylating agents. TG11 and 19 reverted at frequencies ranging from 1 X 10(-5) to 1 X 10(-4) after exposure to doses of ethylmethane sulphonate (EMS) N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) resulting in surviving fractions between 1.0 and 0.1. Reversion frequencies in TG15 ranged from 10(-7) to 5 x 10(-6) over a similar dose range. The relative efficiencies of different monofunctional alkylating agents in causing reversion of TG11 at equitoxic doses were ENU greater than EMS greater than N-ethyl-N-nitroso-guanidine greater than MNU greater than N-methyl-N-nitrosoguanidine greater than methylmethane sulphonate. Revertant frequencies for all three cell lines were maximal immediately after treatment and declined thereafter at a rate inversely proportional to dose. Such kinetics are explicable if reversion is due to miscoding opposite alkylated guanines. Reversion frequencies after N-butyl-N-nitrosourea exposure were 100-fold lower than after MNU and kinetics of expression of revertant colonies differed. Frequencies were low immediately after treatment, increased between 0 and 24 h then remained at a plateau. Similar kinetics were observed after chlorozotocin and bis-chloroethylnitrosourea exposure. This difference in expression kinetics suggests that reversion in this case is not the result of direct miscoding but of errors in excision repair. TG11, 15 and 19 had low spontaneous mutant frequencies which were either unaffected or only marginally increased by treatment with 5-azacytidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylating Agents↗
PubMed1988

Expression of an E.coli O6-alkylguanine DNA alkyltransferase gene in Chinese hamster cells protects against N-methyl and N-ethylnitrosourea induced reverse mutation at the hypoxanthine phosphoribosyl transferase locus.

The spontaneous hypoxanthine phosphoribosyl transferase deficient (HPRT-) mutants of V79 cells (TG11 and TG15) were transfected with a retrovirus-based plasmid containing a truncated form of the Escherichia coli gene which codes for O6-alkylguanine (O6-AG) DNA alkyltransferase (ATase). The resultant cell lines TG11SB5 and TG15SB7 were G418 resistant and expressed high levels of O6-AG ATase activity. The frequency of revertants induced by equitoxic doses of N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) was 10- to 50-fold higher in TG11 than in TG15. In TG11SB5 and TG15SB7 induced revertant frequencies were reduced relative to TG11 and TG15 by factors of 6-8 and 1.5-3.0, respectively, immediately after treatment. On delayed plating the frequency of MNU-induced revertant colonies decreased at a rate inversely proportional to dose in both TG11 and TG11SB5. In contrast, after exposure of TG11SB5 to ENU (50 or 75 micrograms/ml) initial reversion frequencies were low compared with TG11, but then rose to a plateau frequency by 24 h, which was maintained for up to 72 h. The frequency of reversion observed, the degree of protection afforded by the E.coli O6-AG ATase and the kinetics of expression of revertants were thus cell line specific suggesting that DNA sequence specific alkylation and/or preferential repair may be responsible. The initial protection against mutagenesis is consistent with the hypothesis that MNU- and ENU-induced reversion is the result of miscoding opposite O6-AG or O4-alkylthymine residues. Expression of O6-AG ATase activity was variable when cells were continually cultured over long periods despite the presence of the selective antibiotic G418.

Animals↗
PubMed1988

An A-chain ricin immunotoxin targeted against rat class II major histocompatibility complex molecules. In vitro and in vivo effects.

Studies reported here have demonstrated that an antirat class II major histocompatibility complex molecule A-chain ricin immunotoxin could specifically remove, in a dose-dependent manner, the cells capable of stimulating the rat mixed lymphocyte reaction, an in vitro model of transplant rejection. It was further demonstrated that administration of a monoclonal antibody against class II major histocompatibility complex molecules to isolated rat pancreas grafts by hypothermic perfusion resulted in the targeting of cells bearing class II major histocompatibility complex molecules. But administration of the immunotoxin to isolated pancreases in a similar manner did not prolong their survival when allografted across a major histocompatibility barrier.

Animals↗
PubMed1988

Performance-based measurements among elderly drivers and nondrivers.

Although driving is an important ability for maintaining independence in the later years, clinical factors that determine driving status are unknown. Aged male veterans (mean age, 70 years) were recruited from an outpatient clinic (N = 143), including 77 frequent drivers, 41 infrequent drivers, and 25 who drove rarely or not at all. There were 116 (84%) who completed a comprehensive performance-based assessment. There were no significant differences between the three groups in age, formal cognitive testing, or prevalence of stroke history. However, there were significant differences in grip strength, reaction time, static visual acuity, dynamic visual acuity, and peripheral vision. Using stepwise ordinal logistic regression, dynamic visual acuity, nondominant hand grip strength, and total horizontal peripheral visual field were significantly associated with driving frequency (P less than .05), and together explained approximately 45% of the variance. Subtle motor and visual deficits that can be detected by a performance-based assessment may play an important role in determining driving frequency in the elderly.

Activities of Daily Living↗
PubMed1988

Malignant fibrous histiocytoma of the penis.

A 77-year-old caucasian man presented with toxemia and dehydration, with obstruction of the distal penile urethra by a primary malignant fibrous histiocytoma. He died of toxemia and renal failure 6 days after admission.

Aged↗
PubMed1988

The effect of hypothermic ischemia on recovery of left ventricular function and preload reserve in the neonatal heart.

Neonatal and adult myocardium respond differently to ischemia. In addition, the neonatal heart possesses a limited preload reserve. The effect of uninterrupted hypothermic ischemia on recovery of left ventricular function and preload reserve was studied in two groups of isolated rabbit hearts: group 1 (neonates, n = 8), 7 to 10 days old; group 2 (adults, n = 15), 6 to 12 months old. Peak left ventricular systolic pressure, the first derivative of left ventricular systolic pressure, and heart rate were measured at left ventricular pressures of 0, 5, 10, and 15 mm Hg before and after 120 minutes of global ischemia at 27 degrees C. Before ischemia, left ventricular systolic pressure increased significantly at each increment of left ventricular end-diastolic pressure for both groups of hearts. After hypothermic ischemia, recovery of left ventricular systolic pressure was significantly reduced at each level of left ventricular end-diastolic pressure among neonatal hearts (range 75% to 79% of control values). The postischemic recovery of left ventricular systolic pressure in the adult hearts was markedly reduced from baseline values (range 43% to 53% of control values) and was significantly worse than that of neonatal hearts at each level of left ventricular end-diastolic pressure (p less than 0.001). Both groups were able to respond to increasing preload after ischemia. The slope of the curve describing the relationship between left ventricular end-diastolic pressure and percent recovery of left ventricular systolic pressure was not different from zero for neonatal hearts but was significantly greater than zero among the adults (0.22 +/- 0.21 versus 0.73 +/- 0.07, p = 0.0056). After ischemia, the first derivative of left ventricular systolic pressure fell significantly from control values among neonatal hearts (71% of control values). The reduction was considerably greater, however, among the adult hearts (54% of control values). These data indicate that the neonatal heart recovers systolic function better than the adult heart after global ischemia with moderate hypothermia.

Aging↗