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M Fox

Publications and source records attributed to M Fox.

At least 163 records · Page 9Linked to original sources
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↗
PubMed1987

Drug resistance and DNA repair.

DNA repair confers resistance to anticancer drugs which kill cells by reacting with DNA. A review of our current information on the topic will be presented here. Our understanding of the molecular biology of repair of 0(6)-alkylguanine adducts in DNA has advanced as a result of the molecular cloning of the E. coli ada gene but the precise role of this lesion in the cytotoxic effects of alkylating agents in mammalian cells is not completely understood. Less progress has been made in understanding the enzymology and molecular biology of DNA cross-link repair even though such lesions are important for the cytotoxic effects of the widely used bifunctional alkylating agents and platinum compounds. It is evident that drug sensitive or resistant phenotypes are as highly complex as are the effects of DNA damage on cell metabolism and various aspects of these effects are discussed. Few clear correlations have been made between quantitative differences in DNA repair capacity and cellular sensitivity but assays which were developed to measure fidelity and intragenomic heterogeneity in DNA repair are beginning to be applied. Such studies may reveal subtle differences between sensitive and resistant cell lines. The molecular cloning of human DNA repair genes by transfection into drug sensitive rodent cells has been attempted. Some success has been achieved in this area but the functions of the cloned genes have yet to be identified.

Animals↗
PubMed1987

The in vitro lifespan of MRC-5 cells is shortened by 5-azacytidine-induced demethylation.

The minor base 5-methylcytosine (5mC) in DNA may be important for the regulation of gene expression. Random loss of 5mC may occur during pre-replicative DNA synthesis in mortal cell strains, and thus give rise to biochemical aberrations in aging cells. 5-Azacytidine (5azaC) was used to induce loss of 5mC in DNA of human diploid fibroblasts (MRC-5) in an attempt to accelerate in vitro senescence. The 5mC content of DNA was measured by incorporation of [3H]uridine into dividing cells, hydrolysis of DNA and separation of bases by HPLC. In untreated MRC-5 cells, 5mC was 3.6% of the total cytosine (C+5mC) at population doubling (PD) 20 (28% of lifespan) and fell to 1.6% at PD 67 (97% of lifespan). A single pulse treatment with 5azaC (1 microgram/ml) induced demethylation and shortened the lifespan by 10% (6.8 PDs loss). Pulse-treated cells showed temporary growth inhibition, though they subsequently regained normal growth rate and morphology. However, uniform treatment with 0.1 microgram/ml 5azaC between PD 20 and 23 produced no immediate growth inhibition, but a 22% loss of 5mC and 25% decrement in lifespan (16.6 PDs loss). The present results indicate that 5mC levels fall during normal aging of MRC-5 cells and accelerated 5mC loss shortens the in vitro lifespan of these cells. Hypomethylation may thus be responsible for some aspects of in vitro aging.

5-Methylcytosine↗
PubMed1987

Protection of Chinese hamster cells against the cytotoxic and mutagenic effects of alkylating agents by transfection of the Escherichia coli alkyltransferase gene and a truncated derivative.

The cytotoxic and mutagenic effects of various monofunctional and bifunctional alkylating agents have been assessed in V79 Chinese hamster cells that express either the entire O6-alkylguanine (O6AG) and alkylphosphotriester alkyltransferase (ATase) gene (clone 8 cells) or a truncated form that codes only for O6AG ATase activity (clone SB cells). Protection ratios, as determined by D37 values, were greater for clone 8 cells than for SB cells. Significant protection against the mutagenic effects of N-methyl-N-nitrosourea and ethylmethanesulphonate at the hypoxanthine phosphoribosyltransferase (HPRT) locus was observed in clone 8 and SB cells. Streptozotocin and the haloethyl nitrosoureas, chlorozotocin and bis-chloroethylnitrosourea were less efficient in inducing HPRT-deficient mutants and a smaller degree of protection was afforded by the transfected genes. This is possibly due to the propensity of these compounds to induce multi-locus deletions. Southern analysis of DNA from clone 8 and SB cells indicated the presence of multiple copies of the plasmid integrated into clone 8 cells but few copies in clone SB cells. The copy number did not change but ATase levels fell when cells were grown in the absence of G418.

Alkylating Agents↗
PubMed1987

Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat.

Alterations in local prostacyclin and thromboxane synthesis could mediate the changes in vascular perfusion and platelet deposition in acutely rejecting renal allografts and prostaglandin E2 (PGE2) has been implicated in the regulation of the immune response. 6-Keto-prostaglandin F1 alpha (6 KetoPGF1 alpha), thromboxane B2 (TxB2) (the stable degradation products of prostacyclin and thromboxane A2 [TxA2], respectively) and PGE2 were measured in incubates of cortical slices taken from rat renal allografts or isografts one to seven days after transplantation. 6 KetoPGF1 alpha and TxB2 synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals. During the phase of cellular rejection (3-5 days), TxB2 synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues. There was also a small but significant rise in cortical PGE2 synthesis at this time, but vascular and cortical 6 KetoPGF1 alpha production remained unchanged. Renal infarction, occurring 7 days after transplantation, was accompanied by a nonspecific rise in the synthesis of all three prostaglandins by renal cortical slices. Increased tissue TxA2 synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Shedding of oocysts in immunocompetent individuals infected with Cryptosporidium.

In June 1985, we investigated an outbreak of cryptosporidiosis at a day-care center in Florida. Through day-care center-wide stool screening, 33% (28/84) of the children and 22% (4/18) of the staff members submitting stool specimens were found to have cryptosporidiosis. Children 12-35 months of age and their teachers were at highest risk. All but 1 of the Cryptosporidium-positive patients reported diarrhea, which lasted between 1-44 days. Serial stool specimens were obtained from 8 infected individuals (5 children and 3 adults). Duration of oocyst shedding ranged from 8 to more than 50 days and continued in 5 individuals after diarrhea ceased. No relationship was found between duration of oocyst shedding and the age of the patient or duration or severity of diarrhea. Results of the investigation indicate that infected individuals may continue to excrete oocysts and, therefore, may remain infectious for days or weeks after gastrointestinal symptoms disappear.

Adult↗
PubMed1986

Primary tracheoesophageal puncture for voice restoration.

A 93 percent success rate of voice restoration after primary tracheoesophageal puncture was achieved in 15 patients. Patients were usually able to talk within 3 weeks after laryngectomy. Male patients without chronic obstructive lung disease achieved better results. The incidence of complication after this procedure were not significantly different from a group of 111 patients who underwent laryngectomy alone. Finally, early speech acquisition provides a substantial psychologic boost for the patient undergoing total laryngectomy.

Adult↗