Biomedical subjects
M V Williams
Publications and source records attributed to M V Williams.
Human deoxyuridine triphosphate nucleotidohydrolase. Purification and characterization of the deoxyuridine triphosphate nucleotidohydrolase from acute lymphocytic leukemia.
A new fast assay procedure for increasing deoxyuridine triphosphate nucleotidohydrolase activity was developed. With this assay procedure, this enzyme derived from blast cells of patients with acute lymphocytic leukemia was purified at least 1218-fold. The molecular weight was estimated by gel filtration to be 43,000. The enzyme exhibited optimal activity over a pH range of 7 to 8 and the activation energy was estimated to be 6.5 kcal/mol at pH 7.5. While the enzyme had activity in the absence of added divalent cations, the activity could be inhibited by EDTA but not by phenanthroline. The inhibition caused by EDTA could be reversed by Mg2+ or Zn2+. The enzyme had maximal activity in the presence of Mg2+ (40 muM) and Mg2+ (4 mM) stabilized the enzyme at 37 degrees C. Cupric ion (0.5 mM) inhibited (50%) enzyme activity in the presence or absence of Mg2+. The substrate for the enzyme was dUTP and the apparent Km was 1 muM. No other deoxyribonucleoside or ribonucleoside triphosphate served as a substrate for the enzyme.
An enzymatic method for distinguishing deoxyuridine and deoxythymidine nucleotide pools and its application for determining ribonucleotide reductase activity.
A method is described for distinguishing deoxyuridine and deoxythymidine di- and triphosphate pools. The method utilizes a DNA polymerase assay for triphosphate determination and a coupled assay in which the disphosphate is converted to its corresponding triphosphate by nucleoside-diphosphate kinase and the triphosphate is measured by the DNA polymerase assay. By including deoxyruidine-triphosphate nucleotidohydrolase in the reaction mixture, dUTP is removed as a substrate for the polymerase. By determining differences in labelled acid-insoluble product formed in the reaction it is possible to determine dUTP, dUDP, dTDP and dTTP pools. Ribonucleotide reductase activity was determined by converting either CDP or ADP to its corresponding deoxyribonucleoside disphosphate and then using the diphosphate assay described for deoxyribonucleoside pools.
Age-related differences in two stages of central perceptual processes: the effects of short duration targets and criterion differences.
Two experiments investigated age differences in speed of central perceptual processes using a dichoptic backward masking paradigm. Twelve young (mean age = 19.6 years) and 12 old (mean age = 68.5 years) adults served as subjects. Exp. 1 examined age differences in speed of central perceptual processes using an ascending limits procedure and forced-choice responding to control for criterion differences. Target durations from 2 to 30 msec were used to further test the fit of young and elderly masking functions to the additive rule believed to describe masking which arises centrally (Turvey, 1973). Results from Exp. 1 showed a 33% slower speed of processing in the elderly sample. Furthermore, masking functions for both age groups fit the central rule across the wide range of target durations used. Exp. 2 examined the perceptual detectability of a 2- and 20-msec target at 7 stimulus onset asynchronies between target and masking stimuli using a forced-choice procedure. Subanalysis of two different components of the observed masking functions suggested the elderly sample was equally slow in completing both an early and late stage of central perceptual processing.
Age differences in peripheral perceptual processing: a monoptic backward masking investigation.
Peripheral processes in vision were investigated in two experiments involving monoptic backward masking with random noise. For young and old subjects, peripheral processing time (represented by stimulus onset asynchrony of target and mask) was characterized as a power function of target energy. Although processing time for both age groups showed a similar rate of decline with increasing target energy, old subjects processed targets more slowly at all energy levels. Results were independent of education, sex, and criterion differences between young and old. Target duration was related to critical interstimulus interval, such that stimulus onset asynchrony between target and mask was approximately constant for a given target energy within each age group. Evidence suggests that peripheral processing begins with target onset and that processing time is best characterized by a power function relating stimulus onset asynchrony of target and mask to target energy.
Studies on the modes of action of azaserine inhibition of Escherichia coli. Potentiation of phenylalanine reversal.
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Studies on the modes of action of azaserine in Escherichia coli. Mechanism of resistance to azaserine.
Growth of wildtype Escherichia coli was inhibited by azaserine. There was an inverse relationship between the initial rate of uptake of phenylalanine and the azaserine concentration. Moderately azaserine-resistant mutants exhibited an initial rate that was similar to that of an aroP mutant, but highly azaserine-resistant mutants exhibited little, if any, uptake of phenylalanine. All of the azaserine-resistant organisms tested harboured a mutation in the aroP+ gene. However, resistance to the antibiotic was not due solely to this lesion.
The effect of practice on age differences in central perceptual processing.
The effects of practice on performance in a dichoptic masking paradigm was assessed across two age groups (mean age - 66.5 and 18.8 years). For both age groups practice resulted in a reliable reduction in the time separation between the onset of the target stimulus and the onset of the masking stimulus required to escape masking. The magnitude of reduction was equivalent in both age groups, indicating that the amount of practice in this study does not ameliorate previously demonstrated age differences in speed of central perceptual processing. On the other hand, the equivalent improvement in both age groups suggests no age-related decrement in the adaptability of central perceptual processes.
The forgotten philanthropist.
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Pharmacokinetic studies using multiple administration of RO 03-8799, a 2-nitroimidazole radiosensitizer.
It has been shown that the propanolamine 2-nitroimidazole Ro 03-8799, is about an order of magnitude more efficient than misonidazole as a radiosensitizer in vitro, which is more than its electron affinity would predict. However, in vivo studies have so far shown only a minimal improvement compared to misonidazole. One reason for this could be that diffusion to the site of action in the hypoxic cell is restricted by the short half-life in the mouse and the net positive charge carried by the drug at physiological pH. Ways of maintaining a constant blood or tumor concentration over a period of 1--2 hours were investigated so that the tumor response could be assessed after this time. Initial experiments used multiple intraperitoneal or intravenous injections, for which the amount of drug required can be calculated theoretically provided sufficient pharmacokinetic data are available. Later experiments using continuous infusion of the drug were aimed at maintaining the gross tumor concentration equal to that found at the time of peak sensitization following a single administration. Results will be presented using each of these approaches. The technical feasibility and advantages of each method, together with general problems associated with interpreting any radiobiological results obtained using this approach will be discussed.
In vivo testing of a 2-nitroimidazole radiosensitizer (Ro 03-8799) using repeated administration.
The radiosensitizing efficiency of a novel 2-nitroimidazole (Ro 03-8799) has been compared with that of misonidazole. Each compound was assessed by constructing dose response curves for regrowth delay using a range of drug doses. The concentration of each compound was measured in tumor homogenates with high performance liquid chromatography (HPLC). When compared on the basis of administered dose the new compound was no more efficient than misonidazole. Comparison on the basis of measured tumor concentrations showed that Ro 03-8799 was 3--4 times more efficient than misonidazole, but only at very high drug levels. Previous in vitro studies had shown a constant 10-fold difference in potency. In order to eliminate possible artifacts caused by the short half life in mice, repeated injections of Ro 03-8799 were used to maintain a constant tumor concentration for two hours before irradiation. No increase in effectiveness was observed with prolonged exposure. This is a charged compound whose distribution is pH dependent; gross tumor levels should therefore be interpreted with caution.
A closer look: profiling foundations created by health care conversions.
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Mutagenic effect of mercury (II) in eukaryotic cells.
Acute exposure of KB and Chinese hamster ovary cells (AS52) to low concentrations of mercury (II) results in a dose dependent binding of mercury to DNA. This binding of mercury (II) to the DNA occurs at concentrations of mercury that have little if any effect on glutatione levels or on superoxide dismutase activity. Mutational studies with AS52 cells demonstrated that concentrations (0.1 to 0.4 microM) of mercury (II) which were not cytotoxic caused an increase (1.7 to 3.1) in the frequency of mutations in the gpt gene when compared to non-treated controls. These results suggest that there may be risks associated with exposure to non-cytotoxic levels of mercury (II).
Obstacles predicting lack of a regular provider and delays in seeking care for patients at an urban public hospital.
OBJECTIVE: To determine the correlation among obstacles to medical care, lack of a regular source of care, and delays in seeking care. DESIGN: Cross-sectional survey of patients presenting for ambulatory care during a 7-day period. Multiple logistic regression models were used to identify obstacles independently associated with outcome variables. SETTING: Urban public hospital. PATIENTS: A total of 3897 disadvantaged and predominantly minority patients. MAIN OUTCOME MEASURES: Lack of a regular source of medical care and delay in seeking medical care for a new problem. RESULTS: The majority (61.6%) of patients reported no regular source of care. Of 2341 patients reporting a new medical problem, 48.4% waited more than 2 days before seeking medical care. No health insurance (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.89 to 2.61), no transportation (OR, 1.44; 95% CI, 1.23 to 1.70), exposure to violence (OR, 1.21; 95% CI, 1.08 to 1.45), and living in a supervised setting (OR, 1.50; 95% CI, 1.00 to 2.25) were independent predictors of lack of a regular source of care. No insurance (OR, 1.24; 95% CI, 1.02 to 1.51), no transportation (OR, 1.45; 95% CI, 1.19 to 1.77), and less than a high school education (OR, 1.22; 95% CI, 1.08 to 1.49) were independent predictors of delaying care for a new medical problem. CONCLUSIONS: Obstacles in addition to lack of insurance impede provision of medical care to disadvantaged patients. The adoption of universal health care coverage alone will not guarantee access to appropriate medical care.