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Biomedical subjects

R Riley

Publications and source records attributed to R Riley.

At least 19 recordsLinked to original sources
PubMed1992

The enzymology of doxorubicin quinone reduction in tumour tissue.

We have reported previously that enzymes present in the Sp 107 rat mammary carcinoma catalyse doxorubicin quinone reduction (QR) to 7-deoxyaglycone metabolites in vivo [Willmott and Cummings, Biochem Pharmacol 36: 521-526, 1987]. In order to provide insights into the role of QR in the antitumour mechanism of action of doxorubicin, we have attempted in this work to identify the enzyme(s) responsible. NAD(P)H: (quinone acceptor) oxidoreductase (DT-diaphorase) was the major quinone reductase in the tumour accounting for approximately 70% of all the activity measured in microsomes and cytosols (microsomal activity, 28.4 +/- 4.6 nmol/min/mg; cytosolic activity, 94.3 +/- 11.9 nmol/min/mg). Its presence was confirmed by western blot analysis. Low levels of NADH cytochrome b5 reductase (15.6 +/- 6.3 nmol/min/mg) and NADPH cytochrome P450 reductase (14.5 +/- 4.0 nmol/min/mg) were detectable in microsomes. The presence of the latter was confirmed by western blot analysis. Pretreatment of tumours with doxorubicin (48 hr) at a therapeutic dose decreased the level of activity of all the reductases studied by at least 2-fold (P < 0.01, Student's t-test). Doxorubicin was shown not to be a substrate for purified rat Walker 256 tumour DT-diaphorase with either NADH or NADPH as co-factor and utilizing up to 20,000 units of enzyme/incubation but was confirmed to be a substrate for purified rat liver cytochrome P450 reductase. 7-Deoxyaglycone metabolite formation by purified cytochrome P450 reductase had an absolute requirement for NADPH as co-factor, was inhibited by molecular oxygen and dicoumarol (IC50 approx. 50 microM), and modulated by specific reductase antiserum. Reductive deglycoslation of doxorubicin to 7-deoxyaglycones was localized to the microsomal fraction of the Sp 107 tumour, with negligible activity being found in cytosols (NADH, NADPH and hypoxanthine as co-factors) and mitochondria (NADH and NADPH). The tumour microsomal enzyme had an absolute co-factor requirement for NADPH, was inhibited by oxygen and dicoumarol, and modulated by cytochrome P450 reductase antiserum. These data indicate strongly that NADPH cytochrome P450 reductase is the principal enzyme responsible for catalysing doxorubicin QR in the Sp 107 tumour.

Animals↗
PubMed1992

Accidental falls and injuries among seniors.

This study analyzes data on accidental falls for those aged 65 and older. The data are based on mortality statistics from 1980 to 1989 and morbidity statistics from 1985 to 1989. These statistics are provided to the Canadian Centre for Health Information by the provincial governments. Mortality rates and hospital separation rates for accidental falls are highest for those aged 65 and older. Accidents are one of the leading causes of death and hospitalization among seniors. In 1989, for those aged 65 and older, accidental falls accounted for 56% of accidental deaths and 65% of accident-related hospital separations. Mortality and hospital separation rates for accidental falls increased with age. For those aged 65 and older, the mortality rates for accidental falls were higher for men than women. However, the accident-related hospital separation rate was higher for women than men. The reason for this difference is not fully understood, but it has been suggested that while more women fall than men, more men seriously injure themselves. For men requiring hospitalization due to accidental falls, the most common injuries, in descending order, were fractures of the hip, ribs, vertebral column, humerus, and pelvis. For women, the most common injuries were fractures of the hip, humerus, radius and ulna, pelvis, and ankle. Of fall-related injuries resulting in hospitalization, hip fractures were the leading cause of death and proportionately more men than women died of hip fractures.

Accidental Falls↗
PubMed1992

Short-term hospital care for psychiatric illness among seniors.

This study focuses on recent changes in hospital use by seniors (aged 65 or over) who have been treated as inpatients in general and psychiatric hospitals for less than one year with functional psychoses and clinical disorders. The data analyzed are hospital separations for the age groups 65 to 74, 75 to 84, and 85 and over, for the period 1980-89. The data are derived from hospital morbidity statistics submitted annually to Statistics Canada by the provincial ministries of health. Age-specific separation rates for the age groups 75 to 84, and 85 and over increased during 1980-89. However, for the age group 65-74, the rates were fairly stable and in some instances decreased. These increases in short-term hospitalization of the seniors 75 and over are evidence of the appreciation of their treatability and of the improved recognition of these disorders in this age group. Adverse reactions to prescription drugs resulting in psychiatric symptoms may also be a factor in the increasing hospitalization rates. The largest increases in age-specific rates and bed days were for the age group 85 and over. For this age group, the separation rates were higher for men than women. In this age group in 1986, a higher proportion of women than men lived in institutions. For seniors living outside institutions, a larger percentage of men than women lived alone. This situation likely promotes more social isolation for men than women, and may be an important factor in the higher hospitalization rates among men.

Adolescent↗
PubMed1991

Peptic ulcers: mortality and hospitalization.

This study analyzes data on peptic ulcer disease based on deaths for 1951-1988 and hospital separations for 1969-1988. The source of the data are mortality and morbidity statistics provided to Statistics Canada by the provinces. The age-standardized mortality rates (ASMR) for peptic ulcer disease decreased from 1951 to 1988 by 69.4% for men (8.5 to 2.6 per 100,000 population), and 31.8% for women (2.2 to 1.5). Separation rates from hospitals during 1969-1988 for peptic ulcer disease also decreased by 59.8% for men (242.7 to 97.6 per 100,000 population) and 35.6% for women (103.2 to 66.5). Age-specific rates for both mortality and hospital separations increased with age. Epidemiological studies indicate that the incidence of peptic ulcer disease is declining in the general population. The downward trends in mortality and hospitalization rates for peptic ulcer disease reflect this change in incidence, but additional factors probably contribute as well to this decline. Male rates for both mortality and hospital separations were much higher than female rates at the beginning of the study period; but toward the end, the gap between the sexes narrowed considerably, mainly because the male rates declined substantially while the female rates decline moderately. The slower decline in the rates for women may be related to such factors as the increasing labour force participation among women and the slower decline in the population of female smokers.

Adult↗
PubMed1990

The treatment of mental disorders in hospitals.

This article examines mental disorders treated in Canadian general and psychiatric hospitals from 1971 to 1985-86. Significant changes occurred over the period of study. The analysis is based on hospital discharge data from eight provinces. For several decades, mental disorders have been among the leading causes of hospital use. In 1985-86, mental disorders accounted for about 10.8% of total days of care given in general hospitals. The total discharge rate for mental disorders treated in general and psychiatric hospitals declined moderately from 1971 to 1985-86. However the rate for functional psychoses has increased, while for other diagnoses the rates have decreased. The two diagnostic categories most often found in active treatment programs shifted position over the period. In 1971, the rate for general clinical disorders was almost twice that of functional psychoses; since 1981-82, the functional psychoses rate has exceeded the general clinical disorders rate. Discharge rates for functional psychosis for the elderly increased considerably, but remained stable in other age groups. This suggests that mental illness is being diagnosed more often in the elderly, and that treatment of their mental illnesses is more often undertaken.

Age Factors↗
PubMed1989

Isolation and initial characterization of a Schizosaccharomyces pombe mutant exhibiting temperature-dependent radiation sensitivity due to a mutation in a previously unidentified rad locus.

We have isolated a mutant of the yeast Schizosaccharomyces pombe which exhibits sensitivity to UV light when grown at either 30 degrees or 37 degrees C, as compared to the parental wild-type strain. This increased sensitivity is more pronounced when cells are grown at 37 degrees C. The mutant is also sensitive to 18 MeV electrons at the high temperature. Tetrad analysis of spores generated by crossing the mutant and a Rad+ strain revealed that sensitivity to both types of radiation cosegregate 2:2, relative to wild-type resistance, indicating that a single altered chromosomal locus is responsible for the radiation sensitivities observed. In addition, analysis of spores resulting from crosses between the mutant and all other known S. pombe rad mutants indicates that the temperature-dependent sensitivity described in this report is mediated by a mutation in a previously unidentified rad locus.

Alleles↗