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Biomedical subjects

S D Harrison

Publications and source records attributed to S D Harrison.

At least 73 records · Page 4Linked to original sources
PubMed1984

Life change and onset of cancer in identical twins.

The relationship of life change to the onset of cancer was studied in 22 pairs of HLA-identical siblings who were discordant for hematologic malignancies. The twin pairs were hospitalized for bone marrow transplantation. Life change was measured using a well-validated instrument, the Schedule of Recent Experiences (SRE). Contrary to our expectations, we were unable to document increased life changes in the sick twins. The timing of administration of the SRE with respect to the transplant did influence reporting of life events. However, regardless of timing of administration, in the period antedating the diagnosis of malignancy the healthy donor twins had increased or equivalent life changes when compared to their sick twins.

Adolescent↗
PubMed1983

Correlation of metal toxicity with in vitro calmodulin inhibition.

A fundamental biochemical process that is directly and universally related to the toxicity of metals and metal compounds has yet to be identified. Results of studies reported here indicate that the toxicity of a series of divalent metal cations correlates well with the metals' ability to inhibit the Ca2+ receptor protein calmodulin (r = 0.986). Because calmodulin regulates a variety of cellular enzymes and processes including intracellular Ca2+ concentrations, calmodulin inhibition may have value for predicting metal toxicity and for revealing information about the mechanism by which metals induce toxic effects.

Animals↗
PubMed1983

An investigation of the mouse as a model for vincristine toxicity.

The purpose of this study was to investigate the toxicologic responses of mice to vincristine (VCR), an established antitumor drug, and to compare them with those reported for dogs, monkeys, and humans. This comparison was expected to facilitate the continuing appraisal of the mouse as a model for toxicologic responses to antitumor drugs in human patients. In duplicate experiments, male B6D2F1 mice were treated with 1.0, 1.5, 2.0, and 3.0 mg/kg of VCR in single IP doses. These sublethal doses corresponded to 0.25, 0.40, 0.50, and 0.80 LD50. On posttreatment days 1, 3, 6, 10, 14, and 21, groups of mice were killed and blood and other tissues were collected for hematologic (8 tests), clinical chemical (15 tests), and histopathologic (11 tissues) evaluations. VCR produced dose-dependent body weight loss, reticulocytopenia, granulocytopenia, elevated plasma alkaline phosphatase, GPT, and GOT activities, and damage to the gastrointestinal epithelium. These reversible changes were most severe during the first 3 days posttreatment. The mouse was comparable to the dog and the monkey in reflecting the target organ toxicity of VCR in humans. Studies with additional antitumor drugs will be required before the overall predictive reliability of this model can be expressed quantitatively.

Alanine Transaminase↗
PubMed1982

Effects of prochlorperazine on experimental nephrotoxicity.

In early studies of the antitumor drug 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU), animal models consistently predicted that the compound would be nephrotoxic in humans. Nephrotoxicity in cancer patients who had received methyl-CCNU was not confirmed until about 6 years after clinical trials began. We have investigated the possibility that prochlorperazine, a commonly used antiemetic, might affect the development of nephrotoxicity. Prochlorperazine (1, 2, 5, and 8 mg/kg IP on days 1-3) produced a dose-related reduction in the concentrations of plasma urea nitrogen in mice that received nephrotoxic doses of methyl-CCNU (42, 52, or 63 mg/kg IP on day 1). The frequency and severity of renal lesions evaluated histopathologically were reduced significantly as the prochlorperazine dose increased. To study further this apparent protective activity of prochlorperazine, we chose a second nephrotoxin, mercuric chloride (HgCl2, 1 mg/kg IP on day 1) and a rodent species used more commonly as a model for nephrotoxicity, the rat. Prochlorperazine (2.5 or 10 mg/kg IP on days 1-5) inhibited HgCl2-induced urinary excretion of N-acetylglucosaminidase and leucine aminopeptidase. Urinary excretion of these enzymes on day 1 reflected proximal tubular epithelial degeneration and necrosis in rats that received HgCl2 alone. The severity of HgCl2-induced renal lesions evaluated histopathologically on day 16 was significantly reduced by combination treatment with prochlorperazine. Phenothiazines have numerous pharmacologic properties that might account for this observation, and additional studies will be required to establish the mechanism of this protective effect of prochlorperazine against acute nephrotoxicity in rodents.

Animals↗
PubMed1978

Qualitative and quantitative toxicity of single and sequential sublethal doses of 5-fluorouracil in BDF mice.

Qualitative and quantitative toxicity studies were conducted in BDF mice after ip injection of 33, 66, 134, and 200 mg/kg of 5-fluorouracil (5-FU) in daily doses for 1, 2, 3, or 4 consecutive days. Groups of five mice from each schedule and dose level provided blood and selected visceral organs for hematologic and histologic evaluation on posttreatment Days 1, 3, 6, 10, 14, and 21. Comparable groups of five mice were blood donors for biochemical evaluation of pooled plasma samples. The results indicated the onset, severity, and duration of injury to target organs and characterized the relationship of sublethal toxicity to drug dose and frequency of administration. Marrow suppression was reflected in peripheral erythropenia, thrombocytopenia, and leukopenia and also in medullary erythropenia and granulocytopenia. A transient elevation of plasma LDH, loss of body weight, and appearance of microscopic lesions of the gastrointestinal mucosae were additional indices of toxicity. The BDF mouse appears to provide a good qualitative and quantitative prediction of 5-FU toxicity, although the mouse apparently is quantitatively more sensitive than man.

Animals↗
PubMed1978

Hematology and clinical chemistry reference values for C57BL/6 X DBA/2 F1 mice.

We have analyzed hematology data from 504 individual male C57BL/6 X DBA/2 (hereafter called B6D2F1) mice. Clinical chemistry data from an additional 304 individual male B6D2F1 mice have also been analyzed. The mice had served as drug-diluent controls in 24 toxicological evaluations of anticancer drugs administered singly or in combination. The studies were carried out under standardized conditions during an 18-month period between July 1975 and December 1976. Test values corresponding to 9 percentiles have been selected from an ordered ranking of values for each of 18 hematologic tests and 18 clinical chemistry tests. Since 95% of the values for a given test are found between the 2.5th and 97.5th percentiles, test values corresponding to these percentiles provide reference values ("normal" values) for these mice. The other percentiles (5th, 10th, 25th, 50th, 75th, 90th, and 95th) indicate the distribution of values between the reference limits for each test. Since values for all tests do not conform to the Gaussian distribution, this nonparametric analysis provides reference values that are more accurate than might be obtained from calculation of the mean and standard deviation of a given test. The B6D2F1 mouse, commonly referred to as BDF1, has been widely used for preclinical evaluation of anticancer drugs, and these data should be useful to investigators who are conducting qualitative and quantitative toxicity evaluations in these mice.

Animals↗