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Biomedical subjects

R F Walker

Publications and source records attributed to R F Walker.

120 records · Page 7Linked to original sources

Determination of cortisol in human plasma by radioimmunoassay. Use of the 125I-labelled radioligand.

A radioimmunoassay for plasma cortisol featuring the gamma-emitting radioligand 125I-iodohistamine, coupled to cortisol-3-(O-carboxymethyl)-oxime, is described. The new procedure retains much of the specificity associated with the use of anti-cortisol-3-BSA sera with tritium-labelled radioligands, and has the further advantages that running costs are lower and there is a greater potential for automation. Cortisol values obtained by this procedure agree well with those obtained by a published specific radioimmunoassay using the tritiated cortisol radioligand. Specificity of the procedure was checked by comparing values obtained with and without thin-layer chromatography purication: correlation was excellent (r = 0.96). Satisfactory levels of sensitivity, precision, and accuracy were obtained.

Cross Reactions↗

Influence of cotton dust inhalation on free lung cells in rats and guinea pigs.

The influence of cotton dust inhalation on pulmonary leukocyte recruitment has been examined in rats and guinea pigs in an attempt to develop an animal model which can be used to assess the relative pulmonary toxicity of dusts from various varieties of cotton. Statistically significant increases in leukocyte populations in the lungs occur as the result of dust inhalation. Although the response is not influenced by the sex or age of the test animal, species differences do occur; guinea pigs are more sensitive to the effects of exposure than rats. Also, the exposure regimen tends to influence the degree of the response, with intermittent exposure producing fewer cells than continuous exposure for the same period of time. Future investigations will use the information gathered here to employ the most appropriate animal species as a tool to screen varieties of cotton, and thereby to rank them according to their potential to aggravate or to initiate certain pulmonary pathologies.

Age Factors↗

Relative cerebellar weight: a potential indicator of developmental neurotoxicity.

Overt malformations do not always accompany behavioral changes resulting from perinatal exposure to certain drugs. However, the central nervous system (CNS) is the anatomical substrate for behavior, and functional defects may be accompanied by more subtle, structural alterations of the brain. The purpose of this study was to determine if changes in the weights of certain brain regions occur in rats exposed prenatally and/or perinatally to propylthiouracil (PTU) which retards functional development of the brain. Pregnant rats were dosed with PTU during gestation and/or lactation, and on postnatal day 28, auditory startle responses were measured to determine if PTU altered functional development. The brains of all pups were then dissected into 10 separate regions, dried and individually weighed. Brain weights were expressed in absolute and relative (to total brain weight) terms. Pups that were exposed to PTU from days 10 to 21 of gestation grew normally, but their startle responses to auditory stimuli were significantly different (p less than 0.05) from controls. Thus, for the purpose of this experiment, PTU acted as a developmental neurotoxicant because it altered performance on a test of neuromuscular function without being overtly teratogenic. The weights of most brain regions in PTU-treated rats were statistically comparable to controls. However, relative cerebellar weight was significantly (p less than 0.05) different. Therefore, these data suggested that relative cerebellar weight might be used to predict functional defects that appear during development following prenatal or perinatal exposure to certain neurotoxicants. Although cerebellar weight and auditory startle responses were altered by PTU, this study does not establish a causal relationship between the anatomical and functional changes that occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reduced disease in aged rats treated chronically with ibopamine, a catecholaminergic drug.

As part of preclinical safety testing for carcinogenicity, postpubertal (50 days old) rats were dosed (0, 30, 90 or 180 mg/kg/day) with ibopamine (N-methyldopamine, 0,0'-diisobutyroyl ester.HCl; SK&F 100168) for 730 consecutive days. Neoplastic and nonneoplastic lesions were identified histologically in all rats that died during the period of dosing, as well as in those that were killed after it was completed. Six neoplastic lesions (adrenal cortical, mammary, and pituitary adenoma, skin papilloma, pheochromocytoma and mammary adenocarcinoma) and five nonneoplastic lesions (chronic glomerulonephropathy, renal pelvic mineralization, hepatocellular proliferative nodule, galactoceles and chronic cardiomyopathy) were significantly reduced in a dose-related fashion in at least one sex of ibopamine-treated rats. In addition, age-related alopecia and atrophy of the adrenal zona glomerulosa were retarded by ibopamine treatment. Squamous cell skin carcinoma was the only lesion that was significantly (p less than 0.05) increased in the treated groups. Mortality during the study was not significantly different in treated and control groups, indicating that the lower incidence of disease in ibopamine-treated rats was a drug effect and not an artifact of differential survival. Although life span was not measured, ibopamine-treated rats had significantly less malignant lesions than controls at the end of dosing, suggesting a potentially positive effect of treatment on population survival. As the result of these beneficial effects, ibopamine may be useful for future study of factors affecting the occurrence of disease during aging.

Aging↗

Fine particles of cotton dust influence histamine release.

Cotton dust particle distribution in respiratory airways was measured to determine if specific size particles of the heterogeneous dust are concentrated as a function of airway diameter. Previously reported work indicated that the fine particles are responsible for the decrement in pulmonary function which occurs subsequent to cotton dust inhalation. After recovery, particles were sized and counted microscopically. Significant increases in fine particles (5-7 mu) were found in all airways of exposed animals as compared with controls. These particles become more concentrated as the airway diameter decreased. Histamine determinations were made in mice lungs after the animals were exposed to cotton dust for various periods of time to see if such treatment could be correlated with elevations in the concentrations of this biogenic amine. Lung histamine increased as exposure time to cotton dust increased. It is concluded that the lung histamine release occurring after cotton dust inhalation is related to some property of the fine particles of the heterogeneous dust.

Animals↗

Circadian rhythms of testosterone and cortisol in saliva: effects of activity-phase shifts and continuous daylight.

The variations in concentrations of testosterone and cortisol in saliva samples collected by 4 healthy young men whilst on a scientific expedition from Britain to Spitzbergen are described. The rhythms observed in steroid concentrations in saliva were characterized mathematically by cosinor analysis of the levels of testosterone and cortisol determined in saliva samples collected before, during and after the expedition. Whilst in Spitzbergen, the subjects were maintained initially on the British sleep-wake schedule which was later subjected to an 8-h phase change. Variations in testosterone concentrations in saliva appeared to be largely related to subject activity rather than any photoperiodic effect with rapid resynchronization of the circadian acrophase in response to the phase shift of the sleep-wake schedule. In contrast, variation in salivary cortisol levels appeared to be less related to activity and more dependent on the slower resynchronization of an endogenous rhythm of cortisol secretion.

Adult↗