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Biomedical subjects

M J Capps

Publications and source records attributed to M J Capps.

At least 19 recordsLinked to original sources

Ototoxicity and the olivocochlear bundle.

Cochlear hair cell damage due to kanamycin sulfate was studied in chinchillas receiving 200 mg/kg kanamycin for nine days. The drug was given to a group of animals with lesions of the crossed olivocochlear bundle, a group that had received a sham operative procedure, and a group of normal animals. The animals were sacrificed 14 days after the last drug injection and the cochleae removed for examination by surface preparation. The lesioned animals showed markedly less hair cell loss than the control groups, and this was attributed to the fact that the loss of the efferent endings rendered these animals less susceptible to the ototoxic effects of kanamycin.

Animals↗

Comparison of caloric and sinusoidal tests in the vestibulotoxic cat.

In order to evaluate the relative sensitivity of caloric and sinusoidal angular acceleration tests, thermal and rotational stimuli were administered to cats rendered vestibulotoxic with streptomycin sulfate. Three groups of six cats each, receiving daily subcutaneous injections of saline, 100 mg/kg streptomycin or 200 mg/kg streptomycin, were administered optokinetic, caloric and sinusoidal stimuli. Vestibular responses were evaluated by changes in the total slow phase displacement of the eyes and frequency of nystagmic beats. The results demonstrated that the saline treated animals had a decrease in response consistent with habituation; whereas, experimental animals showed a marked, rapid abolition of eye movement. The decrease in response was greater for the larger dose of streptomycin. Caloric or sinusoidal acceleration tests were equally sensitive in monitoring the degree of nystagmic depression. The data suggested that sinusoidal acceleration tests could be easily applied to the clinical vestibular assessment of ototoxicity.

Animals↗

Visual stimulation: effects on vestibular habituation.

The influence of various forms of visual stimulation presented during the course of vestibular habituation to a caloric stimulus was studied. Eye movements which were either complementary or in opposition to the induced vestibular nystagmus were produced with an optokinetic drum. In addition, the effect of visual fixation during vestibular-response periods was studied. In all cases, the cats that received visual stimulation during the majority of the caloric trials habituated more slowly than did animals that received all the habituation trials in total darkness. These data conflict with previous reports of vestibular-visual interactions. Possible explanations for the discrepancy include species differences, distraction provided by the visual stimuli, and the transfer of learning from the dark to light conditions.

Animals↗

Comparative studies of the hepatocarcinogen N,N-dimethylnitrosamine in vivo: reaction sites in rat liver DNA and the significance of their relative stabilities.

The reaction of the hepatocarcinogen N,N-dimethylnitrosamine has been compared with that of methyl methanesulphonate, a methylating agent which is not a liver carcinogen. Consistent differences have been observed in the reaction of rat liver DNA in vivo with these agents; O(6)-alkylation and the production of unidentified acid-labile products were distinctive features of the reaction with the carcinogenic nitroso compound but were undetectable or in low yield, respectively, after reaction with the alkyl sulphonate. Evidence has been obtained for the excision of these reaction products in animals treated with the hepatocarcinogen and the significance of their relative stabilities is discussed.

Alkylation↗

Differences in the patterns of methylation in rat liver ribosomal ribonucleic acid after reaction in vivo with methyl methanesulphonate and NN-dimethylnitrosamine.

1. rRNA was isolated from rat liver at short intervals after the intraperitoneal injection of [(14)C]methyl methanesulphonate (50mg/kg) or NN-di[(14)C]methylnitrosamine (2mg/kg). These doses were chosen to minimize the effects of toxicity. 2. The following methods of hydrolysis of [(14)C]methylated rRNA were employed: enzymic digestion to nucleosides at pH8; alkaline hydrolysis and conversion into nucleosides; acid hydrolysis to bases. 3. The methylation products were analysed by chromatography on columns of Dowex-50 (H(+) form) and Dowex-50 (NH(4) (+) form). 4. With both methylating agents the principal product of methylation was 7-methylguanine. Differences were obtained, however, in the molar proportions of the minor bases 3-methylcytosine, 1-methyladenine and 7-methyladenine. Methylation at the O-6 position of guanine was a significant feature of rRNA obtained from the NN-di[(14)C]methylnitrosamine-treated animals but was not detected in rRNA after treatment with [(14)C]methyl methanesulphonate.

Adenine↗

Ototoxic interactions of ethacrynic acid and streptomycin.

Various aminoglycoside antibiotics and potent diuretics are known to depress cochlear and vestibular function. Several clinical and research studies suggest that the drugs administered together produce enhanced ototoxicity. The present series of experiments determines the depressive effects of ethacrynic acid and streptomycin, alone or in combination, upon the vestibular system of the cat. The changes in function, when quantified, indicate an addition, rather than a potentiation of toxicity, and suggest different sites of action.

Animals↗