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Biomedical subjects

D N McMartin

Publications and source records attributed to D N McMartin.

11 recordsLinked to original sources

Neoplasms and related proliferative lesions in control Sprague-Dawley rats from carcinogenicity studies. Historical data and diagnostic considerations.

Historical data are presented for neoplasms and related proliferative lesions from 1,170 Sprague-Dawley rats that served as controls in 9 carcinogenicity (2 year) studies conducted in the Safety Evaluation Facility of Ciba-Geigy Corporation, Summit, New Jersey. The most common neoplasm was pituitary adenoma, which occurred in 62.2% of the male and 84.7% of the female rats. Incidences of other neoplasms that occurred in more than 6.0% of the rats were, for males, benign pheochromocytoma (19.0%), cutaneous keratoacanthoma (7.9%), pancreatic islet cell adenoma (7.5%), benign testicular interstitial cell tumor (6.5%), and thyroid C-cell adenoma (6.5%). For females these incidences were mammary fibroadenoma (31.3%), mammary adenocarcinoma (16.8%), and mammary adenoma (6.5%). Focal cortical hypertrophy/cystic degeneration of the adrenal, a focal nonneoplastic lesion of zona fasciculata cells that often degenerate into large cysts, was present in 23.4% of all male and 82.7% of all female rats. Criteria for the differential diagnoses of selected neoplasms and related lesions are presented.

Animals

Effect of age on axoplasmic transport of cholinesterase in rat sciatic nerves.

Senile muscle atrophy has been attributed to an impaired ability of old nerves to transport trophic factors. To evaluate the effect of age on axoplasmic transport, we measured the accumulation of cholinesterase activity above a ligature around sciatic nerves of young (7--8 months), middle-aged (19--20 months), and old (31--32 months) male rats. Protein content and cholinesterase activity per mm of nerve were higher in middle-aged and old than in young nerves. However, accumulation of cholinesterase activity was significantly lower by middle age and was strikingly reduced by old age. This large reduction in axoplasmic transport appeared to result from factors other than axonal loss. A model in which old nerves have an increased number of temporary focal blockages of particle movement in axoplasmic channels is proposed to explain the decreased transport.

Aging

Morphologic lesions in aging Syrian hamsters.

The oldest members of most short- and long-lived mammalian species develop many similar morphologic changes. This suggests that the combined occurrence of a variety of age-associated lesions in a group can be used as an indicator of its advanced biological age. Males and females from our colony of aging Syrian hamsters were previously shown to have an equally high incidence of atrial thrombosis and myocardial degeneration, despite the females' much shorter life-span. Other age-associated lesions were then examined histopathologically to determine whether females age faster than males. Hepatic, renal, and splenic amyloidosis were more severe in females than in males and became so at an earlier age. Degenerative lesions were also found in adrenals, thyroids, and brains of both sexes. Atrophy was especially severe in the thymus. The incidence of malignant neoplasms, most of which were of lymphoreticular origin, was similar in both sexes. Female hamsters may age faster than males if biological age can be assessed by these morhologic criteria.

Adrenal Glands

Effect of experimental colchicine encephalopathy on brain protein synthesis and tubulin metabolism.

Colchicine blocks axoplasmic flow and produces neurofibrillary degeneration. Brain slices from mice injected intracerebrally with colchicine incorporated more [14C]leucine into protein and had a decreased uptake of [14C]leucine into the perchloric acid-soluble pool than did their controls. Brain RNA content was decreased and free leucine increased by colchicine-induced encephalopathy. The specific activities of proteins from subcellular fractions of colchicine-injected brain were increased in the nuclear fraction, the 100,000-g supernatant, and its vinblastine-precipitable tubulin. The ratio of the specific activity of the crude mitochondrial fraction to that of the total homogenate was decreased, as would be consistent with impaired movement of newly labeled protein into synaptosomes. Colchicine-injected brain extracts contained one or more cytosol fractions that stimulated ribosomal incorporation of [14C]leucine into protein in a cell-free system. Colchicine-binding-activity measurements indicated loss of soluble and particulate tubulin in colchicine-injected brains; the decrease of soluble tubulin was verified by its selective precipitation with vinblastine. Colchicine encephalopathy did not affect the rate of spontaneous breakdown of in vitro colchicine binding activity. Similarities of colchicine encephalopathy to the neuron's response to axonal damage suggest that colchicine-induced increase in protein synthesis may, in part, reflect a neuronal response to blockage of neuroplasmic transport.

Animals

Spontaneous atrial thrombosis in aged Syrian hamsters. I. Incidence and pathology.

Many of the aging Syrian hamsters maintained in our Division spontaneously develop atrial thrombosis accompanied by a consumption coagulopathy. The 50% mortality level is reached earlier by females (16 months) than by males (24 months). The incidence of thrombosis increases with age, beginning at 13.5 months in females and at 21.5 months in males, and the overall incidence (73%) is nearly the same for both sexes. Bilateral ventricular hypertrophy was found in thrombosed hearts. The hearts of most aged hamsters, whether thrombosed or not, had myxoid valvular thickenings and myocardial degeneration. Myodystrophic changes included hypertrophied nuclei, cytoplasmic vacuolation, fiber atrophy, and finally replacement fibrosis. Thrombosis probably resulted from local blood stasis secondary to cardiac failure. These hamsters may be an especially useful model for comparative study of the effects of aging and myocardial degeneration on spontaneous thrombosis.

Aging

Spontaneous atrial thrombosis in aged Syrian hamsters. II. Hemostasis.

Coagulation and fibrinolysis were studied in a colony of aged Syrian hamsters with spontaneous atrial thrombosis, and the results are consistent with concomitant consumption coagulopathy. In comparison to age- and sex-matched hamsters from the same colony, those with atrial thrombi had significantly prolonged prothrombin and partial thromboplastin times, reduced levels of factors II, VII, VIII and X activities and plasminogen; and concentrations of fibrinogen-fibrin split products in excess of 80 microgram/ml. Hematocrits of the thrombosed animals were significantly decreased, total plasma proteins were increased, leukocyte counts were within normal limits, and platelet counts were about half those of the controls. Thrombosed hamsters had significantly reduced plasma albumin content, increased alpha1-, beta-, and gamma-globulins, and reduced A/G ratios. Aged sick hamsters demonstrable thrombi also had reduced coagulation and fibrinolytic activities and platelet counts, but their fibrinogen levels were markedly elevated, and fibrinogen-fibrin split products were either absent or present in trace amounts. This suggests an earlier and/or less acute form of the thrombotic process.

Aging

Apparent acaridal dermatitis in a C57BL/6 Nya mouse colony.

Dermatitis in a breeding colony of black (C57BL/6 Nya) mice was characterized by intense pruritus leading to self-mutilation and death. The cause appeared to be infestation with the mite, Myobia musculi. Ulceration of the skin resulted in exudation of serum proteins and exposure of the animals' immune defenses to microorganisms and irritants, with subsequent hyperplasia of regional lymph nodes and spleen. Affected mice had an increase in sessile plasma cells, serum immunoglobulin concentration, and percent of circulating granulocytes. The mites were eliminated by treatment with a dichlorvos-ronnel combination in liquid form, which was dispensed onto the bedding with an automatic syringe. The incidence of dermatitis was reduced to zero. Our experience with M musculi in two other strains of mice, both white, indicates that pathogenicity of this mite for mice varies according to the strain, sex, age, and individual differences in sensitivity of the mice as well as the mating ratios employed.

Animals

Incorporation of (14C) leucine into protein and tubulin by brain slices from young and old mice.

Tubulin, the protein of neurotubules, aids in the movement of other proteins and organelles within axons and may be involved in the pathogenesis of senile dementia in man. This led us to investigate the effect of age on the synthesis of tubulin and of total brain protein of mice. Brain slices from 5-, 12-, 18-, and 25 mo.-old mice were incubated with [14C] leucine. The slices were then homogenized and tubulin was precipitated from the 100,000g supernate by vinblastine. Protein synthesis was measured by [14C] leucine incorporation into hot trichloroacetic acid-insoluble protein and tubulin was quantitated by [3H] colchicine binding. The 4 age groups did not differ significantly in the relative specific activities of their total protein or of their tubulin. The content of the colchicine-binding protein (tubulin) also was not affected by age. These findings suggest that, at least in mice, aging does not significantly affect the rate of synthesis of brain protein or tubulin.

Age Factors