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Biomedical subjects

L J Slaughter

Publications and source records attributed to L J Slaughter.

18 recordsLinked to original sources

Toxicological studies with 6-mercaptopurine in neonates.

In previous studies, we found that Sprague-Dawley rats injected with 6-MP monohydrate at 2 mg base/kg sc daily from 2 to 22 days of age had atrophy of thigh and sublumbar muscles when killed at 16 months of age. The first sign of this muscle atrophy was detected grossly (flattened croup with or without paresis) at 12 months of age. In one experiment of the present work, using the same treatment in rats as above, we found that the earliest onset of muscle atrophy observed by light microscopy occurred at 2 months of age. By 4 months the atrophy could be detected grossly. The atrophy did not uniformly involve all muscles of the hindquarters; the thigh (especially the semitendinosus), leg (soleus but not the extensor carpi group), and lumbar vertebral (including the psoas) muscles were involved. Foreleg (biceps), intercostal, and tongue muscles as well as the sciatic nerve and internal organs appeared unaffected. In another experiment, weanling Sprague-Dawley rats given large daily doses of 6-MP from 25 to 45 days of age had normal muscles when killed at 8 months. In a third experiment, Wistar rats injected with 6-MP (2 mg base/kg sc) daily from 2 to 22 days of age and killed at 6 months had muscle atrophy similar to that seen in Sprague-Dawley rats. In the last experiment, mice and hamsters given large daily doses of 6-MP from 2 to 22 days of age had normal muscles when killed at 10 months. It appears from these results that the 6-MP-induced muscle atrophy occurs only after treatment during the neonatal period and that the atrophy may be species-specific.

Animals

Massive sequestration of human sickle cells after transfusion to a baboon.

A baboon was exchange-transfused with sickle cell anemia patients' blood. The animal died suddenly, and postmortem examination showed widespread red cell sequestration, particularly in the spleen and liver. The clinical and pathological findings were similar to those in children with sickle cell anemia who die of acute splenic sequestration syndrome. A control animal, exchange-transfused with normal human blood, tolerated the procedure without difficulties for a period of 4 days, when a delayed transfusion reaction occurred. Thus the baboon can be used as a model for the abnormal circulatory behavior of sickle cells and for the sickle cell sequestration syndrome.

Anemia, Sickle Cell

Acute toxic effects in mice of an extract from the marine algae Gonyaulax monilata.

Unialgal cultures of Gonyaulax monilata were cultured and harvested. A modified Westphall procedure was used to prepare an extract which did not contain saxitoxin, the gonyautoxins and structurally related toxins. The extract was administered i.p. to young adult, male CD-1 mice and produced: sedation, abdominal constriction, fecal clumping in the perianal area, ataxia, tremors, cyanosis, loss of reflexes, convulsions and death (LD50 = 2.28 mg/kg). Gross and microscopic pathology in the treated mice included: acute active hyperemia of the viscera, multifocal areas of necrosis of the musculature of the intestinal wall and diaphragm and the presence of cytoplasmic vacuoles in the peripheral margins of the acinar portion of the pancreas. Clinical pathology of the mice which survived 24 hr included significant elevation in the levels of serum lactic dehydrogenase, glutamic pyruvic and glutamic oxaloacetic transaminases. Some of these mice also had significantly decreased white blood cell counts. The extract administered orally produced similar signs without the abdominal constriction and convulsions (median lethal oral dose = 6.73 mg/kg). Gross pathology findings included extensive and severe congestion of the abdominal visceral organs. Vehicle control mice were normal. In conclusion, G. monilata, previously reported as nontoxic in homeotherms, yields an extract which contains a water soluble glycosidic substance(s) which is lethal to mice.

Animals

Further studies on 6-mercaptopurine-induced muscle atrophy in rats, mice, and hamsters treated as neonates.

In previous studies, we found that Sprague-Dawley rats injected with 6-mercaptopurine monohydrate (6-MP) at 2 mg base/kg sc daily from 2 to 22 days of age had atrophy of thigh and sublumbar muscles when killed at 16 months of age. The first sign of this muscle atrophy was detected grossly (flattened croup with or without paresis) at 12 months of age. In one experiment of the present work, using the same treatment in rats as above, we found that the earliest onset of muscle atrophy observed by light microscopy occurred at 2 months of age. By 4 months the atrophy could be detected grossly. The atrophy did not uniformly involve all muscles of the hindquarters; the thigh (especially the semitendinosus), leg (soleus but not the extensor carpi group), and lumbar vertebral (including the psoas) muscles were involved. Foreleg (biceps), intercostal, and tongue muscles as well as the sciatic nerve and internal organs appeared unaffected. In another experiment, weanling Sprague-Dawley rats given large daily doses of 6-MP from 25 to 45 days of age had normal muscles when killed at 8 months. In a third experiment, Wistar rats injected with 6-MP (2 mg base/kg sc) daily from 2 to 22 days of age and killed at 6 months had muscle atrophy similar to that seen in Sprague-Dawley rats. In the last experiment, mice and hamsters given large daily doses of 6-MP from 2 to 22 days of age had normal muscles when killed at 10 months. It appears from these results that the 6-MP-induced muscle atrophy occurs only after treatment during the neonatal period and that the atrophy may be species specific.

Animals

Muscular degeneration in rats after postnatal treatment with 6-mercaptopurine.

6-Mercaptopurine monohydrate was injected sc at 2 mg base/kg/day from 2 to 22 days of age to four litters of rat pups (four females, four males per litter). Control neonates were injected sc with basic saline (pH 8). Daily observations for signs of toxicity were made during the treatment period and once weekly thereafter until the rats were 6 months of age. The pups were weighed at 2, 12, 23, 34, 100, and 480 days of age. Fertility was tested at 3 to 6 months of age. From 6 months of age on, the rats were examined for tumors at 3-month intervals until the experiment was terminated at 16 months of age. A reduction in body weight of treated rats began between 34 and 100 days of age and became more pronounced by 16 months of age. Fertility was similar in treated and control groups and there were no detectable tumors in either group. The major finding in treated rats was a delayed onset of hind leg paresis that was first detected at 12 months of age. Light microscopic examination of tissues taken from the hind quarters of these rats at 16 months of age revealed a severe atrophic degeneration with fatty infiltration of sublumbar and thigh muscles.

Animals

A histopathological study of canine and feline ovarian dysgerminomas.

Clinical and pathological features of ovarian dysgerminomas occurring in two dogs and a cat are presented. The feline neoplasm had morphological characteristics closely resembling those of dysgerminomas in women. The feline and one canine neoplasm occurred in young animals as compared to other reported animal dysgerminomas. Findings are discussed in relation to other reports of these tumors in animals and in women.

Animals

Development, growth rate, degree of malignancy, and chromosome pattern of Morris transplantable hepatomas.

A spectrum of chemically induced transplantable adenocarcinomas of the rat hepatocyte was developed in inbred strains of rats. For the most part, the tumors showed remarkable stability in growth rate between 1973 and 1976, as determined by months between transfers. A few tumors were slower-growing in 1976 than in 1973, and a few tumors of intermediate growth rate were somewhat slower-growing in 1973 than in 1976. Percentage distributions of chromosomes of six aneuploid hepatoma are presented. The most homogeneous cell lines were a haploid and a hyperdiploid line. The karyotype of each hepatoma had a consistent number of abnormal chromosomes. Lung metastases were observed in almost all cell lines.

Animals