Histology of intervertebral disc protrusion: an experimental study using an aged rat model.

STUDY DESIGN: In vitro experimental intervertebral disc ruptures of aged rats were examined histologically. OBJECTIVES: To clarify the mechanism of intervertebral disc herniations by microscopic investigation of ruptured discs. SUMMARY OF BACKGROUND DATA: Clinically, disc herniations have been classified into two types: extrusion and protrusion. However, the pathogenesis of protrusion type herniations has not yet been demonstrated by any studies. To clarify this issue, it is essential to establish an appropriate model producing disc herniations, and to examine the sequential changes in the structure of herniated discs. METHODS: Lumbar discs of 2-year-old rats were examined histologically and compared with human lumbar discs. To examine structural changes in discs subjected to repetitive motion stress, 400 repetitions of a sequence of flexion (30 degrees ) and axial rotation (6 degrees ) were applied in vitro to the lumbar discs of the animals. RESULTS: The microstructure of normal lumbar discs in aged rats was similar in many ways to the human lumbar discs in a 20- to 40-year-old adult. Of 10 discs subjected to repetitive stress, 4 were ruptured at the junction between the posterior anulus fibrosus and the sacral cartilage endplate. One had an extruded nucleus pulposus, and three had a protruded anulus fibrosus, which displayed disorganized structure containing widened and flaccid lamellae. CONCLUSIONS: The results from this study indicate that disc protrusion can be caused by disorganization of the ruptured annular lamellae, not by focal compression of the nucleus pulposus.

Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats.

We investigated the role of insulin in salt-sensitive hypertension in Dahl salt-sensitive and salt-resistant rats. The rats were kept in metabolic cages, and sodium intake and urinary sodium excretion were measured. In salt-sensitive rats receiving a 0.3% NaCl diet, sodium retention was significantly greater at weeks 1 and 2 in rats that received an insulin infusion than in those receiving a saline infusion. Mean arterial blood pressure and plasma norepinephrine levels were significantly higher at week 3 in insulin-treated rats than in saline-treated rats (mean arterial pressure, 137 +/- 3 mm Hg versus 119 +/- 3 mm Hg, p < 0.05; plasma norepinephrine, 0.40 +/- 0.02 ng/ml versus 0.27 +/- 0.01 ng/ml, p < 0.05). Insulin did not influence sodium retention, mean arterial pressure, or plasma norepinephrine in salt-resistant rats. Coadministration of an alpha-blocker (bunazosin, 10 mg/kg per day for 3 weeks) in salt-sensitive rats abolished the insulin-induced elevations in mean arterial pressure and sodium retention. When salt-sensitive rats were fed a low salt diet (0.03% NaCl), insulin did not raise mean arterial pressure. Thus, insulin elevated blood pressure only in the salt-sensitive model. The sympathetic nervous system and sodium retention in the early phase of insulin overload may contribute to elevation of mean arterial pressure in this model.

Infectious murine type-C viruses released from human cancer cells transplated into nude mice.

Type-C virus particles were revealed by electron microscope in 6 of 9 tumours of cultured and biopsied human cancers heterotransplanted into nude mice. Some tumours in nude mice were explanted for in vitro cultivation. The virus particles were also found in the cultures derived from the virus-positive tumors. They were mostly found extracellularly, but the particles in budding process were also encountered frequently. Cytological study and karyotype analysis of the cultured cells proved these virus-releasing cells as of hus of human origin. From the close correlation between the statistical virus counts and the complement fixation titers for murine gs antigen of the tumors and their cultures, these viruses propagated in human cancer cells were confirmed to be infectious viruses of nude mouse origin. The virus replicating in human cancer cells was readily infected in some of innocent human cancer cells by co-cultivation. It is to be emphasized that infection of animal endogenous viruses on heterotransplanted human cancer cells is a bothersome contamination for human cancer research, especially when searching for a human tumor virus candidate.

Inhibition of senile amyloidosis of mice by biscarboxyethyl germanium sesqui-oxide.

A mouse strain, ICR/SLC, was involved in spontaneous amyloidosis with high incidence. The amyloid deposition in this strain was seen mainly in the mucosal propria of duodenum and terminal ileum, liver, spleen, adrenal cortices, and renal glomeruli. The mice, orally administered more than 300 mg/kg of organic germanium for 22 months since 5 weeks old, did not develop amyloidosis. Half of the mice, given 30 mg/kg of organic germanium for 22 months developed amyloidosis. The mice given 5% carboxymethylcellulose, the solvent of organic germanium, were affected with systemic amyloidosis with high frequency. The results showed that the organic germanium successfully inhibited the occurrence of senile amyloidosis with dose response. The agent did not have any apparent relation to the incidence of hepatic cell carcinoma or pulmonary adenoma which is frequently combined with aged mice. Although the actual mechanism involved is not clear, the evidence of the inhibition of senile amyloidosis by organic germanium may give a light to elucidate the pathogenesis of amyloidosis.

Heterotransplantation of cultured human cancer cells and human cancer tissues into nude mice.

Twenty-seven out of 31 cultured human cancer cell lines transplanted subcutaneously into nude mice produced solid tumors. Direct transplantation of surgical materials proved less successful. In 35 attempts, only 1 of 6 gastric cancers, 2 of 3 liposarcomas, and 1 of 3 osteosarcomas were accepted. No positive tumor formation was noted after the inoculation of 3 nasopharyngeal carcinomas or 1 breast cancer. None of lymphomatous neoplasms and leukemias produced any tumor in 12 and 3 attempts, respectively. The histological and cytological characteristics of the tumors developed were studied with light and electron microscopes, in relation to the features in vitro and those of the parent tumors. Histological similarity of the tumors that developed in nude mice to their parent tumors were noteworthy. Serial transplantation was performed successfully in 9 cell lines and 2 tissues. Preservation of tissue construction ability and other differentiation abilities of in vitro cultured human cancer cells were ascertained in varying degrees.