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Uridine diphosphoglucose dehydrogenase in the intervertebral disc.

Intervertebral discs of an old sheep and a young pig were examined for the presence of cells containing the enzyme uridine diphosphoglucose dehydrogenase. In the sheep, the inner anulus had a higher proportion of active cells than the outer anulus; in the pig, there was no difference. From a consideration of cell numbers, it is suggested that there is an accumulation of glycosaminoglycans in the centre of the disc rather than an increased production rate. Notochordal cells in the pig disc contain uridine diphosphoglucose dehydrogenase and are capable of producing glycosaminoglycans.

Alcohol Oxidoreductases

Three-dimensional observation of collagen framework of lumbar intervertebral discs.

Lumbar intervertebral discs obtained from rats, dogs and humans were examined by scanning electron microscopy. The nucleus pulposus was constructed of a loose network of fine fibrils and formed lamellated membranes in the peripheral areas. The annulus fibrosus was composed of concentric lamellae of fibrous bundles that ran uniformly in each lamella and crossed over to the bundles of adjoining lamellae. The lamellae were made of fine fibrils measuring 0.1-0.2 mu in diameter, corresponding to matured collagen fibrils. The cartilage plate consisted of a close meshwork of collagen fibrils which interconnected with the annular fibrils. From these results, it was concluded that the intervertebral disc was well developed for shock absorption at the light microscopic and ultrastructural levels. In specimens treated with chymotrypsin, the extra-fibrillar substances were easily digested in the nucleus, as well as in the annulus. The intervertebral disc may thus be easily affected by chemical agents.

Animals

The effect of lactate and pH on proteoglycan and protein synthesis rates in the intervertebral disc.

The intervertebral disc is the largest avascular tissue in the body. Its metabolism is mainly anaerobic, and thus lactate is produced at a significant rate. As a result the lactate concentrations in the center of the disc may be 8-10 times as high as in the plasma. The pH in the disc center is thus acidic. Because low values of pH are known to affect proteoglycan synthesis in other cartilages, the authors measured the effect of lactate levels and pH on 35S-sulphate and 3H-proline incorporation rates in the nucleus of bovine coccygeal discs and in human disc obtained during percutaneous nucleotomy. The maximum incorporation rate occurred at pH 7.2-pH 6.9. Here the rate was 40-50% greater than at pH 7.4. Below pH 6.8 the rate fell steeply, more so for sulphate than for proline. At pH 6.3 the sulphate incorporation rate was around 20 percent that at pH 7.4. The results indicate that proteoglycan synthesis rates in particular are sensitive to extracellular pH, and that the peak rate occurs around the level of pH seen in vivo. Factors that cause lactate levels to rise, such as a fall in O2 levels as the result of smoking or vibration (Holm and Nachemson, 1988) could lead to a fall in proteoglycan synthesis rates, ultimately leading to a fall in proteoglycan content and to disc degeneration.

Animals

Staining of glycosaminoglycans of intervertebral disc tissue.

Intervertebral discs of six species were stained with Alcian blue and PAS methods to identify glycosaminoglycans. The polyanions are most concentrated in 'ring-like' pericellular areas and in material lying between individual lamellae and bundles of collagen. A slight increase occurs early in life and towards the disc centre. The concentration of glycosaminoglycans cannot be correlated with species which are known to suffer from clinical disc disease, though there appears to be a higher concentration in the discs of the cat and dog than in other species studied.

Animals

Histochemical study of the human intervertebral disc.

The human intervertebral discs which were obtained by cadavers and anterior discectomy are investigated histochemically. Chondroitin-4S, chondroitin-6S, dermatan sulfate, hyaluronic acid and keratan sulfate were detected in the human intervertebral disc by various histochemical methods. pH2.5, pH1.1 toluidin blue metachromasia and 0.4M MgCl2 alcianophilia became weaker with increasing age, and the herniated disc were weaker than controlled discs in the same age group. Chondroitin-4S and chondroitin-6S were distributed throughout the discs. There was no clear localization of the various glycosaminoglycans in the human intervertebral disc, with the exception of keratan sulfate. There was no histologically and histochemically observable difference in the cervical and lumbar discs.

Adult

Proteoglycans of the intervertebral disc. Absence of degradation during the isolation of proteoglycans from the intervertebral disc.

Proteoglycans extracted with 4M-guanidinium chloride from pig intervetebral discs, and purified by equilibrium density-gradient centrifugation in CsCl, were of smaller hydrodynamic size than those extracted and purified in the same way from the laryngeal cartilage of the same animal. Whether this difference in size arose from degradation during the extraction and purification of the proteoglycans of the disc was investigated. Purified proteoglycans labelled either in the chondroitin sulphate chains or in the core protein were obtained from laryngeal cartilage by short-term organ culture. These labelled proteoglycans were added at the beginning of the extraction of the disc proteoglycans, and labelled cartilage and unlabelled disc proteoglycans were isolated and purified together. There was no appreciable loss of radioactivity after density-gradient centrifugation nor decrease in hydrodynamic size of the labelled cartilage proteoglycans on chromatography on Sepharose 2B, when these were present during the extraction of disc proteoglycans. It is concluded that disc proteoglycans are intrinsically of smaller size than cartilage proteoglycans and this difference in size does not arise from degradation during the extraction.

Animals

Variations in size of the bony lumbar canal in patients with prolapse of lumbar intervertebral discs.

Prolapse of the lumbar intervertebral disc is one of the commonly accepted causes of low back pain. Most patients respond well to conservative treatment, but some may not respond at all. Though the reason for this variation is not clearly understood, it is felt that a developmentally narrow spinal canal might have some relation to the persistence of backache and sciatica. The canal was therefore measured at each of the lumbar vertebral level by a method described by Jones and Thomson (1969) in 100 consecutive patients operated upon for prolapsed lumbar intervertebral discs, in 100 normal patients for comparison. This method does not give direct measurements of the bony spinal canal but provides a ratio of the size of the canal to the adjacent vertebral body. We found a trend towards the presence of a narrower than normal lumbar canal in patients with prolapsed lumbar intervertebral discs. It is concluded that in patients with prolapsed lumbar intervertebral discs necessitating operation, the canal tends to be narrower than normal, and such narrowing enhances the effect of any disc protrusion leading to severe symptoms of backache and sciatica.

Adolescent

Sheathing of collagen fibrils in human intervertebral discs.

In 25 human intervertebral discs studied by electron microscopy, sheathing collagen-like fibrils by electron-dense cylinders was observed. The sheaths consisted of layers of dense granules 3 to 12 times the diameter of the enclosed collagen-like fibrils, and they appeared to be more frequent in older discs.

Adult

Neural elements in human cervical intervertebral discs.

This study attempted to characterize neural elements within the human cervical intervertebral disc. Cervical intervertebral discs were obtained from four adult human subjects at autopsy. Discs were stained in bulk with gold chloride, sectioned, and viewed with the light microscope. Nerve fibers appeared to enter the disc in the posterolateral direction and course both parallel and perpendicular to the bundles of the anulus fibrosus. Nerves were seen throughout the anulus but were most numerous in the middle third of the disc. Receptors resembling Pacinian corpuscles and Golgi tendon organs were seen in the posterolateral region of the upper third of the disc. These results provide further evidence that human cervical intervertebral discs are supplied with both nerve fibers and mechanoreceptors.

Adult

Age-related phenomena in the lumbar intervertebral discs. Lipofuscin and amyloid deposition.

In 69 lumbar intervertebral discs from 69 autopsies, lipofuscin was seen in discs from individuals older than 50 years of age and amyloids in the discs of individuals older than 40 years of age. In 261 intervertebral disc tissue specimens collected at the time of surgery for disc herniation, lipofuscin was seen in the discs of individuals older than 20 years of age and amyloids in the discs of individuals older than 15 years of age. It is speculated that amyloids and lipofuscin are a sign of aging in the intervertebral disc as in other tissues. Furthermore, amyloids and lipofuscin were seen in the operated discs of young individuals than in the autopsy cases.

Adolescent

Calcification of intervertebral discs in childhood.

Over 75 cases of intervertebral disc calcification in childhood have been reported, but the illness is seldom considered in the differential diagnosis of back pain inchildren. This paper reports two children who required surgery for intervertebral disc calcification. The histologic changes, which have not been described previously, include an amorphous calcification within the nucleus pulposus without any inflammatory reaction. The etiology of disc calcification remains unknown, but it can be differentiated both clinically and pathologically from other causes of calcified intervertebral discs and from spondylarthritis.

Biopsy

Type III collagen in the intervertebral disc.

Several collagen types have now been isolated from the intervertebral disc, although type III collagen has previously only been extracted from human pathological disc. In this study, type III collagen has been isolated from normal human and bovine intervertebral disc and immunolocalized in sections of rat, sheep, bovine and 'normal' human intervertebral disc of various ages. Staining with antisera to type III collagen is localized primarily around the cells. Results indicate that cells of the disc sit in 'chondrons', similar to those seen in the deep and mid zones of articular cartilage. We suggest that type III collagen is present in the intervertebral disc and hypothesize that it may be involved in the organization of the pericellular environment, perhaps linking the chondron capsule to the interterritorial matrix.

Animals

Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleolysis: a hypothesis concerning regeneration of the disc after chemonucleolysis.

Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment.

Adolescent

Elastic fibers in human intervertebral discs.

Although previous studies failed to demonstrate elastic fibers in intervertebral discs, electron microscopy of twenty human intervertebral discs obtained at autopsy and operation revealed characteristic elastic fibers in both the annulus fibrosus and the nucleus pulposus. Their contribution to the mechanical properties of the intervertebral disc remains to be determined.

Adolescent

Intervertebral disc abnormalities associated with vertebral metastasis: observations in patients and cadavers with prostatic cancer.

Abnormalities of intervertebral discs associated with vertebral metastasis from prostatic carcinoma are described in an investigation utilizing patient and cadaveric material. Radiographic and pathologic findings indicate that discal abnormality in this situation relates to three potential processes: intervertebral disc degeneration (intervertebral osteochondrosis); cartilaginous (Schmorl's) nodes; discal invasion by tumor. In most patients with vertebral metastasis, the adjacent intervertebral disc appears normal, a useful radiographic finding suggesting the presence of tumor rather than infection. Occasional patients with vertebral metastasis demonstrate roentgen abnormalities of the adjacent intervertebral disc indicating the occurrence of one or more of the above processes.

Humans

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.

Adult

Intervertebral disc disease.

This article describes the functional anatomy of intervertebral discs and their relationship to the vertebrae and spinal cord. The pathologic events and clinical complications of intervertebral disc disease are described. A discussion of proper staging of disc disease and appropriate conservative management of degenerative disc disease is included.

Animals

Identification of human intervertebral disc stromelysin and its involvement in matrix degradation.

Human intervertebral disc when maintained in organ culture released a latent casein-degrading metalloproteinase into the medium in a manner analogous to cultures of human cartilage. This enzyme was demonstrated to be immunologically identical to prostromelysin. It was also found that the amount of procollagenase secreted by both cartilage and disc cells was considerably less than that of prostromelysin. Tissue extraction confirmed that the low level of procollagenase observed was not due to retention of the enzyme within the tissue. Human intervertebral disc link proteins were found to possess the same N-termini as those of their counterparts in human articular cartilage, where it appears that stromelysin is responsible for generating molecular heterogeneity. These results suggest that intervertebral disc cells are capable of secreting prostromelysin, which can become activated within the extracellular matrix and hence contribute to the age-related and degenerative changes in the disc.

Adult