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Scanning electron microscope studies on the synovial membrane.

Synovial membranes from human and rabbit joints were observed by scanning electron microscopy. 1. The surfaces of synovial membranes present locally variable appearances. In some parts cytoplasmic processes of lining cells extend long and flat causing an appearance like overlapping renal podocytes, whereas in other parts the cells protrude in cauliflower-like or more smooth-surfaced round bodies. 2. In cracked surfaces of synovial membranes, two types of lining cells are distinguished. One is the cell which has more surface processes and numerous granules in the cytoplasm, the other is the cell which has fewer processes and better developed endoplasmic reticulum without granules. 3. Fibroblasts apparently forming collagen fibers are observed in the subsynovial tissue. Two types of fibrogenesis are found. In the first type microfibrils seem to be formed extracellularly, whereas in the second type bundles of filaments are preformed in the cytoplasm and they appear to be extruded directly from the cell surface.

Adolescent

Properties of fibrinogen-antigenic material on the rheumatoid synovial membrane and in the rheumatoid synovial fluid.

Fibrin deposits on rheumatoid synovial membranes and fibrinogen-antigenic material in rheumatoid synovial fluid were found to be identical by crossed immunoelectrophoresis into immunoglobulin against fibrinogen, by SDS-polyacrylamide gel electrophoresis, and by gel filtration on Sepharose CL 6B. The material was found to be neither fibrinogen nor fibrin, but degradation products. One of the fragments was purified by preparative agarose electrophoresis, and the physicochemical properties of this fragment were found to be different from those obtained by plasmin digestion of fibrinogen or fibrin. This indicates that other proteases than plasmin are responsible for the degradation products. The material was easily degraded by plasmin to D- and E-antigenic end products, identical to those obtained by plasmin digest of fibrinogen. The solubility of the material was poor in synovial fluid compared to serum and buffer. On the basis of these results, it is suggested that the fibrinlike material on the synovial membrane represents fibrinogen degradation products from the inflamed tissue. These products are likely released into the synovial fluid, and when their concentration here exceeds their solubility, they precipitate on the synovial membrane.

Arthritis, Rheumatoid

Ultrastructure of the synovial membrane.

The normal synovial membrane as seen by electron microscopy is bordered by one to three layers of lining cells that include some with phagocytic function, others rich in endoplasmic reticulum for protein synthesis and additional cells with mixed properties. Lining cells with prominent Golgi apparatus probably produce the synovial hyaluronic acid. The synovial matrix contains collagen and mucopolysaccharide. It offers little barrier to diffusion of most materials. Superficial capillaries and venules are fenestrated and presumably allow rapid exchange of fluid and electrolytes. Deeper venules have thick endothelium that can separate at intracellular junctions and can phagocytize circulating particles. Other identified synovial structures are fibrocytes, macrophages, lymphatics, mast cells, non-myelinated nerves and fat.

Animals

Predominantly T-cell infiltrate in rheumatoid synovial membranes.

Lymphocytes infiltrating synovial membranes were characterized in eight patients with proliferative rheumatoid synovitis. Surface immunoglobulins were studied with use of immunofluorescence, and the C3 receptor was detected by adherence of red cells coated with antibody and complement - both are B-cell markers. Spontaneous rosette formation with sheep erythrocytes was used as a T-cell marker. To obtain viable lymphocytes in suspension, the villous synovium of five of these patients was digested with collagenase and deoxyribonuclease. Populations enriched in lymphocytes could be obtained by velocity sedimentation. Whereas only 9 to 35 per cent of lymphocytes bore surface immunoglobulins, the majority (70 to 85 per cent) formed sheep-erythrocyte rosettes. Cells bearing the C3 receptor constituted a distinct minority of synovial lymphocytes in frozen-tissue sections, and were found in follicle-like accumulations. These data indicate that the predominant infiltrating lymphocyte in proliferative rheumatoid synovitis is a T cell.

Adolescent

Characteristics of mononuclear cell populations in chronically inflamed synovial membranes.

Mononuclear cells infiltrating synovial membranes in chronic synovitis were characterised both in situ and in cell suspensions by surface markers and histochemical techniques. T-lymphocytes were the predominant infiltrating cell in rheumatoid arthritis as well as in other forms of chronic arthritis, including ankylosing spondylitis and arthritis associated with Crohn's disease. B-lymphocytes were found exclusively in rheumatoid synovial membranes. These cells were demonstrable both in true germinal centres and, focally and diffusely, in nodular mononuclear infiltrates lacking the histochemical characteristics of germinal centres. The synovial lining cells, unlike mononuclear phagocytes, had no demonstrable receptors for C3 and Fc.

Adult

[Scanning electron microscopy study of the synovial membrane in rheumatoid arthritis].

A comparative study under the scanning electron microscope of rheumatoid synovial membranes, 5 arthrosic synovial membranes, one tuberculous membrane, and 3 normal synovial membranes showed the pathological changes in the synovial membrane due to rheumatoid arthritis: Inflammatory aspect of the synovial fringes, surrounded by turgid and proliferative villous processes. Granular appearance of the endo-articular surface like a "pebble beach". Dome-shaped synoviocyte layer, standing out well above the subjacent intimal layer, associated with small round cells, also with a raised margin, covering most of the endo-articular surface. Plasma membrane of the superficial synovial cells, covered with numerous and various differentiations and abundant microvillous processes. Reticular deposits or layers, covering the apical poles of the synoviocytes.

Arthritis, Rheumatoid

B-cells of the synovial membrane. II. Differentiation during development of the synovial cavity in the mouse.

Study of pre- and postnatal development of the metatarsophalangeal joint of the mouse shows that the synovial cavity (SC) forms before any differentiation of the synovial mesenchyme. The primitive cleft results from degradation of a thin vascular mesenchymal layer in direct contact with the chondrogenic layers. Differentiation of the synovial membrane coincides with clarification of the SC (3rd to 6th day of postnatal life). When dilatation of the SC occurs (6th to 8th day), the two intimal cells types (A- and B-cells) are well identified. The B-cells already show typical features at day 6; their content of typical dense secretory vesicles is comparable to that of the adult B-cells at day 13. The specific secretory function of B-cells could be correlated with the particular structure of the intimal interstitial tissue and could account for the origin of some protein(s) of the synovial fluid.

Animals

[A quantitative ultrastructural analysis of fenestrations and basal laminae of the blood capillaries in the knee joint synovial membrane (author's transl)].

Studies were carried out on the materials comprising the knee joint synovial membrane, kidney and lung from 13 young dogs and the knee joint synovial membrane obtained surgically from a 16-year old boy. The number of endothelial fenestrations of the blood capillary in the synovial membrane was 330 per 100 mu2 of the fenestrated vascular bed in 3--4 day-old dogs, 938 in 1 month-old dogs, 570 in 2 month-old dogs and 530 in the boy. The conspicuous peak in the development of vascular endothelial fenestrations seen in the synovial membrane of the dogs at 1 month of postnatal age appears to reflect a rapid increase in the mechanical load for the knee joint about 1 month after birth. A similar peak was absent for the blood capillaries in the renal glomeruli where the endothelial fenestrations continued to increase for the first 2 months of the postnatal period in dogs. The basal laminae of blood capillaries in the synovial membrane were often observed to be multi-layered, and this was remarkable especially in the human material. However, the thickness of the laminae of blood capillaries in the synovial membrane, as well as in the renal glomeruli and the lungs, showed a gradual increase with advance of the postnatal age of puppies up to 2 months.

Adolescent

[Influence of carrageenin inflammation on prostaglandin release from rat synovial membrane and action of anti-inflammatory drugs (author's transl)].

Carrageenin was injected into the knee joint cavity of rats, and influence of anti-inflammatory drugs on prostaglandin (PG) release in vitro from inflamed synovial membrane was studied. Release of PGE and F from inflamed synovial membrane was increased. Aspirin suppressed PGE and F release from non-inflamed and inflamed synovial membrane in vivo and in vitro, but suppression of PGF release was more intense. Hydrocortisone suppressed release of PGE and F from inflamed synovial membrane in vivo, and did not influence PG release in vitro. Release of PGE and F fron non-inflamed synovial membrane was not influenced by hydrocortisone in vivo and in vitro. PGE content in inflamed synovial membrane was increased markedly, and PGE and F content in inflamed and non-inflamed synovial membrane was decreased markedly by aspirin in vivo. Content of PGE and F in non-inflamed and inflamed synovial membrane showed a tendency to decrease with hydrocortisone administration in vivo, but such was not significant.

Animals

Cathepsin D activity in bovine articular cartilage, synovial membrane and fluid: degradation of cartilage proteoglycans from same joint.

Cathepsin D type proteases were extracted from articular cartilage, synovial membrane, and synovial fluid from normal, adult bovine knee joints. A sensitive enzyme assay made it possible to measure protease activity in the different tissues from individual joints. Highest activity was found in the synovial membrane, while cell free synovial fluids contained comparatively low activity. The degrading effect on articular cartilage proteoglycans (PGC and PGS), isolated from the same joints, was demonstrated by gelfiltration on Sepharose columns and by viscometry. Gelfiltration profiles of incubation mixtures indicated a proteolytic effect on PGC and on PGS), at pH 3.5, in concentrations of enzyme and proteoglycans found in cartilage tissue. No effect at neutral pH was obtained despite a 100-fold increase of enzyme concentration. These findings were supported by viscometry data. The degrading effect of enzymes from all sources was completely inhibited by pepstatin.

Animals

[Diagnostic value of synovial membrane immunofluorescence].

The immunofluorescent study of 93 synovial membranes of persons suffering from various types of arthropathy has shown that the only element sufficiently specific to have real diagnostic value is the presence of cells with a fluorescent cytoplasm. This appearance was in fact found in 63% of the cases of rheumatoid arthritis, irrespective of their being either seropositive or seronegative, in 69% of the cases of probable rheumatoid arthritis, in only 15% of the unclassified cases of arthritis, in 28% of the cases of various types of arthritis (20% with exclusion of a case of mixed connectivitis and of a case of Waldenström's macroglobulinemia with rheumatoid arthritis) and in 0% of the cases of mechanical arthropathy. The results of immunofluorescent examination compare favorably with those of standard histology: the classical histologic appearance of rheumatoid synovitis with a node-forming tendency of the infiltrate was observed in only 36% of the verified cases of rheumatoid arthritis, while immunofluorescence was positive in 63% of the cases in this group. In the category of unclassified arthritis, these percentages were comparable, viz. 19% and 20%, repectively. The presence of cells with fluorescent cytoplasm during immunofluorescent examination of the synovial membrane may be regarded as an additional criterion supporting the diagnosis of rheumatoid arthritis.

Adult

Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease.

The synovial membrane histologic sections from patients with six common rheumatic diseases were reviewed without knowledge of the clinical diagnosis. After histopathologic evaluation, the synovial membrane characteristics were grouped according to the patient's clinical diagnosis, and included 29 patients with rheumatoid arthritis, 13 with systemic lupus erythematosus, 17 with degenerative joint disease, 10 with acute bacterial arthritis, 8 with gout, and 13 with pseudogout. The only specific characteristics identified were bacteria (infectious arthritis), crystals (gout, pseudogout), and lymphoid follicles (rheumatoid arthritis). Nevertheless, other characteristic features of differential diagnostic utility were recognized, including the intensity and nature of synovial lining cell hyperplasia and of leukocyte infiltration. Light microscopic histopathologic changes in the common rheumatic diseases are not specific, but are of diagnostic utility. Complete and exhaustive review of each pathologic synovial membrane characteristic provides more justification for the routine use of synovial membrane biopsy as an adjunct to arthrocentesis in the evaluation of common rheumatic diseases.

Arthritis

Ultrastructural changes produced in rheumatoid synovial membrane by chrysotherapy.

Biopsies of rheumatoid synovial membrane before and after chrysotherapy were examined with the light and electron microscopes, and subjected to electronprobe x-ray analysis. The main change noted was the occurrence of electron-dense deposits of characteristic morphology within pre-existing lysosomes. Such deposits were also seen in other varieties of lysosomal bodies. X-ray analysis showed the presence of gold, phosphorus, osmium, and calcium in these deposits. The present study shows that gold enters the pre-existing lysosomes, supporting the concept that the beneficial effects of chrysotherapy are due to its action on the lysosome.

Adolescent

Immunofluorescence of synovial membrane multifactorial analysis of the results.

Synovial membrane taken by needle biopsy from the knee joint of 61 patients with various rheumatic diseases were studied using immunofluorescence methods. Staining techniques and their controls were detailed. Classical statistical tests and principal components multifactorial analysis of the data emphasized some differences between the pathological groups. Connective tissue diseases seemed to be characterized by plasma cells fluorescence and mixed immunoglobulins and complement deposits. These were mostly localized to extracellular spaces in sero-positive rheumatoid arthritis and to blood vessels in sero-negative rheumatoid arthritis and systemic lupus erythematosus. On the contrary, isolated immunoglobulins without complement were mostly found in the other inflammatory arthritis, while negative results were obtained in non inflammatory arthropathy. Immunoglobulin classes did not seem to have any diagnostic value. On the contrary, rheumatoid factor was specific for rheumatoid arthritis, whatever the serological pattern was, and it was particularly frequent in patients suffering from rheumatoid arthritis associated with a Sj5AOGREN SYNDROME. A strict relationship between classical histological findings and immunofluorescence results was not always found; so, immunological methods can be aquivocal.

Arthritis

[The synovial membrane in rheumatoid arthritis: change in the glycosaminoglycan pattern].

For examination of glycosaminoglycane (GAG) in the normal synovial membrane and in the synovial membrane of patients with rheumatoid arthritis (RA) fat free dry tissue was digested with papain. The GAG was fractonated with cetylpyridiniumchloride according to Svejcar's and Robertson's techniques and afterwards it was characterised in detail. The total amount of GAG per gramme of fat free dry tissue was the same in RA and in controls. The GAG distribution pattern was significantly changed: 1. A large fraction of hyaluronic acid was found in acutely inflamed tissue with only few scars. 2. In tissue with much cicatrization, however, acute processes accompanied by large amounts of hyaluronic acid appeared unimportant. There the L-iduronic acid content of the Ch-4-S and the Ch-6-S fractions (increased hybridization) and its total amount was increased. The tendency to increased epimerization of D-glycuronic acid to L-iduronic acid in the GAG-chains was clearly shown by an increase of the GAG-fraction, which contains relatively pure dermatane sulphate.

Adult

Changes in the collagen of synovial membrane in rheumatoid arthritis and effect of D-penicillamine.

1. Normal synovial membrane contains approximately equal proportions of two genetically distinct forms of collagen, types I and III. The proportion of these two collagens is unchanged in rheumatoid synovium but in addition a small amount of basement membrane collagen is present. Tissue culture of rheumatoid synovium confirms the synthesis of both type I and III collagens. 2. In young normal synovium both type I and type III collagens are stabilized by a reducible keto cross-link, which is replaced in adult tissue by an as yet unknown non-reducible cross-link. During the proliferation of the collagen in adult rheumatoid synovium a high proportion of the keto cross-link is present. This cross-link is not susceptible to cleavage by D-penicillamine, nor does the drug have any effect on the rate of synthesis in vitro. The mode of action of D-penicillamine in rheumatoid arthritis does not appear to involve a direct effect on the synovial membrane collagen.

Aged

[The synovial membrane in articular chondrocalcinosis. Clinico-pathological data].

The study of 25 samples of synovial membrane taken from 118 subjects with articular chondrocalcinosis makes it possible to identify three histological aspects : the complete forms showing a crystalline deposit of calcium pyrophosphate of variable volume and alterations of an inflammatory or degenerative type ; incomplete forms showing no calcium deposit, but in which one can observe two sorts of modifications : forms of chondroid metamorphism or inflammatory stigmatas causing an indeterminate chronic synovitis ; finally, forms of superficial fibrosis of the chorion are sometimes encountered. In all, the synovial membrane in articular chodrocalcinosis is often little different from an arthrosic or senile one. However, the presence of crystalline deposits rich in calcium and phosphorous and varying in size can, in the face of certain articular manifestations of uncertain cause, point to the existence of an articular chondrocalcinosis.

Calcium Pyrophosphate

[Synovial membrane permeability for plasma proteins and protein syntheses in rheumatic diseases].

1. The permeability of the synovial membrane for proteins is larger in rheumatoid arthritis than in osteoarthrosis, in rheumatoid arthritis with high CRP activity larger than in rheumatoid arthritis with low CRP activity. 2. The diffusion by the synovial membrane in most plasma proteins takes place depending on their molecular weight. Of the 14 proteins tested only haptoglobin and fibrinogen did not follow this regularity. 3. While the non-immune proteins proved in the synovial fluid only come from the blood plasma, the immune globulins IgG, IgA, and IgM as well as lysozyme are partly also locally synthetized and enriched in rheumatoid arthritis. In rheumatoid arthritis lysozyme is present in the synovia not only in free, but in most cases also in cell-bound form.

Arthritis, Rheumatoid