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Biomedical subjects

J Sany

Publications and source records attributed to J Sany.

At least 127 records · Page 7Linked to original sources
PubMed1990

Abnormal serum bone Gla protein levels in multiple myeloma. Crucial role of bone formation and prognostic implications.

The signification of serum bone Gla protein (serum BGP, osteocalcin) has been investigated in multiple myeloma. As a first step, quantitative iliac crest bone biopsies were performed in 19 patients; the serum BGP levels strongly correlated with histologic parameters of bone formation (r = 0.72-0.84, P less than 0.001) but not with those of bone resorption (r = 0.10). These results confirm that serum BGP is a marker of bone formation in multiple myeloma, as previously described in many other bone disorders. As a second step, serum BGP was measured in 117 patients with multiple myeloma as a systemic indicator of the degree of bone formation. Twenty-one percent of the patients had abnormal serum BGP levels (25 cases). The 14 patients with increased values (mean, 13.2 +/- 2.7 ng/ml) and thus increased bone formation belonged to a subgroup characterized by a lower osteolytic potential and a more indolent disease. On the other hand, the 11 patients with decreased values (mean, 1 +/- 0.3 ng/ml) and thus reduced bone formation had an advanced disease, extensive lytic bone lesions, a hypercalcemia frequently and a poor survival (mean, 4 months; range, 1-12). The biochemical investigations of the whole patient population, including serial studies in individual patients, have shown a large scatter of serum BGP levels, suggesting major differences in the bone formation rates. However, an overall inverse correlation was found between serum BGP and osteolytic potential. These results have confirmed the important role of the inhibition of bone formation in the occurrence of bone lesions in multiple myeloma and the interest of serum BGP to select a myeloma patient subgroup with low osteolytic potential and characterized by abnormally increased levels of this marker.

Adult↗
PubMed1990

[Cytokines and rheumatoid polyarthritis].

Cytokines play a role in the chronicity of inflammation, the formation of lesions and the persistence of the immune response observed in rheumatoid arthritis (RA). The dysregulation of the cytokines observed in RA is of great immunopathological importance. There is an increase in the macrophage-derived cytokines such as interleukin 1, the tumor necrosis factor alpha and interleukin 6. At the same time, there is a decrease in the lymphocyte-derived cytokines such as interleukin 2, interferon gamma and interleukin 4. Certain growth factors (transforming growth factor beta, platelet derived growth factor, granulocyte macrophage-colony stimulating factor) also play a role in RA. The study of the role of these various cytokines in the formation and maintenance of articular and extra-articular lesions in RA is carried out.

Arthritis, Rheumatoid↗
PubMed1990

T cell receptor expression and activation of synovial lymphocyte subsets in patients with rheumatoid arthritis. Phenotyping of multiple synovial sites.

Two-color flow cytometry analysis of peripheral blood and synovial lymphocytes from rheumatoid arthritis patients was performed using monoclonal antibodies directed against T cell subsets, T cell activation markers, and T cell receptors. The results showed an abnormally high percentage (greater than 15%) of CD3+, CD4-, and CD8- T cells expressing a specific receptor containing a gamma chain. Phenotypic analysis of lymphocytes infiltrating both knee joints of individual rheumatoid arthritis patients revealed very similar subset distribution and activation levels, despite strong differences in the clinical status between the 2 sites.

Arthritis, Rheumatoid↗
PubMed1990

Low levels of interleukin-4 and high levels of transforming growth factor beta in rheumatoid synovitis.

Since interleukin-4 (IL-4) displays agonistic effects on both T and B cells, we studied whether this lymphokine is involved in rheumatoid synovitis, a disease characterized by intense T cell infiltration and B cell stimulation. Rheumatoid arthritis synovial fluids (RA SF) contained no (less than 15 pg/ml) or very low amounts (less than 25 pg/ml) of IL-4, as measured by a sensitive and specific enzyme-linked immunosorbent assay. No IL-4 was produced by unstimulated rheumatoid synovial membrane. RA SF were found to inhibit phorbol myristate acetate (PMA)-dependent proliferation of normal peripheral blood lymphocytes (PBL). An inhibitory fraction with an apparent molecular weight of 150 kd was isolated by gel filtration. The inhibitory fraction strongly blocked the proliferation of PBL induced by PMA, PMA + IL-2, or PMA + IL-4. However, this fraction was less effective in blocking the proliferation of PBL induced by PMA + IL-2 + IL-4. High levels of transforming growth factor beta (TGF beta) were found in these RA SF, and an anti-TGF beta antibody was able to partially reduce the inhibitory activity. RA SF were found to inhibit phytohemagglutinin-induced IL-4 production by PBL. These data indicate that IL-4, similar to other T cell lymphokines, cannot be detected in RA SF and that RA SF contains an inhibitory activity, related in part to TGF beta, which blocks mitogen-induced proliferation of PBL, at least in part through an inhibition of T cell-derived lymphokine release.

Antibodies↗
PubMed1990

Functional studies of soluble low-affinity interleukin-2 receptors in rheumatoid synovial fluid.

Since abnormal regulation of interleukin-2 (IL-2) has been demonstrated in rheumatoid arthritis (RA), the functional role of low-affinity soluble IL-2 receptors (sIL-2R) purified from RA synovial fluids (SF) was studied. Picomolar levels of sIL-2R were detected in RA SF using an enzyme-linked immunosorbent assay. Levels were higher in serum and SF from RA patients than in controls (P less than 0.001) and higher in RA SF than in paired RA serum (P less than 0.01). Soluble IL-2R from RA SF had estimated molecular weights of 40-50 kd and 80-100 kd by gel filtration analysis. The 80-100-kd peak is likely to be a dimer of the 40-50-kd peak, since a single 45-kd peak was found after elution from sodium dodecyl sulfate-polyacrylamide gels. Since inhibitory activity for lymphocyte proliferation was found in the 80-100-kd range, the sIL-2R were purified with an anti-CD25 affinity column and further analyzed. The purified fractions did not interfere with the proliferation of mitogen-stimulated lymphocytes or with the binding of radiolabeled IL-2 to CTLL-2 cells, although direct binding of IL-2 was demonstrated. The affinity of sIL-2R from RA SF for binding IL-2 was in the range of 25 nM, which is similar to the affinity of sIL-2R purified from a human T cell clone, indicating that both sIL-2R are low-affinity receptors for IL-2. We conclude that the concentration and binding affinity of low-affinity sIL-2R purified from RA SF render them unable to interfere with IL-2-related activities.

Arthritis, Rheumatoid↗
PubMed1990

Interleukin 2 (IL 2) inhibitor in rheumatoid synovial fluid: correlation with prognosis and soluble IL 2 receptor levels.

A soluble activity inhibiting over 50% of the CTLL-2 cell line response to recombinant human interleukin 2 (IL 2) was found in 17 of 29 (59%) rheumatoid synovial fluids. To study the prognosis value of this activity, 16 rheumatoid synovial fluids were collected before a radiation synovectomy of the knee with 7 mCi of 90Yt. Patients with a good clinical result after the synovectomy had a lower IL 2 inhibitory activity than those with a bad or incomplete result (P less than 0.01). Levels of inhibitory activity and of soluble IL 2 receptors were correlated with each other and with the response of the synovitis to the radiation synovectomy. These results extend the clinical usefulness of soluble IL 2 receptor measurements and indicate a correlation between the immune activation of the rheumatoid synovitis and its clinical activity.

Adult↗
PubMed1990

Distribution of T-cell receptor-bearing lymphocytes in the synovial membrane from patients with rheumatoid arthritis.

Using immunohistology and monoclonal antibodies directed to the T-cell receptor (TCR) chains, we have analysed the distribution of TCR-bearing lymphocytes within the membrane of rheumatoid arthritis (RA) patients. Alkaline phosphatase staining for TCR alpha beta-bearing lymphocytes showed a distribution paralleling that of the total T cells. Staining for the TCR gamma delta chains revealed a moderate and rather homogeneous distribution of T gamma delta lymphocytes within the RA synovium. As evidenced by simultaneous staining for alpha beta and gamma delta receptors, the relative count of T gamma delta to alpha beta-expressing cells is close to the peripheral count (e.g.5%), and lower than that previously observed in the synovial fluid. Interestingly, the peripheral type V gamma 9-J gamma P rearrangement using the T gamma delta cell subset was relatively decreased in the synovial membrane, as compared to synovial fluid and peripheral blood, suggesting that the T gamma delta distribution in the rheumatoid synovium resembles a thymic-like situation.

Antibodies, Monoclonal↗
PubMed1990

Osteoblast stimulation in multiple myeloma lacking lytic bone lesions.

The reasons why some patients with multiple myeloma (MM) do not develop severe bone loss, or even develop sclerotic bone lesions, remain unclear. In order to answer this question at the cellular and tissue level, we evaluated the histological bone condition of 10 patients with MM who never developed lytic bone lesions during the course of their disease (including two patients with sclerotic MM). Myeloma-induced bone changes in the close vicinity of myeloma cells were evaluated by quantitative histology (bone histomorphometry). All 10 patients presented a significantly increased osteoblastic activity. This was associated with an increased bone resorption in seven of the 10 cases. Three patients had a pure osteoblastic presentation. These features were the reverse of the pattern observed in seven patients with lytic bone lesions: increased bone resorption with decreased bone formation. Almost all of these 10 patients showing excessive osteoblastic activity had increased serum bone gla protein levels, a specific marker of bone formation. Finally, 90% of these patients were lambda MM (70% of them were IgG lambda MM), an immunoglobulin subtype previously associated with the sclerotic MM variants. In conclusion, a subset of patients with MM never develop severe bone loss because of the stimulation of osteoblastic activity. These patients belong to the same family as osteosclerotic MM, presenting more frequently the IgG type and lambda subtype.

Aged↗
PubMed1990

Anti-F(ab')2 antibody response to the injection of anticlass II HLA alloantibodies in patients with rheumatoid arthritis.

Placenta eluted gamma globulins (PEGG) contain antibodies against class II HLA antigens and have been used for treating patients with rheumatoid arthritis (RA). In view of the potential use of antibodies to class II HLA for treating autoimmune diseases we looked for the immunobiological effects of PEGG injections in patients. No modulation of class II HLA was seen at the surface of circulating mononuclear cells after one week of daily PEGG injections. In some patients, antibodies to F(ab')2 fragments of PEGG-IgG were produced. These antibodies reacted against F(ab')2 of any IgG as well and did not prevent anticlass II HLA antibodies from binding to class II HLA, thus showing no characteristics of classical antiidiotypic antibodies. The appearance of anti-F(ab')2 antibodies was not correlated with the clinical course of the disease. Their significance is discussed.

Animals↗
PubMed1990

Radiologic progression during intramuscular methotrexate treatment of rheumatoid arthritis.

The radiographic evolution of joint lesions in 41 patients with severe and longstanding rheumatoid arthritis (RA) (mean duration: 12.9 years) treated with methotrexate (MTX) for more than 24 months (mean 31.2 months) was studied in a double blind manner by 2 rheumatologists using Larsen's score. All the patients were clinically improved. The radiological study of hands and wrists was possible in only 37 of 41 patients for surgical reasons. We found a deterioration of joint lesions in 31 cases (83.8%), a stabilization in 6 cases (16.2%). MTX does not appear to be able to slow down the radiographic evolution of RA. Whether it could prevent the radiologic progression in early RA remains to be elucidated.

Adult↗
PubMed1990

[Long-term tolerability of tiopronin (Acadione) in the treatment of rheumatoid arthritis. Apropos of 140 personal cases].

One hundred and forty patients with classic or definite rheumatoid polyarthritis were treated with N2 mercapto-propionly-glycine: thiopronine (Acadione) at an average dose of 1 g per day over a mean duration of 11.7 months + 10.7 months. The retrospective study of these cases, followed between 1980 and 1988 by the same medical team, permits to evaluate the long-term tolerance of the product. Adverse reaction, always subsiding were observed in 55 p. cent of the patients, requiring discontinuation of the treatment in 40 p. cent of the cases. These side effects occur in 3/4 of the cases, during the first 6 months of the treatment. The intolerance mainly affect skin and mucosae: 46 cases (32.8 p. cent) resulting in 32 instances (22.8 p. cent) discontinuation of the treatment because of stomatitis, pruritus, various types of erythema, pemphigus (1 case). Fourteen patients presented a renal failure (10 p. cent) requiring in 8 instances (5.7 p. cent) discontinuation of the thiopronine because of nephrotic syndrome (3 case) and proteinuria (5 cases). Haematological disorders were observed in 13 instances (9.2 p. cent), justifying, in 10 instances (7.1 p. cent) discontinuation of the treatment because of thrombopenia or leucothrombopenia. The other side effects observed are the following: digestive disorders 15 cases (10.7 p. cent) requiring discontinuation of the treatment in 3 instances (2.1 p. cent), agueusia in 6 instances (4.2 p. cent) requiring discontinuation of the treatment in one case; miscellaneous disorders 13.5 p. cent for which the responsibility of thiopronine is not precisely established (especially hepatic cholostasis, muscle disorders), requiring discontinuation the the treatment in 1.4 p. cent of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗
PubMed1990

[Pathogenic role of antinuclear antibodies in lupus disease].

The majority of anti-nuclear antibodies do not have a proven pathogenic role in systemic lupus erythematosus (SLE). The pathogenicity of native anti-DNA antibodies, suggested by clinical data, is difficult to confirm. It is linked to several factors: isotype and avidity of these antibodies, affinity for DNA, size of immune complexes. DNA, anti-DNA antibodies and cross-reactive anti-DNA idiotypes (16/6) have been isolated from human and NZB mouse glomeruli. Moreover, DNA has a particular affinity for the glomerular membrane due to its cross-reactivity with some constituents of this membrane. Anti-SSA (Ro) antibodies may play a role in some cases of nephropathy in SLE and participate in photosensitization. They are associated with neonatal lupus, with some cases of fetal death in black women and with the atrioventricular heart block. However, factors other than these antibodies are needed to induce such lesions. Anti-U1 RNP antibodies do not protect against kidney involvement in SLE; however, they can decrease suppressive function by penetrating into suppressor T cells. Anti-Sm antibodies may have particular immunoregulation properties. Some antinuclear antibodies may at least in part, be responsible for the lesions in SLE, in conjunction with other still-unknown factors.

Animals↗
PubMed1989

[Immunoglobulin D multiple myeloma. A retrospective study in the Languedoc region].

Between January 1, 1972 and December 31, 1985, 28 cases of IgD myeloma were diagnosed in the Languedoc region, southern France. These cases did not show the male predominance and early development usually found with this type of myeloma. Comparisons with a series of myelomas of all types detected in the same region during a similar period revealed an increased frequency of extramedullary clinical localizations, osteolytic lesions, anaemia and renal impairment. The monoclonal component was sometimes meagre, but it could be detected by electrophoresis on cellogel in 81 per cent of the cases. The lambda isotype, largely predominant, might account for these biological abnormalities and for a particularly sombre prognosis: the median survival was 11 months as against 29 months with myelomas of all types. There was no statistically significant correlation between any of the clinical and laboratory findings and the duration of survival.

Adult↗
PubMed1989

Treatment of chronic knee synovitis with arthroscopic synovectomy after failure of intraarticular injection of radionuclide.

Although satisfactory results have been obtained with conventional synovectomy of the knee, there are frequent complications, and a long period of rehabilitation is necessary after this surgery. We performed arthroscopic synovectomy of the knees of 30 patients (33 knees), 22 of whom had rheumatoid arthritis. These patients underwent the procedure after failure to respond to an intraarticular injection of either osmic acid or yttrium 90. The operated knee was moved 3-5 hours after the arthroscopy, and the patients walked the next day. No rehabilitation was needed. The followup period ranged from 6 months to 36 months, with an average of 17.7 months. Except for 1 patient with severe arthritis, all patients experienced improvement. Results were rated as "good" or "very good" in 27 knees. Six months after synovectomy, the patients were asked to rate their improvement; the mean +/- SEM degree of improvement was 79.1 +/- 22.9%. All patients had significant improvement in the range of motion of the knee. One patient required manipulation of the knee (while under anesthesia) soon after the arthroscopy. There were no other complications. There was no detectable radiographic evidence of disease progression in 24 patients who were seen 1 year after the procedure or in 9 patients who were seen 2 years after the arthroscopy. Thus, arthroscopic synovectomy appears to be an effective and simple treatment for chronic knee synovitis, and has a low morbidity rate.

Adolescent↗