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J Sany

Publications and source records attributed to J Sany.

At least 19 recordsLinked to original sources
PubMed1995

Expression of a multidrug resistance gene in human rheumatoid synovium.

The objective of this study was to assess the expression of a multidrug resistance (MDR) phenotype, implicated in the cellular resistance of tumor to chemotherapy, in rheumatoid synovial membrane. Synovial membrane from 16 rheumatoid (RA) patients was studied. Six patients with osteoarthritis constituted the control group. The cell membrane expression of the glycoprotein Pgp 170, encoded by the MDR 1 gene, was determined by an immunoperoxidase technique using two different monoclonal antibodies (JSB 1, C 219). The polymerase chain reaction (PCR) methods were used in parallel to detect the presence of the MDR 1 gene mRNA in the synovial cells. Pgp 170 was expressed on the cell membrane of five RA patients and MDR 1 cellular transcription was detected in one other RA patient. We did not observe any association between synovial glycoprotein expression and age, disease activity, and a specific treatment with a long-acting drug. However, MDR protein expression was associated with the successive treatment with more than three disease-modifying antirheumatic drugs (DMARDs). We concluded that the synovial membrane expresses a glycoprotein recognized by the antibodies JSB 1 and C 219. The absence of concomitant MDR 1 transcription suggests the expression of an atypical MDR phenotype in the synovial membrane, distinct from the Pgp 170 encoded by the MDR 1 gene. The implications of the MDR phenotype and the resistance of RA to DMARDs is further discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The B cell repertoire in rheumatoid arthritis. III. Preferential homing of rheumatoid factor-producing B cell precursors in the synovial fluid.

OBJECTIVE: We sought to compare the frequencies of precursors producing IgM rheumatoid factors (IgM-RFs) in synovial fluid and peripheral blood B cells from patients with rheumatoid arthritis (RA). METHODS: We used limiting-dilution analysis of Epstein-Barr virus-activated B cells from seropositive and seronegative patients. B cell precursors producing IgM against insulin, an irrelevant autoantigen, were also assessed for comparison. RESULTS: On average, IgM-RF-producing precursors were 15-fold higher in the synovial fluid than in the peripheral blood of seropositive RA patients, but not in seronegative RA patients. The frequency of B cell precursors producing IgM against insulin was lower in the synovial fluid than in the peripheral blood of both the seropositive and the seronegative patient groups; moreover, the concentrations were similar in both groups. CONCLUSION: The findings provide evidence against a nonspecific accumulation of IgM-producing cells in the synovial fluid, and suggest that there is an active attraction of the RF-producing B cell precursors toward sites of inflammation in RA.

Adult↗
PubMed1992

Precision of the Larsen and the Sharp methods of assessing radiologic change in patients with rheumatoid arthritis.

OBJECTIVE: To compare the sensitivity of Sharp's and Larsen's radiographic scoring methods for detecting change in rheumatoid arthritis (RA) over time. METHODS: Radiographs of the hands and wrists were taken at the beginning and at the end of a 2-year followup period, in 42 patients with active RA. Films were scored blindly using both scoring methods. Patients were under treatment with methotrexate (intramuscular injections). RESULTS: Radiographic evidence of progression or amelioration was detected in 25 patients by Larsen's method and in 35 patients by Sharp's method. The relative sensitivity to change over time was greater for Sharp's method (0.01 less than P less than 0.025). CONCLUSION: Sharp's radiographic scoring method seems to be more sensitive to change over time than is Larsen's method. The clinical importance of the change needs to be definitively established.

Adult↗
PubMed1992

T cell receptor gamma variable gene locus polymorphism in patients with rheumatoid arthritis.

OBJECTIVE: We sought new susceptibility markers for rheumatoid arthritis (RA) among the T cell receptor gamma (TCR gamma) genes. METHODS: We analyzed restriction fragment length polymorphisms (RFLP) of the first variable subgroup of TCR gamma genes in a group of French control subjects and a group of French RA patients. RESULTS: No significant difference in Eco RI RFLP was found between the 2 study populations: Allele frequencies were virtually identical. There was no polymorphism using Hind III. CONCLUSION: These results exclude TCRV gamma I polymorphism as a disease susceptibility marker in RA.

Arthritis, Rheumatoid↗
PubMed1992

IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study.

OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.

Adult↗
PubMed1992

Analysis of monoclonal rheumatoid factors obtained from the B-cell repertoire in rheumatoid arthritis.

We have sought to determine whether rheumatoid factors (RF) produced in rheumatoid arthritis (RA) were different from physiological RF produced in normal, healthy adults. RF-secreting clones were established following Epstein-Barr virus (EBV) stimulation of peripheral blood lymphocytes. Ten RF-secreting clones were established from seven RA patients and 16 from six healthy controls. All monoclonal RF (MRF), except two in each group, were monoreactive and ten of these were shown to have low to medium affinity for IgG,Fc, irrespective of their origin. A majority (74%) of the MRF bound to protein A, indicating that genes of the VHIII family were preferentially used for synthesizing these autoantibodies. The expression of cross-reactive idiotypes (CRI) by the MRF did not allow distinction between those derived from RA patients and controls. The VHI-associated CRI G8 and VHIII-associated CRID12 were expressed at low frequency in both panels of RF. These CRI have been shown to be expressed at high frequency in RF paraproteins. However, the idRQ idiotype was expressed within both panels of RF. A possible distinction between polyreactive and monoreactive MRF appeared to be light chain usage since all (four) polyreactive RF used lambda chains while the normal kappa/lambda ratio was observed for monoreactive RF. The frequency of EBV-activated cells secreting IgM bearing CRI or secreting RF was determined and showed that CRI expression occurred with a higher frequency than did RF, suggesting a dissociation between CRI expression and RF activity.

Animals↗
PubMed1992

Non-Hodgkin's lymphoma associated with primary Sjögren's syndrome.

OBJECTIVES: To evaluate the prevalence, the incidence and clinical presentation of non-Hodgkin's lymphoma associated with primary Sjögren's syndrome. METHODS: Sixty-two patients with primary Sjögren's syndrome were analyzed retrospectively in an open investigation. RESULTS: Of 62 patients with primary Sjögren's syndrome, 4 of them (6.4%) developed non-Hodgkin's lymphoma (6.9 cases per 1000 per year). All of them were women. Non-Hodgkin's lymphoma always developed after the onset of primary Sjögren's syndrome with a time interval ranging from 3 to 27 years. Pathological findings showed two diffused mixed small and large cell cleaved lymphomas and two diffused large cell cleaved lymphomas. Three cases had extra-nodular localizations. All of these 4 patients are still alive and in complete remission 2 to 8 years after the diagnosis of non-Hodgkin's lymphoma. CONCLUSION: This study confirms the association of non-Hodgkin's lymphoma in primary Sjögren's syndrome. These non-Hodgkin's lymphomas frequently had extra-nodal localizations. Good sensitivity to treatment, when necessary, provided good prognosis.

Adult↗
PubMed1992

[Rheumatoid aortic insufficiencies: severity of the prognosis].

Rheumatoid aortic incompetence is infrequent, with only 43 cases published in the literature. Seven additional patients (5 females and 2 males) with rheumatoid arthritis (RA) and aortic incompetence are reported herein. All seven patients had seropositive RA with severe joint disease and extraarticular manifestations (nodules, cutaneous vasculitis, multiple neuritis). Development of aortic incompetence was unrelated to age or duration of RA. The aortic disease was diagnosed upon the development of sudden heart failure (pulmonary edema) in three patients and during a routine evaluation in the other four. The course was extremely severe with a fatal outcome in five patients, of whom the youngest was only 24. Only one patient had valve replacement surgery; however, this patient died 8 days after the procedure. Mean survival in the seven patients was 20 months (range 7-56) from diagnosis and 11 months (range 1-28) from the first manifestation of heart failure. Histologic studies done in the only patient who had surgery demonstrated a rheumatoid granuloma in the pericardium and lymphocytic infiltrates in the pericardium and aortic valve.

Adolescent↗
PubMed1992

[Therapeutic maintenance dose with methotrexate in rheumatoid polyarthritis. Prospective study of 191 cases].

One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice.

Adult↗
PubMed1991

[Rheumatoid wrist].

The wrist is involved, often as the initial lesion, in 85% of patients with rheumatoid arthritis. . An early diagnosis results in a better management. At an advanced stage the functional disablement may be severe; it can be due to instability of the wrist, sometimes associated with palmar dislocation of the carpus, to rupture of tendons facilitated by dorsal dislocation of the ulnar head, and to the limited mobility of the wrist, notably in supination. Treatment is part of the overall management of rheumatoid arthritis, with surgery playing a major role.

Arthritis, Rheumatoid↗
PubMed1991

Autoantibodies in D-penicillamine-induced myasthenia gravis: a comparison with idiopathic myasthenia and rheumatoid arthritis.

The distribution of autoantibodies was studied in patients with rheumatoid arthritis (RA) treated by D-penicillamine and who developed myasthenia gravis (MG). The anti-human acetylcholine receptor (AChR) antibodies were specifically associated with clinical symptoms of MG without any difference in the pattern of specificities in idiopathic (id-MG) or in induced MG (DPen-MG). Conversely, anti-nuclear antibodies were elevated in DPen-MG sera compared to id-MG sera (P less than 0.001) but were also compared to patients with RA treated by D-penicillamine (or thiopronine) and who did not develop MG. Anti-denatured DNA antibodies were enhanced in sera from treated patients, whether they had presented or not a MG disease. Anti-histone antibodies were associated with RA. These observations suggest that the immunological imbalance in RA patients, can be increased by a drug treatment which may trigger the appearance of a second autoimmune disease such as MG, where anti-AChR antibodies are associated with anti-nuclear antibodies.

Adult↗
PubMed1991

The B cell repertoire in rheumatoid arthritis. I. Frequency of EBV-inducible circulating precursors producing autoantibodies.

The frequency of B cell precursors producing antibodies against various autoantigens (Fc fragment of IgG, F(ab')2 fragment of IgG, type II collagen, cytoskeleton filaments and insulin) was determined in patients with rheumatoid arthritis (RA) using immortalization of peripheral blood B cells by the Epstein-Barr virus (EBV) and limiting dilution analysis. Equally large numbers of B cell precursors producing IgM-rheumatoid factors (RFs) were present in the peripheral blood of seronegative and seropositive RA patients and of controls. On average, 1 out of 15,000 B cells could be induced by EBV to secrete IgM-RFs, which represents 0.5-1% of the EBV-induced proliferating clones. By cloning or somatic hetero-hybridization of EBV cell lines derived from patients and controls, we obtained two types of monoclonal RFs: one polyreactive, reacting with Fc but also with the other autoantigens tested, and the other monoreactive, reacting with Fc only and that previously had only been found in the RA B cell repertoire. Moreover, patients and controls had similar numbers of circulating B cell precursors secreting IgM antibodies against other autoantigens that might be regarded as specific targets of RA (F(ab')2 fragment of IgG and type II collagen), and against cytoskeleton filaments that are targets of natural autoantibodies, increased in RA. The frequencies of EBV-induced B cells producing antibodies against all these autoantigens were of the same order of magnitude as the frequency of EBV-induced B cells producing RFs. The patients also possessed a similar number of precursors producing antibodies against insulin, an autoantigen irrelevant to the pathogenesis of the disease, taken as control. These data tend to demonstrate no abnormality in the autoantibody repertoire of B cells activable by EBV in RA, especially those secreting RFs. In vitro spontaneous RF secretion by circulating B cells was observed in seropositive RA patients but not in seronegative patients and in the controls tested. We enumerated the number of B cells spontaneously secreting RFs in seropositive RA patients and found that it correlated with the serum RF titer, but not with the number of RF-secreting B cells activated by EBV. The mean frequency values of B cells secreting RFs either spontaneously or after EBV infection were of the same order of magnitude, showing that the expanded population of in vivo-activated B cells was not (at least partially) infectable by EBV. This raised the possibility that EBV triggers a repertoire which may not reflect the status of B cells secreting autoantibodies in autoimmune diseases.

Age Factors↗
PubMed1991

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P less than 0.01). A significant (P less than 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P less than 0.05 by comparison with those with early MM). A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow.

Bone Development↗