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J Sany

Publications and source records attributed to J Sany.

At least 73 records · Page 4Linked to original sources
PubMed1996

In vivo migration of tonsil lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: involvement of LFA-1.

Integrin-adressin binding is a critical step in lymphocte attachment to target tissues. The mucosal recognition systems (alpha E beta 7, alpha 4 beta 7, MADcam-1) have been implicated in the autoimmune process in rheumatoid arthritis. We developed a model for in vivo study of radio-labelled lymphocyte circulation and their attachment to human rheumatoid synovium. We studied the homing of tonsil lymphocytes, considered as mucosal lymphocytes, and the involvement of alpha E beta 7 integrin and LFA1 in the homing of tonsil lymphocytes. We engrafted human rheumatoid synovium subcutaneously in 6 week old SCID CB17 mice. Three weeks later, we injected intraperitoneally 20 IO6 human peripheral blood or tonsil mononuclear cells, previously labelled with 3 mCFi HMPAO-99mTc. A mouse total body scintigram was obtained 20 h postinjection. The same protocol was performed after treatment of the MNC and mAb against LFA-1 (CD11a) or alpha E beta 7 (CD103). Tonsil MNC retention in the rheumatoid synovial graft 20 h post-injection was enhanced compared to blood MNC (12731 +/- 8297cpm/200 pixel) versus 5982 +/- 4713cpm/200 pixel, p < 0.05). A monoclonal antibody against LFA 1 decreased the activity in the graft (4152 +/- 1287 cpm/200 pixel), p < 0.05. No significant difference in tonsil MNC attachment to rheumatoid synovial tissue was observed with a mAb against alpha E beta 7 (8057 +/- 5009 cpm/200 pixel). Our results showed an increase in radiolabelled mucosal MNC migration in synovial tissue engrafted in SCID mice compared with blood MNC. Moreover, the date suggest that LFA-1 but not the alpha E beta 7 integrin is involved in tonsil MNC binding to synovial tissue in RA.

Animals↗
PubMed1996

Validation of the French version of the arthritis impact measurement scales 2 and comparison with the french version of the Nottingham Health Profile. "Quality of Life in Rheumatology" Task Force.

Appropriate attention can be directed to quality of life indices in the evaluation of therapeutic interventions only if reliable, valid measurement tools with good sensitivity to change are available. The goal of this study was to validate the French version of the Arthritis Impact Measurement Scales 2 (AIMS2), called EMIR (Echelle de Mesure de l'Impact de la polyarthrite Rhumatoïde) and to compare it with the validated French version of the Nottingham Health Profile, called ISPN (Indicateur de Santé Perceptuelle de Nottingham). The French version of the AIMS2 (37 items, 12 dimensions) was obtained via several independent translations and back-translations, followed by selection of the most relevant items by a panel of experts and a preliminary evaluation in rheumatoid arthritis patients. The measurement properties of EMIR (reliability, validity and sensitivity to change) were investigated in a cohort of rheumatoid arthritis patients who were put under methotrexate therapy and followed up for six months. Reliability was evaluated by test-retest at a ten-day interval (intraclass coefficients of correlation). Principal component factorial analysis was used to study construct validity and Cronbach's alpha coefficients to study internal consistency. Convergent validity was evaluated based on correlations between the quality of life scores obtained in selected dimensions of the EMIR and a number of other parameters (number of painful/swollen joints, pain severity score on a visual analog scale, erythrocyte sedimentation rate). Sensitivity to change after three and six months was determined by calculating mean standardized response means. The EMIR and ISPN were compared based on scores and sensitivity to change for the dimensions that investigated the same concepts. One hundred twenty-seven rheumatoid arthritis patients scheduled for methotrexate therapy were entered into the study. Principal component analysis established that all dimensions of the EMIR were independent from one another, except the "walking and bending" dimension. Internal consistency was satisfactory for each of the 12 dimensions, with Cronbach's alpha coefficients ranging from 0.70 to 0.90. Most correlations between quality of life scores and clinical or laboratory parameters were significant, indicating satisfactory convergent validity. The reliability study also yielded satisfactory results, with intraclass coefficients ranging from 0.65 to 0.90. Sensitivity to change after three and six months was significant for 11 of the 12 dimensions (mean standardized responses, 0.30 to 0.77). Sensitivity to change was slightly better for the EMIR than for the ISPN. Analysis of scores demonstrated that these two instruments did not measure quality of life in exactly the same way but complemented each other.

Adult↗
PubMed1996

In vivo migration of radiolabelled lymphocytes in rheumatoid synovial tissue engrafted in SCID mice: implication of beta 2 and beta 7-integrin.

OBJECTIVE: Integrin-adressin binding is a critical step in lymphocyte attachment to target tissues. The lymphocyte function associated antigen (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) pathway has been shown to be involved in the homing of lymphocytes to arthritic joints in animal models. The mucosal recognition system [alpha E beta 7/E-cadherin, alpha 4 beta 7/mucosal vascular adressin cellular adhesion molecule 1 (MADCAM-1)] has been implicated in the autoimmune process of nonobese diabetic mice and in rheumatoid arthritis (RA). We developed a model for in vivo study of radiolabelled lymphocyte circulation and attachment to human engrafted rheumatoid synovium, and studied the involvement of LFA-1 and alpha E beta 7 integrin. METHODS: We engrafted human RA or osteoarthritis (OA) synovium subcutaneously in 6-week-old SCID/CB17 mice. Three weeks later, we injected intraperitoneally 20 x 10(6) human peripheral blood lymphocytes (PBL) labelled with 3 mCi 99mtechnetium hexamethyl propylenamine oxime. A mouse total body scintigraphy was obtained 20 h postinjection. The same protocol was performed after pretreatment of the PBL with monoclonal antibodies (Mab) against CD11a (25-3) or against alpha E beta 7 human mucosyl lymphocyte marker 1. RESULTS: PBL migrated in the rheumatoid synovial graft 20 h postinjection (activity in the region of interest of the graft: 7699 +/- 4383 cpm/200 pixel or 4.43 +/- 2.65% of initial activity) versus OA engrafted synovial tissue (1453 +/- 1137 or 0.74 +/- 0.6% of initial activity), p = 0.007. The homing to the engrafted rheumatoid synovial tissue of PBL from healthy subjects was not significantly different from the migration of PBL from patients with RA. A Mab against alpha E beta 7 significantly decreased lymphocyte attachment to rheumatoid synovial tissue (3094 +/- 3808 cpm/200 pixel or 2.65 +/- 2.4% of injected activity), p < 0.03. The same results were obtained with Mab against CD11a (5007 +/- 4190 cpm/200 pixel or 2.27 +/- 1.2%), p < 0.01. Our results show increased blood lymphocytes homing to rheumatoid synovial tissue engrafted in SCID mice versus OA tissue. CONCLUSION: The data suggest that both LFA-1 and mucosal recognition integrin alpha E beta 7 are involved in lymphocyte binding to target tissues in RA.

Animals↗
PubMed1996

Validity, reliability, and sensitivity to change of a French version of the arthritis impact measurement scales 2 (AIMS2) in patients with rheumatoid arthritis treated with methotrexate.

OBJECTIVE: To develop and validate a cross cultural version of the Arthritis Impact Measurement Scales 2 (AIMS2) to be used by French speaking populations. METHODS: A French version of the AIMS2 was obtained using back translation, committee review, and pretesting. The French AIMS2 was studied in 127 patients with rheumatoid arthritis (RA) about to receive therapy with methotrexate (MTX). Construct validity of the questionnaire was assessed by factor analysis. Convergent validity was evaluated by correlation coefficients with joint counts, pain assessment, and sedimentation rate. Reliability was assessed by test-retest procedure at a 10-day interval, Cronbach's coefficients of internal consistency, and within scale factor analyses. Sensitivity to change after 12 and 24 weeks of therapy with MTX was assessed with computation of standardized response means (SRM) and paired t test comparisons. RESULTS: Factor analyses of the French version clearly identified the same scales of the AIMS2, except for the walking and bending scale which loaded on several factors. Convergent validity of the physical and symptom components of the instrument was demonstrated by significant correlations with clinical and laboratory features. All the scales were reliable (intraclass correlation coefficients: 0.65 to 0.90; percentage of explained variance larger than 50% in all but one scale; Cronbach's alpha: 0.70 to 0.90). Sensitivity to change was demonstrated in 11 of the 12 scales (SRM: 0.30 to 0.77). Most of the improvement was noted by Week 12. CONCLUSIONS: This cross cultural adaptation of AIMS2 in French is valid, reliable, and responsive in patients with RA in whom MTX therapy is instituted. It would permit international comparison studies. This study provides evidence for construct validity and responsiveness of the original version of the AIMS2, not demonstrated previously.

Activities of Daily Living↗
PubMed1996

Mononuclear cell retention in rheumatoid synovial tissue engrafted in severe combined immunodeficient (SCID) mice is up-regulated by tumour necrosis factor-alpha (TNF-alpha) and mediated through intercellular adhesion molecule-1 (ICAM-1).

The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.

Animals↗
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↗
PubMed1995

Rheumatoid factor associated with a secretory component in rheumatoid arthritis.

The authors' objective was to study the serum secretory immunoglobulin A (S-IgA) concentration and the presence of rheumatoid factor (RF) complexed with a secretory component (SC) in rheumatoid arthritis (RA). Sixty-three RA patients were studied. There were 49 healthy subjects in the control group. The S-IgA concentration and the presence of IgA isotype RF were determined by ELISA in the serum. The presence of SC complexed to RF (SC-RF) was studied by a sandwich-type enzyme-linked immunosorbent assay with an antibody against the SC used to capture S-immunoglobulin, and associated anti-globulin activity was revealed with a peroxidase-conjugated human IgG Fc fragment. We observed a significant increase in S-IgA in RA (mean 76.8 micrograms/ml +/- 152.9 S.D.), as compared to controls (mean 13.6 micrograms/ml +/- 11.9 S.D.) (P < 0.01). Forty-one per cent of RA patients presented a S-IgA concentration above the upper threshold, but we did not observe any association with disease activity. S-IgA concentration was correlated with the presence of IgA-RF. Twenty-seven RA patients had a positive SC-RF versus one in the control group (P < 0.01). The presence of SC-RF was associated with an increased S-IgA concentration (P < 0.0001), and the presence of RF-IgA (P < 0.002). However, no association with disease activity was noted. Our study showed that serum S-IgA was increased in RA, and that part of the RF were complexed with SC. These results suggest contribution of mucosal lymphocytes in the pathogenesis of RA.

Adult↗
PubMed1995

Total and free methotrexate pharmacokinetics, with and without piroxicam, in rheumatoid arthritis patients.

The pharmacokinetic profile of total and free methotrexate (MTX) and the effect of piroxicam on MTX pharmacokinetics was studied in 20 rheumatoid arthritis patients receiving a stable dosage of MTX (10 mg/week). Plasma protein binding ranged from 25 to 55%. To describe the variations with time of the unbound fractions a mathematical characterization relationship between the total and free MTX was used. Total and free MTX were correlated with the sigmoid maximum effect model. The slope factor (gamma) was proportional to the number of binding sites. The free fraction for a given patient can be evaluated from this relationship. Total clearance of MTX was not statistically different with piroxicam (8.0 l/h for total MTX, 13.7 l/h for free MTX) vs without piroxicam. Likewise, there were no significant difference in tmax, area under the plasma concentration vs time curve, distribution and elimination half-lives, mean resonance time, and volumes of distribution. Although the highest observed total MTX concentration was significantly lower with piroxicam, there were no significant pharmacokinetic interactions between low-dose MTX and piroxicam.

Adult↗
PubMed1995

Prognostic factors in rheumatoid arthritis. Comparative study of two subsets of patients according to severity of articular damage.

Clinical and biological profiles at the onset of the disease, obtained retrospectively, and human leucocyte antigen typing were studied in 47 rheumatoid arthritis (RA) patients with severe articular damage (group 1) and in 47 patients with limited radiological abnormalities (group 2). The two groups were matched according to disease duration (mean: 8.1 yr). Systemic manifestations were more frequent in group 1. Erythrocyte sedimentation rate (ESR), platelet counts, C-reactive protein (CRP), rheumatoid factor and IgG titres were higher and haemoglobin level lower in group 1. HLA class II genotyping demonstrated that 95.7% of patients in group 1 were Dw4, Dw14 or DR1 as compared to 55.3% in group 2 and 37.1% in normal controls. Two RA-linked DRB1 genes were detected in 34.1% of patients in group 1, vs 8.5% in group 2 and 7.9% in controls. Multiple logistic regression analysis demonstrated that ESR, CRP and genetic markers were the most relevant independent variables and when combined could indicate the outcome in early RA. These data confirmed that different RA subtypes with different prognoses could be associated with particular clinical, biological and genetic profiles. Moreover, some of these factors could serve as predictive markers for outcome at the onset of RA.

Adult↗
PubMed1995

Radiolabelled lymphocyte migration in rheumatoid synovitis.

OBJECTIVES: To study the ability of technetium-99m hexamethyl propylene amineoxime (HMPAO) labelled lymphocyte scintigraphy to quantify synovial inflammation, and to analyse the kinetics of lymphocyte retention in the joints of patients with rheumatoid arthritis (RA). METHODS: After isolation of the lymphocytes, the cells were radiolabelled in vitro with 250 MBq 99mTc-HMPAO. The scans were performed 30 minutes, three hours and 20 hours after injection. RESULTS: An increase of the scintigram signal obtained at 20 hours was associated with a high joint swelling and joint pain score (F test = 3.07, p < 0.002), but not with the radiological score. A positive joint scintigram was predictive of active synovitis. Although the scintigram variation over time did not reach statistical significance, the kinetics of the scintigram signal tended to differ according to the disease duration: in early RA, active arthritis could be clearly imaged as early as 30 minutes, increased at three hours and the signal intensity persisted at 20 hours. In contrast, in long standing disease, the affected joints were imaged at 30 minutes, persisted unchanged at three hours, and the scintigram score decreased significantly at 20 hours. CONCLUSIONS: The study shows that 99mTc-HMPAO joint scintigraphy may be used to detect and to localise active rheumatoid arthritis.

Aged↗
PubMed1995

T cell receptor distribution in rheumatoid synovial follicles.

OBJECTIVE: In rheumatoid arthritis (RA) joint erosion is accompanied by T cell infiltration of the synovial tissue. The resulting T cell receptor (TCR) repertoire is a combination of antigen driven shaping, nonspecific selection by endothelial cell-T cell interactions, and cytokine mediated chemoattraction. Considering the conflicting results of molecular biology studies of the TCR repertoire in RA, we attempted to obtain new data to clarify the situation through microscopic distribution analysis of TCR beta chain diversity in synovium follicular CD4/CD8 subsets. METHODS: We used dual color fluorescence confocal microscopy with CD4/CD8 monoclonal antibodies (Mab) and a panel of new anti-V beta Mab. The analysis focussed on lymphocyte rich, follicle-like areas of synovial tissue from 4 patients with RA. RESULTS: The expression of individual TCR beta families varied between areas within the T cell follicles, and between patients. Normal absolute levels of some beta chains can be completely skewed towards one subset, indicating that overall TCR evaluation is insufficient. CONCLUSION: Confocal microscopy analysis of localized TCR diversity in RA synovium offers novel insight into overall V beta gene usage, which appears to be the accumulation of several localized microexpansions.

Antibodies, Monoclonal↗
PubMed1995

A study of ovarian function in rheumatoid arthritis.

Ovarian function was evaluated prospectively in 16 female rheumatoid arthritis patients in the childbearing age. None of the patients was using oral contraceptives. The control group included 31 women with tubal sterility. Serum levels of estrone, 17 beta-estradiol and progesterone were assayed and used to determine an estrogen index and a luteal index. An ovulatory score was calculated as the sum of the estrogen and luteal indices. Estrogen levels were lower in the rheumatoid arthritis group than in the control group, but the difference was not significant. No statistically significant difference was found for progesterone levels, suggesting that luteal function was normal in the rheumatoid arthritis patients. The rheumatoid arthritis group had a significantly lower mean ovulatory score reflecting a decreased likelihood of ovulation as compared with the control group (p < 0.01). This abnormality may explain why fertility is reduced in women with rheumatoid arthritis.

Adult↗
PubMed1995

Dysregulation of the hypothalamo-pituitary axis in rheumatoid arthritis.

OBJECTIVE: To study the dynamic response of the hypothalamo-pituitary- adrenal axis and of prolactin (PRL) pituitary secretion in rheumatoid arthritis (RA). METHODS: We performed a cortisol releasing hormone (CRH) provocation test followed by determination of adrenocorticotropin hormone (ACTH), beta-endorphin, and cortisol concentration, and then a thyrotropin releasing hormone (TRH) provocation test followed by assessment of PRL pituitary secretion in 10 patients with RA and 5 control subjects. All were women under 40 years of age. Hormone concentrations were assessed by radioimmunoassay. RESULTS: Basal PRL cortisol, and ACTH concentrations were similar in patients with RA and controls. We observed a dissociation between the pituitary secretion of beta-endorphin and of ACTH in response to CRH in RA. The ACTH peak and total ACTH production (area under the curve, AUC) were similar in the 2 groups. In contrast, basal beta-endorphin was increased in RA (12.6 +/- 1.41 vs 8.29 +/- 0.144 pg/ml), and the response upregulated (AUC: 83,080 +/- 12,000 vs 54,200 +/- 2400) after CRH compared to controls (p < 0.05). Cortisol adrenal response curve was blunted, but did not reach statistical significance. In contrast, the PRL response to TRH was increased at 120 and 150 min (3461 +/- 303 vs 1897 +/- 520 muIU/ml)(p < 0.01) in patients with RA, independent of disease activity. CONCLUSION: We observed upregulated pituitary PRL secretion in RA, and a dissociation of ACTH stress. The implication concerning the neuroendocrine system in the chronic immune response in RA is discussed.

Adrenocorticotropic Hormone↗
PubMed1994

Objective and subjective sleep disturbances in patients with rheumatoid arthritis. A reappraisal.

OBJECTIVE: To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology. METHODS: Nineteen RA patients and 19 age-matched healthy control subjects underwent all-night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self-report questionnaire on their first night. RESULTS: Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis. CONCLUSION: Sleep is severely disturbed in patients with RA, regardless of the inflammatory disease activity. The specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients.

Adult↗
PubMed1994

Methotrexate concentrations in synovial membrane and trabecular and cortical bone in rheumatoid arthritis patients.

OBJECTIVE: To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients. METHODS: Ten RA patients (9 women, 1 man; mean +/- SD age 49.2 +/- 10.6, mean disease duration 13.2 +/- 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean +/- SD MTX treatment duration was 26.4 +/- 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean +/- SD of 19.7 +/- 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues. RESULTS: The mean +/- SD plasma concentration was 0.0252 +/- 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 +/- 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 +/- 0.164 and 0.286 +/- 0.126 nmoles/gm, respectively. CONCLUSION: After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients.

Adult↗