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Biomedical subjects

Jacques Morel

Publications and source records attributed to Jacques Morel.

8 recordsLinked to original sources
PubMed2006

Recommendations of the French Society for Rheumatology. TNFalpha antagonist therapy in rheumatoid arthritis.

OBJECTIVES: To develop recommendations for TNFalpha-antagonist therapy in patients with rheumatoid arthritis (RA) seen in everyday practice, under the aegis of the French Society for Rheumatology. METHOD: We used the methods recommended by the French Agency for Healthcare Accreditation and Evaluation, the AGREE collaboration, and the European League against Rheumatism (EULAR). The recommendations focus on patient selection, monitoring, and treatment adjustments. RESULTS: Criteria for selecting patients eligible for TNFalpha-antagonist treatment of RA include: 1) a definitive diagnosis of RA; 2) disease activity for longer than 1 month, including presence of objective signs of inflammation; or radiographic progression; 3) previous failure of methotrexate in the highest tolerated dosage or of another disease-modifying antirheumatic drug in patients with contraindications to methotrexate; 4) absence of contraindications to TNFalpha-antagonist therapy. When starting TNFalpha-antagonist therapy 1) a thorough baseline evaluation should be conducted; 2) any of the three available agents can be used, as no differences in efficacy have been identified in patient populations; 3) concomitant methotrexate therapy is recommended regardless of the TNFalpha antagonist used; and 4) patients should receive standardized follow-up at regular intervals. Treatment adjustments should be based on the following: 1) the treatment objective is achievement of a EULAR response; 2) when such a response is not achieved, the dosage or dosing interval can be changed, or the patient can be switched to another TNFalpha antagonist; 3) in patients who experience intolerance to a TNFalpha antagonist, another TNFalpha antagonist may be tried, depending on the nature of the adverse event; 4) occurrence of a remission should lead to a reduction in symptomatic medications, most notably glucocorticoids where used; in the event of a prolonged remission, either the TNFalpha antagonist or the concomitant disease-modifying antirheumatic drug may be reduced. CONCLUSION: These recommendations are intended to help physicians use TNFalpha antagonists in their everyday practice with RA patients. They do not constitute regulations.

Antirheumatic Agents↗
PubMed2005

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces rheumatoid arthritis synovial fibroblast proliferation through mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt.

A hallmark of rheumatoid arthritis (RA) is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLSs), and the RA FLS has therefore been proposed as a therapeutic target. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on RA FLSs and, therefore, suggested as a potential drug. Here we report that exposure to TRAIL-induced apoptosis in a portion (up to 30%) of RA FLSs within the first 24 h. In the cells that survived, TRAIL induced RA FLS proliferation in a dose-dependent manner, with maximal proliferation observed at 0.25 nm. This was blocked by a neutralizing anti-TRAIL antibody. RA FLSs were found to express constitutively TRAIL receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) on the cell surface. TRAIL-R2 appears to be the main mediator of TRAIL-induced stimulation, as RA FLS proliferation induced by an agonistic anti-TRAIL-R2 antibody was comparable with that induced by TRAIL. TRAIL activated the mitogen-activated protein kinases ERK and p38, as well as the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway with kinetics similar to those of TNF-alpha. Moreover, TRAIL-induced RA FLS proliferation was inhibited by the protein kinase inhibitors PD98059, SB203580, and LY294002, confirming the involvement of the ERK, p38, and PI3 kinase/Akt signaling pathways. This dual functionality of TRAIL in stimulating apoptosis and proliferation has important implications for its use in the treatment of RA.

Apoptosis Regulatory Proteins↗
PubMed2004

Signal transduction pathways: new targets for treating rheumatoid arthritis.

Biotherapies and other new treatments introduced over the last few years have considerably enriched the therapeutic armamentarium for rheumatoid arthritis. Nevertheless, primary refractoriness or secondary escape phenomenon may occur, indicating a need for identifying new treatment targets. Promising candidates can be found among compounds involved in signal transduction pathways, most notably protein kinases (mitogen-activated protein kinase, MAPK and phosphatidylinositol-3 protein kinase, PI3) and transcription factors (nuclear factor kappa B, NF-kappaB; activating protein 1, AP-1; CCAAT/enhancer-binding protein, C/EBP and signal transducer and activator of transcription, STAT). Inhibition of signal transduction pathways may be achievable via three main strategies: pharmacological inhibitors, anti-sense or more specific inhibitors such as oligionucleotides or interfering mRNA, and induced overexpression of naturally occurring inhibitors. Clinical trials are under way to evaluate pharmacological inhibitors such as p38 MAPK. Although the preliminary results are promising, proof of safety has not yet been obtained. Signal transduction pathways are involved in normal processes, whose inhibition might produce untoward effects.

Arthritis, Rheumatoid↗
PubMed2003

Polymorphism of HLA-DMA and DMB alleles in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the contribution of HLA-DM alleles to susceptibility to systemic lupus erythematosus (SLE) in a Caucasian population. METHODS: HLA-DMA and DMB alleles were studied in 73 patients with SLE, 147 randomly selected controls, and 86 HLA-DRB1 genotype matched controls by oligotyping of polymerase chain reaction amplified genomic DNA with sequence-specific oligonucleotide probes. RESULTS: There was a significant presence of HLA-DMA*0103, DMA*0104, and DMB*0102 in the SLE patients compared with the randomly selected controls. After stratification of patients and matched controls according to DRB1 genotypes, only HLA-DMA*0104 was increased in SLE patients negative for the SLE susceptibility HLA-DR alleles. For the patients and controls positive for HLA-DR allele-susceptibility for SLE, HLA-DMA*0103, DMA*0104, DMB*0102, and DMB*0103 alleles tended to be more frequent, but without reaching statistical significance. No correlation was found between HLA-DM phenotype frequencies and any clinical or biological manifestations of SLE. CONCLUSION: This is the first study evaluating the influence of HLA-DM in a Caucasian SLE population. Our results suggest that HLA-DMA*0104 may represent a novel allele of susceptibility to SLE.

Adolescent↗