Biomedical subjects

T W J Huizinga

Publications and source records attributed to T W J Huizinga.

58 records · Page 4Linked to original sources

PubMedDate not supplied

Correlation between expression of CD44 splice variant v8-v9 and invasiveness of fibroblast-like synoviocytes in an in vitro system.

OBJECTIVES: Rheumatoid arthritis is characterized by inflammation, hyperplasia of the synovial membrane, pannus formation and degradation of cartilage and bone. Fibroblast-like synoviocytes are thought to be involved in the invasion and subsequent degradation of cartilage. Two processes play a role in cellular invasion: cellular migration and degradation of the extracellular matrix. The adhesion molecule CD44 and chemokine receptors are instrumental in migration and invasion. Both components have been reported to play a role in tumour metastasis but also appear to be implicated in the destruction of synovial joints in rheumatoid arthritis. CD44, an ubiquitously expressed receptor for the glycosaminoglycan hyaluronan, contains 9 exons that are alternatively spliced and this gives rise to the expression of multiple splice variants, each exhibiting different functional capacities. METHODS: In this report we describe an analysis of the expression of chemokine receptors and CD44 splice variants in diseased synovial tissues using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). We have correlated our findings with the clinical diagnosis of rheumatoid or osteoarthritis, with invasion into the extracellular matrix in vitro, and with the rate of proliferation of fibroblast-like synoviocytes. RESULTS AND CONCLUSIONS: We conclude that fibroblast-like synoviocytes from both osteo- and rheumatoid arthritis express a number of different chemokine receptors and CD44-splice variants, but none of these correlate with a particular diagnosis. However, elevated expression of CD44v8-9 was found to correlate negatively with the invasive capacity of fibroblast-like synoviocytes.

Alternative Splicing↗

PubMedDate not supplied

Comparison of the baseline disease activity of early oligo- and polyarthritis in sequential years.

OBJECTIVE: Many early arthritis clinics (EACs) have been started in the last decade in order to detect and treat rheumatoid arthritis early. The present study evaluates whether the disease activity at admission of patients with early oligo- and polyarthritis changed during the period 1993--1998 in two EACs in the Netherlands. METHODS: Patients were selected who were diagnosed after one year as having rheumatoid arthritis (RA) or oligo- or polyarthritis (UPA), had a symptom duration of less than 2 years, and were referred from two Dutch EACs between 1993 and 1998. The data from the two clinics were combined and stratified by referral year. Differences in baseline disease characteristics as well as changes in radiological and functional scores after two years of follow-up between referral years were analysed by ANOVA using Bonferroni corrected p levels. RESULTS: A total of 405 patients (66% females; median age 57 yrs (18-93): 80% diagnosed as RA, the remainder as UPA) were included in the study. The year-groups did not differ significantly in demographic characteristics or in the duration of complaints (median 6 months). The number of patients with a diagnosis of RA declined over the years, as did the mean baseline erythrocyte sedimentation rate (ESR), in RA and UPA patients. The functional status (Health Assessment Questionnaire: HAQ) was enhanced in 1998 compared with the previous years (p < 0.001). Radiographic progression (Sharp/van der Heijde score) after the 2-year follow-up decreased (p < 0.001) in the later referral years compared to the referral group of 1994. Disease modifying anti-rheumnatic drugs (DMARDs) were started in an earlier stage and the prescription rate of sulfasalazine and methotrexate increased over the years, whereas the number of patients not treated with DMARDs declined. CONCLUSION: The pattern of patient referral changed over 6 years towards fewer patients who fulfilled the RA diagnosis and a lower ESR (among UPA as well as RA patients), whereas the number of swollen joints and the duration of complaints remained the same. The radiological progression declined over time, probably due to less inflammation at the first visit and the increased use of DMARDs.

Adolescent↗

PubMedDate not supplied

Undifferentiated arthritis--disease course assessed in several inception cohorts.

The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Because early aggressive treatment might offer an effective means to slow disease progression in RA, it is important to identify UA patients who will develop RA and treat them as early as possible. At the same time, inappropriate treatment of patients with a more benign disease course should be avoided. Here, an overview is given of the characteristics and numbers of patients with UA who evolve into RA. UA is defined as any arthritis that has the potential for a persistent course, without fulfilling the classification criteria for specific rheumatic disorders. To compare endpoints in the different databases, the 1987 ACR criteria for RA were used. In the nine databases employing a similar definition for undifferentiated arthritis, the proportion of patients with UA that evolved into RA within 1 year varied from 6% to 55%. These differences arise in large part from differences in the inclusion criteria and in the definitions used for UA and RA. The data from the various cohorts support a hypothesis that a considerable proportion of UA patients are actually patients with RA in a very early stage. Controlled intervention studies with early antirheumatic treatment in these patients are mandatory in order to provide further insight into the natural course of UA and to define a treatment strategy that will successfully slow or prevent disease progression.

Antirheumatic Agents↗

PubMedDate not supplied

Fibroblast-like synoviocytes from patients with rheumatoid arthritis are more sensitive to apoptosis induced by the viral protein, apoptin, than fibroblast-like synoviocytes from trauma patients.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) show characteristics of transformation. Because the chicken anemia virus protein, apoptin, induces apoptosis solely in transformed cells, it was investigated whether FLS from patients were more sensitive to apoptin-induced apoptosis than FLS from normal joints obtained from trauma patients. METHODS: FLS were transduced with maltose-binding protein (MBP)-apoptin recombinant protein or MBP as a control protein by microinjection. After 24 hours, cells were fixed and stained with immunofluorescence to detect apoptin or MBP and the number of dead cells was assessed. Furthermore, phosphorylation of apoptin was analysed in FLS from patients with RA and from trauma patients by in vitro kinase assay. RESULTS: FLS from patients with RA were significantly more sensitive to apoptin-induced apoptosis than FLS from trauma patients (p = 0.0263). Furthermore, MBP-apoptin induced more apoptosis than MBP in RA FLS (p = 0.004). No phosphorylation of apoptin was observed in FLS from patients with RA. DISCUSSION: FLS from patients with RA are more sensitive to apoptin-induced apoptosis than normal FLS, which is consistent with a transformed phenotype of these cells. However, given the lack of phosphorylation of apoptin in RA FLS the mechanism of action of apoptin seems to differ between tumour cells and RA FLS. This study indicates that apoptin may help to identify a new therapeutic pathway against hyperplasia of the synovium and joint destruction in RA.

Adult↗