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Biomedical subjects

E Kruithof

Publications and source records attributed to E Kruithof.

23 records · Page 2Linked to original sources

Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity.

OBJECTIVES: To compare the macroscopic and microscopic characteristics of synovial tissue in rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA) after exclusion of possible biases induced by disease duration or activity, or both. METHODS: Synovial biopsy specimens were obtained by needle arthroscopy in patients with early RA (n=16), late RA (n=14), early SpA (n=23), and OA (n=12). Macroscopic and microscopic features were scored on a four point scale and analysed as a function of disease duration (early versus late RA), local and systemic disease activity, and diagnosis. RESULTS: Except for the maximal synovial lining thickness, no significant differences were seen between early and late RA. For disease activity, synovial histology was only weakly correlated with C reactive protein in RA, but seemed to be strongly dependent on effusion of the biopsied joint in all disease groups. After stratification for local disease activity, no disease related differences were found in patients without joint effusion. In contrast, important differences were found between patients with RA and SpA with active joint effusion. Synovial vascularity was macroscopically increased in SpA versus RA (p=0.017). A straight vessel pattern was only seen in RA, while tortuous vessels were preferentially seen in SpA. Vascularity was also microscopically increased in SpA compared with RA (p=0.031), and correlated with the macroscopic vascularity (r(s)=0.36, p=0.036). CD3+ (p=0.008), CD4+ (p=0.008), and CD20+ (p=0.024) lymphocytes were overrepresented in RA compared with SpA. The integrin expression in RA was characterised by a decrease of alphaVbeta3 in the synovial lining (p=0.006) and an increase of alphaVbeta5 in the sublining (p<0.001). CONCLUSIONS: The immune architecture of the synovial membrane is more dependent on local disease activity than on disease duration. Synovium obtained from clinically affected joints shows important histological differences between RA and SpA.

Adolescent↗

Effects of a loading dose regimen of three infusions of chimeric monoclonal antibody to tumour necrosis factor alpha (infliximab) in spondyloarthropathy: an open pilot study.

OBJECTIVE: To evaluate the efficacy and safety of a loading dose regimen of three intravenous infusions with infliximab in patients with active spondyloarthropathy. METHODS: A monocentre, open-label pilot study of 21 patients with different subtypes of spondyloarthropathy was conducted. Treatment resistant patients with active disease (fulfilling inclusion criteria) received three infusions of 5 mg/kg infliximab (at weeks 0, 2, and 6). Standard clinical assessments were performed at baseline, and on days 3, 7, and 14, and from then on every two weeks. In patients who fulfilled criteria for ankylosing spondylitis, axial assessment was performed at baseline and on days 14, 42, and 84. RESULTS: In all global assessments (visual analogue scale of patient global assessment, patient pain assessment, doctor global assessment), erythrocyte sedimentation rate, and C reactive protein, a highly significant decrease could be seen already at day 3 (compared with baseline), which was maintained up to day 84. In patients with peripheral disease (n=18), tender and swollen joint count significantly decreased. In patients with axial disease (n=11), functional and disease activity indices significantly improved. Moreover in eight patients with psoriatic arthritis a significant decrease of the psoriasis area and severity index was observed. The treatment was well tolerated in all patients; no significant adverse events were seen. CONCLUSION: In this open-label pilot study of a loading dose regimen of three infusions of chimeric monoclonal antibody to tumour necrosis factor alpha in patients with active spondyloarthropathy, there was a fast and significant improvement of axial and peripheral articular manifestations, without major adverse experiences.

Adult↗

Polyarteritis nodosa mimicking polymyalgia rheumatica.

We report a case of polyarteritis nodosa with a clinical presentation mimicking polymyalgia rheumatica, as well as pathological findings of non-giant-cell arteritis on temporal artery biopsy with symptoms of jaw claudication. Although certain clinical syndromes have been attributed to specific types of systemic vasculitis, considerable overlap occurs. Obtaining tissue biopsy in cases of vasculitis is mandatory for diagnosis and classification.

Aged↗

Modulation of the plasminogen activation system by inflammatory cytokines in human colon carcinoma cells.

Inflammation may promote malignant invasion by enhancing cancer cell-associated proteolysis. Here we present the effect of inflammatory cytokines on the plasminogen activation system of eight human colon carcinoma cell lines. Tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) increased in several, but not all, cell lines the production of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and plasminogen activator inhibitor type 1 (PAI-1) as analysed by zymography, enzyme immunoassays and Northern analysis. Interleukin 6 (IL-6) had no effect. uPA receptor (uPAR) mRNA levels were also upregulated. However, each individual cell line responded differently following exposure to TNF-alpha or IL-1 beta. For example, there was a dose-dependent up-regulation of uPA and PAI-1 in SW 620 cells, whereas increased uPA production in SW 1116 cells was not accompanied by an increase in PAI-1. The TNF-alpha stimulatory effect was blocked by anti-TNF-alpha Fab fragments. All cell lines expressed both types of TNF receptor mRNAs, whereas no transcript for TNF-alpha, IL-1 beta, IL-6, IL-6 receptor or the IL-1 receptors was found. Our results demonstrate that TNF-alpha and IL-1 beta stimulate the plasminogen activation system in tumour cell but the responses differed even in cells derived from the same tissue origin.

Blotting, Northern↗

Chromosomal localization of the human urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 genes: implications in colorectal cancer.

Activation of the proenzyme of urokinase (uPA) on the surface of cancer cells has been implicated in the initiation of focal proteolytic mechanisms that permit invasion and metastasis by colon cancers. The activity of uPA on the cell surface appears to be a function of the number of uPA-specific receptors (uPAR) and the extent of inhibition of uPA by plasminogen activator inhibitors (PAI). The mapping of the genes coding for uPAR, and for PAI-2, was performed to determine whether their chromosomal localization suggested their involvement in the genetic alterations associated with cancer cell DNA. This study confirms the localization of the human urokinase plasminogen activator receptor gene to chromosome 19q and, using in situ hybridization, provides a precise localization to chromosome 19q13.2. In addition, our results confirm the previous allocation of the human plasminogen activator inhibitor-2 gene to a location 18q21.3-->18q22.1, a location that corresponds to the commonest (> 70%) somatic deletions found in colorectal carcinomas. The mapping of the uPAR and PAI-2 genes enables the elucidation of their possible involvement in the genetic alterations that determine the invasive and metastatic phenotypes in colorectal cancer.

Chromosome Mapping↗