[Ultrasound diagnosis of rheumatic/inflammatory joint diseases].

Ultrasonography is an inexpensive and readily available imaging technology for joints and surrounding soft tissues. Examination usually requires only a few minutes, is safe and can be repeated frequently because no radiation is involved. The method depends much on the training and skills of the examiner and sonographic pictures should always be interpreted in context with history and clinical findings.

[Pathogenesis of rheumatoid arthritis].

Background: Despite ongoing intensive research using sophisticated new molecular tools and methods, the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) is still not completely understood.

Hypotheses: In this paper the two favorite hypotheses of the pathogenesis of rheumatoid arthritis currently discussed are introduced and compared. Hypothesis 1 is focussing on the central role of the T cells and T cell dependent phenomena in the pathogenetic scenario of RA.

Differential role for IL-2 and IL-15 in the inhibition of apoptosis in short-term activated human lymphocytes.

Interleukin (IL)-15 is a newly described cytokine with properties similar to IL-2. Even though it does not share sequence homology with IL-2, both cytokines bind to the same receptor with the noted exception of a cytokine specific alpha-chain. In this study the authors compared IL-2 and IL-15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL-2 for 2 days) from apoptotic cell death.

Biologic agents in the treatment of inflammatory rheumatic diseases.

In 1996, experience in treating autoimmune rheumatic diseases with biologic agents has further improved. New data have been published using different principles directed against cell surface antigens or against proinflammatory cytokines or applying anti-inflammatory cytokines such as interleukin-10 and interleukin-4. In addition, combination therapies with anti-tumor necrosis factor-alpha monoclonal antibody and methotrexate have shown sustained long-lasting beneficial effects.

In vitro apoptosis and expression of apoptosis-related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases.

Objective: To analyze factors related to apoptosis in systemic lupus erythematosus (SLE) peripheral blood mononuclear cells (PBMC) and to compare the findings in SLE PBMC with those in normal donor PBMC or PBMC from patients with other autoimmune diseases.

Methods: PBMC from normal healthy donors or patients with SLE, mixed connective tissue disease (MCTD), rheumatoid arthritis (RA), or various vasculitides were isolated. The percentage of apoptosis after activation through different signaling pathways was quantified using propidium iodide staining.

NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy.

The aim of this study was to investigate if dynamic gadolinium-DTPA-supported magnetic resonance (MR) imaging can monitor the therapeutic effect of a fast-acting immuno-modulating drug like anti-tumour necrosis factor alpha (anti-TNF-alpha) monoclonal antibody (moab) in patients with rheumatoid arthritis (RA). Dynamic MR imaging was performed on 64 joints in a total of 18 patients before and after infusion with either a placebo or 1 or 10 mg/kg of anti-TNF-alpha moab. Additionally, treating the placebo group and reinfusing the verum group with either 3 or 10 mg/kg was monitored by quantitative nuclear magnetic resonance (NMR).

Small DNA fragments isolated from human T-cell clones are enriched in sequences involved in DNA bending.

IL-2 deprivation induces apoptosis in human IL-2-dependent T-cell clones. This process is characterized by typical cell morphology, changes in the cellular membranes and fragmentation of chromatin into units of single and multiple nucleosomes. We isolated apoptotic DNA of an IL-2-deprived T-cell clone and sequenced randomly selected fragments representing single and multiple nucleosomes.

Osteonecrosis in systemic lupus erythematosus, steroid-induced or a lupus-dependent manifestation?

Osteonecrosis (ON) is a well-known complication in patients with systemic lupus erythematosus (SLE) often associated with steroid therapy. In a cohort of 280 SLE patients followed over the last 10 years, seven patients developed symptomatic ON, one of them after septic arthritis of the hip. Two other patients developed ON several years after discontinuing steroids.

Cyclosporin A in the treatment of systemic lupus erythematosus: results of an open clinical study.

In order to define the effects and safety of cyclosporin A (CsA) in systemic lupus erythematosus (SLE), we conducted an open clinical trial with 16 SLE patients. During an observation period of up to 64 months and an average treatment period of 30.3 months, 16 SLE patients, who did not have adequate disease control or experienced side-effects with their previous immunosuppressive therapy, were treated with CsA (3-5 mg/kg).

Biologic agents in the treatment of inflammatory rheumatic diseases.

As in previous years, throughout 1995 biologic agents have been explored and tested in open and controlled clinical trials with regard to their efficacy in treating autoimmune rheumatic diseases, especially rheumatoid arthritis. Promising data have been collected from a placebo-controlled double-blind four-center study of a monoclonal anti-tumor necrosis factor-alpha antibody in rheumatoid arthritis patients. This type of treatment was demonstrated for the first time to effectively interfere with ongoing inflammatory processes in this disease entity.

Increase of intracellular calcium is the essential signal for the expression of CD40 ligand.

CD40 ligand (CD40L) is present on activated but not on resting T cells. In contrast to the activation markers CD25 and CD71, a strong CD40L expression could be induced by calcium ionophore alone but not by phorbol 12-myristate 13-acetate (PMA). Ionomycin induced a very early mRNA and protein surface expression of CD40L within the first 2 h, whereas CD25 and CD71 did not appear earlier than 6 h after stimulation.

Further novel milbemycin antibiotics from Streptomyces sp. E225. Fermentation, isolation and structure elucidation.

Ten novel alpha and beta class milbemycins have been isolated and characterized from the Streptomyces sp. E225, which has previously been shown to produce four related milbemycins. Some of the metabolites contain new structural features including, VM48641 which possesses an alpha-methoxyl substituent at C-27, and VM48642 which contains a furan ring at the terminus of the C-26 side chain.

In vivo blockade of TNF-alpha by intravenous infusion of a chimeric monoclonal TNF-alpha antibody in patients with rheumatoid arthritis. Short term cellular and molecular effects.

Due to the unknown etiology of RA, specific treatment is not available. Recently, in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF-alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven to be highly effective in the treatment of RA. In parallel to this trial, we tested the consequences of cA2 infusion in ex vivo and in vitro experiments.

99m-Tc-HMPAO-SPECT in diagnosis of early cerebral vasculitis.

The objective of this study was to evaluate whether mild neurological symptoms suggestive of neuropsychiatric involvement may be associated with cerebral perfusion defects as detected by functional brain imaging with 99m-Tc-HMPAO-SPECT (single photon emission computed tomography). SPECT analysis for the early detection of central nervous system (CNS) involvement was evaluated in 40 consecutive patients with systemic vasculitis or with Sneddon's syndrome. Of these, 18 patients showed overt neuropsychiatric symptoms, so-called major symptoms (e.

Biologic agents in the treatment of inflammatory rheumatic diseases.

Due to our increasing knowledge of mechanisms underlying pathogenic events in autoimmune rheumatic diseases, biologic agents have been further explored and tested in open and controlled clinical trials. Based on the results of placebo-controlled trials, monoclonal antibodies to CD4+ T cells have been found ineffective in treating rheumatoid arthritis. However, this type of monoclonal antibody might be useful for combination therapy with monoclonal antibody, against tumor necrosis factor-alpha.

[Experimental therapy of rheumatoid arthritis with cytokine antagonists].

Although the etiology of rheumatoid arthritis is still unknown, our knowledge of pathophysiologic mechanisms in this disease has markedly increased. Especially the immunological characterization of cells involved in the inflammatory process and their secretory products (cytokines) allowed new experimental therapeutic approaches. Apparently, the cytokines TNF alpha, IL-1, and IL-6, predominantly produced by accessory cells, play an important role in the actual articular and extraarticular inflammation.

Differential effects of transferrin receptor antibodies on growth and receptor expression of human lymphocytic and myelocytic cell lines.

J64, a monoclonal antibody against the human transferrin receptor, has been shown to induce interleukin-2 production by HUT78 cells. It also causes growth inhibition of several cell lines and stimulated lymphocytes. These effects were also present using transferrin-free culture conditions.