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We investigated the effects of photopheresis in systemic sclerosis by analysing its influence on lymphocytes with regard to apoptosis and expression of bcl-2 and fas. Peripheral blood lymphocytes isolated immediately before and 24 h after photopheresis were investigated for apoptosis, bcl-2 and fas expression by fluorocytometry, and compared to controls. In addition, leucocytes from systemic sclerosis patients taken directly from the photopheresis system were tested for apoptosis after 24 h in culture. fas expression was similar in controls and patients with systemic sclerosis just before photopheresis, but increased 24 h after photopheresis, mainly due to an increase of CD4+CD95+ cells. bcl-2 was overexpressed in scleroderma peripheral lymphocytes, but not influenced by photopheresis. As compared to healthy controls, the percentage of apoptotic cells 24 h after photopheresis was high in cultured lymphocytes, but not ex vivo. The significant increase in fas on peripheral lymphocytes observed in this study may be a major operative mechanism of photopheresis in addition to (and possibly related to) the induction of apoptosis.

The appearance of gouty tophus in magnetic resonance imaging (MRI) is characteristic. On T1- and T2-weighted SE images, the signal intensity of tophaceous lesions is similar to that of muscles. According to the histology, T2-weighted SE images demonstrate extremely hyperintense signals, which reflect the high protein content in the amorphous center of the tophus. The microscopic urate crystals deposited there have no MRI signal and are of no further diagnostic impact. Vascularized granulation tissue surrounding the tophus center enhance after intervenous application of contrast agents (Gadolinium). The inflamed tophus is associated with local edema, causing high signal intensity. MRI is superior to plain radiography for early detection of intraosseous tophi. Involvement of anatomical structures such as ligaments and tendons can be evaluated sufficiently. For peripheral joints, axial slice orientation is most helpful.

Recurrent arthritis, fever and lymphadenopathy are symptoms of adult onset of Still's disease (AOSD). Differential diagnosis requires the exclusion of infections or malignant lymphomas. We report on a case of AOSD showing destructive lymphadenopathy, immunophenotyping of peripheral blood leucocytes revealed strong activation of T-lymphocytes. Bone marrow biopsy also showed an increase of lymphopoietic cells to 23%. Analysis of peripheral blood lymphocytes (PBL) after remission showed no remaining signs of activation. Analysis of lymphocyte activation by flow cytometry correlated with disease activity.

Objective: To investigate the expression of bcl-2 in healthy and osteoarthritic articular cartilage at the transcriptional level and at the protein level., Methods: bcl-2 mRNA was detected by reverse transcriptase/polymerase chain reaction. The expression of bcl-2 protein was studied using flow cytometry analysis with a monoclonal antibody against intracellular bcl-2 and by immunohistochemistry., Results: mRNA for bcl-2 was detectable in chondrocytes of both healthy and osteoarthritic cartilage. bcl-2 protein was present in the chondrocytes of the middle layer of cartilage by immunohistochemical staining. In osteoarthritis (OA), chondrocytes adjacent to cartilage defects expressed a particularly high signal intensity. Flow cytometry analysis demonstrated the presence of bcl-2 protein in virtually all chondrocytes., Conclusion: Our results show that bcl-2 is expressed in healthy adult and osteoarthritic human cartilage. The increased staining of chondrocytes adjacent to osteoarthritic defects indicates a differential regulation of programmed cell death during the degenerative process in OA.

A 23-year old patient suffered from transient oligoarthritis and second degree AV block. The diagnosis of stage II systemic Lyme borreliosis was supported by a history of tick bites and the detection of both IgG and IgM borrelia antibodies in the patient's serum. The ECG-findings (bradyarrhythmia and AV block II) were detected several weeks after the onset of arthritis, whilst the patient reported no cardiac symptoms. Treatment was started with ceftriaxone and then continued with doxycycline because of an allergic reaction to the first antibiotic.

The effects of 17 beta-estradiol (E2) on the serum levels of the circulating endothelial-leukocyte, intercellular, and vascular adhesion molecules [ELAM-1, ICAM-1 (CD54), and VCAM-1] were evaluated in healthy male volunteers after single im injection of 10 mg E2 valerate. In addition, a time course of the effects of E2 on circulating adhesion molecules (AMs), cortisol serum levels, differential blood counts, and surface expression of the lymphocyte function-associated antigen-1 (CD11a/CD18), CD3, CD4, CD19, and CD25 on leukocytes was studied in another group of volunteers. A 5% decrease in circulating ICAM-1 (P = 0.045 vs. placebo) was found when a single time point (96 h after E2 injection) was studied. However, this decrease was smaller than the intrasubject (day to day) variability observed, and there was no consistent and time-dependent effect of E2 on circulating AMs. Circulating neutrophils increased 2.3-fold over baseline after E2 treatment (P = 0.0008 vs. placebo). The mean coefficients of variation for the intrasubject (day to day) and intersubject variability of circulating AMs were between 5.4-7.5% and 20-29%, respectively. Our findings indicate that the effect of E2 on circulating AMs is not distinguishable from the intrasubject variability observed after placebo treatment. Thus, an effect of E2 on adhesion molecules is unlikely to contribute to the antiatherogenic-cardioprotective effect of E2. The pronounced E2-mediated increase in neutrophils deserves further studies to elucidate its (patho-)physiological implications.

Objective: Defective regulation of programmed cell death (apoptosis) may play a role in the development of autoimmune diseases, and the proto-oncogene bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of bcl-2 in the peripheral lymphocytes of patients with systemic lupus erythematosus (SLE), a prototypical autoimmune disease., Methods: Levels of bcl-2 expression in the lymphocytes of patients with SLE and, for comparison, in the lymphocytes of healthy controls and patients with rheumatoid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2-color cytofluorography and RNA analysis., Results: In SLE patients, a significant proportion of T cells expressed increased amounts of bcl-2 protein. By fluorescence-activated cell sorter analysis, bcl-2--enriched lymphocytes were found in the CD45RO+ as well as in the CD45RO-, and also in the CD4+ and CD8+, lymphocyte subpopulations. Mononuclear cells of patients with SLE showed increased amounts of bcl-2 messenger RNA. An increased percentage of strongly bcl-2 positive peripheral T lymphocytes was found in patients with bacterial infections, but not in those with RA., Conclusion: Although the occurrence of circulating T lymphocytes with abnormally high bcl-2 expression is not specific for SLE, it is evidence for a dysregulation of lymphocytic programmed cell death in this autoimmune disease.

Objective: To determine the value of the circulating intercellular adhesion molecule (cICAM-1) as a marker for the inflammatory and fibrotic processes in systemic sclerosis (SSc)., Methods: We determined serum levels of cICAM-1 and of the soluble interleukin-2 receptor (sIL-2R) by an enzyme-linked immunosorbent assay in 33 patients with SSc. These values were compared to the concentrations of acute phase reactants and to the extent of skin involvement in diffuse and limited scleroderma., Results: cICAM-1 was elevated in patients with diffuse SSc (498 +/- 134 ng/ml) as compared with 82 healthy controls (312 +/- 71 ng/ml) (mean +/- SD, p < 0.0001). The elevation of cICAM-1 did not correlate with the duration of disease, the pattern of organ manifestations or the type of treatment. While the concentrations of acute phase proteins were not elevated in SSc, a significant correlation between increased serum sIL-2R and cICAM-1 was observed., Conclusion: Increased levels of cICAM-1 indicate an activation of immune processes in SSc. The clinical value of the cICAM-1 determination in SSc can only be judged in longitudinal studies.