Interferon-gamma receptor signaling is not required in the effector phase of the alloimmune response.

BACKGROUND: Gene transcripts for the Thl cytokines interleukin (IL)-2 and interferon-gamma (IFN-gamma) are frequently detected during allograft rejection. The relative importance of these cytokines in facilitating allograft rejection is unclear. Recently, we have shown that IL-2-deficient mice reject islet allografts. In the IL-2-deficient system, IFN-gamma gene transcripts are abundantly expressed. METHODS: To determine the relative importance of IFN-gamma-dependent effector mechanisms in mediating allograft rejection, the present study utilized IFN-gamma receptor-deficient mice as islet allograft recipients. Grafts were analyzed by immunohistology, and cytokine expression was measured by competitive template reverse transcriptase polymerase chain reaction. RESULTS: IFN-gamma receptor-deficient mice reject islet allografts by a process that is T cell-dependent. Although IFN-gamma receptor signaling is absent, these mice do not show a clear Th2 type response. CONCLUSION: Although the signals evoked through the IFN-gamma receptor may play a role, they are not essential to allograft rejection.

Interpreting complex urinary patterns with MDI LABLINK: a statistical evaluation.

The measurement of urinary marker proteins is not a generally accepted laboratory practice because the results are difficult to interpret. MDI-LABLINK is software for classifying patterns of specific urinary marker proteins. The interpretations are completely user definable thanks to a specific 'pattern definition database'. Our interpretation set is based on Hofmann and Guder's work in measuring and interpreting single urinary proteins. We include additional marker proteins in order to adapt Boesken's SDS-PAGE classification. During the last 3 years, 1905 patterns were fully differentiated and identically interpreted. Firstly, the samples were classified into three patterns: normal (25.8%), predominantly glomerular (27.2%, selective, unselective, mixed, and with additional tubular proteins) and predominantly tubular (36.9%, complete/incomplete form, with additional glomerular proteins); 8.9% showed postrenal proteinuria. Secondly, glomerular selectivity measured by using urinary transferrin/IgG ratio alone correlates well with the established SI index (the ratio between IgG and transferrin clearances). Thirdly, the creatinine concentration substantiates the validity of the sample. The quality of the preanalytical phase can be improved through the ongoing education of the medical staff. Finally, measurement of urinary albumin and alpha-1-microglobulin is mandatory where kidney disease is suspected, has to be ruled out, or requires close monitoring, even when the total protein concentration is normal.

[Transplantation immunology: is the manipulation of the cytokine network therapeutically justified?]. / Transplantationsimmunologie: Ist die Manipulation des Zytokinnetzwerks therapeutisch sinnvoll?

Classical allograft rejection is a cellular-mediated immune response in which the activation of the CD4+ T helper (Th) cell plays a crucial role. After activation the Th cell produces a variety of cytokines which are essential for initiating allograft rejection. Th cells can be distinguished by their cytokine profile. Th 1 cells produce IL-2 and IFN gamma, which are associated with rejection. Th2 cells are characterized by the production of IL-4 and IL-10, cytokines which are found in models when tolerance is induced. These findings are called the "Th1/Th2 paradigm" and lead to the following hypothesis: Th1 cells are responsible for allograft rejection and manipulation of the cytokine network towards a Th2 type cytokine pattern results in tolerance or delayed rejection. This study attempts to answer the question whether the Th1/Th2 paradigm is a pure association or corresponds to a mechanism which might be used therapeutically. Allograft rejection in the absence of the proinflammatory cytokines IL-2 and IFN gamma occurs almost unaltered. Moreover, supplying the anti-inflammatory cytokines IL-4 and IL-10 did not result in delayed rejection. Therefore, therapeutic manipulation of the very complex cytokine network will most likely fail. Blocking cytokine-independent T cell activation might be a better concept for induction of allograft tolerance.

[Elbow joint]. / Ellbogengelenk.

The elbow joint is a key joint for positioning of the hand. Four operations have to be considered for the rheumatoid elbow: removal of rheumatoid nodules and bursectomy, resection of the radial head, synovectomy, and arthroplasty. Synovectomy and arthroplasty are carefully analyzed, both from the point of view of recent international literature as well as personal experience. Synovectomy of the elbow is highly effective even when performed relatively late (stage 3 according to Larsen-Dahle-Eek) insofar as pain relief and swelling are concerned. In long-term disease, deterioration as assessed by radiology can usually not be prevented, but clinical improvement may be the reason for the relatively rare indication for arthroplasty. According to recent literature, the results of elbow arthroplasty vary greatly. Fully constrained hinges should no longer be used, and no decision has been made so far on whether semiconstrained or nonconstrained surface replacement is preferred. We use the semiconstrained GSB Mark II prosthesis, which has provided results in nearly 50 cases that rank among the best reported from the point of view of pain relief, improvement of ROM, and low complication rate. Use of our so-called transtricipital approach to the elbow has proved particularly valuable, especially with regard to lack of extension and muscle strength.

[Complement and its role in immune response]. / Das Komplement und seine Rolle in der Immunantwort.

The complement system as a part of innate immunity is considered to provide rapid tough incomplete antimicrobial activity. However, besides providing a first-line defence, innate immunity plays additional important roles: it initiates and improves the slower, but more specific, acquired immune response. The recognition and destruction of noxious substances, as well as initiation of the acquired immune response, are accompanied by potentially hazardous inflammation. The inflammatory process has thus to be tightly regulated. In this overview, innate immunity and its interactions with acquired immunity are discussed with the main focus on the complement system. Our scientific interests are integrated into the discussion on complement.