Die Beanspruchung des menschlichen Ellenbogengelenks

Zusammenfassung Bei 80 Objekten werden die Gelenkflächen des menschlichen Ellenbogengelenks untersucht. Die Trochlea und das Capitulum humeri sowie das Caput radii zeigen keine nennenswerten Unterschiede in der Ausdehnung der mit typischem Gelenkknorpel bedeckten Flächen. Dagegen lassen sich für die Ulnazange drei charakteristische Formgruppen abgrenzen: In 3 Fällen kann eine einheitliche Knorpelfläche beobachtet werden. Bei etwa zwei Drittel der untersuchten Objekte liegt im mittleren Bereich der Incisura trochlearis in horizontaler Richtung ein 2–5 mm breiter knorpelfreier Streifen, der den Gelenkknorpel in 2 vollständig getrennte Flächen unterteilt. Das restliche Drittel der Objekte besitzt eine unvollständige Trennung der Gelenkfläche. Unter Berücksichtigung der Vorstellungen von Pauwels über die causale Histogenese der mesenchymalen Stützgewebe sowie der Materialverteilung im Knochengewebe in Abhängigkeit von der einwirkenden Spannungsgröße werden die morphologischen Befunde den für die jeweiligen Skeletelemente von Pauwels ermittelten Spannungsdiagrammen gegenübergestellt. An der Trochlea und dem Capitulum humeri und am Caput radii findet sich eine geradezu ideale Übereinstimmung in der Ausdehnung der Knorpelfläche und der Knochendichte unter den Gelenkflächen mit den entsprechenden Spannungsdiagrammen. An der Ulna trifft dies nur für einen geringen Teil der Objekte zu. Für die unterschiedliche Ausgestaltung der Incisura trochlearis werden zwei mögliche Ursachen diskutiert: 1. die Resultierende R verharre während des Bewegungsablaufes in einzelnen Positionen innerhalb der Incisura trochlearis verschieden lange; 2. der Krümmungsradius der Trochlea humeri sei größer als derjenige im mittleren Bereich der Ulnazange, so daß hier wegen des fehlenden Kontaktes der Gelenkflächen keine Druckübertragung möglich ist.

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The stress of the human elbow jointI. Functional morphology of the articular surfaces

Summary The articular surfaces of 80 human elbow joints are analysed. The trochlea and capitulum humeri and the caput radii of the investigated individuals show no particular differences in the extent of their surfaces covered with typical articular cartilage. On the other hand the form of the incisura trochlearis is rather variable. Three characteristic formgroups are to be discerned. In three objects a continuous cartilage surface has been observed. In 50 of the investigated joints there is a small intersection free from cartilage in the midst of the incisura trochlearis, dividing the articular cartilage in two isolated surfaces. In the rest of the analysed objects the articular surface is divided only partially. According to Pauwels' hypothesis on the causal histogenesis of the mesenchymal supporting tissues and of the density distribution of the bone dependence upon the magnitude of the local unit stress the morphological findings in the single investigated parts of the elbow joint are confronted with the corresponding stress diagram as described by Pauwels. In the trochlea and capitulum humeri and in the caput radii a nearly ideal correspondence of the extent of the articular surface and the density of the bone tissue with the unit stress diagrams are found. In the ulna this correspondence exists only in few of the analysed objects. For the different form of the incisura trochlearis two possible explanations are discussed: 1, during the motion the resultant of forces may stay for a different time in their single positions in the incisura trochlearis; 2. the curvature radius of the trochlea humeri may be greater than that one of the incisura trochlearis in the central area. So no pressure occurs in this part of the articular surface.

Mit freundlicher Unterstützung durch die Deutsche Forschungsgemeinschaft.     

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Dendritic cells lose ability to present protein antigen after stimulating antigen-specific T cell responses, despite upregulation of MHC class II expression

Immature dendritic cells (DC) take up, process and present protein antigens; mature DC are specialized for stimulating primary T cell responses with increased expression of MHC class II and co-stimulatory molecules, but are incapable of processing and presenting soluble protein. The current study examined whether maturation of DC is triggered by T cell recognition of antigens presented by immature DC. Human DC derived from CD34+ progenitor cells by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-6 (IL-6) in serum-free medium could prime naive CD4+ T cells to keyhole limpet hemocyanin (KLH) and ovalbumin (OVA). The cultured DC retained the ability to prime T cells to native protein for at least 15 days. To test for changes in DC function after participation in an immune response, DC were co-cultured with either allogeneic or autologous CD4+ T cells. DC co-cultured with autologous T cells retained the ability to prime T cells to intact protein antigens. By contrast, DC which had previously stimulated an allogeneic T cell response lost ability to prime T cells to soluble proteins. However, such induced a MLR and stimulated peptide-specific primary CD4+ T cell responses. This indicated that did not die or lose the ability to prime, but lost the ability to process and present subsequent antigens. Following participation in T cell activation, DC increased surface expression of MHC class II, co-stimulatory molecules CD40 and B7.2, and the intercellular adhesion molecule-1 (ICAM-1). In addition, our data suggest that interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are involved in this T cell-mediated DC maturation.     

Effective antiretroviral therapy reduces degradation of tryptophan in patients with HIV-1 infection

Antiretroviral therapy (ART) has a significant impact on HIV-1 RNA levels, the CD4 cell count, and immune activation. We examined whether these changes are associated with a change in the rate of tryptophan degradation (expressed as the kynurenine to tryptophan ratio, kyn/trp) as an estimate for the activity of interferon-gamma inducible enzyme indoleamine (, )-dioxygenase (IDO). Plasma levels of tryptophan, kynurenine, and neopterin were measured pretherapy and 6 months postinitiation of therapy in 45 patients with HIV-1 RNA levels of less than 1000 copies/ml 6 months after initiation of ART. Before ART, the patients had decreased tryptophan and increased kynurenine concentrations compared to healthy controls. During ART, average tryptophan levels increased; in the same time kynurenine and kyn/trp decreased (P < 0.001), although not to normal levels. Since pretherapy tryptophan concentrations correlated inversely with neopterin, and kynurenine correlated with viral load and neopterin but not with CD4 cell count, the data support the view that HIV production may induce immune activation and consequently tryptophan is degraded at a higher rate. In agreement, kyn/trp positively correlated with neopterin (r(s) = 0.60, P < 0.001), with virus load (r(s) = 0.37, P = 0.013), and very weakly with CD4(+) cells counts (r(s) = 0.30, P = 0.049). The change in the kyn/trp ratio during ART correlated more strongly with the change in neopterin levels (r(s) = 0.49, P = 0.001) than with the change in HIV RNA levels and weakly with the CD4 cell count. The data underscore the fact that both neopterin production and tryptophan degradation are triggered by immune activation. Tryptophan degradation is increased in HIV infection and partially reversed under ART. The data agree with the concept that immune activation is the common background of IDO activation which may be an important factor underlying T-cell hyporesponsiveness.     

The Role of the Calcium Channel α2δ-1 Subunit in Skeletal Muscle

Journal of Muscle Research and Cell Motility -     

Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design

Oxygen plays an important role in the cultivation of primary cellsex vivo. In this study, we used hermetically sealed tissue culture well inserts equipped with oxygen electrodes to measure the oxygen utilization of cultured human bone marrow mononuclear cells (BM MNCs). The oxygen uptake rate (OUR) of BM MNCs was determined during a 14-day culture in which both adherent and nonadherent cells were present. Early in the culture, the cells exhibited very low OURs. The specific OURs (uptake rate per cell) were at approximately 0.005 μmol/10⁶ cells/hr shortly after the initiation of culture. The OUR then increased as the cultures developed. After about 8 to 10 days of cultivation the specific OURs had increased to 0.038±0.006 and 0.025±0.005 μmol/10⁶ cells/hr for adherent and nonadherent cells, respectively, after which no further increase was observed. Based on these oxygen uptake rate data, a mathematical model of oxygen diffusion was formulated and use to investigate issues associated with hematopoietic bioreactor design, including initial cell density, medium depth, reactor configuration, and oxygen partial pressure.In situ OUR measurements confirmed predicted oxygen limitations based on the mathematical model and the experimentally determined OURs. High-density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallelplate bioreactors with thin liquid layers.