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C Waldmann

Publications and source records attributed to C Waldmann.

10 recordsLinked to original sources

Transforming growth factor-beta1 in autoimmune hepatitis: correlation of liver tissue expression and serum levels with disease activity.

BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) is considered the most important mediator of hepatic fibrogenesis. At the same time, TGF-beta1 is an immunosuppressive cytokine. Development of fibrosis, often rapid, is a characteristic of autoimmune hepatitis, as is spontaneous systemic immunosuppression. The aim of our study was therefore to define the role of TGF-beta1 in autoimmune hepatitis. METHODS/RESULTS: Using the MV 1Lu bioassay, we found markedly elevated serum levels of TGF-beta1 (median 109 ng/ml) in active autoimmune hepatitis, which normalised when patients reached biochemical remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compared to active disease). With a newly established ELISPOT-assay for TGF-beta1-producing cells, we could exclude an increase in TGF-beta1-producing peripheral blood cells as a source of the elevated TGF-beta1. However, by in situ hybridisation and immunohistochemistry, we found strong TGF-beta1 expression in the inflamed liver. In addition to non-parenchymal and infiltrating cells, many hepatocytes showed strong staining for TGF-beta1. TGF-beta1 expression in the liver normalised in remission, yet was still somewhat increased in patients with biochemical remission but remaining histological disease activity. CONCLUSIONS: These results suggest that TGF-beta1 is an important mediator in active autoimmune hepatitis. They support the theory that immunosuppressive therapy needs to be guided by histology, as prevention of the development of cirrhosis presumably requires near complete suppression of TGF-beta1 in the liver; this is only found when there is no longer any histological evidence of inflammation.

Adolescent↗

Antigen-presenting function and B7 expression of murine sinusoidal endothelial cells and Kupffer cells.

BACKGROUND & AIMS: Inflammatory liver disease as well as rejection of liver allografts are thought to be mediated by resident antigen-presenting cells in the liver. At the same time, in vivo antigen presentation in the liver appears to be a more tolerogenic than systemic antigen challenge. The aim of this study was to show and characterize the antigen-presenting capability of sinusoidal endothelial cells and Kupffer cells. METHODS: Purified murine sinusoidal endothelial cells and Kupffer cells were studied for their ability to serve as accessory cells and antigen-presenting cells by proliferation assays. They were also studied for their expression of interleukin 1 and the B7 costimulatory molecules by Northern blotting, polymerase chain reaction, and flow cytometry. RESULTS: Both cell types expressed interleukin 1 messenger RNA and could serve equally well as accessory and antigen-presenting cells. B7-2 messenger RNA and surface expression on sinusoidal endothelial cells and on Kupffer cells was shown. Antibodies to the B7 molecules inhibited antigen presentation. Addition of interleukin 10 as a regulatory cytokine secreted by Kupffer cells was suppressive. CONCLUSIONS: Sinusoidal endothelial cells carry functional B7-2 molecules and can serve as effective antigen-presenting cells. However, antigen presentation by sinusoidal endothelial cells may be locally down-regulated by interleukin 10.

Animals↗

Cytochrome oxidase activity reveals parcellations of the pigeon's ectostriatum.

The endogenous cytochrome oxidase activity of the pigeon's ectostriatum, the primary telencephalic structure of the tectofugal visual pathway, was histochemically demonstrated and a heterogeneous distribution of the reaction product was observed. In cross-sections the medial, central and ventrolateral parts of the ectostriatum showed high levels of activity while the centroventral and dorsolateral ectostriatum remained weakly labelled. Only slight left-right and interindividual variations were found in the pattern of labelling. These data demonstrate for the first time anatomical subdivisions within the ectostriatal core and open the possibility of functional parcellations within this structure.

Animals↗

The dopaminergic innervation of the pigeon caudolateral forebrain: immunocytochemical evidence for a 'prefrontal cortex' in birds?

The dopaminergic (DA) innervation of the caudal telencephalon of the pigeon was investigated with an antiserum against glutaraldehyde-conjugated dopamine. It was found that the DA-like fibers were distributed within the Paleostriatum augmentatum and the dorsal Archistriatum in a dense meshwork of fibers, while most of the remaining part of the caudal forebrain was innervated by dopaminergic axons which were coiled up like baskets around unlabelled neurons. Within the basket-type innervated structures, the Neostriatum caudolaterale (Ncl) could be distinguished by the high density of its dopaminergic fibers. Retrograde tracer injections into Ncl revealed afferents from the Area ventralis tegmentalis (AVT) and the n. tegmenti pedunculo-pontinus pars compacta (TPc). Since large numbers of DA-like perikarya could be detected in AVT and TPc, it is supposed that these two structures constitute the main source of the dopaminergic innervation of the Ncl. Previous studies had suggested that the Ncl represents an avian equivalent to the mammalian prefrontal cortex. The present results reveal an organization similar to that of the mesocortico-prefrontal system and would thus strengthen this hypothesis.

Animals↗