Biomedical subjects

J Müller-Derlich

Publications and source records attributed to J Müller-Derlich.

3 recordsLinked to original sources

PubMed1997

Fluorescence videomicroscopic assessment of xenogeneic microcirculation and impact of antibody removal by immunoadsorption.

BACKGROUND: Alterations in microcirculation are considered central to the pathogenesis of hyperacute xenogeneic rejection (HXR) of vascularized xenografts, but currently there exist no data describing these microhemodynamic alterations. METHODS: Rat livers were perfused in situ with either isogeneic rat blood or xenogeneic human blood. The microcirculation of these xenoperfused livers was investigated directly using intravital fluorescence microscopy, and compared with that of isogeneic hemoperfused livers. In addition, the impact of antibody depletion by immunoadsorption was investigated. RESULTS: Although a homogenous microcirculation was found during isogeneic liver perfusion (index of acinar perfusion 90.4%/sinusoidal perfusion rate 93.6%), xenoperfusion resulted in a rapid breakdown of the microcirculation (47.5%/67.1%, respectively). Perfusion deficits were found predominantly in the periportal areas. Immunoadsorption reduced the total amount of IgM and IgG by 75.2% and 96.2%, respectively, and caused a significantly improved liver perfusion (80.2%/84.4%) and liver function, as indicated by bile production. In contrast, the massive hepatic leukocyte and platelet accumulation observed during perfusion with untreated xenogeneic blood was not altered by antibody depletion. CONCLUSIONS: Thus, the combination of isolated rat liver perfusion and intravital fluorescence microscopy enables the observation and quantification of the early phase of HXR. This is an important step forward for sensitive characterization of the rejection process and will enable the mechanisms involved in HXR to be elucidated. Antibody depletion was shown to improve liver function and perfusion, but did not reconstitute liver viability to the level of the isogeneic perfusion. These findings highlight the need for additional therapeutic regimens in xenografting.

Acute Disease↗

PubMed1993

Antibody-based immunoadsorption as a therapeutic means.

Polyclonal antibodies against human low-density lipoprotein (LDL), covalently coupled to Sepharose CL-4B, are used to remove LDL from the plasma of familial hypercholesterolemic patients. During a single treatment LDL-cholesterol is lowered by more than 60%, and plasma viscosity is decreased by 10%. The usual treatment frequency is once a week. The possible development of human antisheep antibodies was followed for up to 5 years. The ELISA signal rose slightly above baseline reaching a plateau within the first year. Clinically, there have been no signs of column-related adverse reactions. Due to the versatility of immunoapheresis it is also applicable to deplete IgG by coupling antihuman IgG antibodies. These columns might be indicated for patients with high panel reactivity to enable organ transplantation and for patients with autoimmune disease. In vitro tests with plasma from high-panel-reactive dialysis patients have shown that IgG could be depleted by 95% across all subclasses and that panel reactivity could be reduced from 91 to 25%.

Animals↗

PubMed1988

Two distinct mechanisms for deletion in mitochondrial DNA of Schizosaccharomyces pombe mutator strains. Slipped mispairing mediated by direct repeats and erroneous intron splicing.

Mutator strains of the fission yeast Schizosaccharomyces pombe produce mitochondrial respiratory deficient mutants at a high rate, and roughly 20% of these mutants carry deletions in the range of 50 to 1500 base-pairs. To elucidate the mechanism of deletion we have sequenced ten deletion mutants in the mosaic gene encoding apocytochrome b (cob) and three in the split gene coding for the first subunit of cytochrome c oxidase (cox1). Of 13 deletions, ten are correlated with the presence of direct repeats, which could promote deletions by slipped mispairing during DNA replication. In some of these mutants, the termini are located in possible DNA secondary structures. In three independently isolated mutants with identical deletions in the cob gene, the 5' deletion endpoint coincides with the 3' splice point of the intron, whereas the 3' endpoint of the deletion exhibits pronounced homology with the 5' splice point of the intron. This result suggests that these deletions might be initiated by erroneous RNA splicing.

Base Sequence↗