Biomedical subjects

Stefan Müller

Publications and source records attributed to Stefan Müller.

58 records · Page 4Linked to original sources

PubMed2002

The phylogeny of howler monkeys (Alouatta, Platyrrhini): reconstruction by multicolor cross-species chromosome painting.

We performed multidirectional chromosome painting in a comparative cytogenetic study of the three howler monkey species Alouatta fusca, A. caraya and A. seniculus macconnelli (Atelinae, Platyrrhini) in order to reconstruct phylogenetic relationships within this genus. Comparative genome maps between these species were established by multicolor fluorescence in-situ hybridization (FISH) employing human, Saguinus oedipus and Lagothrix lagothricha chromosome-specific probes. The three species included in this study and previously analyzed howler monkey species were subjected to a phylogenetic analysis on the basis of a data matrix comprised of 98 discrete molecular cytogenetic characters. The results revealed that howler monkeys represent the genus with the most extensive karyotype diversity within Platyrrhini so far analyzed with high levels of intraspecific chromosomal variability. Two different multiple sex chromosome systems were identified. The phylogenetic analysis indicated that Alouatta is a monophyletic clade which can be derived from a proposed ancestral Atelinae karyotype of 2n = 62 chromosomes by a chromosome fusion, a fission, a Y-autosomal translocation and a pericentric inversion. Following these suggestions, the genus Alouatta can be divided into two distinct species groups: the first includes A. caraya and A. belzebul, the second A. s. macconnelli, A. sara, A. s. arctoidea and A. fusca.

Alouatta↗

PubMed2002

Role of an intact splenic microarchitecture in early lymphocytic choriomeningitis virus production.

An acute infection with lymphocytic choriomeningitis virus (LCMV) is efficiently controlled by the cytotoxic-T-cell (CTL) response of the host, and LCMV titers in the spleen and peripheral solid organs usually fall sharply after day 4 to 6 postinfection. Surprisingly, infection of immunodeficient recombination-activating gene 2-deficient (RAG2-/-) mice with 5 x 10(2) PFU of LCMV-WE causes about 80-fold-lower LCMV titers in the spleen on day 4 postinfection compared with C57BL/6 control mice. This could not be attributed to NK cell activity, since common gamma-chain-deficient RAG2-/- mice lacking NK cells show low LCMV titers comparable to those for RAG2-/- mice. Furthermore, the reduced early LCMV production in spleens could not be explained by an enhanced gamma interferon production in RAG2-/- mice. Analysis of mutant mice exhibiting various defects in the splenic microarchitecture, including (i) tumor necrosis factor alpha-negative (TNF-alpha-/-), lymphotoxin alpha-negative (LTalpha-/-), B-cell-deficient muMT mice, (ii) immunoglobulin M-negative mice, and (iii) RAG2-/- mice reconstituted with wild-type versus TNF-alpha-/- LTalpha-/- B cells, revealed a clear correlation between an intact splenic marginal zone, rapid early replication of LCMV in the spleen, and efficient CTL induction. These results suggest that by the preferential infection of the highly organized splenic microarchitecture, LCMV seems to successfully exploit one of the key elements in the chain of the adaptive immune system. Not only does the early tropism of LCMV for the splenic marginal zone trigger a potent immune response, but at the same time the marginal zone may also become a target of early CTL-mediated immunopathology that impairs immune responsiveness.

Adoptive Transfer↗

PubMedDate not supplied

Standardized qualitative evaluation of scar tissue properties in an animal wound healing model.

There is a great need to establish reproducible methods for evaluative studies of wound treatment and wound healing. Validation of the healing process through optical techniques, as well as histologic and immunohistochemical methodologies, have been improved and to some extent have become well-established assays. Data relating to biomechanical properties, e.g., evaluation of the tensile strength of scar tissue that forms in experimental wound treatment strategies, are less widely available. We chose the domestic pig as an animal model in which to examine epidermal wound healing. We implanted specially made chambers that served to isolate the wounds and prevent epidermal migration from the edges. We performed histologic and immunohistochemical analyses as well as evaluation of biomechanical qualities of scar tissue using laser tensiometry. Pig skin is well suited for wound healing studies, and wound creation, implantation of the chambers, and the regular changing of dressings could all be carried out in the operating theater. In addition to established macroscopic evaluation and microscopic documentation, the need for objective biomechanical assessment of scar tissue by measuring tensile strength has been met using laser tensiometry. By optimizing methods for measuring tensile strength, it is possible to evaluate the biomechanical quality of scar tissue formed following different courses of wound treatment, as well as histologic assessment.

Animals↗

PubMedDate not supplied

Hyperoxia-induced improvement of the in vitro response to gemcitabine in transitional cell carcinoma.

BACKGROUND: Anemic tissue hypoxia can decrease the effects of chemotherapy in bladder cancer. Hypoxia leads to overexpression of hypoxia-inducible factor (HIF) and increased synthesis of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). Tumor cell survival, invasion and angiogenesis thereby compromise treatment. MATERIALS AND METHODS: Monolayer cultures of RT112, RT4, T24 and TCC SUP cells were incubated with or without gemcitabine and different gas mixtures (hypoxia, normoxia or hyperoxia). Cell proliferation (microculture tetrazolium assay), VEGF (enzyme-linked immunosorbent assay) and HIF-1alpha (Western blot analysis) were determined. RESULTS: Hypoxia led to increased proliferation of transitional cell carcinoma (TCC) cells and elevated levels of HIF-1alpha and VEGF. Hyperoxia inhibited cell growth and lowered the concentration of VEGF. Treatment with gemcitabine was less effective under hypoxia. CONCLUSION: Hypoxia enhances TCC growth and may intensify angiogenesis mediated by VEGF. Hypoxia compromises treatment with gemcitabine. Correction of anemia might provide advantages in chemotherapeutic strategies for TCC.

Antimetabolites, Antineoplastic↗