Biomedical subjects

R G Hanselmann

Publications and source records attributed to R G Hanselmann.

9 recordsLinked to original sources

PubMed2002

Polyploidization and centrosome hyperamplification in inflammatory bronchi.

OBJECTIVE AND DESIGN: Inflammatory and tumorous bronchi were screened in order to obtain new tumor relevant cytogenetic parameters. MATERIAL OR SUBJECTS: Bronchial cells of 32 patients were cultivated by standard cell culture procedures. METHODS: Tetraploidy and aneuploidy was determined by enumeration of chromosome 7 and 8 versus the number of centrosomes. The resulting data were correlated with histopathological data. RESULTS: Tetra- and aneuploidy of epithelial cells were detectable in 76% of tumor cell cultures, 75% of high grade inflammatory tissues and 40% of non- and low grade-inflammatory tissues. Additionally, we observed centrosome hyper-amplification and multipolar mitoses not only in the tumor but also in the early stages of inflammation. CONCLUSION: Inflammatory bronchi already show tumor-specific features and may consequently represent the preliminary genetic stage of cancer development in bronchi.

Adult↗

PubMed2001

The scanning near-field optical microscope as a tool for proteomics.

The identification of the entire genetic code of human DNA is more or less completed. With this knowledge, research in identifying the real information lying in the genes, will begin. This information is contained in the proteins, which are the main biological actors in the cell. For this reason proteins will be targeted in biological investigations in the future. The structure, affinity and reactivity of each identified protein has to be determined, which is a primary goal in the field of proteomics. This will require new and better strategies to identify protein-protein interaction. Our approach, based on the detection and visualization of single proteins by scanning near-field optical microscopy (SNOM), has allowed us to visualize various fixed and fluorochrome-labelled proteins at the nanometer scale. Subsequently SNOM may then be developed to efficiently detect the specific behavior of a certain protein in response to other biomolecules.

Bacterial Proteins↗

PubMed2001

Polyploidization: a Janus-faced mechanism.

Normal human somatic cells are diploid. But sometimes certain tissues of the human body contain elevated numbers of tetraploid cells. This tetraploid cell population seems to represent the first step of an ongoing process of polyploidization. All tissues containing tetraploid cells have in common the fact that they are subjected to stress, which is caused by a variety of circumstances like inflammation, elevated metabolism, ageing, repair processes or selection pressure. Tetraploid cells are supposed to play a beneficial role in these stress situations, because they are known to be more resistant in general and because they are characterized by an elevated biosynthetic activity. In contrast to their beneficial character, they have a big potential concerning the malignant development of a tissue: they play a crucial role in early morphological stages of the pathway hyperplasia-metaplasia-dysplasia-carcinoma. This report links several intracellular mechanisms with each other, which potentially determine the real fate of tetraploid cells.

Humans↗

PubMed2000

p53 and c-Jun functionally synergize in the regulation of the DNA repair gene hMSH2 in response to UV.

The tumor suppresser protein p53 is critical for guarding the genome from incorporation of damaged DNA (Lane, D. P. (1992) Nature 358, 15-16). A relevant stress that activates p53 function is UV light (Noda, A., Toma-Aiba, Y., and Fujiwara, Y. (2000) Oncogene 19, 21-31). Another well known component of the mammalian UV response is the transcription factor c-Jun (Angel, P., and Karin, M. (1991) Biochim. Biophys. Acta 1072, 129-157). We show here that upon UV irradiation p53 activates transcription of the human mismatch repair gene MSH2. Interestingly, this up-regulation critically depends on functional interaction with c-Jun. Hence, the synergistic interaction of a proto-oncogene with a tumor suppresser gene is required for the regulation of the mammalian stress response through activation of expression of MSH2.

Base Sequence↗

PubMed1998

Tetraploidization is a physiological enhancer of wound healing.

To investigate the role of chromosomal alterations in the process of wound healing on the cellular level, we analyzed biopsies from well-healing (10) and chronic defect (8) wounds. Classical chromosome preparation and fluorescence in situ hybridization were performed with cultured cells and smear preparations. Results from both techniques showed an unusual high rate of tetraploid cells (4 n) in granulation tissue of well-healing wounds (6.5-60%), whereas we found only a low amount of tetraploid cells (from 0 to 5.5%) in chronic wounds. In fibroblast control cultures, there was a percentage of 2-5.5%. In chromosome preparations, we noticed an increased number of nonclonal structural and numerical chromosome aberrations in both well-healing and chronic wounds. Our data show clearly that especially tetraploidization is a typical phenomenon in the well-healing wound, where it apparently supports the healing process.

Cells, Cultured↗

PubMed1998

[Significance of molecular biology research for trauma surgery exemplified by wound and bone healing].

During the past years molecular biology has become increasing interesting for medical research. These techniques allow the identification of intra-, extra- and intercellular mechanisms, which are important for physiological and pathophysiological processes. Because healing takes place at the cellular level, molecular biology is also relevant for traumatological research. As of yet, there are only a few papers which deal with molecular biological and traumatological problems. For this reason, we only have little knowledge of the function of genes and proteins during wound and fracture healing, for example. To demonstrate the possibilities of molecular biology, we present an experimental strategy by which these techniques can help to answer special traumatological questions.

Animals↗

PubMed1997

Identification of human semaphorin E gene expression in rheumatoid synovial cells by mRNA differential display.

Rheumatoid arthritis (RA) is characterised by chronic inflammation of synovial tissue with aggressive proliferation of synovial cells causing destruction of cartilage and bone. Immunopathological mechanisms, infectious causes and genetic factors have been discussed, but the etiology of the disease has not been understood until now. Especially, the mechanisms driving tumourlike growth and invasive behaviour of fibroblastoid synovial cells have not been identified yet. Our aim is to find cellular factors which are mediators for such pathways. One possibility to approach this, is searching for disease-relevant genes. We applied the mRNA-differential display technique to compare mRNA expression patterns of normal and rheumatic synovial fibroblasts. We identified an upregulation of the human semaphorin E gene in rheumatoid synovial fibroblastoid cells. Interestingly semaphorin E is a member of a protein-family described to play an immunosuppressive role via inhibition cytokines. A relevance of this finding towards the pathogenesis of RA is discussed.

Arthritis, Rheumatoid↗

PubMed1995

Differential expression of heat shock protein 70 in well healing and chronic human wound tissue.

Heat shock protein 70 (hsp 70) is an important member of the heat shock protein family, which is induced by different forms of stress. We attempted to find out if hsp 70 is also involved in wound healing, which likewise resembles a stress situation for cells too. Therefore we collected tissue samples from well healing and chronic human wound tissue. We used Northern- and Western-blot analysis to study the expression of hsp 70. At the protein level we found a strong correlation between well healing wounds and high expression of hsp 70, whereas chronic wounds showed no or weak expression. Interestingly hsp 70 mRNA did not show this significant correlation, displaying a variant expression pattern in the same kind of wound tissue, possibly due to unknown posttranscriptional regulating step, which has to be investigated in further studies. To localize hsp 70 mRNA and protein was used insitu hybridization and immunohistochemistry. Both displayed an overexpression in endothelial cells of capillary vessels.

Base Sequence↗

PubMedDate not supplied

Centrosome multiplication accompanies a transient clustering of polyploid cells during tissue repair.

Cells from different human wounds were analyzed concerning their degree of ploidy. The experiments showed an increased tetraploidization rate in well-healing wounds especially during inflammation and proliferation. Recent data described a polyploidization in different tissues, which is accompanied and maybe caused by the multiplication of the centrosome. We show here for the first time that cells from nonmalignant tissue, namely human wound cells, are characterized by an extensive centrosome multiplication. In an effort to identify a certain mechanism, by which the centrosome may act as a modulator of the cells' ploidy, we focused our interest on p53, whose interaction with the centrosome was recently described. Applying a wound model onto p53-wildtype (wt) and p53-knockout (ko) mice, we could show that polyploidization was not reversible in p53-ko mice during wound healing. The lack of p53, the centrosome multiplication, and the polyploidization therefore may contribute to the physiological process of tissue repair in physiologically "normal" tissue.

Animals↗