Search PubMed⌕ Search

Biomedical subjects

H Tesch

Publications and source records attributed to H Tesch.

At least 109 records · Page 6Linked to original sources
PubMed1992

Heterogeneous expression of c-myb protein in human leukemia detected by simultaneous two color flow cytometric analysis.

The expression of c-myb mRNA and protein was analyzed in fresh leukemic cells by Northern-blot analyses and by immunofluorescent staining using monoclonal c-myb specific antibodies. Staining of the cells was evaluated by flow cytometry. The results demonstrate c-myb mRNA expression predominantly in acute lymphocytic leukemia (ALL, 4/4 cases), acute myeloic leukemia (AML, 17/17) and chronic myeloic leukemia (CML, 12/12) but rarely in chronic lymphocytic leukemia (CLL, 1/17). Immunofluorescent analyses revealed expression of c-myb protein in the nucleus of ALL (5/7) and AML (9/9) with a good correlation of c-myb-positive cells and with the number of proliferating (Ki67-positive) blast cells.

Antigens, Surface↗
PubMed1992

Activation of cytokines in Hodgkin's disease.

The complex histological pattern in Hodgkin's disease and in part in large cell anaplastic lymphomas (ALCL) suggests that close interactions exist between the tumor cells and reactive bystander cells. These interactions are most likely mediated by short ranged cytokines. The production of cytokines was analyzed in primary tissues and cell lines from Hodgkin's disease and ALCL by enzyme linked immunosorbent tests (ELISA), Northern blotting, immunohistological staining and in situ hybridization experiments. Our results indicate that Hodgkin's disease derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, IL9, TNF alpha and TNF beta but not IL1 beta, IL2, IL3 and G-CSF. In addition, the receptors for IL6 were detected in some of the cell lines. The expression of IL6 and IL6 receptors and IL9 has been confirmed for some primary tissues of Hodgkin's disease. From our data, we conclude that IL6, IL9 and additional cytokines are involved in the biology of Hodgkin's disease and ALCL.

Cell Line↗
PubMed1992

Oncogene and growth factor expression in ovarian cancer.

The varying tumor-biological behavior of ovarian carcinomas probably influences both their operability and response to chemotherapy, which are the most relevant prognostic factors. The phenotype of different ovarian carcinomas is obviously associated with an activation of the EGF/TGF-alpha signal pathway, including c-myc and c-jun expression. Analysis of EGF-R, TGF-alpha, c-myc and c-jun expression in 33 stage III/IV, and 2 stage I/II ovarian carcinomas with biochemical, molecular-chemical and immunohistochemical methods showed a correlation between the mRNA and protein levels of EGF-R and TGF-alpha for tumors with low or high expressing rates. However, the concentration of measurable free EGF-Rs seems to depend on the amount of TGF-alpha expression by the tumors. The EGF-R binding ligand TGF-alpha is produced by epithelial tumor cells; stromal cells are usually TGF-alpha-negative, as shown by immunohistochemistry. High expression rates of EGF-R. TGF-alpha and c-myc were detected in 6, 7, and 10 out of 35 ovarian carcinomas, respectively. C-jun mRNA was detected in 18/19 cases studied. Non-malignant tissues originating from myometrium or ovary expressed no (or only small amounts of) EGF-R or TGF-alpha mRNA, whereas a high c-myc expression was found in 1/7 normal myometria, and in 2/5 normal ovaries. There was no strong correlation between EGF-R/TGF-alpha and c-myc/c-jun expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1992

Hodgkin and Reed-Sternberg cells express interleukin 6 and interleukin 6 receptors.

Interleukin 6 (IL-6) is a pleiotropic lymphokine which can stimulate a variety of cells including B and T lymphocytes. It has been suggested that IL-6 plays a crucial role in several diseases such as human plasmacytoma, cardiac myxoma or Castleman's Disease by autocrine or paracrine stimulation. To analyse whether IL-6 is involved in the biology of Hodgkin's Disease (HD), we investigated the expression of IL-6 and IL-6 receptor (IL-6R) in cell lines and primary specimens from patients with HD. IL-6 specific transcripts were detected in three out of six HD derived cell lines by Northern blot analysis and in the culture supernatants of four HD derived cell lines by ELISA. Its biological activity was confirmed by proliferation of an IL-6 dependent cell line. By in-situ hybridization experiments IL-6 specific transcripts were detected in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues in two out of three patients. mRNAs specific for the IL-6 receptor were detected in five HD derived cell lines. Staining of HD derived cell lines revealed expression of the receptor molecules in five cell lines; Western blot experiments confirmed the 80kDa receptor protein in the cells. Immunohistology in primary specimens revealed expression of the receptor molecules on H and RS cells in 8 out of 16 cases with HD. Expression was mostly detected in the mixed cellularity subtype of HD. Elevated levels of IL-6 were detected in the sera of more than 50% of patients with HD. Taken together our data suggest that IL-6 might be involved in the biology of HD.

Adolescent↗
PubMed1992

Analysis of c-myc, bcl-1 and bcl-2 translocations in human lymphoma by pulsed-field gel electrophoresis.

Translocations of the c-myc, bcl-2 and the putative bcl-1 oncogene are recurrent events in B-cell lymphoma. Since it is likely that the rearranged genes contribute to the malignant phenotype of the tumor cells, such oncogene translocation is of major interest. The molecular detection of translocations using conventional Southern hybridization analysis is complicated by the fact that translocation breakpoints are dispersed over large chromosomal regions. In order to overcome this problem we used pulsed-field gel electrophoresis (PFGE) to detect c-myc, bcl-2 and bcl-1 translocations in 29 lymph node biopsies. C-myc translocation could not be detected in this group, either with standard Southern analysis of PFGE. Translocations of the bcl-2 gene were detected by PFGE in 5 samples and the breakpoints were mapped in all cases to the third exon of bcl-2 by standard Southern analysis. Furthermore, we also found rearrangements of the bcl-1 locus in 3 samples. Mapping of the breakpoint failed in one of these cases, which strongly indicates the existence of a breakpoint outside the bcl-1 major breakpoint region. Thus, PFGE allows the rapid detection of translocations in human lymphomas within large stretches of DNA.

Adult↗
PubMed1992

Expression of truncated transcripts of the proto-oncogene c-fps/fes in human lymphoma and lymphoid leukemia cell lines.

The human c-fps/fes proto-oncogene is expressed as a transcript of about 3.0 kb in both normal and leukemic myeloid cells. We have detected truncated c-fps/fes transcripts of about 0.9 kb in a panel of human lymphoma and lymphoid leukemia cell lines, but not in normal untransformed hematopoietic cells. Analysis of the chromatin structure of the c-fps/fes gene revealed DNAase I-hypersensitive sites in the 5' region of the gene and in exon 16. The presence and absence of these sites correlates with the expression of the 3.0 kb and 0.9 kb c-fps/fes RNAs respectively. The truncated transcripts initiate at two distinct sites within exon 16 of the c-fps/fes gene. The genomic region 5' to the transcription initiation sites is G+C rich but does not contain typical promoter consensus sequences. Sequence analysis of a cDNA clone of the truncated c-fps/fes transcripts did not reveal any point mutation and the truncated transcripts are normally spliced using the regular splice donor and acceptor sites. A putative open reading frame encompasses the phosphotransfer motif and the autophosphorylation site of the fps/fes kinase domain. In vitro transcription/translation of a cDNA clone corresponding to the truncated c-fps/fes transcripts revealed a protein of 17 kDa. There are no translocations or rearrangements in or around the c-fps/fes gene in cell lines which express the truncated c-fps/fes transcripts. This alternative transcription of c-fps/fes may indicate a novel activation process of this proto-oncogene.

Base Sequence↗
PubMed1991

Partial trisomy 1q. A nonrandom primary chromosomal abnormality in myelodysplastic syndromes?

Cytogenetic and clinical data of 11 patients with de novo myelodysplastic syndromes and partial or total trisomy of the long arm of chromosome 1 are presented. In eight of these patients trisomy 1q was the sole karyotypic change and therefore can be classified as a primary chromosome anomaly. A remarkably young median age of 36.5 years was noticed in this patient group.

Adolescent↗
PubMed1991

Patterns of DNA methylation in selected human genes in different Hodgkin's lymphoma and leukemia cell lines and in normal human lymphocytes.

The human genome, like many other genomes, harbors highly specific patterns of DNA methylation which have not yet been systematically studied. In a limited investigation on the genes for tumor necrosis factors-alpha and -beta, a surprising interindividual concordance in the patterns of DNA methylation at the nucleotide level has been demonstrated earlier by using the genomic sequencing method on DNA from individuals of very different ethnic origins. Patterns of DNA methylation could perhaps serve as indicators for genetic activities. These activities would not have to be restricted to gene transcription but could relate to other genetic activities in the cell. DNA methylation patterns are known to be cell type-specific. We have now initiated a study of these DNA patterns in human lymphocytes and in human cell lines of different malignant origins. Several of the proto-oncogenes, parts of the genes for tumor necrosis factor-alpha and -beta, the insulin receptor and lamin C have been used as hybridization probes. We have relied to some extent on the documented observation that the methylation patterns at 5'-CCGG-3' (HpaII/MspI) sequences yield a reflection of patterns at all 5'-CG-3' sequences. Three main types of patterns have been observed. Some of the probed segments are completely unmethylated; others are fully methylated, most of the areas are partly methylated exhibiting complex patterns at the 5'-CCGG-3' sites. In different tumor cell lines, different DNA methylation patterns are apparent for the same DNA probes. Comparisons of the methylation patterns in a given DNA segment between DNA from primary normal human lymphocytes and DNA from different tumor cell lines reveal changes in these patterns in several instances.

Base Sequence↗
PubMed1991

DNA methylation profiles in the human genes for tumor necrosis factors alpha and beta in subpopulations of leukocytes and in leukemias.

The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting technique. In the human tumor necrosis factor alpha (TNF-alpha) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In one such case, all 5-methyl-2'-deoxycytidine residues have been replaced by cytidine. In a chronic lymphatic T-cell leukemia, all 5-methyl-2'-deoxycytidine residues have been substituted by cytidine. In normal B lymphocytes, in two cases of chronic lymphatic B-cell leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences in this gene segment are devoid of methylation. In the TNF-beta gene, DNA methylation is decreased in several examples of acute or chronic myeloid leukemias in comparison to normal human granulocytes or monocytes, whose DNA is almost completely methylated between nucleotides 700 and 900. In human T and B lymphocytes, the main producers of TNF-beta, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin lymphomas, all 5'-CG-3' sequences are unmethylated in this region. The DNA from the human HeLa cell line is highly methylated at all 5'-CG-3' sequences in the TNF-alpha and -beta genes. The TNF-alpha gene is transcribed in the cells of one case of acute myeloid leukemia in which the analyzed region of the TNF-alpha gene is completely unmethylated. The TNF-beta gene is not transcribed in any of the malignant cells tested.

Adult↗
PubMed1991

Human chronic lymphocytic leukemia cells regularly express mRNAs of the protooncogenes lck and c-fgr.

Protooncogenes, the cellular homologues of transforming retroviral oncogenes, have been suggested to participate in malignant transformation of various cell types. The role activated protooncogenes might play in chronic lymphocytic leukemia (CLL) is not yet clear. We investigated the expression of the protooncogenes lck and c-fgr encoding two protein tyrosine kinases by Northern-blot analysis in 21 patients with B-CLL and transcripts of both genes were detected in all cases. In contrast to CLL B cells, normal B cells from peripheral blood of a healthy donor separated by magnetic sorting did not express c-fgr and lck. The results suggest a possible role for these two protooncogenes of the src family in the activation and/or transformation of human B lymphocytes.

Adult↗
PubMed1990

Chromosomal in situ hybridization of a Hodgkin's disease-derived cell line (L540) using DNA probes for TCRA, TCRB, MET, and rRNA.

The Hodgkin's lymphoma-derived cell line L540, which exhibits multiple marker chromosomes and a genotype characteristic of T-cell origin, showed expression of MET oncogene. L540 was studied by in situ hybridization for chromosomal rearrangements concerning the regions where genes for TCRA and TCRB chains, for MET oncogene, and for rRNA are located. All four genes were demonstrated to be involved in the formation of marker chromosomes. Especially remarkable was the participation of rDNA-bearing regions in two different translocations.

Cell Line↗
PubMed1990

High affinity IL-2 receptors on a Hodgkin's derived cell line.

Hodgkin and Sternberg Reed (H and SR) cells, the putative malignant cells of Hodgkin's disease carry regularly T-cell activation antigens, like CD30 and CD25 (low affinity IL-2 receptor). We have investigated the Hodgkin cell line L540, bearing characteristic markers of H and SR cells for its expression of the low affinity IL-2 receptor (IL-2R) and for IL-2. Expression of the low affinity IL-2R was found on mRNA level, by detection of specific 3.5 kb and 1.4 kb mRNA and on the protein level by immunoprecipitation of a 55,000 mol. wt molecule from detergent extracts of surface iodinated cells, however IL-2 specific mRNA was not detected. Scatchard plot analysis revealed the presence of 2 x 10(3) high affinity IL-2Rs. Crosslinking experiments directly demonstrated the high affinity IL-2R to consist of the 55,000 mol.wt light chain (L), and the 70/75,000 (H1/H2) heavy chains. IL-2 was rapidly internalized by these receptors, suggesting that they can be functional. The expression of functional IL-2Rs might be involved in induction or differentiation of Hodgkin's disease.

Fluorescent Antibody Technique↗