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Biomedical subjects

H Abts

Publications and source records attributed to H Abts.

At least 19 recordsLinked to original sources

Expression of p56lck in B-cell neoplasias.

The protooncogene p56lck is considered to participate in malignant transformation of lymphoid cells. In order to evaluate the role of this tyrosine kinase in B cell neoplasias, we investigated the expression of p56lck by Western blot analysis. In 12/16 Burkitt's lymphoma derived cell lines, 3/3 lymphoblastoid cell lines, 1/6 Hodgkin's disease derived cell lines, and 10/10 freshly isolated chronic lymphocytic leukemia cells constitutive expression of the protein was detected. Protein tyrosine kinase assays detected a catalytic active form of p56lck in all p56lck expressing samples. Stimulation experiments of the different cell lines and primary tumour cells by the phorbol ester TPA and the B-cell specific stimulation with SAC/anti-IgM respectively indicated a change of the expression level in comparison with the unstimulated cells and, a higher molecular weight species of the protein tyrosine kinase p56lck was observed. This was probably due to hyperphosphorylation of p56lck. No correlation between an infection with the Epstein-Barr virus and the expression of p56lck was found in the cell lines used and in primary tumour cells. Inhibition of p56lck activity by the specific inhibitor 4-amino-6-hydroxyflavone revealed a decrease of proliferation of the T-cell line Jurkat, but not of the Burkitt's lymphoma cell lines. In the analysed cell lines we found a reduction of the kinase activity of p56lck of approximately 70%. These results suggest that lck may contribute to the maintenance of the transformation of the analysed B cell neoplasias but that lck does not support a model for an initial event in B cell transformation.

Antibodies, Anti-Idiotypic↗

Expression and upregulation of microtubule-associated protein 1B in cultured retinal pigment epithelial cells.

PURPOSE: During routine cell culture and under pathologic conditions, human retinal pigment epithelial (RPE) cells lose epithelial characteristics and change their morphology. In this study, changes in gene expression in RPE cells of different generations were evaluated by polymerase-chain-reaction-based differential display mRNA analysis (DD-RT-PCR). METHODS: Total RNA was prepared from freshly isolated and cultured human RPE cells of passages P0 and P3 and was subjected to DD-RT-PCR. One band with enhanced expression was excised, reamplified, and partially sequenced, using a modified dideoxy chain termination approach. Expression of the corresponding protein was ascertained by immunocytochemical analysis. RESULTS: Differential display RT-PCR showed enhanced expression of a specific RNA in P3 cells compared with that in P0 cells. Sequence alignment revealed 98% identity with the 3' end of the coding sequence of human microtubule-associated protein 1B (MAP1B). Confirmation of induced expression of MAP1B mRNA was obtained by PCR with specific primers and by immunocytochemical analysis in cultured RPE cells and in surgically removed epiretinal membranes from patients with proliferative vitreoretinopathy. No expression of MAP1B mRNA or protein was detected in freshly isolated RPE cells. CONCLUSIONS: Differential display RT-PCR in RPE cells with subsequent sequence analysis allows characterization of the maturation- and differentiation-dependent expression of previously undetected genes and gene products in cultured RPE cells.

Animals↗

Promotion of IL8, IL10, TNF alpha and TNF beta production by EBV infection.

Burkitt's lymphoma (BL) represents a high malignant B cell tumour. It has been proposed that cytokines are responsible for some of the characteristics of BL. We have analysed a panel of different BL and lymphoblastoid cell lines (LCLs) for the expression of cytokines, including: IL 1 alpha, IL 1 beta, IL2, IL3, IL4, IL6, IL8, IL10, TNF alpha and TNF beta and for the soluble cytokine receptor for IL2 (slL2R). Our results show that expression of IL8, IL10, TNF alpha or TNF beta was detected frequently in several of the Burkitt or lymphoblastoid cell lines. There was a correlation between Epstein-Barr virus (EBV) infection and cytokine protein production. Our results suggest that EBV promote the expression of IL8, IL10, TNF alpha and TNF beta.

Burkitt Lymphoma↗

CD95 (Fas/APO-1) antibody-mediated apoptosis of human retinal pigment epithelial cells.

CD95 (Fas/APO-1) is a cytokine receptor protein that signals apoptosis. Here we report that human retinal pigment epithelial cells express CD95 but are rather resistant to agonistic CD95 antibodies. Resistance to CD95 antibodies is overcome by preexposure to the cytokines, tumor necrosis factor-alpha or interferon-gamma, or by coexposure to CD95 antibodies and inhibitors of RNA or protein synthesis. The cells are resistant to tumor necrosis factor-alpha even in the presence of cycloheximide and only moderately sensitized to tumor necrosis factor-alpha-mediated toxicity by coexposure to actinomycin D. CD95-mediated apoptosis is inhibited by dexamethasone both after cytokine sensitization and upon coexposure to CD95 antibodies and actinomycin D or cycloheximide. Induction of apoptosis via CD95 may be involved in the regulation of retinal pigment epithelial proliferation at the vitreoretinal interface.

Antigens, Surface↗

Paroxystic neuropsychological symptoms as the early expression of hepatic encephalopathy. A case report.

A 52-year-old patient presented with paroxystic episodes of generalized apraxia, anomia, agraphia and acalculia. The transient character of these attacks was supported by several neuropsychological examinations. Initially a tentative diagnosis of multiple TIA's was made. Treatment consisted of antiplatelet aggregation therapy. Three years later, however, paroxystic neuropsychological symptomatology occurred more frequently with an increase of severity. The patient was again seen and the differential diagnosis included epilepsy or a metabolic disturbance, in casu hepatic encephalopathy. A therapeutic trial with carbamazepine was started but the patient deteriorated further. He developed a flapping tremor and became stuporous. The blood ammonia was high and there were triphasic waves on the EEG. A probable diagnosis of hepatic encephalopathy was made and carbamazepine therapy was withdrawn. There was a good response on low protein diet and lactulose.

Hepatic Encephalopathy↗

Expression of interleukin-2R alpha and interleukin-2R beta in Hodgkin's disease.

Hodgkin and Reed-Sternberg cells, the putative malignant cells of Hodgkin's disease (HD), carry regularly the CD25 antigen that forms one chain of the interleukin-2 (IL-2) receptor (IL-2R alpha). To analyze the putative role of IL-2R expression in Hodgkin's disease, we have investigated the expression of both IL-2R alpha and IL-2R beta chains in HD-derived cell lines and in primary specimens from patients with HD. Expression of IL-2R alpha and IL-2R beta was detected in all HD-derived cell lines. In addition, soluble IL-2R alpha molecules were demonstrated in the supernatants of three of these cultured cell lines. In primary tissues, IL-2R alpha and IL-2R beta were seen in some but not all cases. Staining was detected in Hodgkin and Reed-Sternberg and in lymphoid cells. There was a remarkable difference in the pattern of expression, in that IL-2R alpha- but not IL-2R beta-positive cells from HD patients were clustered in frozen sections. We conclude from these data that IL-2R expression might be involved in the biology of HD.

Adolescent↗

Visualization of brainstem perfusion using a high spatial resolution SPECT system.

The authors explored the high spatial resolution of a three-head rotating SPECT system, equipped with lead super-fine fanbeam collimator. The brainstem was high-lighted in a three-dimensional reconstruction, showing perfusion small structures such as mesencephalon, pons, and medulla oblongata. The visualization of brainstem perfusion sets new landmarks in functional neuroimaging and, moreover, was obtained with a commercially available three-head SPECT system.

Brain Stem↗

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↗

Clinical and pathophysiological aspects of neurological complications in renal failure.

A review of the neurological complications presenting in uremia and an account of their presumed pathophysiology is given. With the introduction of different dialytic procedures during the last twenty years, the incidence and severity of neurological complications have declined. Nevertheless, some disturbances related to the uremic syndrome fail to respond to dialytic therapy and these therapeutic measures may even be responsible for the appearance of some new abnormalities. The clinical manifestations of uremic encephalopathy and polyneuropathy are presented. The review of the presumed pathophysiology of these syndromes illustrates the still existing controversies. Nevertheless, some promising new lines of research are reviewed. In addition, some complications of uremic treatment, including dialysis disequilibrium syndrome and dialysis encephalopathy are presented.

Brain Diseases, Metabolic↗

Expression of interleukin-6 and interleukin-6 receptor in Hodgkin's disease.

Interleukin-6 (IL-6) is a multipotent lymphokine that can mediate differentiation of B cells into Ig-secreting cells, stimulate the growth of plasmacytomas, hybridomas, and T cells, and induce acute-phase proteins in liver cells. It has been suggested that IL-6 is involved in the pathogenesis of several diseases by autocrine or paracrine pathways. To examine whether IL-6 is possibly involved in the pathophysiology of Hodgkin's disease (HD), we analyzed the expression of IL-6 and IL-6 receptor mRNA and protein in cell lines and primary specimens from patients with HD. IL-6-specific transcripts were detected in three of six HD-derived cell lines by Northern blot analysis. In the culture supernatants of four HD-derived cell lines, IL-6 was detected by radioimmunoassay. Biologic activity of IL-6 was confirmed by proliferation of an IL-6-dependent cell line. In situ hybridization experiments showed IL-6-specific transcripts in Hodgkin (H) and Reed-Sternberg (RS) cells in primary tissues of two patients. In addition, mRNAs specific for the IL-6 receptor were detected in five HD-derived cell lines. Immunostaining experiments showed expression of IL-6 receptor molecules on H and RS cells in 8 of 16 cases with HD. Thus, our data suggest that IL-6 might be involved in the pathophysiology of HD.

Antibodies, Monoclonal↗

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↗

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↗

CD20 positive human B lymphocytes separated with the magnetic cell sorter (MACS) can be induced to proliferation and antibody secretion in vitro.

A method is described for the efficient purification of human B lymphocytes from peripheral blood by magnetic separation. Biotinylated, superparamagnetic particles were coupled to target cells by fluorescein isothiocyanate conjugated avidin and biotinylated monoclonal antibodies directed against cell surface antigens. This combination permitted flow cytometric control of the magnetic separation. Ficoll-Paque-separated peripheral blood mononuclear cells were first eliminated from monocytes by leucine-methyl ester treatment. B cells were enriched to 97% after magnetic depletion of CD3-positive T cells and magnetic enrichment of CD20-positive B cells. The separated B cells could be induced to proliferation and antibody production by various in vitro stimuli.

Antibody-Producing Cells↗

[Vaginal applicator combination for radium therapy of advanced vaginal and cervix carcinomas].

A vaginal applicator combination for intracavitary radium therapy in cancers of the female genitals was developed. By means of several stages which may be combined moreover with tube filters, different combinations and different radium quantities are applicable which can be adjusted to the results of medical examination using symmetric or asymmetric radium sources. The loading of the applicator combination is executed by straight genuine tube filters which were fixed by weld.

Female↗