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Biomedical subjects

L Kopper

Publications and source records attributed to L Kopper.

At least 37 records · Page 2Linked to original sources
PubMed1997

Expression of syndecan-1 in human B cell chronic lymphocytic leukaemia.

Syndecan-1 is considered an important transmembrane proteoglycan in cell-microenvironment interactions, but its exact function in normal or in transformed B cells is still unknown. In this study, RNA was isolated from peripheral cells of chronic lymphocytic leukaemia (B-CLL) and 'normal', non-leukaemic patients, as controls. Reverse PCR showed no or very low syndecan-1 mRNA expression in controls, while in 11/13 B-CLL the circulating leukaemic cells expressed syndecan-1. Similar results were obtained for interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Furthermore, syndecan-1 protein was detected in the majority of circulating B-CLL cells by flow cytometry and immunocytochemistry using anti-syndecan-1 MAb. Control cells were practically negative. Further study is required to understand the biological significance of syndecan-1 on B-CLL cells.

Adult↗
PubMed1996

Diffuse plasmacytosis in a child with brainstem glioma following multiagent chemotherapy and intensive growth factor support.

The use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to abrogate chemotherapy-induced neutropenia has become a routine part of many cancer treatment regimes. However, there are still very few data available about possible complications related to repeated or prolonged use of these agents in patients with malignant solid tumors. The authors report a child with brainstem glioma who received repeated cycles of multiagent chemotherapy with G- or GM-CSF support. During this period of 10 months, no clinical side effects were observed that could have been attributed to growth factor administration. However, postmortem histological examination revealed the presence of diffuse plasmacytosis, a rare hematological disorder in childhood. Undifferentiated plasma cells of nonmonoclonal origin could be demonstrated infiltrating bone marrow, lungs, and lymph nodes of the patient. Based on previously published in vitro and in vivo evidence on the interleukin-6 (IL-6)-mediated stimulatory effect of G- and GM-CSF on myeloma cell proliferation, the authors suggest a possible link between extensive growth factor support and the development of plasmacytosis in this patient.

Adolescent↗
PubMed1996

Possible involvement of protein kinase C-epsilon in phorbol ester-induced growth inhibition of human lymphoblastic cells.

Sustained activation of members of the protein kinase C (PKC) family is known to influence the growth and differentiation of various cell types, however, the specific roles for individual isoforms mediating these cellular events have yet to be elucidated. Activation of PKC by phorbol esters leads to growth inhibition in certain cell lines. The HT58 human B lymphoblastic cell may serve as a cellular model system to investigate the participation of individual isoforms in the initial events of growth arrest induced by phorbol ester. Determination of cell cycle and investigation of apoptosis were performed by flow cytometric measurements. Phorbol ester-induced translocation and down-regulation of the conventional alpha, beta and the novel epsilon isoforms of PKC were demonstrated by Western blot analysis. At lower concentrations (o.5 ng/ml) phorbol myristate acetate (PMA) stimulated a G1 arrest with retention of viability in the human HT58 B lymphoblastic cell. The protein kinase inhibitor staurosporine at a concentration of 25 nM did not significantly alter HT58 cell viability. However, staurosporine (25 nM) induced apoptosis in cells preincubated for 4 hr with 0.5-1.0 ng/ml PMA. The translocation of PKC-epsilon was observed within 39 min exposure to 0.5 ng/ml PMA. After a 4 hr treatment, evidence for down-regulation and and altered phosphorylation state of PKC-epsilon was seen. In contrast, the conventional alpha and beta isoforms were practically uneffected by this PMA treatment. At higher PMA concentrations (50 ng/ml) the alpha and beta isoforms showed a significant down-regulation. The preferential alterations in PKC-epsilon observed under the conditions required for PMA to influence the growth and survival of HT58 cells suggest a role for the Ca(2+)-independent epsilon isoform in mediating the initial events of the phorbol ester stimulated cellular responses.

Apoptosis↗
PubMed1995

Modulation of heparan-sulphate/chondroitin-sulphate ratio by glycosaminoglycan biosynthesis inhibitors affects liver metastatic potential of tumor cells.

Previous data have indicated that the proteoglycan (PG) pattern is different on tumor cells with different liver metastatic potential. We selected "conventional" glycosaminoglycan (GAG) biosynthesis inhibitors, beta-D-xyloside (BX), 2-deoxy-D-glucose (2-DG), ethane-l-hydroxy-l,l-diphosphonate (ETDP) and the newly discovered 5-hexyl-2-deoxyuridine (HUdR), to modulate PGs on highly metastatic/liver-specific 3LL-HH murine carcinoma and HT168 human melanoma cells and to influence their liver colonization potential. These compounds all induced remarkable changes in GAG biosynthesis, but to varying degrees: glucosamine labelling was affected mainly by 2-DG, and HUdR and sulphation by BX and HUdR. Furthermore, the ratio of heparan sulphate/chondroitin sulphate (HS/CS) of PGs was increased by ETDP and decreased after treatment by HUdR. In addition to changes in PG metabolism, tumor-cell proliferation and adhesion to fibronectin were affected; BX and 2-DG stimulated cell proliferation and adhesion, while HUdR inhibited both proliferation and adhesion. Most interestingly, HUdR, the most effective inhibitor of HS/HSPG, depressed the formation of liver colonies, while ETDP, the most effective inhibitor of CS/CSPG, stimulated the appearance of liver colonies. These observations indicated that, at least in these experimental systems, tumor cells with a high HS/CS ratio are more likely to form liver metastases; consequently, anti-HS agents could also be anti-metastatic.

Animals↗
PubMed1995

[Flow cytometric examinations of patients after radical surgery for prostatic cancer].

Biological behavior of prostatic cancer is influenced by different tumor factors. The proliferative activity of the malignancies could be one of those parameters which serve as basis to design therapy and to estimate prognosis. Here ploidity and S-phase fraction of 44 prostatic cancer obtained by radical prostatectomy were compared to other known tumor characteristics (PSA, staging, grading). There are correlations between the PSA concentration, grading, staging and S phase fraction. The ploidity correlates with the grading. Neither of kinetic parameter correlated with the nodal involvement.

Aged↗
PubMed1995

Modulation of drug-induced apoptosis in a human B-lymphoma cell line (HT58).

The cytotoxic effect of etoposide (ETO), a topoisomerase II inhibitor, and staurosporine (STA), a non-selective protein kinase inhibitor, were studied on a human lymphoma cell line of B-cell origin (HT58). Apoptosis, induced dose dependently by both drugs, was accompanied with nucleosomal DNA fragmentation detected by flow cytometry. On the other hand, induction of cell death failed using phorbol ester (PMA), anti-IgM antibody (a-IgM) or dexamethasone (DEX), although, all of these agents arrested the cells in G1. Furthermore, PMA pretreatment retarded ETO-induced apoptosis, but enhanced STA cytotoxicity. DEX increased the sensitivity of cells to STA, but did not to ETO. Activity of STA or DEX was only slightly modified by a-IgM pretreatment. The results support the possibility that different apoptotic pathways exist in HT58 cells. The differences in pathways could be manifested either in the signaling routes, or in the molecular effectors of apoptosis.

Alkaloids↗
PubMed1994

Phosphorylation of poly(ADP-ribose)polymerase protein in human peripheral lymphocytes stimulated with phytohemagglutinin.

Intracellular phosphorylation of poly(ADP-ribose)polymerase was assayed in streptolysin-O-permeabilized human lymphocytes. Whereas 32P incorporation from [gamma-32P]ATP into immunoprecipitated enzyme protein was undetectable in resting cells, significant phosphorylation of this enzyme was observed in lymphocytes treated with phytohemagglutinin. The phosphorylation of poly(ADP-ribose)polymerase in permeabilized cells was not stimulated by phorbol ester, while phorbol-induced phosphorylation of other proteins and of a specific oligopeptide substrate of protein kinase C was observed. However, the specific inhibitory pseudosubstrate peptide of protein kinase C blocked the phosphorylation of poly(ADP-ribose)polymerase induced by phytohemagglutinin. Therefore, a potential role of a member of the protein kinase C family in the phytohemagglutinin stimulated intracellular phosphorylation of poly(ADP-ribose)polymerase is conceivable.

Bacterial Proteins↗
PubMed1993

Significance of cellular DNA content in human liver tumors.

The nuclear DNA content of 26 liver tumors (1 adenoma, 10 focal nodular hyperplasia and 15 hepatocellular carcinoma) was measured by flow cytometry (FCM) on formalin-fixed, paraffin-embedded tissues. All lesions developed in noncirrhotic liver and were negative for HBsAg. DNA aneuploidy was found in 1/10 FNH (one hypodiploid) and in 11/15 HCC (73%). Intratumoral heterogeneity was observed in three cases. In HCC the ploidy level showed no correlation with tumor size or histopathological grading. Results support the potential of FCM to measure DNA content in archival pathological specimens, and also that DNA content itself has no diagnostic value.

Adenoma↗
PubMed1992

[Theoretical possibility of using gene therapy in malignant diseases].

The rapidly growing knowledge in molecular biology opened new methodological approaches, pharmacological targets, such as gene transfer or application of antisense oligomers. It is necessary to be familiar with the benefits and drawbacks of gene therapy to avoid the traps of unrealistic expectations and hopes, to solve moral and practical problems of gene manipulations and to find its proper values and rationals in the management of malignant tumors.

DNA, Recombinant↗
PubMed1992

[Pathology--on a molecular level (determination of nucleic acids from fixed embedded samples)].

Molecular biological techniques may open new avenues to pathological archives. Fixed and paraffin embedded blocks are a suitable source of nucleic acids, especially of DNA, for retrospective analysis. The quality of DNA depends mainly on the fixation procedure. High molecular weight DNA allows Southern hybridization, but fragmented DNA also became a target with the appearance of polymerase chain reaction (PCR). PCR has rising applicability and enables amplification of required sequence even from one section. Using these techniques on archieved materials a wide variety of informations, e.g. correlation between morphology, phenotypic expression and gene alteration, will be available.

Blotting, Northern↗
PubMed1992

Ki-1 positive (anaplastic, large cell) lymphoma (case reports and review).

Ki-1 positive (anaplastic, large cell) lymphoma is a subgroup of non-Hodgkin lymphomas identified recently by Ki-1 (or BER-H2) (CD 30) monoclonal antibody. The clinicopathological features of two such pediatric cases of lymph node origin described here, and also the available literature emphasize the heterogenous nature of Ki-1 positive lymphomas, in almost every respect. Nevertheless, the Ki-1 antibody serves as an important diagnostic tool to differentiate lymphomas from other anaplastic, large malignancies.

Antibodies, Monoclonal↗
PubMed1991

Flow cytometric analysis of DNA content in focal nodular hyperplasia and hepatocellular carcinoma.

DNA index of twenty-three surgically removed, formalin-fixed and paraffin-embedded liver specimens (10 focal nodular hyperplasias--FNH, and 13 hepatocellular carcinomas--HCC) were studied by flow cytometry. Diploid value appeared in 9/10 FNH (one was hypodiploid), while 10/13 HCC (77%) had DNA aneuploidy (one hypo- and 9 hyperdiploid). The presence of normal DNA content in 3 HCCs suggests that DNA aneuploidy only cannot indicate the malignant transformation of a benign lesion (e.g. FNH).

Adolescent↗
PubMed1990

Investigations on the antitumor effect and mutagenicity of alpha-MSH fragments containing melphalan.

alpha-MSH fragments containing melphalan were tested in vivo on L1210 leukemia and on human amelanotic melanoma xenograft in mice and in vitro on human amelanotic melanoma cell lines. The compounds exhibit significant antitumor activity, but no selectivity in targeting of melanoma can be achieved. There is a difference between melphalan and the melphalyl-peptide in their action on protein synthesis. The peptide derivatives also are less mutagenic than melphalan, according to the SCE assay, furnishing further evidence for the positive effect of natural carrier molecules.

Amino Acid Sequence↗
PubMed1990

[Acute kidney failure caused by rhabdomyolysis].

Rhabdomyolysis developed in the muscles of the left lower extremity of a 43 year old man leading to myoglobinuria and acute renal failure. The diagnosis of rhabdomyolysis was strengthened by muscle and renal biopsy. The renal functions were restituted after peritoneal dialysis performed four times (12 hours each) within two weeks. The possible role of alcohol or Dalgol intoxication as well the disturbed circulation in the development of rhabdomyolysis is discussed. Authors point out the benefit of peritoneal dialysis in acute renal failure caused by rhabdomyolysis.

Acute Kidney Injury↗
PubMed1990

Ultrastructural localization and internalization of proteoglycan epitopes in a human non-Hodgkin (B) lymphoma.

In a human non-Hodgkin (B) lymphoma xenograft (HT-117) heparan sulphate (HS) proved to be the main cell surface glycosaminoglycan, in contrast to the chondroitin sulphate dominance in normal lymphoid cells. Using anti-proteoglycan (PG) antibodies and immunoelectronmicroscopy, two heparan sulphate proteoglycans (transferrin receptor (TfR) and fibroblast membrane type) and one chondroitin sulphate proteoglycan (articular cartilage type) molecule were co-localized as random clusters on the surface of these lymphoma cells. Double labelling revealed that during internalization, which occurred via endosomes avoiding the lysosomal system, the different proteoglycan (PG) antigens became separated. The TfR and fibroblast membrane type HSPG epitopes reappeared on plasmalemmal vesicles derived most probably from the multivesicular endosomes, representing a unique form of exocytosis. It is suggested that different cell membrane PGs are integrated into subunits of yet unknown function in these human non-Hodgkin (B) lymphoma cells.

Animals↗
PubMed1990

Proteoglycan-targeted antibodies as markers on non-Hodgkin lymphoma xenografts.

A family of mono- and polyclonal antibodies raised against proteoglycans or their "subcomponents" served as novel markers to characterize the phenotypes of three non-Hodgkin lymphoma xenograft lines (HT 58 lymphoblastic, HT 117 centroblastic, HT 130 centrocytic) together with normal, human peripheral blood B lymphocytes. These xenografted NHL lines, maintained by serial transplantations on artificially immunosuppressed mice, expressed very similar B-cell-related antigens and differences on the cell surface (HT 58 greater than HT 117 greater than HT 130 greater than B cells) when they were exposed to monoclonal antibodies (mAb) to cartilage proteoglycans. Anti-proteoglycan antibodies used in this study recognize complex epitopes of core protein segment associated with carbohydrate, shared by human cartilage proteoglycans and certain lymphoma cells. The binding of these antibodies was independent of cell-cycle phase. The results suggest that the anti-proteoglycan mAbs could be used as new phenotypic markers to individualize non-Hodgkin lymphomas.

Animals↗
PubMed1990

Bigenotypic and biphenotypic appearance of immunoglobulin light chains in 1 of 3 non-Hodgkin's lymphoma xenografts.

Chromosomal analysis of three human non-Hodgkin's lymphoma (NHL) xenografts revealed common extra 14q+ segment and other individual clonal markers without involvement of immunoglobulin light-chain regions. Two NHL xenografts (HT 58 and HT 130) showed restricted lambda light chain expression and deleted kappa and rearranged lambda genes. However, in HT 117 both kappa and lambda chains were present on the cell surface, and both light chain genes showed rearranged alleles. This unique phenomenon could have resulted from either disturbed regulation of isotype exclusion or from the malignant transformation of light chain 'uncommitted' B cells.

Animals↗