Search PubMed⌕ Search

Biomedical subjects

T Tursz

Publications and source records attributed to T Tursz.

At least 145 records · Page 8Linked to original sources
PubMed1988

Constitutive expression of HLA class II antigens on EBV positive malignant cells from nasopharyngeal carcinoma: possible involvement in T cell infiltration.

Undifferentiated nasopharyngeal carcinoma (NPC) was originally referred to as "lymphoepithelial carcinoma." Two main cell types are constantly associated within these tumors: the malignant epithelial cells which harbor the Epstein-Barr virus (EBV) genome, and the nonmalignant lymphocytes mostly of the T lineage. Three characteristic features of malignant NPC cells might explain T cell migration within NPC tumor tissue: HLA class II molecule expression, IL-1 production, and presence of EBV antigens. Homogeneous suspensions of malignant NPC cells were derived from a nude-mouse transplantable tumor in order to specify the status of HLA class II molecules in these tumors. These suspensions were stained for HLA class II antigens and analyzed by flow cytometry in comparison with other carcinoma cell lines. Three characteristics of transplantable malignant NPC cells were demonstrated: constitutive and coordinate expression of DR, DP, and DQ molecules, and concomitant expression with the CDw40 antigen ("B lymphocyte carcinoma cross-reacting antigen").

Adolescent↗
PubMed1988

[Contribution of immunology and molecular biology].

Recent technical advances in immunology and molecular genetics have allowed to better delineate Ewing sarcoma among other small round cell tumors of bone and soft tissues. Ewing cells present with a characteristic translocation t (11;22) (q23-24; q11-12) shared with neuroepithelioma. They express a series of cell-surface antigens associated with the neuroectodermal differentiation lineage. These data open new avenues for exploring the origin and the mechanism of transformation of these tumors and to conceive new therapeutical approaches.

Antigens, Surface↗
PubMed1987

Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines.

The status of the neural cell adhesion molecule NCAM gene which is mapped to human chromosome 11q23-24 has been investigated in Ewing-tumor-derived cell lines which present the t(11;22)(q23-24;q12) translocation characteristic of this malignancy. No rearrangement was detected when 2 different non-overlapping probes to mouse NCAM were used. The expression of the NCAM gene was analysed at both the protein and messenger levels in material extracted from Ewing cell lines, human neuroblastoma cell line and fetal mouse brain. Immune blot and immunoprecipitation studies showed that the neuroblastoma cell line contained more NCAM material than the Ewing lines. In neuroblastoma but not in Ewing, the NCAM material had the electrophoretic characteristics of molecules with long polysialic acid chains. After treatment with endosialidase, the diffusely migrating neuroblastoma material was resolved into 3 discrete bands of 120, 140 and 180 kDa. In Ewing extract, high-molecular-weight NCAM species were also detected with a 3-band pattern more reminiscent of mature brain. Endoglycosidase F treatment of Ewing NCAM indicated that all 3 species were largely N-glycosylated. Northern blot analysis confirmed that NCAM was expressed more abundantly in neuroblastoma than in Ewing cell lines. Among the 4 NCAM messengers (7.0, 6.5, 4.3 and 4.1 kb) detected in the neuroblastoma, the 6.5 kb species was largely predominant. The Ewing messenger RNA pattern was clearly different as the largest 7.0-kb species was virtually absent and the other bands were of similar intensities.

Animals↗
PubMed1987

Identification of a subset of normal B cells with a Burkitt's lymphoma (BL)-like phenotype.

Fresh biopsy cells from cases of Burkitt's lymphoma (BL) display a homogeneous cell surface phenotype. The cells were found to be reactive with the pan B cell marker B1, and consistently co-expressed the BL-associated glycolipid antigen, BLA, and the common acute lymphoblastic leukemia antigen, CALLA, but lacked the B cell "activation" antigens characteristically expressed on EB virus-transformed normal B cells. Microscopic and cell sorter analysis of cells isolated from a series of fresh normal tonsils have identified a subpopulation of normal B cells carrying the same cell surface markers. That BLA and CALLA could be co-expressed on individual B cells was demonstrated by two-color immunofluorescence (IF) of tonsils in suspension, and immunoperoxidase (IP) staining of serial tonsil sections. These BLA+, CALLA+, "activation" antigen- cells were further characterized as B1+, sIgM+, sIgD-, C3d/EB virus receptor+ and were susceptible to virus-induced transformation in vitro. IF studies on Percoll-fractionated tonsillar cell populations and direct examination of IP-stained tonsil semi-thin sections indicated that the BLA+, CALLA+ cells were localized in germinal centers. Their morphological characteristics matched those of BL cells, and their location within germinal centers was consistent both with the known phenotype of germinal center tonsillar B cells and with the description of BL as a proliferation of centroblasts. We suggest that this population of tonsillar germinal center B cells provides the normal counterpart of BL tumor cells.

Antibodies, Monoclonal↗
PubMed1987

Neuroectoderm-associated antigens on Ewing's sarcoma cell lines.

The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22)(q23-24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.

Antigens, Neoplasm↗
PubMed1987

Antitumor activity against L1210 mouse leukemia of immunotoxins containing a monoclonal antibody to the glycolipid globotriaosylceramide.

Since immunotoxin (IT) containing the antiglobotriaosylceramide monoclonal antibody was found to be cytotoxic in murine L1210 leukemia cells, its potential antitumor activity could be evaluated in animals using the L1210 model. In vitro, L1210 cells incubated IT before grafting in DBA/2 mice failed to induce leukemia. All tumor cells were neutralized by IT. In animals, a significant but limited therapeutic effect on leukemic mice was obtained when IT was injected i.p. shortly after L1210 cell grafting. In contrast, no toxic effect of IT was observed in non-leukemic mice at doses far above those used in our therapeutic treatment. The potentiation effect of chloroquine on IT was moderated when a cloning efficiency assay was used, but 70% of the mice grafted with in vitro chloroquine-treated L1210 cells were cured with IT treatment.

Animals↗
PubMed1987

Lymphocyte subsets in tumour of patients with undifferentiated nasopharyngeal carcinoma: presence of lymphocytes with the phenotype of activated T cells.

We have analyzed lymphocytes infiltrating nasopharyngeal carcinomas, using a combination of immunoperoxidase staining of frozen and paraffin-embedded sections, and immunofluorescence on lymphocyte suspensions recovered from teased tumours. A panel of monoclonal antibodies was used to define lymphocytic subsets on frozen sections of 14 different tumours. The vast majority of peri- and intra-tumoral lymphocytes were stained by OKT3 antibody. In 8 sections, T4 positive cells were largely predominant, while T8 positive cells were the majority in three sections. Twenty-nine paraffin-embedded sections from other NPC patients stained with HNK-1 antibody showed a variable percentage of positive cells reaching 6 to 15% in nine patients. Most HNK-1 positive cells had the morphology of large granular lymphocytes typical of natural killer cells. Double staining experiments on lymphocytes isolated from 7 tumours revealed a constant presence of T3 positive, HLA-DR positive lymphocytes (from 6 to 29% of mononuclear cells), and of lymphocytes coexpressing the T3 and the Tac (IL-2 receptor) antigens (from 5 to 12% of mononuclear cells). Lymphocytes with a phenotype of activated T-cells are thus constantly found in NPC tumours.

Antigens, Surface↗
PubMed1987

Epstein-Barr virus-containing epithelial cells from nasopharyngeal carcinoma produce interleukin 1 alpha.

Nasopharyngeal carcinoma (NPC) is a human epithelial cancer that is constantly associated with the Epstein-Barr virus (EBV). Investigations on this tumor have been limited so far by the difficulty of culturing NPC cells for long periods. C15 is an NPC tumor that has been successfully carried in nude mice for greater than 2 yr. C15 cells isolated from the animal were shown to produce a soluble factor with interleukin 1 (IL-1) activity. Its biochemical (Mr, approximately equal to 17,000; pI approximately equal to 5) and immunological properties are identical to those of IL-1 alpha. RNA gel blot analysis showed IL-1 alpha, but not IL-1 beta, transcripts in C15 cells, in sharp contrast to monocytes that express IL-1 beta predominantly. Media from short-term cultures of fresh NPC biopsies also contained a strong IL-1 activity. Several lymphoblastoid cell lines obtained by EBV infection of normal B lymphocytes have been shown to produce IL-1 and use it as an autocrine growth factor. The production of IL-1 by malignant EBV-containing epithelial cells indicates that different types of EBV-infected cells produce IL-1. A relationship might exist between EBV and constitutive production of IL-1. The IL-1 produced by the malignant epithelial cells in vivo could stimulate the development of the pronounced T-cell infiltrate observed in NPC tumors.

Animals↗
PubMed1987

Epstein-Barr virus-containing B-cell line produces an interleukin 1 that it uses as a growth factor.

We report the establishment of a spontaneous interleukin 1 (IL-1)-producing subclone derived from the human Epstein-Barr virus (EBV)-containing B-lymphoblastoid cell line (721 LCL) and show that the IL-1 produced by this B-cell subclone is distinct from other types of IL-1. The parental cell line 84.5, a deletion mutant of the 721 LCL cell line, can be induced to produce IL-1 activity when stimulated by certain inducers such as phorbol 12-myristate 13-acetate in the presence of fetal calf serum. From this parental 721/84.5 clone, a subclone, termed 3B6, has been developed. This 3B6 subclone has an immature B-cell phenotype, expresses only HLA class II DP subregion antigens, and spontaneously releases IL-1 in the culture supernatant with relatively few inhibitory molecules under serum-free culture conditions. The 3B6-derived IL-1 was purified from 3B6 conditioned medium with a three-step procedure. The molecular weight of this IL-1 is 13,500, and the isoelectric point values are pH 4.9 and 5.1 without any component focusing near pH 7. The N-terminal amino acid sequence differs markedly from those reported for the two IL-1 species produced by monocytes. The purified material shares several biological properties with monocyte IL-1, since it could induce the proliferation of murine thymocytes, the production of interleukin 2 by phytohemagglutinin-stimulated cloned HSB2 T cells, and the proliferation of human fibroblasts. However, this IL-1 activity could not be blocked by polyclonal anti-monocytic IL-1 antibodies, and, more importantly, it was not pyrogenic in rabbits. Finally, it promotes the growth of B-cell clones derived from the parental 721/84.5 lines in the absence of fetal calf serum, which suggests that it could act as an autocrine growth factor in this Epstein-Barr virus-transformed B-cell line.

B-Lymphocytes↗
PubMed1986

T cell activation via CD2 [T, gp50]: the role of accessory cells in activating resting T cells via CD2.

Monoclonal antibody (MAb) GT2 defines a unique epitope on the CD2 molecule. GT2 triggers T cell mitosis in combination with any MAb directed against 9.6/T11(1) or D66, two previously defined CD2 epitopes. We have shown already that accessory cells (AC) are required for plenary T-PBL activation by any pair of Ab directed against D66 + 9.6/T11(1). In this study, we further investigated their role and found it to vary with the anti-CD2 pair used. When purified T-PBL preparation is used, the level of [3H]TdR incorporation observed with anti-(GT2 + 9.6/T11(1)) Ab was not significant; however, it did prove significant, although greatly reduced, with the other anti-CD2 pairs tested. This was due to qualitative differences in the process of T-PBL activation, and the role of AC, because: anti-(GT2 + 9.6/T11(1)) did not induce IL 2-R expression on purified T-PBL, whereas the other anti-CD2 pairs tested did; anti-(GT2 + 9.6/T11(1)) did not induce detectable IL 2 secretion from purified T-PBL, whereas the other anti-CD2 pairs tested induced a low amount; and anti-CDw18 Ab inhibited the mitogenic effect of anti-(GT2 + 9.6/T11(1)) on PBMC by preventing both IL 2-R expression and IL 2 secretion, whereas anti-CDw18 Ab enhanced the mitogenic effect of the other anti-CD2 pairs tested. Paraformaldehyde-fixed AC fully restored, and recombinant IL 1 partially restored purified T-PBL mitosis triggered by all anti-CD2 pairs tested. To induce IL 2 synthesis, the necessity to cross-link anti-CD2 Ab was demonstrated by coupling one Ab on Sepharose beads and adding the second Ab in the soluble phase: under these circumstances, anti-CD2 pairs were mitogenic solely in the presence of AC. These data can be interpreted as follows. Most anti-CD2 pairs require minimal contact between AC and T-PBL to induce plenary levels of IL 2 synthesis. When anti-(GT2 + 9.6/T11(1)) are used, additional contact is necessary, both for IL 2-R expression and IL 2 synthesis, which would include CDw18 for stabilization. We believe these differences could be related to different conformational changes on the CD2 molecule, depending on the epitope on which the antibodies bind, and could account for different signaling to T cells.

Animals↗
PubMed1986

Purification to homogeneity and NH2-terminal amino acid sequence of a novel interleukin 1 species derived from a human B cell line.

A subclone, referred to as 3B6, derived from a DR-negative EBV-transformed B cell line, has been found to spontaneously produce IL 1. 3B6-IL 1 displays a pI of 5 on FPLC chromatofocusing. It has been purified to homogeneity by a sequence of ion-exchange chromatography and affinity chromatography on procion red agarose. The homogeneous material migrated with an apparent m.w. of 13,500 on SDS-PAGE. The overall recovery of IL 1 activity was estimated at 57%. The final material had a specific activity of 7.8 X 10(6) half-maximal units/mg and represented a 50,000-fold purification. A partial NH2-terminal amino acid sequence has been obtained that is different from those reported from monocytic IL 1. However, this molecule can formally be identified as IL 1 on its spectrum of biologic activities. In addition to inducing the proliferation of murine thymocytes in the co-stimulator assay. 3B6-IL 1 is active on both human T and B cells, respectively, in inducing IL 2 synthesis by cells from a subcloned HSB 2 line and promoting the proliferation of anti-IgM-stimulated human peripheral blood B lymphocytes. Furthermore, 3B6-IL 1 acts as a growth factor for normal human fibroblasts and for the 3B6 line itself. However, 3B6-IL 1 is not pyrogenic in rabbits. Thus, the 3B6 cell line was shown to produce a new molecular species of IL 1, with respect to its NH2-terminal sequence, which shared all of the studied biologic activities of monocytic IL 1 except for pyrogenicity.

Amino Acid Sequence↗
PubMed1986

A 93-kDa glycoprotein expressed on human cultured monocytes and dendritic reticulum cells defined by an anti-K562 monoclonal antibody.

An IgG2a monoclonal antibody, referred to as 12B1 and raised against the K562 cell line, reacted with adherent monocytes maintained in culture for several days but not with bone marrow or peripheral blood cells including freshly isolated monocytes. Among human leukemic cell lines, 12B1 reacted essentially with the promyelocytic HL60 cell line. 12-O-Tetradecanoylphorbol 13-acetate treatment, but no other differentiation inducer, strongly enhanced its reactivity on K562, HL60 and the histiocytic U937 cell line. Immunoperoxidase staining of sections of normal human tissues showed that 12B1 specifically recognized dendritic reticulum cells in germinal centers of lymph nodes, spleen and tonsils. The 12B1-detected antigen is a highly glycosylated polypeptide of an apparent molecular mass of 93-86 kDa. The 12B1 antigen appears to be a new glycoprotein marker shared by adherent monocytes and dendritic reticulum cells. The association of the 12B1 epitope with cells which present antigen and/or exert accessory function suggests that this molecule could play a role in these activities.

Antibodies, Monoclonal↗
PubMed1986

Phenotypic characterization of Ewing sarcoma cell lines with monoclonal antibodies.

The histogenesis of Ewing sarcoma, the second most frequent bone tumor in humans, remains controversial. Four Ewing cell lines were analyzed by immunological methods. A panel of antibodies directed to T, B, and myelomonocytic markers gave negative results. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. Ganglioside GD2, a marker of neuroectodermal tissues and tumors, was present on all lines. These were also stained by the mouse monoclonal antibody HNK-1, which detects a carbohydrate epitope present on several glycoconjugates of the nervous system, including two glycoproteins, the myelin-associated glycoprotein and the neural cell-adhesion molecule (N-CAM), and an acidic glycolipid of the peripheral nervous system. The P61 monoclonal antibody, which reacts with a peptide moiety of N-CAM, and a rabbit antiserum, raised to purified mouse N-CAM and not recognizing the HNK-1-defined epitope, were also reactive. By contrast, all antibodies specific for hematopoietic cell surface antigens were totally negative. Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin. The recent finding that the human N-CAM gene is located at the vicinity of the breakpoint on chromosome 11 indicates that it might be involved in genetic rearrangements occurring in this region.

Antibodies, Monoclonal↗
PubMed1986

Natural killer susceptibility of human cells may be regulated by genes in the HLA region on chromosome 6.

Natural killer (NK) cells exist in each individual in the absence of any intentional immunization. They are able to kill a wide range of targets from tumoral as well as from normal origin. However, their exact physiologic role is not clearly understood. In this study we report results about a human Epstein-Barr virus-transformed B-cell line from which variants perturbed in the expression of HLA molecules have been derived. Our results indicate that in these cell lines an inverse relationship exists between expression of HLA antigens and susceptibility to NK lysis. The original cell line is highly resistant to NK lysis. On the contrary, the variant perturbed in class I antigen expression is highly susceptible. Variant perturbed in class II antigen expression is intermediate in susceptibility. Interferon, which induces HLA class I expression and NK resistance in the unrelated classical K-562 target cells, does not change either HLA expression or NK susceptibility in the variant cell lines. The difference between the original cell line and the variants does not reside in the ability to be bound by NK effectors. Our results suggest a different role for HLA molecules. By some unknown mechanism discussed here, the presence of HLA molecules at the surface of a cell would prevent this cell from being killed by NK cells. The loss of this "good health" signal would lead to the elimination of the cell through NK lysis.

Antigens, Surface↗
PubMed1986

[Histo-prognostic classification of undifferentiated carcinoma of nasopharyngeal type. Importance of the study of the stroma].

A total of 102 cases of undifferentiated carcinoma of nasopharyngeal type (UCNT) were reviewed to attempt their classification into histologic forms of different prognosis. Each slide reviewed was evaluated for predominant tumoral tissue architecture, and the quality, amount and topography of the stroma. Immunoperoxidase studies in 80 cases allowed definition of the immunologic profile of the lymphoplasmocytic stroma. For equivalent clinical stages, the different histologic types are defined as a function of the architecture: cordonal or diffuse, compact or fragmented; these forms, when combined with cytologic characteristics and quality of stroma distinguished 3 microscopic groups of different evolution. The fragmented diffuse forms appear to have the best prognosis (85.5% survival at 5 years), the compact cordonal forms the worse prognosis (13.2% survival at 5 years): the intermediate or diffuse compact forms were of fair prognosis (42.8% survival at 5 years). Application of histology to determine prognosis of UCNT should allow future adaptation of treatment (radiotherapy and/or chemotherapy) to each case.

Adolescent↗