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G Klein

Publications and source records attributed to G Klein.

At least 523 records · Page 29Linked to original sources
PubMed1988

Further studies on chromosome 15 trisomy in murine T-cell lymphomas: mapping of the relevant chromosome segment.

Trisomy 15 is the most common chromosomal aberration in murine T-cell lymphomas. The relevant chromosomal region responsible for the growth advantage of the 15-trisomic cell has not been defined. In order to map this region, we have induced thymic lymphomas by chemical carcinogens (DMBA or MNU) in mice with 2 different constitutional translocations, T(7;15)9H homozygotes and [T(7;15)9H X T(5;15)4Ad] FI hybrids. Twenty-two tumors developed in 90 carcinogen-treated mice. Among the 14 cytogenetically analyzed thymic lymphomas, 4 were diploid and 5 were aneuploid, with no chromosome-15-associated changes. Five lymphomas showed partial duplication of chromosome 15. Four of them have duplicated the segment distal to the C/DI breakpoint of T9H, while the 5th carried an interstitial duplication of the D2 sub-band of the T(7;15) translocation chromosome. These findings suggest that the duplication of the D 2/3 region, known to contain the c-myc and the pvt-I genes (Banerjee et al., 1985), rather than other regions of chromosome 15, contributes to the development and/or progression of murine T-cell leukemias.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Effects of dimethyl sulfoxide treatment on H-2 expression and susceptibility to NK- or cytotoxic T-lymphocyte-mediated lysis of the YAC-1 lymphoma and its beta 2-microglobulin-deficient variant.

The effects of dimethyl sulfoxide (DMSO) on H-2 expression and susceptibility to NK- and cytotoxic T-lymphocyte (CTL)-mediated lysis in the murine T-cell lymphoma YAC-1 and its beta-2-microglobulin (beta 2m)-deficient variant were studied. Fluorescence-activated cell sorter analysis revealed induction of H-2Kk and beta 2m 3 days after culture of YAC-1 with DMSO, whereas optimal H-2Dd induction required more than 1 week. H-2Kk and H-2Dd induction by DMSO was equal to pretreatment of YAC-1 cells with 50-100 and 10-20 U/ml interferon (IFN)-gamma, respectively, but the T-cell differentiation antigens Lyt-1, Lyt-2, Thy-1, and L3T4 remained unaffected. DMSO protected YAC-1 cells from NK lysis as efficiently as 10-20 U IFN/ml, whereas susceptibility to anti-H-2a-, H-2Kk-, and H-2Dd-specific CTLs was augmented as in IFN-treated YAC-1 cells. In contrast, the beta 2m-deficient variant, which remained H-2 negative at the cell surface after DMSO treatment, also remained NK sensitive. Thus DMSO can induce H-2 expression and alter the sensitivity of murine lymphoma cells to different effector cells.

Animals↗
PubMed1988

[Assessment of the genotoxic risk caused by the gyrase inhibitor ofloxacin using sister chromatid exchange rate analysis].

Ofloxacin (Tarivid) is a 4-quinolone of the latest generation. Its mechanism of action is the inhibition of the enzyme gyrase which plays a central role in the bacterial DNA-metabolisms. Thus Ofloxacin blocks the reading of the chromosomes and impairs the cell's function and ability to reduplicate leading to eradication of the pathogens. The genotoxicity of Ofloxacin was assessed by analyses of SCE (sister-chromatid-exchange-rates), which is a sensitive and qualitative parameter indicating chromosomal damages. In vitro no change of the SCE-frequencies could be demonstrated in human lymphocytes; in vivo, however, a slight influence not be excluded, which is also true for eventual additive on synergistic effect with other mutagenic factors.

Dose-Response Relationship, Drug↗
PubMed1988

Selective acceptance of MHC class I-deficient tumor grafts in the brain.

H-2-deficient (H-2-) tumor variants were accepted equally well compared with H-2+ wild-type cells in the brain of syngeneic mice, while the H-2- cells were selectively eliminated when inoculated extracranially. This indicates a specific absence or suppression of the defense against MHC class I-deficient cells in the brain, suggested to be mediated by NK cells. In contrast, T cell-mediated immune reactions could clearly be detected in the brain under the same experimental conditions. This was shown in control experiments where H-2+ tumor cells were rejected from the brain of preimmunized or allogeneic mice. The present findings may be important for the understanding of neurotropic virus infections, immunology and immunotherapy of brain tumors, as well as for the growing interest in tissue grafting within the central nervous system.

Animals↗
PubMed1988

Afferent and efferent cellular interactions in natural resistance directed against MHC class I deficient tumor grafts.

H-2-deficient variants, selected from the murine lymphoma RBL-5, were recently shown to be less tumorigenic in syngeneic mice compared with the corresponding H-2-positive wild-type cell line. The present study focused on the detailed cellular interactions leading to the specific rejection of H-2-deficient cells in vivo. In vivo experiments with mixed tumor inocula, measuring either tumor outgrowth or rapid elimination, showed that the presence of H-2-positive lymphoma cells did not suppress the rejection of H-2-deficient cells. Conversely, H-2-deficient cells did not activate a rejection of H-2-positive cells. H-2-deficient cells were selectively eliminated even when they were present in a 10-fold excess compared with the H-2-positive lymphoma cells in the same inoculum. In vitro, H-2-deficient cells were more sensitive to killing by spleen cells from mice treated with interferon or natural killer-inducing agents. The presence of cold H-2-deficient cells did not activate the killing of H-2-positive cells, and H-2-positive cells did not inhibit killing of H-2-deficient cells. Such mixing experiments revealed a more efficient cold target inhibition by the H-2-deficient cells, although no difference was seen between these and the H-2-positive wild-type cells in target binding assays. When Thy-1.2+, nylon wool adherent or phagocytic populations were removed from normal spleen effectors, the difference in spontaneous cell-mediated cytotoxicity between the H-2-deficient and the H-2-positive cells persisted. This result was also obtained when spleen cell effectors from nude mice or asialo GM1+ effectors, positively enriched by fluorescence-activated cell sorter, were used. The results show that the selectivity in the rejection of H-2-deficient cells was not determined in the afferent arm alone. The present data fit with a previously proposed model where natural killer cells would bind equally well to both major histocompatibility complex class I negative and class I positive target cells, but only the latter would be able to present a postbinding inhibitory signal allowing them to escape killing which results in outgrowth in vivo and poor cold target competition in vitro.

Animals↗
PubMed1988

Proteins in normal and malignant cells, cross-reacting with the latent membrane protein encoded by Epstein-Barr virus.

Human B lymphocytes transformed by infection with the Epstein-Barr virus (EBV) express a new membrane protein of 63 kDa (latent membrane protein, LMP) encoded by the virus. The function of this protein in the virus-cell interaction is not known. In this work we have identified in EBV- human and mouse cell molecules which cross-react with LMP. Two types of reagents were employed: (a) antibodies against LMP-derived synthetic peptides, affinity purified from antisera against a fusion protein containing the carboxy half of the LMP molecule and (b) antisera prepared by immunizing rabbits directly with the peptide conjugates. Cross-reactions were determined by radioimmunoblotting experiments. At least six molecules (Mr = 110, 85, 63, 53, 45 and 23 kDa), present in a variety of human cells (peripheral blood lymphocytes, B cell lines and epithelial cell lines) were found to cross-react with the LMP-derived peptides. Cross-reacting proteins were also identified in normal mouse tissues. The specificity of the cross-reacting antibodies was confirmed by inhibition experiments with the corresponding peptide. Furthermore, antibodies eluted from individual bands were shown to bind to the same band when reacted with new blots of the same extracts. Our data suggest that normal cells contain a family of highly conserved proteins cross-reacting with the LMP molecule. If, indeed, these proteins share common functions, their study may lead the way to unraveling the function of LMP.

Animals↗
PubMed1988

Localization of the rat immunoglobulin lambda light chain locus to chromosome 11.

Previous experiments using rat/mouse somatic cell hybrids have localized the rat c-myc gene to chromosome 7 (Sümegi et al. 1983), the rat immunoglobulin kappa locus to chromosome 4 (Perlmann et al. 1985), and the rat immunoglobulin heavy chain locus to chromosome 6 (Pear et al. 1986). Using a similar approach, we now report the localization of the rat immunoglobulin lambda light chain locus to chromosome 11.

Animals↗
PubMed1988

Rat c-raf oncogene is located on chromosome 4 and may be activated by sequences from chromosome 13.

Activated forms of the protooncogene c-raf have been found to transform established lines of rodent fibroblasts after transfection with DNA from several human and rat tumors. Using Southern blot analysis of DNAs from rat x mouse somatic cell hybrids, we have mapped c-raf to rat chromosome 4. An exogenous sequence that was found juxtaposed to c-raf within transforming DNA originally derived from a rat hepatocellular carcinoma was localized to chromosome 13.

Animals↗
PubMed1988

Combined treatment with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha up-regulates the expression of HLA class I determinants in Burkitt lymphoma lines.

Cell lines derived from Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL) have a low or defective expression of polymorphic HLA class I determinants compared to EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin and are resistant to lysis by cytotoxic T lymphocytes (CTL) specific for the corresponding determinants (M. G. Masucci, S. Torsteinsdottir, J. Colombani, C. Brautbar, E. Klein, and G. Klein, Proc. Natl. Acad. Sci. USA 84, 4567, 1987; S. Torsteinsdottir, C. Brautbar, E. Klein, G. Klein, and M. G. Masucci, Int. J. Cancer, 41, 913, 1988). In order to investigate whether this phenotypic trait of the tumor cells can be modulated by agents known to enhance HLA class I antigen expression, pairs of LCL and BL lines were cultured in the presence of recombinant human interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Three low HLA A11 expressor EBV-negative BL lines, DG 75, BL 28, and BL 41, reacted significantly stronger with the anti-HLA A11 monoclonal antibody (Mab) AUF 5.13 after combined treatment with 500 U/ml IFN-gamma and 500 U/ml TNF-alpha. Reactivity with the AUF 5.13 and with other anti-polymorphic class I Mab's was up-regulated also in in vitro EBV-converted sublines of BL 28 and BL 41. The increment of antigen expression depended on the baseline expression in untreated cells. It was largest for the low expressor lines and decreased proportionally to the level of up-regulation induced by EBV conversion. Up-regulation of HLA A11 was accompanied by induction of sensitivity to HLA A11-specific CTLs in BL 28 and its converted subline E95A BL28 while BL 41 and E95A BL 41 remained resistant. The treatment did not affect significantly HLA A11 expression of two EBV-carrying, low HLA A11 expressor BL lines, WW-1-BL and WW-2-BL, and of the EBV-carrying BL 72 line that had a high spontaneous expression. The results suggest that the down-regulation of class I antigen expression is reversible in some but not all BL lines.

Antibodies, Monoclonal↗
PubMed1988

Independent variations of myc amplification, inducibility, maturation, and proliferation states in HL60.

We have investigated the possible relationship between c-myc gene activity and other variable traits in HL60. In a panel of variant lines, a good correlation was observed between myc gene copy number and the level of myc mRNA. There was no correlation between myc amplification or expression and the resistance of the lines to induction of terminal neutrophilic or monocytic differentiation. Therefore, myc mRNA level does not appear to determine the ability of the variant HL60 lines to respond to inducers of differentiation. Flow cytometric analyses of the expression of a differentiation antigen (AGF 4.36) revealed stable negative and positive subpopulations in growing HL60. myc amplification, expression, and inducibility were identical in these subpopulations, suggesting that variation of these traits in HL60 sublines and variants is not due to maturation state differences. myc gene copy number was also identical in transferrin receptor positive (proliferating) and negative (resting) populations. These data contradict the notion that myc amplification has been important in determining the in vitro biological properties of HL60.

Cell Division↗
PubMed1988

Antibodies in human sera against the Epstein-Barr virus encoded latent membrane protein (LMP).

Antibodies reactive with the Epstein-Barr (EBV)-encoded latent membrane protein, LMP, were detected in human sera. Membrane fractions of the EBV-carrying Raji cells and a fusion protein (LMFP), that represents the carboxy part of LMP, were used as antigens. These were assayed by the reduction of the leukocyte migration inhibition (LMI) reaction. Reactivity with LMFP was detected in 10 of 14 sera from patients with Burkitt's lymphoma (BL) and in 3 of 23 sera from healthy EBV-seropositive individuals. The antibody levels were higher in the BL sera. Since the tumor cells do not express LMP, this may be due to the high virus load in the patients.

Antibodies, Viral↗
PubMed1988

Do human renal cell carcinomas arise by a double-loss mechanism?

Combined consideration of a constitutional t(3;8) that was regularly associated with renal cell carcinoma (RCC) within a large family and cytogenetic and restriction fragment length polymorphism studies on sporadic RCC has led to the tentative conclusion that RCC may arise by a similar double-loss mechanism as retinoblastoma and Wilms' tumor. This hypothesis predicts single-hit kinetics for the age distribution of hereditary RCC and two-hit kinetics for sporadic tumors, in analogy with Knudson's original prediction for retinoblastoma and Wilms' tumor. We have compared the age distribution of 51 hereditary and 56 sporadic cases of RCC sampled from the literature. The age-incidence curve of the hereditary RCC is compatible with a single event, whereas the sporadic tumors arise as predicted from a two-hit curve. We therefore suggest that RCC arises by the loss of a recessive cancer gene, probably localized to the short arm of chromosome 3 (in band 3p14.2).

Adult↗
PubMed1988

Surface marker characterization of EBV-carrying cells in blood of healthy seropositive individuals.

We have determined the phenotype of EBV-carrying cells in human blood by establishing spontaneous LCLs from populations selected according to three B cell markers, B1, B2, and 35.1C5. LCLs grew from the B1-positive, B2-positive, B2-negative and 35.1C5-positive population. Thus, EBV-carrying cells in blood of seropositive individuals are restricted to the B cell lineage. These B cells may or may not express the B2 epitope, and they may be derived from the lymph node mantle zone or the splenic marginal zone. These in vivo EBV-carrying cells could enter the viral productive cycle and transform coresident B cells during the initial 3 days in vitro. The characteristic of the LCLs with regard to these 3 B cell markers did not correspond to the original B cell population from which they were derived.

Adult↗
PubMed1988

Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency.

Wild-type strains of Epstein-Barr virus (EBV) can be distinguished on the basis of variations in the molecular weight of virus-encoded, growth transformation-associated proteins. This approach was used to study the persistence of EBV in two seropositive recipients of allogeneic bone marrow transplants. The first patient received marrow from her EBV-seronegative brother, became EBV seronegative after grafting, and remained so for greater than 1200 days. Subsequently, she became infected with a new EBV strain that differed from her pretransplant strain but was indistinguishable from the virus isolated from her husband. The second patient received marrow from his EBV-seropositive brother. This patient showed only a transient decrease in IgG antibodies to EBV capsid antigen. His pretransplant strain differed from the virus of his donor. On days 252 and 915 after transplantation, lymphoblastoid cell lines were grown from the peripheral blood of the patient and were found to carry exclusively the virus of the donor. These results suggest that the latently EBV-infected host cells reside in a cellular compartment that can be destroyed by graft-versus-host reactivity, irradiation, or cytotoxic drugs. Hemopoietic tissue is the most likely candidate.

Adult↗
PubMed1988

BamHI E region of the Epstein-Barr virus genome encodes three transformation-associated nuclear proteins.

Recombinant vectors carrying DNA fragments from the BamHI E region of the B95-8 Epstein-Barr virus (EBV) genome were transfected into COS-1 cells, and the transient expression of EBV-encoded nuclear antigens (EBNAs) was analyzed by using polyvalent human antisera and rabbit antibodies to synthetic peptides. Vector DNA containing two rightward open reading frames in the BamHI E fragment, BERF2a and BERF2b, induced the expression of a nuclear antigen identical serologically and with respect to size to the larger of the two polypeptides previously designated as EBNA4 in B95-8 cells. An antigen corresponding to the smaller polypeptide was induced in cells transfected with constructs that contained two neighboring reading frames, BERF3 and BERF4. This antigen also reacted with a rabbit antiserum to the synthetic peptide 203, deduced from BERF4. Thus, the findings show that the two components of the EBNA4 doublet in B95-8 cells are encoded by separate genes. The antigen encoded by BERF2a and/or BERF2b has been designated as EBNA4 and the antigen encoded by BERF3 and/or BERF4 has been designated as EBNA6. Polyvalent human antisera detected EBNA4 and EBNA6 in 9 of 11 lymphoid cell lines carrying independent EBV isolates. In the remaining two lines, either EBNA4 or EBNA6 was not detectable.

Animals↗