1,721,062 research outputs found

    Immunological cross-reactivity between H-2Dk product and DTIC-treated H-2d lymphoma

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    The experiments reported here concern the characterization by techniques of in vitro cell-mediated immunity of the antigens induced by 5-(3,3' dimethyl-1-triazine)-imidazole-4-carboxamide (DTIC) on L1210, a chemically-induced lymphoma of DBA/2 mice (H-2d). This series of experiments with the DTIC-treated L1210 tumour show the presence of an 'H-2D'-like antigen which resembles the Dk gene product/s of the H-2k haplotype

    Functional studies of H-2k-like epitopes on DTIC treated and untreated L1210 (H-2d) clones

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    Following 'in vivo' treatment with 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), murine leukemic cells acquire new antigenic specificities not detectable on parental cells and responsible for the rejection of the tumour by syngeneic hosts. 'In vivo' and 'in vitro' experiments pointed out an immunological cross reactivity between DTIC treated and untreated lines. Furthermore, specific CTLs raised against DTIC treated L1210 tumour cells (H-2d) were cytotoxic for H-2k target cells. The aim of this study is to investigate whether the H-2k cross reactivity displayed by L1210/DTIC is related to the drug treatment rather than due to an antigen already present in the parental line and maintained after treatment. Cloned cells from L1210, obtained by limiting dilution 'in vitro', were recloned 'in vivo' and then treated with DTIC. Syngeneic and allogeneic CTLs raised 'in vitro' against parental and treated clones showed lytic activity against H-2k target cells. Treated and untreated clones were then checked for the presence of H-2k-like determinants using monoclonal antibodies. One of these, HB-53 (IgG2bKkDk) was highly positive with all the clones tested in binding assay using iodinated Fab anti-mouse Ig, fluorescence and FACS analysis. Others displayed a low reactivity against both treated and untreated clones without significant differences. After neuraminidase treatment of two clones (D and D/DTIC), the H-100.5 (anti H-2Kk)-reactive epitope was dramatically exposed on the DTIC tumour cells but not on the parental clones. These data suggest that the H-2k cross reactivity is related to the presence of a TAA that is maintained after treatment.(ABSTRACT TRUNCATED AT 250 WORDS

    Changes in H-2 antigen expression on a murine spontaneous leukaemia (K36) detected by cell-mediated cytotoxicity assay

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    Cellular cytotoxicity experiments were done to test the potential of the extra H-2 antigenic specificities on the K36 spontaneous leukaemia as targets. In addition, experiments were performed to rule out the possibility that the target determinants could be normal cross-reacting alloantigens, e.g., T1, Qa, non-H-2 and previously undetected H-2 public specificities, which are more readily detectable on tumours than on normal cells. We used F1 hybrid mice, in which one parent was of the strain of origin of the tumour (K36) and the other parent of the B10 congenic series, i.e., (AKR x B10)F1. These cells were stimulated by lymphoid cells from other B10 congenic strains, B10.A and B10.D2, and tested against the test tumour K36 and several PHA blast controls. Several K36 sublines as well as a cloned line of K36 (K36.16) were used and significant cytotoxicity against an H-2(d)-like target on these tumour cells was obtained. These data exclude the possibility of a cross-reactive alloantigen, e.g., undetected H-2 public specificity, or differentiation antigens. These results with the K36 tumour were consistent with our immunochemical studies (see Schmidt & Festenstein, 1980) and were confirmed and extended by cold target inhibition experiments. In these experiments, B10.BR cells were sensitized by B10.D2 lymphoid cells and tested against B10.D2(51chromium-labelled PHA blasts). Two kinds of normal unlabelled lymph node suspensions as well as the K36.16 tumour cell suspension were used. Significant specific inhibition of between 19% and 40% was obtained using K36 and between 23% and 37% using B10.D2 (positive control). AKR cells (negative control) in contrast were unable to reduce the percentage specific cytotoxicity. Since it was already known that the H-2K(k) gene products are missing from this tumour (Schmidt & Festenstein, 1980), it was of interest to test whether cytotoxic effectors directed against the H-2k(k) gene products were able to kill the K36 tumour. Accordingly, B10.D2 lympoid cells were sensitized to B10.BR (C3H.OH) and B10.A targets, respectively, and tested against K36 and appropriate controls. Only weak killing was observed when sensitization was effected against the K end of the H-2(k) haplotype (i.e., using B10.A as the sensitizing cell) but strong and significant cytolysis was found when the sensitization was against the whole H-2(k) haplotype or against the H-2D(k) gene product. These results were confirmed by cold target inhibition studies. These experiments provide further indications for the H-2(d)-like characteristics of these allodeterminants. We have already excluded some of the possible explanations for these findings (i.e., cross-reactions with H-2 and non-H-2 normal specificities). The cold target inhibition experiments rule out non-specific viral effects. Thus, we favour an alteration in regulatory genes leading to repression of the H-2K(k) product and derepression of the H-2D(d) product, but cannot formally rule out highly cross-reactive H-2-like virally encoded determinants

    DTIC xenogenized lines obtained from an L1210 clone: clonal analysis of cytotoxic T lymphocyte reactivity

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    Antineoplastic compounds can induce on tumour cells new antigens that undetectable on parental cells and which are transmissible as a genetic character. In this study mouse leukaemia L1210 was cloned in vitro by limiting dilution and one cloned line was recloned in vivo. Four subcloned tumour cell lines (A,D,R,S) were xenogenized in vivo by DTIC treatment (A/DTIC, D/DTIC, R/DTIC, S/DTIC) following a schedule previously described. Up to 10(7) cells of these xenogenized subclones, injected i.p., were rejected by syngeneic hosts, although they grew in immunosuppressed hosts. The DTIC treated subclones were lysed by in vivo-primed, in vitro-restimulated (with the relevant subclone) lymphocytes. The cytotoxic lymphocyte activity was not strictly specific since parental, DTIC-untreated cells were also lysed, although less efficiently. CTL directed against the D/DTIC subclone were cloned by limiting dilution. Ninety-four CTL clones were assayed against L1210 subcloned cells, DTIC-treated and untreated, and against different murine tumours (syngeneic or allogenic). Three specific antigens could be identified in the 51Cr release assay. The DTIC subclones expressed one antigen that was specifically recognized by a set of CTL clones. A number of CTL clones were able to lyse the L1210 subcloned cell exclusively, targetting a tumour-associated antigen that did not appear to be modified in the DTIC-treated subclones. A third antigen was demonstrated in the parental and DTIC treated D subclone. On the basis of these results it was postulated that there was at least one common DTIC-inducible antigen specific and reproducible within an identical cell population. Moreover, DTIC treatment did not modify histocompatibility antigens or TAA pre-existing in L1210 cells. The findings discussed here provide new information about permanent xenogenization of tumour cells, which might be exploited for experimental chemo-immunotherapy of cancer

    Invitro Induction of Immunological-tolerance

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    IL-2 was previously shown to induce cytotoxic effectors with a broad spectrum of target specificities in thymus and spleen cell cultures. This study was designed to show whether T cells activated by H-2 allogeneic cells in MLC or by syngeneic tumor cells in MLTC are also potential targets for these cytotoxic effectors. We found that thymocytes activated in vitro for 5 days by rIL-2 were capable of killing tumor cells as well as activated T cells. Thymocytes activated by IL-2 were accordingly utilized as a means of effecting clonal deletion of T cells activated by H-2 allogeneic target cells in MLC. To establish whether the unresponsiveness is specific. IL-2-activated thymocytes were added as third party cells to MLC and MLTC. The results showed that both T cells, proliferating in response to H-2 allogeneic cells, and CTL, reactive against syngeneic tumors or H-2 allogeneic cells, are eliminated from the T cell pool. Only alloreactive T cells are specifically eliminated in MLC by IL-2-activated thymocytes, as the remaining T cells are capable of proliferating and generating CTL in response to antigenically unrelated third party allogeneic cells. The possibility that unresponsiveness might be due to soluble factors was ruled out by studies performed with a diffusable "chamber insert" culture system. The results provide evidence that IL-2-activated thymocytes induce in vitro T cell tolerance

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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