1,721,000 research outputs found
Monoclonal-antibody Against Ifn-gamma Inhibits Moloney Murine Sarcoma Virus-specific Cyto-toxic Lymphocyte-t Differentiation
No full textThe role of autochthonous IFN- production was evaluated in immune reactions to Moloney murine sarcoma virus (M-MSV)-induced tumors which are characterized by spontaneous regression mainly caused by virus-specific CTL activity. A functional IFN- depletion, induced by repeated administration of mAb anti-IFN- at the site of virus inoculation, prevented tumor regression in M-MSV-injected mice. Moreover, this antibody inhibited in vitro both proliferation and differentiation of M-MSV-specific T lymphocytes obtained in bulk cultures, but not growth and lytic activity of the already differentiated virus-specific CTL clone CHM-14 stimulated with rIL-2 and relevant tumor Ag. In addition, in mice receiving mAb treatment the frequency of M-MSV-specific CTL precursors, evaluated by means of limiting dilution analysis, was strongly reduced in comparison with that of control mice injected only with virus. Because CTL secrete IFN- following antigenic stimulation, the possibility that non-T effector cells recruited by this lymphokine might mediate tumor regression was also considered. Adoptive immunotherapy experiments, performed in T cell-deficient (Tx + BM) and in sublethally irradiated mice, demonstrated that transfer of CHM-14 CTL clone, which secretes IFN-, was able to counteract M-MSV tumor growth despite the local mAb anti-IFN- treatment which may have prevented host cell recruitment. Moreover, repeated local rIFN- inoculations in Tx + BM mice did not counteract M-MSV tumor progression, thus confirming that other IFN- properties such as non-T cell recruitment, antiviral or anti-proliferative IFN- activities have little or no relevance when M-MSV-specific CTL are lacking. On the whole, these results indicate that in M-MSV-injected mice, tumor enhancement after mAb anti-IFN- treatment is principally caused by impaired differentiation of virus-specific CTL precursors
Invitro Induction of Immunological-tolerance
No full textIL-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
Therapeutical effect of 4'-deoxy-4'-iododoxorubicin-loaded LAK cells in mice bearing lung metastases.
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Methoxymorpholinyl doxorubicin (PNU152243) antitumor activity in vivo: Involvement of cytochrome P450 (CYP)-mediated drug metabolism
No full textRole of anti-LFA-1 and anti-ICAM-1 combined MAb treatment in the rejection of tumors induced by Moloney murine sarcoma virus (M-MSV).
No full textWe investigated the effect of combined treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (MAbs) in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which spontaneously regress due to the generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated systemic administration of both MAbs to M-MSV-injected mice enhanced tumor growth and delayed regression, while treatment with a single MAb had a similar, though less pronounced, effect. The immune depression achieved could not be attributed to lymphocyte depletion, because no reduction in the total number of leukocytes was detected in the peripheral blood or spleen of these mice. However, anti-LFA-I MAb, alone or in combination with anti-ICAM-I MAb, prevented lymphocyte homing in tumor-draining lymph nodes. Cytofluorimetric analysis disclosed a profound down-modulation of LFA-I and ICAM-I molecule expression on T cells following in vivo MAb treatment. Moreover, in anti-LFA-I MAb-treated mice, the receptor was coated to saturation, while anti-ICAM-I MAb treatment brought about ICAM-I-molecule-coating levels below saturation. Evaluation of M-MSV-specific CTL precursor (p) frequency in lymphoid organs of mice receiving combined MAb treatment showed that CTL generation was greatly reduced 10 days after M-MSV injection, and returned to control levels by day 15. Our findings indicate that systemic administration of MAbs to LFA-I and ICAM-I molecules brings about a strong immune suppressive effect which is mainly due to a block in T-lymphocyte re-circulation, and activation by tumor cells. However, this immune-depressive effect is only temporary, and strictly dependent on continuous MAb administration. Thus, our data suggest that treatment with anti-LFA-I and anti-ICAM-I MAbs combined is unable to induce T-cell tolerance in a highly immunogenic system
Role of adhesion molecules in the immune reaction to M-MSV-induced tumors.
No full textWe have investigated the in vivo role of 2 different adhesion molecules, LFA-1 and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)-induced tumors, which undergo a peculiar spontaneous regression due to generation of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the site of virus inoculation, enhanced tumor growth and delayed regression, while i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew progressively and caused host death. Evaluation of the immunological response in MAb-treated mice showed reduced generation of virus-specific CTL precursors (p) in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally treated mice overlapped with that of control mice injected with virus only. FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and lacked cytotoxic activity when assayed against target cells bearing relevant tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low frequency of CTLps was detected in lymph nodes draining the tumor area, and within the tumor. Our results indicate that enhanced tumor growth, depending on the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL-14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph nodes and subsequently by the lack of generation of tumor-specific CTLs
Responses of Mouse Lymphocytes To Extracellular Adenosine 5'-triphosphate (atp) - Lymphocytes With Cyto-toxic Activity Are Resistant To the Permeabilizing Effects of Atp
No full textThe effects of extracellular ATP on plasma membrane permeability in mouse lymphocytes were studied with plasma membrane depolarization, uptake of ethidium bromide, and release of lactate dehydrogenase as indicators of increased permeability. Extracellular ATP induced sustained depolarization of plasma membrane potential as well as uptake of low m.w. fluorescent markers in mouse lymphocytes derived from thymus and spleen, and in two lymphoma lines YAC-1 and MBL-2. The fully ionized form ATP4- rather than MgATP2- mediated the increased permeability of the plasma membrane. Although prolonged exposure to exogenous ATP ultimately lysed the lymphocytes, two CTL populations (CHM-14 clone and CTLL-2 line) and IL-2-treated spleen lymphocytes with unrestricted killing activity were highly resistant to the permeabilizing action of extracellular ATP at all concentrations tested. In addition, CTL derived from primary immune peritoneal exudate and enriched by in vitro culture for 5 days in the presence of specific stimulator cells were also resistant to this permeabilizing effect. These findings show that exogenous ATP has a lytic effect on mouse lymphocytes but not on CTL, and suggest a role for ATP in cell-mediated cytotoxicity
Variations on the Author
Full text link“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
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