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Biomedical subjects

G Biasi

Publications and source records attributed to G Biasi.

At least 55 records · Page 3Linked to original sources
PubMed1989

[Antalgic efficacy of tiaprofenic acid in models of acute rheumatic pain].

Twenty patients suffering from acute lumbosacral syndromes (Group A) and eight patients suffering from acute gout (Group B) were treated with parenteral tiaprofenic acid (TA). In Group A TA was administered for 7 days at the dosage of 400 mg/daily for the first four days (1 200 mg vial i.m. in the morning, 1 in the evening), from the 5th to the 7th day with 200 mg/daily (1 vial in the evening) and, in Group B, TA was administered for 6 days at the dosage of 600 mg on the first day, (with 1 vial/8 hours of TA 200 mg by parenteral route) the 2nd and 3rd day with 1 vial/12 hours and the 4th and 6th day with 1 vial/daily in the evening. TA was found to be active on all clinical parameters evaluated. The tolerability was also good: only 4 patients with acute lumbosacral syndrome suffered from local pain.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Resistance of lymphokine-activated T lymphocytes to cell-mediated cytotoxicity.

We observed that lymphokine-activated T lymphocytes, obtained in short- and long-term cultures following stimulation with recombinant interleukin-2 (rIL-2), are resistant to cell-mediated cytotoxicity. In particular, lymphokine-activated killer (LAK) cells do not undergo self-lysis or lysis by alloreactive cytotoxic T lymphocytes (CTL), in line with recent reports concerning CTL clones. Similar findings were further confirmed in a lectin-dependent cell cytotoxicity assay. LAK cell lysis resistance was not due to an inability to recognize itself, since inactivated LAK cells used as cold competitors inhibited tumor cell lysis in a dose-dependent manner. In contrast, the addition on Day 0 of irradiated LAK cells or alloreactive CTL, as well as a CTL clone having LAK-like activity to rIL-2-stimulated cultures abrogated or strongly reduced LAK cell generation. Therefore, LAK cell precursors were most likely susceptible to the lytic activity of differentiated cytotoxic cells, as no inhibition was detected when cell to cell contact was prevented by using a diffusible chamber culture system. These findings, on the whole, suggest that the emergence of the lysis-resistant phenotype is most likely the result of a selective process occurring in vitro that leads to the elimination of lysis-susceptible lymphocytes present in culture.

Animals↗
PubMed1989

In vitro induction of immunological tolerance.

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.

Animals↗
PubMed1988

Monoclonal antibody against IFN-gamma inhibits Moloney murine sarcoma virus-specific cytotoxic T lymphocyte differentiation.

The 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.

Animals↗
PubMed1985

Reversibility of lymphokine-induced NK-like activity in virus-specific cytotoxic T-lymphocyte clones.

A limiting dilution microculture system, supplemented with a source of interleukin-2 (IL-2), was employed to evaluate the frequency of Moloney-murine leukaemia/sarcoma virus (M-MuLV/M-MSV)-specific cytotoxic T-lymphocyte precursors (CTL-p) which also exhibited NK-like activity. Spleen cells, obtained from M-MuLV/M-MSV regressor mice, were restimulated in bulk secondary mixed leucocyte-tumour cell cultures (MLTC), and subsequently plated in a culture medium supplemented with two different supernatants (SN) produced following PMA-stimulation of the same EL-4 thymoma cell line. SN 20, obtained from the cell line maintained in vitro, contained IL-2 and only negligible amounts (less than 3 U/ml) of interferon (IFN), while SN 19, obtained after passage of the ascitic form of EL-4 thymoma in syngeneic mice, contained both IL-2 and IFN in high titres. The frequency of CTL-p specific for MBL-2 lymphoma cells was high and comparable in cultures supplemented with both SN (1/2 X 84 cells and 1/2 X 40 cells, respectively), while the frequency of CTL-p directed against NK-susceptible YAC-1 target cells was low in SN 20 (1/90 cells) and high in SN 19 (1/5 X 40 cells). An analysis of individual microcultures established at low cell dose (1 cell/well) indicated that specific and NK-like activity could be ascribed to the same precursor cells. Furthermore, using different long-term CTL clones, we observed that, after passage in SN 20, double-reactive clones gradually lose the capacity to lyse NK-susceptible targets, while most of MBL-2 specific clones acquired NK-like activity following a few passages in SN 19. Therefore, the induction of NK-like activity is reversible and may be modulated by soluble factors present in supernatant in which CTL clones are maintained. Double-reactive clones were unable to lyse NK-resistant allogeneic tumour cells or normal syngeneic blast cells. A few clones cross-reacting with H-2d alloantigens also exhibited NK-like activity when maintained in SN 19. The different pattern of CTL clone activity was associated with a morphological change in the clones themselves: the acquisition of double activity was accompanied by an increase in cell size and the appearance of numerous cytoplasmic granules. All CTL clones were phenotypically Thy-1+ and Lyt-2+ on indirect immunofluorescence and complement-dependent cytotoxicity investigation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Reduction in precursors of cytotoxic T lymphocytes and of cells with natural killer-like activity in spleens of cyclophosphamide-treated mice.

The effect of cyclophosphamide (CY) on precursors of cytotoxic T lymphocytes (CTL), specific for Moloney-murine leukemia virus (M-MuL V)- induced antigens, and on the precursors of cells having natural killer (NK)-like activity was studied by means of limiting dilution assay. Pre-treatment with a single CY dose of 100 mg/kg induced a marked reduction not only in the total spleen cell number but also in the frequencies of M-MuL V-specific CTL, and NK-like cell precursors. Maximal effect was obtained 2 days after CY injection, and a gradual recovery in both total spleen cell number and cytotoxic activity was achieved by day 12. These results confirm that CY exerts a strong but transient immunodepressive effect.

Animals↗
PubMed1984

Virus-specific T cell response prevents lymphoma development in mice infected by intrathymic inoculation of Moloney leukaemia virus (M-MuLV).

Previous work on mice neonatally injected with Moloney-murine leukaemia virus (M-MuLV) had shown that T cell lymphoma development correlates with virus infection of lymphoreticular cells (T and B lymphocytes and macrophages) as well as with a lack of generation of virus-specific cytotoxic T lymphocytes (CTL) due to clonal deletion of CTL precursors. In the present report, viral antigen expression and T cell response in mice injected as adults with M-MuLV intrathymus (i.t.) was investigated. Only thymic and splenic T lymphocytes from these mice express virus-induced antigens since they were lysed by virus-specific CTL, and stained by anti-M-MuLV fluorescent serum. In addition, the percentage of M-MuLV-infected T cells increased with increasing post- inoculation times. However, these mice could mount a strong cellular immune response against M-MuLV-infected cells, as detected by massive mixed leucocyte tumour cell culture and by evaluation of virus- specific CTL precursor frequency. Finally, i.t. injected mice were not viraemic and did not develop lymphomas during an observation period of 12-15 months. These data, in contrast with the recent hypothesis that T cell lymphoma development depends on a chronic stimulation of virus-specific T lymphocytes, indicate that the cellular immune response is sufficient for prevention of neoplastic transformation, despite a persistent viral infection of the thymus and peripheral T lymphocytes.

Animals↗
PubMed1983

Protection from spontaneous lymphoma development in SJL/J(v+) mice neonatally injected with dualtropic SJL-151 virus.

In previous studies dualtropic type C retroviruses were isolated from spontaneous B-cell lymphomas that appear with a high incidence in SJL/J(v+) mice. In this report the possible in vivo pathogenic effect of one cloned dualtropic isolate, designated SJL-151, was investigated. SJL/J(v+) and CBA/J mice, neonatally injected with SJL-151 alone or in combination with SJL-ecotropic virus, were initially studied for virus recovery 4-8 weeks after infection by spleen cell cocultivation with mouse SC-1 and mink ML indicator cells. Whereas ecotropic virus was easily detected in treated mice, dualtropic virus was recovered only from the spleen cells of animals coinfected with SJL-ecotropic and SJL-151 viruses. With a panel of monoclonal antibodies the recovered dualtropic viruses showed an antigenic profile similar to that of the originally injected SJL-151 virus. Whereas virus-injected mice did not show lymphoma induction or acceleration, a remarkable decrease in spontaneous lymphoma incidence was observed in the SJL/J(v+) mice receiving SJL-151 virus alone. A virus-specific antibody response was detectable in these mice, but a similar serum reactivity was also demonstrated in SJL/J(v+) mice coinfected with SJL-ecotropic virus and SJL-151 virus, which subsequently developed lymphomas with the usual high incidence, thus rendering an antibody-mediated protective mechanism untenable. The possibility of viral interference, as an alternative mechanism for lymphoma prevention, is discussed in view of the findings that persistence of SJL-151 virus or de novo generation of dualtropic virus did not occur in aged SJL/J(v+) mice injected neonatally with SJL-151 virus alone.

Age Factors↗
PubMed1983

Role of accessory cells in the induction of a secondary cytotoxic response to Moloney murine sarcoma virus-induced tumors.

The role of Ia-positive accessory cells in the generation of a secondary cytotoxic response to tumor-associated antigens induced by Moloney murine sarcoma virus (M-MSV) was evaluated. Spleen cells from M-MSV-immune A.TL mice, depleted of accessory cells by anti-Iak serum plus C treatment and stimulated in secondary mixed leukocyte tumor cell culture (MLTC) with syngeneic Ia-negative A6ATL Moloney leukemic cells, failed to generate virus-specific cytotoxic T lymphocytes (CTL). CTL generation in Ia-depleted MLTC may be reconstituted by the addition of nonimmune Ia-positive spleen or peritoneal cells obtained not only from syngeneic A.TL but also from I-incompatible A.TH mice. This lack of restriction observed in accessory cell function is explained in terms of a nonspecific mechanism of CTL triggering mediated by soluble factors. In fact, IL 2 as well as supernatants obtained from I region-incompatible cultures consisting of M-MSV-immune, Ia-depleted A.TL spleen cells and A.TH Ia-positive cells, reconstituted secondary virus-specific CTL generation.

Animals↗
PubMed1983

Selective failure of accessory cell function in Moloney murine leukemia virus-tolerant mice.

Accessory cell activity of spleen cells from M-MuLV neonatally injected (tolerant) mice was studied to evaluate their ability to take part in in vitro CTL generation against tumor-associated antigens induced by M-MSV. In contrast with accessory cell activity in normal spleen cells, spleen cells from M-MuLV-tolerant mice are unable to reconstitute the in vitro virus-specific CTL generation of M-MSV immune, Ia-depleted spleen cells. A selective defect seems to characterize M-MuLV-tolerant mice as their spleens constitute a good source of accessory cells for alloantigen CTL generation.

Animals↗