PubMed Health⌕ Search

Biomedical subjects

E Garaci

Publications and source records attributed to E Garaci.

At least 109 records · Page 6Linked to original sources
PubMed1983

Modulation of natural killer (nk) cell activity during FLV-P virus infection of mice.

We analyzed the effects of a polycythemic substrain of Friend leukemia virus, i.e. the FLV-P virus, on splenic NK activity of DBA/2 susceptible mice. One day after virus injection a significant increase of NK activity was found, which persisted until day 10. On the other hand, 14-21 days after virus injection a marked and significant depression of activity was measured. This depression was associated with the appearance of suppressor cells able to inhibit the lytic activity of untreated splenocytes when mixed in vitro in the 4 h 51Cr-release assay. The suppressor cell population was insensitive to treatment with anti-Thy 1.2 plus complement, was adherent to Sephadex G-10 and nylon, but did not adhere to plastic, suggesting it is neither a T-cell nor a typical macrophage. The possible relevance of NK activity modulation in relation to the induction of leukemia is discussed.

Animals↗
PubMed1983

Modulation of endogenous prostaglandins by thymosin-alpha 1 in lymphocytes.

The effects of thymosin-alpha 1 on the stimulation of specific release of prostaglandin E2 (PGE2) from splenic lymphocytes and thymocytes were studied. Experiments were also performed to study in parallel the absolute levels of thymosin-alpha 1 in the blood and the induction of serum FTS activity and of azathioprine sensitivity of spleen cells from adult thymectomized (ATx) mice. A significant difference in the release of PGE2 between normal splenocytes and splenocytes from ATx mice was observed. Thymosin-alpha 1 at certain concentrations was able to stimulate PGE2 release from lymphocytes of ATx mice while inhibiting release in lymphocytes of normal mice. Also, thymocytes were stimulated to release PGE2 after incubation with alpha 1 in a manner similar to that seen in spleen cells of ATx mice. Approximately the same concentrations of alpha 1 was found to also correct the low azathioprine sensitivity of splenocytes from ATx mice. Determinations of FTS-like activity in the blood and the pharmacokinetics of alpha 1 after administration of this synthetic molecule show a clear dissociation. A maximum peak of alpha 1 activity was obtained after 1 hr, while maximal FTS-like activity was observed after 24 hr. The inhibition of the induction by alpha 1 of FTS-like activity and of Thy 1.2 antigen by indomethacin suggests that the action of alpha 1 requires prostaglandin biosynthesis.

Animals↗
PubMed1983

The relationship between prostaglandins and virus replication: endogenous prostaglandin synthesis during infection and the effect of exogenous PGA on virus production in different cell lines and in persistently infected cells.

African Green Monkey Kidney cells were shown to normally synthesize immunoreactive PGE1. Infection of these cells with Sendai virus did not alter rates of PGE1 synthesis, while it stimulated interferon production. PGAs, that we have previously shown to be potent inhibitors of Sendai virus replication in this system, at the same dose (4 micrograms/ml), also strongly inhibited the replication of this virus in HEp-2 cells and in VERO cells, a monkey kidney cell line that does not produce interferon. PGA1 was found to be effective in several cell and virus models, suggesting a broad spectrum of antiviral actions. Finally, we confirmed the observation that PGA1-treatment prevents the establishment of a "carrier state" by Sendai virus, and PGA1-cured cells did not show any sign of persistent infection for periods as long as 110 days after Sendai infection. Attempts to cure already established persistently infected cells were only partially successful.

Alprostadil↗
PubMed1983

Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice.

Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity. Several immunological in vitro functions also appeared to be dramatically depressed. Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C. albicans infection appeared to be unchanged. However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge. To gain some insight into the mechanisms underlying this late increase in resistance to C. albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes. The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C. albicans after administration of cyclophosphamide.

Animals↗
PubMed1983

Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.

Animals↗
PubMed1983

Effects of in vivo Friend leukemia virus infection on levels of serum thymic factors and on selected T-cell functions in mice.

The levels of serum thymic factor(s) (STF), of Thy-1.2 positivity of splenocytes [as measured by their azathioprine (AZ) sensitivity], and of Thy-1.2-positive "spontaneous" spleen rosette-forming cells (SSRFCs), as well as the presence of infectious virus in the thymus, were assessed as a function of time after virus inoculation in susceptible DBA/2, partially resistant BALB/c, and fully resistant C57BL/6 mice given the polycythemia- or anemia-inducing strain of Friend leukemia virus (FLV-P and FLV-A, respectively). As early as Days 2 to 3, the levels of STF and of AZ sensitivity of splenocytes were profoundly decreased in DBA/2 mice, and, to a lesser extent, in BALB/c mice given FLV-P; however, SSRFCs/spleen were increased in both mouse strains. Conclusive evidence of infectious FLV-P was obtained in the thymuses of DBA/2 mice soon after infection. In mice of the same strains infected with FLV-A, STF levels were similarly decreased, but AZ sensitivity of splenocytes was unaffected, and SSRFCs were decreased. Evidence of early FLV-A infection in the thymus of DBA/2 mice was likewise obtained. In C57BL/6 mice given FLV-A, STF levels, AZ sensitivity of splenocytes, and SSRFC showed changes similar to, but of lower magnitude than, those in BALB/c mice. On the other hand, in C57BL/6 mice given FLV-P, the decrease in STF and AZ sensitivity was almost as pronounced as in susceptible DBA/2 mice in the face of complete absence of infectious virus or viral markers in the thymuses. The observed changes are ascribed to virus infection in view of the following: (a) good temporal correlation between these changes and virus infection; (b) absence of any change in mice given heat-inactivated viruses or spleen homogenate of normal DBA/2 mouse spleen; (c) overall good correlation between mouse genotype and genetic (Fv-1 and Fv-2) restrictions of virus infection on one hand and the magnitude of the observed changes on the other. In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex. All changes described so far were transient, since they were not detectable beyond 42 days after virus inoculation in overtly leukemic animals. The observed derangements of thymus-derived immune functions may play an important cofactor role during the onset of leukemia in mice genetically permissive to Friend leukemia virus replication and transformation, but they do not seem relevant to the maintenance of leukemia.

Animals↗
PubMed1983

Relationships among tumor load, route of tumor inoculation, and response to immunochemotherapy in a murine lymphoma model.

The combined effects of nonspecific immunostimulation with Candida albicans (CA) and chemotherapy were studied in (BALB/cCr X DBA/2Cr)F1 and (C57BL/6Cr X DBA/2Cr)F1 mice bearing virus-induced LSTRA lymphomas. Paradoxically, animals treated with a relatively high number of tumor cells responded better to therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) than those challenged with a low number of tumor cells. However, the majority of mice subjected to low initial tumor load were cured when they were treated with chemotherapy or chemotherapy plus booster injection of CA at a relatively "late" stage of the disease, i.e., when high tumor load was present in tumor-bearing hosts. It has been shown that this phenomenon, provisionally called high tumor load protection, occurs when the animals are challenged ip but not when they are challenged iv with the tumor and is abolished by total-body gamma-irradiation. Moreover, marked host protection can be attained when immunostimulated mice, inoculated iv with lymphoma cells, are subjected to simultaneous challenge with high inocula of the same tumor ip, followed by BCNU administration. These data stress the importance of the peritoneal cavity for successful CA plus drug treatment and suggest that optimal tumor "antigen load" should be present at the time of CA and/or BCNU administration.

Animals↗
PubMed1982

Cellular mechanisms underlying the adjuvant activity of Candida albicans in a mouse lymphoma model.

Inactivated Candida albicans (CA) possesses strong anti-tumor activity when combined with cytoreductive chemotherapy in a mouse lymphoma model. In the present study, experiments were performed in order to elucidate the mechanism(s) underlying CA immunoadjuvant activity. In vivo chemotherapy studies proved that the synergistic anti-tumor effects were lost in athymic (nu/nu) mice and were also abrogated by radiations. In vitro tests did not suggest a major involvement of natural cytotoxic effectors such as macrophages and natural killer cells nor did CA effects appear to be mediated by induction of interferon. It was concluded that the immunoadjuvant activity of CA largely relies on host responses against tumor-associated transplantation antigens with no major involvement of natural resistance immune mechanisms.

Adjuvants, Immunologic↗
PubMed1982

The role of the peritoneal cavity in successful treatment of a murine lymphoma with chemotherapy and non-specific immunostimulation.

The influence of the route of administration and treatment schedule of a yeast immunoadjuvant, Candida albicans (CA) on the degree of success achieved with an immunochemotherapy regimen in a virus-induced murine lymphoma has been evaluated. To this end, histocompatible CD2F1 mice received IP or IV inoculations of LSTRA lymphoma cells and were subjected to various treatments with inactivated CA and bis,1,chloroethyl nitrosourea (BCNU). The results showed that CA may significantly increase the antitumor efficiency of BCNU when (a) the tumor is inoculated IP and not IV; (b) CA is administered before (on day -14) and after (on days +1 and/or day +8) LSTRA challenge; (c) CA is given IP as a post-tumor treatment. To ascertain whether the immunoadjuvant effect was anatomically restricted to the peritoneal cavity (PC), spreading of IP injected lymphoma was studied by means of LSTRA cells labeled with 3-5'iodo-deoxyuridine 125I (125IUdR) and tumor bioassay in spleen, lung, kidney, liver, and PC of recipient mice. The results showed that IP tumor challenge led to early (1 h) generalized neoplasia in both untreated and CA-pretreated hosts. Therefore, the combined antitumor effects of chemotherapy and CA are not restricted to the PC but rather the result of systemic immunity. In conclusion, in our system the PC seems to be a preferential site for eliciting generalized antilymphoma host responses markedly amplified by selected schedules of immunoadjuvant administration.

Adjuvants, Immunologic↗
PubMed1982

Antiviral effect of prostaglandins of the A series: inhibition of vaccinia virus replication in cultured cells.

Prostaglandins of the A series potently inhibited the production of vaccinia virus in mouse L fibroblasts. With the highest non-toxic dose of PGA1, 4 micrograms/ml, the replication of the virus was inhibited by 95 . 3%. The antiviral activity was dose-dependent and specific for the A series. At the dose used, PGA1 was not toxic to uninfected cells and did not alter cell metabolism as measured by DNA, RNA and protein synthesis. PGA1 did not influence the adsorption of the virus by the host cells and the antiviral activity was not dependent on the presence of PGA1 during the early stages of infection. PGA treatment delayed and partially inhibited virus DNA synthesis and, while it did not produce any change in the pattern of protein synthesis in uninfected cells, it altered both the rate and the pattern of virus protein synthesis. We conclude that PGA1 selectively inhibits one or more steps involved in the replication of vaccinia virus in mouse L fibroblasts.

Adsorption↗
PubMed1982

Increase of mouse resistance to Candida albicans infection by thymosin alpha 1.

Studies were carried out to assess the ability of thymosin alpha 1 to prolong the survival of mice challenged with Candida albicans. Two- to four-month-old mice were treated with graded doses of thymosin alpha 1 before, after, or before and after intravenous challenge with C. albicans. Significant resistance ot lethal infection was afforded by 100 micrograms of thymosin alpha 1 per kg given before or before and after challenge, whereas no protection was found in mice treated with thymosin alpha 1 administered at any dose level after inoculation. Pretreatment with thymosin alpha 1 also prevented the increased susceptibility to C. albicans infection of mice pretreated with cyclophosphamide on day -6. The results showed that thymosin alpha 1 was capable of protecting untreated or cyclophosphamide-pretreated mice from C. albicans infection at an optimal dose and schedule of administration.

Animals↗
PubMed1981

Impairment of in vitro generation of cytotoxic or T suppressor lymphocytes by Friend leukemia virus infection in mice.

Spleen cells collected from DBA/2 (H-2d) mice inoculated with the polycythemic variant of Friend-Leukemia Virus Complex (FLV-P) were tested for T-dependent immune functions, such as the in vitro generation of cytotoxic T lymphocytes (CTL) and of non-specific T suppressor lymphocytes (STL). CTL were generated against H-2b splenocytes, and STL were obtained following a 5-day lymphocyte culture without stimulator cells. A progressive and severe impairment of the generation of both CLT and STL was found from 2 weeks onward after infection, being almost totally abolished 3-4 weeks after virus challenge. Suppressor cells (SC) capable of inhibiting CTL generation was detected in FLV-P bearing mice. Suppressor activity was unaffected by anti-Thy 1.2 serum and complement but was removed following iron-magnet depletion or passage through nylon-wool column. Moreover complete recovery of the competence of CTL generation was attained when FLV-P infected splenocytes were passed through nylon-wool column. It is concluded that FLV-P infection depresses T-dependent cytotoxic and suppressor responses in mice, by the appearance of non-T adherent phagocytic cells, capable of impairing CTL generation in vitro.

Animals↗
PubMed1981

Prostaglandins of the A series inhibit Sendai virus replication in cultured cells.

Prostaglandins of the A series (PGA) were shown to be potent inhibitors of Sendai virus replication in African green monkey kidney cells in culture. This antiviral activity was specific for PGA. The effective dose (4 micrograms/ml) was not toxic to the cells and did not alter either host cell metabolism of infectivity of the virus. PGA did not affect the first stages of virus replication and seemed to act by inhibiting virus maturation and/or budding from the cells. The antiviral action of PGA was pharmacological, was not mediated by cAMP and was completely reversible. Possible mechanisms of action include post-translational binding to virus proteins or interaction with interferon.

Animals↗