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Biomedical subjects

F Bistoni

Publications and source records attributed to F Bistoni.

At least 199 records · Page 11Linked to original sources

Comparison between natural reactivity (NR) against Candida albicans and natural killer (NK) activity against YAC-1 tumour cells.

Cytotoxic activity against Candida albicans was measured in vitro in a 4-h 51Cr-release assay. The levels of reactivity correlated well with the number of polymorphonuclear cells in the effector population, being augmented by the enrichment of polymorphonuclear granulocytes. To exclude the possible role of contaminating natural killer cells, natural killer activity against tumour cells was compared with natural reactivity against Candida albicans in vitro. The findings indicate that there are many differences between these reactivities including organ and strain distribution, age dependency, adherence to nylon, and susceptibility to modulation by immuno-adjuvants and to treatment with anti-Thy 1.2 antiserum plus complement. These data further define in vitro polymorphonucleate-mediated cytotoxicity against Candida albicans on the basis of the above-mentioned criteria and clearly demonstrate that this in vitro reactivity could not be due to the presence of contaminating natural killer cells in the effector cell population.

Age Factors↗

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↗

Suppression of Friend leukemia cell-induced tumours by cellular preparations of Candida albicans.

Inactivated cellular preparations and cell wall materials of Candida albicans (CA) were tested for their capacity to suppress the growth of Friend Leukemia Cell (FLC)-induced tumours and the infection by Friend Leukemia Virus (FLV) in histocompatible mice. Factors affecting the inhibition of tumor growth by CA cellular preparations were: i) the schedule of agent administration; ii) the method of cell inactivation; iii) the FLC load. In particular, mice given 10(7) yeast cells, inactivated by cold alkali, on days -14 and +1 with respect to 10(4) FLC challenge on day 0 did not develop tumors. A crude cell wall fraction derived from cells extracted with hot alkali was still effective in reducing (but not suppressing) tumour growth whereas a purified, particulate glucan fraction (glucan "ghosts", essentially consisting of beta 1,3-1,6 glucan) was ineffective. No cellular preparation or cell wall fraction exerted anti-FLV effects (as shown by splenomegaly measurements) nor did any CA material induce interferon-like activity in the serum of animals injected with either FLC or FLV. Therefore, the observed antitumor activity by CA was not mediated by antiviral effects but possibly due to an "adjuvant-type", nonspecific, immunopotentiation of host antitumor response, as documented in other animal tumor models.

Animals↗

Phagocytic killing of Candida albicans by different murine effector cells.

Three major phagocytic populations in the mouse were tested in vitro for killing of Candida albicans by means of 51Cr release assay: early inflammatory peritoneal polymorphonuclear cells (PMN), unfractionated or adherent spleen cells and resident peritoneal macrophages (PEC). Considerable candidacidal activity was found in the early inflammatory neutrophil and adherent spleen cell populations. On the contrary, only limited activity was found to be associated with resident peritoneal macrophages. The phagocytic killing apparently involved multiple mechanisms.

Animals↗

Use of turkey red blood cells in the passive haemagglutination test for studying tetanus immunity.

Passive haemagglutination (HA) assays were performed using turkey red blood cells (TRBC-HA) on sera from normal healthy people, from normal people previously immunized against tetanus, and from tetanus patients receiving human antitetanus immunoglobulins. The TRBC-HA test was compared with haemagglutination assays using sheep red blood cells (SRBC-HA) and with the neutralization (NT) test, and was found to be more sensitive than the SRBC-HA test and showed good correlation with the NT test.While the SRBC-HA assay calls for adsorption of sheep red blood cell agglutinins from the sera to be tested, the use of turkey red blood cells does not require any such adsorption. In addition, the TRBC-HA assay can be performed in 40 minutes compared with 6 hours for the SRBC-HA assay. All these advantages make the TRBC-HA assay a more useful test for screening large numbers of sera in the evaluation of tetanus immunity of normal people and of patients with wounds when seen in the emergency room of hospitals.

Animals↗

Determination of immunity against tetanus infection by passive haemagglutination assay.

Evaluation of anti-tetanus antibody level in human sera is of primary importance for a prophylaxis of tetanus infection. Many efforts have been made to develop simple, sensitive and reproducible in vitro methods for detecting and quantifying antibodies to tetanus toxin. We have recently developed an HA assay using lyophilized turkey red blood cells (TRBC-HA). In this paper we demonstrated that the TRBC-HA test is more sensitive than the most widely used sheep red blood cell assay (SRBC-HA) and that TRBC-HA assay shows a high correlation with the neutralization test (NT). Furthermore, comparisons of TRBC-HA assay with enzyme-linked immunosorbent assay (ELISA) and counterimmunoelectrophoresis (CIE) indicate that TRBC-HA and ELISA assays detected the same antibody level with a sensitivity up to 400-fold higher than that determined by CIE. However, TRBC-HA also offers many advantages over the ELISA test, because TRBC-HA can be performed in only 40 minutes instead of the 24 hrs. needed for the ELISA, it is less expensive than ELISA and requires no special equipment. Therefore, the overall results suggest that the TRBC-HA is the most appropriate method for rapid and sensitive determination of tetanus antibody levels.

Antibodies↗

[The use of passive hemagglutination with turkey erythrocytes for the effective prevention of tetanus in wounded patients].

The passive haemagglutination assay is at present the most common method available for evaluating tetanus antibody levels. We recently developed a modification of the technique of HA by Mai and Rosin using turkey red blood cells (TRBC-HA) instead of sheep red blood cells (SRBC-HA). TRBC-HA assay seems to offer the advantages of being more sensitive and easier to perform than the SRBC-HA method. More important, with the TRBC-HA assay, we found that the HA values greater than 0.5 H.U./ml always correspond to NT values greater than 0.01 IU/ml. Therefore this value (0.5 H.U./ml) was chosen as a discriminating level between protected and non protected persons. On this rationale base we have tested sera from injured persons in order to individualize a single prophylactic treatment under a rationale guideline against the alternative of a blind intervention under anamnestic basis. Among 437 persons tested 248 did not remember if they had been vaccinated or not. According to the anamnestic basis all these persons should require injection of human antitetanus Ig plus a basic course of vaccination. On the contrary antitetanus antibody levels monitored by TRBC-HA assay indicate that 132 were protected and did not require any treatment; 79 were partially protected and required a boosting of tetanus toxoid and only 37 were not protected and needed human antitetanus IgG plus a complete course of vaccination. These results underline the necessity of monitoring a single person for antitetanus antibodies in order to prevent both under or over evaluation of their tetanus immune status.

Female↗

A radiolabel release microassay for phagocytic killing of Candida albicans.

The chromium release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans.

Animals↗

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↗

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↗

Immunopotentiation of anticancer chemotherapy by Candida albicans, other yeasts and insoluble glucan in an experimental lymphoma model.

Several yeast species in the genera Candida, Saccharomyces and Cryptococcus showed powerful immunoadjuvant, chemotherapy-synergic effects against a histocompatible, virus-induced murine lymphoma. Sensitizing and booster intraperitoneal injections of 2 x 10(7) yeast cells on days -14 and +1 (with respect to tumor challenge on day 0) followed by treatment with antiblastic drugs (on day +5) were required to elicit optimum activity. The antitumor effect was not markedly influenced by the morphological growth form of merthiolate-inactivated C. albicans nor by the nature of the carbon source in the growth medium, except for C. albicans cells grown in a medium containing stearic acid, which were not effective. These cells had a higher ratio of soluble to insoluble cell wall components, as compared to glucose-grown cells, but this finding alone could hardly explain the lack of antitumor effects. Previous observations, suggesting that the alkali-acid insoluble beta-glucan (in the form of cell wall ghosts) is the only component of yeast cell walls endowed with antitumor activity comparable to that of whole cells, were confirmed and extended; the soluble mannan and glucan-protein fractions were unable to replace whole cells and glucan ghosts even as sensitizers or as boosting agents.

Adjuvants, Immunologic↗

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↗

[Microbiological diagnosis of tetanus and serological verification of the immunological status. Serological monitoring in the course of therapy and prophylaxis].

The tests for tetanus aetiological diagnosis are briefly surveyed: with particular attention to Passive Haemagglutination on Turkey Red Blood Cells (P.H./T.R.B.C.), for the assessment of antitoxin serum level. The P.H./T.R.B.C. proves a valuable tool in different occasions: -in patients, to control the immunotherapy; -in subjects at risk, to apply a correct prophylaxis; -in the whole population, to verify the outcome of compulsory vaccination.

Antibodies, Bacterial↗

Protection test and early antibody response to tetanus immunization.

The Authors carried out a research work to study the dose-dependence of antibody response in BD2F, mice injected with tetanus toxoid. Experimental data show that it is possible to obtain an earlier resistance at least 14 days after immunization, increasing ten-fold the usual anatoxin dose administered in humans. The protection test toward 4 MLD i.v. injected of tetanus toxin proved a valuable tool for assessing the first appearance of acquired immunity.

Animals↗

[Technic for studying antitetanus immunity].

The Authors carried out a research work on problems relating to technical aspects to the tetanus immunity tests. Some interesting conclusions have been reached: - Purified and diluted tetanus toxin is best preserved at - 20 degrees C, in pH 7.4 physiological salt solution added with 1% peptone. - Vaccination in small laboratory animals must be done injecting adsorbed anatoxin by a microsyringe, in order to avoid dilution of the original compound. - Protection test using low, i.v. toxin doses is more reliable than serological tests in assessing the acquired resistance level in immuno-prophylaxed animals. - Passive haemagglutination test is much more sensitive when done with turkey instead of sheep red blood cells.

Animals↗