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Biomedical subjects

B Bizzini

Publications and source records attributed to B Bizzini.

At least 91 records · Page 5Linked to original sources
PubMed1987

Synergy between low-dose chemotherapy and immunotherapy in mouse L1210 leukemia.

A high dose of 4 mg/kg of daunorubicin (DAU) given in combination with immunostimulation by the P40 immunomodulatory fraction of Corynebacterium granulosum and glutaraldehyde (GA)-treated tumor cells coupled with tetanus toxoid (P40 + GA-L1210-Tet) was more effective than DAU alone for treatment of L1210 mouse leukemia. A combination of low doses of DAU (0.0625-0.25 mg/kg) and P40 + GA-L1210-Tet was more effective than either P40 + GA-L1210-Tet or DAU alone. The cured mice were resistant to challenge with a high tumorigenic dose of L1210 tumor cells. A combination of various doses of mitomycin (1-4 mg/kg) with P40 + GA-L1210-Tet was more effective than mitomycin alone and was at least as effective as P40 + GA-L1210-Tet alone. Administration of DAU (0.5-4 mg/kg) to noninoculated C57BL/6 X DBA/2 mice resulted in increase of stimulation in vitro of collected spleen cells by mitogens.

Animals↗
PubMed1987

[Effects of vaccination in urinary infections caused by Escherichia coli in rats].

The preventive effects of the immunomodulator P40 on the experimental E. coli infection of the lower urinary tract of the rat have been reported previously. In the present paper are presented the results obtained with the aid of vaccination using the same experimental model of infection in the rat. Active specific immunization of the animals with a vaccine consisting of the same strain as that used for infecting the rats afforded significant protection toward the infection. It is concluded that such vaccines could also be used in humans, either alone or in combination with other therapies with the aim at preventing recurrencies or relapses of infections of the lower urinary tract which were resistant to antibiotherapy.

Animals↗
PubMed1987

Preliminary experimental and clinical results with inactivated allergens conjugated to the Corynebacterium granulosum-derived immunomodulator P40.

Allergoids have been used successfully for immunotherapy of allergic disorders. It has appeared to us that the effect of allergoids could be potentiated by their coupling to an immunomodulator. In the present study we show that a conjugate made up of the coupling of ovalbumin through glutaraldehyde action to the C. granulosum-derived immunomodulator P40 is completely devoid of antigenicity and of cross-reactivity with ovalbumin. This conjugate was found to significantly inhibit mast cell degranulation. It also proved to be capable of protecting against the lethal systemic anaphylactic shock sensitized mice. Immunotherapy was performed in patients hypersensitive to either the pollen of Dactylis glomerata or to the house dustmite allergens using the conjugates made of the specific allergens and of the P40. Clinical improvement was observed in a significant percentage of the patients subjected to immunotherapy. Administration of the conjugates did not result in untoward reactions in any of the patients.

Allergens↗
PubMed1986

Experimental modification of postnatal cerebellar granule cell migration in vitro.

Histotypic migration of [3H]thymidine pulse-labeled granule cell neurons in cerebellar folium explants was monitored in the presence of antibodies to cell adhesion molecules and quantified by automatic image analysis. When explants were cultured in the presence of monovalent antibody fragments to cell adhesion molecules L1 and N-CAM, an inhibition of cell migration of 33.3 +/- 4.4% and 13.9 +/- 2.1%, respectively, was observed. In the presence of an equimolar mixture of monovalent antibody fragments to L1 antigen and N-CAM no additive effects in inhibition of cell migration were seen. Antibodies to the L2 carbohydrate epitope which is common to L1, N-CAM and other cell surface glycoproteins showed a similarly small effect on cell migration as antibodies to N-CAM. Monoclonal antibodies to cell surface antigen M2 and polyclonal antibodies to mouse liver membranes reacting with the surface of all cerebellar cell types did not alter the migratory behavior of granule cells. Cultivation of explants in the presence of neuraminidase, ganglioside binding toxins, as well as glycosaminoglycans and glycosaminoglycan degrading enzymes, also did not modify the extent of cell migration under the culture conditions used.

Animals↗
PubMed1986

Neural induction and in vitro initial expression of neurofilament and tetanus toxin binding site molecules in amphibians.

Tetanus toxin (Tt) binding site and neurofilament (NIF), the intermediate-sized filaments, are neuronal markers essentially described in mammals and birds; are these molecular markers present in urodela neuronal cells and are they expressed immediately after neural induction? Our findings are based on immunofluorescent localization of NIF and Tt proteins using three previously characterized antisera against 200 kDa and 70 kDa neurofilament components and against fragment IIc derived from purified tetanus toxin. Embryonic undifferentiated neuronal cells from Pleurodeles waltlii neural plate and/or neural fold (early neurula stage) are cultured isolated in vitro without further chordamesodermal influence. At the beginning of the culture none of the undifferentiated neuronal precursors bind antibodies against NIF or Tt components. The binding is detected when phenotypical differentiation takes place (2/3-day cultures). Both the cell bodies and the cell processes are stained. After 2-3 weeks, immunostaining of the neurones is very distinctive and bright; the non-neuronal cultured cells do not exhibit any labelling. These observations indicate the early acquisition of NIF and Tt binding site expression by neuronal precursor cells (late gastrula stage).

Animals↗
PubMed1986

Involvement of gangliosides in rabies virus infection.

The role of gangliosides in rabies virus infection of chick embryo-related (CER) cells was investigated. Cultured cells were pretreated with neuraminidase to render the cells transiently non-susceptible to viral infection. Incubation of these desialylated cells with gangliosides allowed them to incorporate exogenous gangliosides and they recovered their susceptibility to rabies virus infection. Infection of CER cells was monitored by specific fluorescence 24 h after virus inoculation. The use of individual purified gangliosides or mixtures of two gangliosides to restore cellular susceptibility to viral infection showed that GT1b and GQ1b were the most effective. The disialogangliosides were also active, principally GD1b, whereas GM1, GM3 were poorly active and GD3 inactive. Incubation of rabies virus with gangliosides prior to virus infection reduced the percentage of infected cells. The results indicate that highly sialylated gangliosides are part of the cellular membrane receptor structure for the attachment of infective rabies virus. However, it is possible that other glycoconjugates such as glycoproteins or glycolipids also participate as components of a receptor structure for rabies virus.

Animals↗
PubMed1985

The use of antibody Fab fragments specifically directed to two different complementary parts of the tetanus toxin molecule for studying the mode of action of the toxin.

The injection of 500 minimal lethal doses (MLDs) of tetanus toxin into mice routinely causes a flaccid-type paralysis and death within 8 h. Non-precipitating antibody fragments (Fab) directed against each of two papain cleavage products of tetanus toxin (Ibc and IIc) were used to study this botulinum toxin-type effect of tetanus toxin. Ibc (100,000 daltons) is a toxic fragment which does not bind to gangliosides but will produce a flaccid type paralysis when injected into mice. Treatment of intact tetanus toxin (500 MLDs) with Fab-Ibc prevents the flaccid type paralysis and such mice will die from a spastic paralysis after about 24 h. IIc (50,000 daltons) is an atoxic fragment of tetanus toxin which binds tightly to gangliosides. Treatment of tetanus toxin with Fab-IIc prior to intracerebral injection converts the characteristic spastic paralysis to a flaccid paralysis. It is proposed that the botulinum toxin-type effect of tetanus toxin complexed to Fab-IIc results from the inability of such complexes to be transported to the central nervous system. Moreover, the ability of Fab-Ibc to prevent flaccid paralysis, but not spastic paralysis, suggests that both types of paralysis may be mediated by the same portion of the tetanus toxin molecule.

Animals↗
PubMed1985

The restoration of impaired macrophage functions using as immunomodulator the Corynebacterium granulosum-derived P40 fraction.

Many microorganisms and compounds of microbial origin exhibit immunomodulatory activities and have been extensively used in immunotherapy of experimental animal tumors and in patients with neoplasia. In this paper we describe the effect of the C. granulosum-derived P40 fraction on the growth and metastatization of the transplantable epithelioma T8 of Guèrin. Moreover, we evaluated the effect of P40 treatment on several depressed macrophage functions of tumor-bearing rats. In particular, the phagocytic and chemotactic activities of such cells were studied, as well as the antiviral intrinsic and extrinsic activities against HSV-1 and the anti-Toxoplasma gondii activity. All these functions were depressed in untreated tumor-bearing rats. Administration of a single intravenous injection of P40 fraction led to the restoration of all depressed macrophage activities to normal values. In particular, the possibility of restoring the antimicrobial activity of macrophages from tumor-bearing rats by treatment with this immunomodulator is of great concern when one considers the increasing incidence of opportunistic infections in immunocompromised hosts. Results are discussed in terms of both the possible mechanism of action of P40 and of its possible target cells.

Adjuvants, Immunologic↗
PubMed1985

Total and IgE antibody levels following booster immunization with aluminum absorbed and nonabsorbed tetanus toxoid in humans.

Total and IgE serum antibodies to tetanus toxoid were measured in 32 healthy adults, 3-4 weeks following booster immunization with either plain or aluminum hydroxide-absorbed tetanus toxoid. Whereas no difference in the total antibody values was observed, the level of anti-tetanus toxoid IgE antibodies was significantly higher in the group boostered with the adjuvanted vaccine.

Adult↗
PubMed1985

Relation of spastic and flaccid paralysis to retrograde transport of 125I-tetanus toxin and its 125I-Ibc fragment. Modulating effect of F (ab) antibodies directed to specific areas on the toxin molecule.

The injection into mice of small doses of tetanus toxin induces spastic paralysis as is well-known, whereas large doses of toxin produce flaccid paralysis. The hypothesis has been put forward that the type of symptoms produced may depend on the axonal transport or the lack of axonal transport of the toxin molecule to the central nervous system. In the present paper we show that the lethal flaccid paralysis occurring in mice injected with a very large dose of toxin develops in the absence of any uptake and axonal transport of the toxin molecule. We also confirm that a tetanus toxin-derived fragment, the Ibc fragment, which is not transported retrogradely, produces flaccid paralysis. The blockage with the aid of specific antibody F(ab) fragments of the area on the toxin molecule which is involved in binding and axonal transport does prevent the toxin from being transported to the CNS and causes it to produce flaccid paralysis.

Animals↗
PubMed1985

[Treatment of recurrent urogenital infections by immunomodulation].

In recurrent urogenital infections in which no curable cause can be found, long term antibiotic therapy is often the only possible form of treatment. After performing appropriate skin tests, the authors evaluated the effectiveness of vaccination consisting of antigen therapy and an immunostimulant, P 40, in 20 patients. The recurrent infections were controlled in the cases in which this combination was used; in half of the cases, maintenance vaccination was required for a period of 2 or 3 years.

Adjuvants, Immunologic↗
PubMed1984

Concanavalin A inhibits nicotinic acetylcholine receptor function in cultured chick ciliary ganglion neurons.

The effects of various lectins and toxins on neuronal nicotinic acetylcholine receptor function have been studied in primary cultures of chick ciliary ganglion neurons. Neuronal response to acetylcholine receptor activation was measured by a cation flux method at 4 degrees C in a high potassium-low sodium medium designed to stabilize membrane potential near zero, with acetylcholine as the agonist and cesium-137 as the tracer ion. Exposure to 1 mM acetylcholine for 30 s produced a 5-10-fold stimulation of cesium-137 influx. Acetylcholine-stimulated influx was inhibited more than 95% by 10 microM D-tubocurarine, but was insensitive to both 1 microM tetrodotoxin and 1 microM alpha-bungarotoxin. Concanavalin A (50 micrograms/ml) inhibited agonist-induced ion flux by 80% at 4 degrees C. Succinyl-concanavalin A was ineffective at concentrations up to 250 micrograms/ml, and could not protect against the concanavalin A inhibition. However, inhibition by concanavalin A was eliminated by prior incubation of the lectin with 0.2 M alpha-methyl-D-mannoside and subsequent co-incubation with the sugar. Wheat germ agglutinin, lentil lectin, cholera toxin and tetanus toxin were without effect at either 4 degrees C or 37 degrees C. These results suggest a specific interaction between concanavalin A and neuronal nicotinic acetylcholine receptors.

Acetylcholine↗
PubMed1984

Glial cells in the pineal gland of mice and rats. A combined immunofluorescence and electron-microscopic study.

Antigenic markers characteristic of astrocytes and their differentiative states (i.e., glial fibrillary acidic protein (GFAP), vimentin, and M1 and C1 antigens) were investigated in the pineal gland of mouse and rat using double immunolabeling techniques. In both species the so-called interstitial cells as characterized by TEM were shown to be astrocytes, since they expressed vimentin, but neither fibronectin (a marker for fibroblasts and endothelial cells) nor the neuron-specific L1 antigen or tetanus toxin receptors. Subpopulations of vimentin-positive pineal astrocytes were also GFAP- and C1- antigen-positive. M1- antigen-positive cells were not detected. It is concluded that a considerable proportion of interstitial cells in the pineal gland of rat and mouse are immature astrocytes which, in contrast to other parts of the central nervous system, persist into adulthood.

Animals↗
PubMed1984

Prevention and treatment of L1210 mouse leukemia by immunization with xenogenized tumor cells combined with immunostimulation by the P40 fraction of C. granulosum and chemotherapy.

The effect on L1210 leukemia in mice of immunostimulation, in combination or not with chemotherapy with either daunorubicin or mitomycin, was studied. Immunostimulation with the immunomodulator P40 isolated from C. granulosum, together with xenogenized syngeneic tumor cells (GA-L1210-Tet: L1210 tumor cells inactivated with glutaraldehyde and coupled with tetanus toxoid), on days -14 and -7 before and days 2 and 9 after tumor inoculation, resulted in significant increase of the mean survival time as compared to control group with or without chemotherapy. Administration of P40 or P40 + GA-L1210-Tet cells, before or before and after inoculation of L1210 cells partly inactivated in vitro with antineoplastic agents, leads to a marked prolongation of mean survival time and to inhibition of ascitic tumor growth in a high percentage of mice. About 50% of the mice treated with P40 + GA-L1210-Tet cells and surviving the first challenge were resistant to rechallenge, providing that P40 + cells were reinjected before the second challenge, whereas all mice treated with P40 alone and surviving the first inoculation, were susceptible to rechallenge. The major conclusion is that treatments of combining chemotherapy, active immunization and nonspecific immunostimulation in the applied sequence are more effective than single treatments for control of L1210 mouse leukemia.

Adjuvants, Immunologic↗
PubMed1984

Neutralization of tetanus toxin by distinct monoclonal antibodies binding to multiple epitopes on the toxin molecule.

Fifty-seven hybridomas producing antibodies to tetanus toxoid or to the Ibc or B-IIb fragment of the toxin were isolated independently. Competitive inhibition studies demonstrated that monoclonal antibodies from mice immunized with the toxoid bound to at least 20 different epitopes on the toxoid molecule. Similar competitive binding studies revealed eight distinct epitopes on the B-IIb fragment and three to five epitopes on the Ibc fragment of the toxin. Neutralization of toxicity was effected by nine distinct monoclonal antibodies from hybridomas of toxoid-immunized mice and by one monoclonal antibody from B-IIb-immunized mice. Mixtures of two, three, and four different monoclonal antibodies in a variety of combinations exerted a synergistic effect of ca. 200-fold over that observed with individual monoclonal antibodies, indicating that efficient neutralization may involve the simultaneous binding of at least two antibody molecules to different specific regions of the toxin molecule. Only one toxoid-induced monoclonal antibody failed to bind to tetanus toxin. All neutralizing antibodies bound to epitopes on the heavy chain of tetanus toxin. Six of these were directed toward epitopes on the NH2-terminal half, whereas four bound to epitopes on the carboxy-terminal half of the heavy chain. Only one monoclonal antibody bound preferentially to the light chain, but two other monoclonal antibodies appeared to bind to both chains, indicating some homology between these two chains.

Animals↗