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Biomedical subjects

R Arnon

Publications and source records attributed to R Arnon.

At least 199 records · Page 11Linked to original sources
PubMed1982

Anti-influenza response achieved by immunization with a synthetic conjugate.

The peptide corresponding to sequence 91--108 of the hemagglutinin of type A H3N2 influenza virus has been synthesized by the solid-phase peptide synthesis method and covalently attached to several macromolecular carriers. The conjugate with tetanus toxoid was used for immunization of rabbits and mice. The immunoglobulin fraction of the rabbit antiserum showed the presence and antipeptide antibodies by both agar gel diffusion and radioimmunoassay. In the latter assay, the antibodies showed marked crossreactivity with the intact virus of the A/Texas/77 strain. The antibodies were also capable of inhibiting the hemagglutination of chicken erythrocytes by the virus; the highest hemagglutination inhibition titer (1:32) was achieved with a serum-resistant strain of A/Texas/77. When the in vitro virus plaque formation assay was used with monolayers of Madin--Darby canine kidney (MDCK) cells, the number of plaques was reduced on interaction with the immunoglobulin fraction of the antiserum, which was effective up to a dilution of 1:32. Preliminary results indicate that C3H/DiSn mice immunized with the peptide--tetanus toxoid conjugate are partially protected against a further challenge with A/Texas mouse-adapted influenza virus. The results are thus indicative of the efficacy of the synthetic material in eliciting anti-influenza immune response.

Animals↗
PubMed1982

Reduced toxicity of daunorubicin by conjugation to dextran.

Daunorubicin-dextran conjugate (dau-dex) was compared to free daunorubicin for acute and subacute toxicity and efficacy in tumor chemotherapy. LD50 and LD2 values of dau-dex are about threefold higher than those of the free drug. The therapeutic index of dau-dex is also higher, manifesting a "safe-region" in which no mortality occurs either from YAC lymphoma or from drug toxicity. Dau-dex caused almost no damage to heart tissue during the 2 months following four injections of the therapeutic dose and caused no change in the differential count of bone marrow cells. Altogether, the subacute toxicity of dau-dex is much lower than that of free daunorubicin, as expressed by negligible histologic damage to all organs examined and compared to the massive atrophy of spleen and bone marrow effected by the free drug.

Animals↗
PubMed1981

Dynamics of antibody- and lectin-mediated endocytosis of hapten-containing liposomes by murine macrophages.

The uptake by murine macrophages of liposomes, exhibiting one of a variety of haptenic groups on their surfaces, was greatly enhanced by the addition of an intact antibody or a lectin specific for the incorporated hapten. The uptake of untreated liposomes was slow and linear over long periods, whereas upon addition of the antibody or lectin, over 30-fold increase in the maximal rate of uptake was observed. The process reached a plateau after 90-120 min. The interaction of the antibody- or lectin-treated liposome with the macrophages apparently resulted in an active endocytosis of soluble fluorescent, intraliposomal marker had a granular intracellular pattern in treated cells. The uptake was sensitive to azide and the liposome constituents could not be detected at the cell surface. The size of the liposomes as well as the state of stimulation of the macrophages (thioglycollate stimulated vs. normal) did not seem to have a major effect on the phagocytic process. The time required to reach the plateau in uptake was independent of liposome composition or antibody concentration and is, apparently, an intrinsic property of the cells. The implication of this phenomenon on the dynamics of the relevant macrophage receptors is discussed.

Adsorption↗
PubMed1981

Genetic analysis of susceptibility to experimental allergic encephalomyelitis in guinea-pigs.

Genetic analysis of susceptibility to experimental allergic encephalomyelitis (EAE) was performed in guinea-pigs. The results indicate the existence of two Ir genes to EAE in susceptible strain 13 guinea-pigs. One gene is linked to the major histocompatibility complex (MHC) of this species, while the other one is located outside the MHC. The two genes segregate independently and both of them must be expressed to render the animal susceptible to EAE.

Animals↗
PubMed1981

The immunologic response in mice unresponsive to experimental allergic encephalomyelitis.

The suppressor cells that are involved in antigen-induced protection against EAE in mice were investigated with respect to their effect on the immune response. The cellular immune response to the basic encephalitogenic protein (BE) and to PPD were studied in mice with either actively induced or adoptively transferred unresponsiveness to EAE. The results demonstrate that the DTH response to BE, as assayed in the radiometric ear skin test, was suppressed in mice protected against EAE. Moreover, the passive transfer of DTH response to BE by effector lymphocytes was also inhibited by the preinjection of suppressor cells. On the other hand, the suppressor cells did not affect the response to PPD in all these experiments. The results indicate that suppressor cells that mediate unresponsiveness to EAE regulate also the cellular immune response to BE in a specific manner. These suppressor cells are probably active both at the induction and the effector phase of the immune response.

Animals↗
PubMed1981

Unresponsiveness to experimental allergic encephalomyelitis in mice: replacement of suppressor cells by a soluble factor.

A soluble suppressor factor has been prepared from cells of mice rendered nonsusceptible to experimental allergic encephalomyelitis (EAE) by treatment with mouse spinal cord homogenate in incomplete Freund's adjuvant. The specific activity of this factor can be augmented by using a cell population enriched on plates coated with anti-mouse Fab and the specific antigen, mouse basic encephalitogen (MBE). The resultant suppressor factor had the same biologic activities as the cells from which it originated. Thus, it suppressed specifically the delayed-type hypersensitivity (DTH) response to MBE in vivo, and blocked in vitro the effector lymphocytes that adoptively transfer the DTH response. The suppressor factor reactivity was manifested also by the capacity to suppress the activity of macrophage migration inhibition factor produced by sensitized lymphocytes in the presence of the specific antigen MBE. The suppressor factor is antigen-specific and can bind the MBE in vitro and thus compete with its antibody binding. The most significant activity of the soluble suppressor factor is its ability to interfere with the induction of clinical EAE.

Animals↗
PubMed1980

Antibodies as carriers for oncostatic materials.

Daunomycin conjugates to antitumor antibodies prepared either by direct binding or by binding via dextran retain both the antibody and the drug activity. Thus, the exert specific cytotoxicity in vitro toward tumor cells that the antibodies recognize. The macromolecular conjugates are able to penetrate the cells and concentrate in or on the nuclei. In vivo, the antitumor antibodies accumulate preferentially at the tumor metastases. Daunomycin-antibody conjugates are more active than the free drug in prolongation of survival of mice transplanted with the YAC lymphoma cells.

Animals↗
PubMed1980

Anti-ganglioside antibodies in multiple sclerosis.

Serological activity against several purified brain gangliosides has been demonstrated in sera of a proportion of multiple sclerosis patients, but not in normal individuals. The activity was determined by the capacity of the sera to bring about complement-dependent lysis of liposomes containing the respective ganglioside in their lipid bilayer. An apparent correlation is indicated between the severity of the disease and the extent of liposome lysis. Cerebrospinal fluid of the patients did not induce lysis, probably due to low antibody concentration.

Autoantibodies↗
PubMed1980

Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity.

In a previous study we demonstrated that antiviral response against the coliphage MS-2 can be elicited by immunization with a synthetic antigen consisting of a conjugate (P2-A -- L) of a synthetic fragment (P2) of the virus coat protein attached to a synthetic polymeric carrier. The antiviral response was induced when the antigen was administered in complete Freund's adjuvant or when it was administered in incomplete adjuvant, provided that a peptidoglycan was covalently attached to it. In the present study we demonstrate the adjuvant effect of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in this system. Immunization with a mixture of MDP and P2-A -- L brought about only slight enhancement in the titer of neutralizing antibodies, as compared to the immunization with P2-A -- L in saline. The best results were achieved when the MDP was chemically conjugated to P2-A -- L. This completely synthetic material, when administered in aqueous solution, yielded highly inactivating antiserum with a titer similar to that obtained with complete Freund's adjuvant in the absence of MDP. MDP-P2-A -- L elicited also a humoral immune response to MDP, but with much lower titer than that induced by complete Freund's adjuvant containing P2-A -- L only. It was also observed that the capacity of MDP-P2-A -- L to increase resistance against infection was more than a 100-fold greater than that of unconjugated MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastase. In vitro and in vivo studies with Lewis lung carcinoma.

The present study was undertaken in order to evaluate the possibility of using anti-tumor antibodies as specific carriers of chemotherapeutic drugs to tumor metastases. Xenogeneic and syngeneic antisera were prepared against a metastasizing C57BL tumor, the Lewis lung carcinoma (3LL). The binding of absorbed xenogeneic and syngeneic anti-3LL sera or their Ig fractions to 3LL tumor cells was assayed by direct and indirect methods. Antisera prepared against tumor cells from a local growth reacted to a similar extent with those obtained from the lung metastases. Radioiodinated immunoglobulins from syngeneic antisera injected into mice bearing metastases localized preferentially in metastasis-bearing lungs as compared to several other organs tested. No such preferential uptake was observed either in mice bearing metastases injected with iodinated normal Ig or in normal mice injected with iodinated anti-3LL Ig. This relative accumulation in the metastasis-bearing lungs was observed 3-4 days after the inoculation, when the whole Ig fraction was used, whereas a specific antibody-enriched preparation localized as early as 24 h after injection. Daunomycin--anti-3LL-Ig conjugates were effective inhibitors of tumor cells from both local and the metastatic growths. They were more active than either the free drug or drug conjugates of normal Ig, in in vitro assays.

Animals↗
PubMed1979

The effect of Cop 1, a synthetic polypeptide, on chronic relapsing experimental allergic encephalomyelitis in guinea pigs.

Cop 1, a synthetic polypeptide, was evaluated for its effect on a chronic relapsing form of experimental allergic encephalomyelitis (EAE). Pretreatment of juvenile Strain 13 guinea pigs with Cop 1 in incomplete Freund's adjuvant (IFA) which were subsequently challenged with guinea pig spinal cord in complete Freund's adjuvant (CFA) had a marked effect in delaying or preventing the appearance of clinical signs of EAE. Administration of Cop 1 on appearance of clinical signs of EAE prevented progression of the first episode of the disease. Although relapses were not always prevented, they were modified on their duration and intensity both clinically and histologically.

Animals↗