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Biomedical subjects

R Arnon

Publications and source records attributed to R Arnon.

At least 163 records · Page 9Linked to original sources
PubMed1986

A novel lipid-conjugated marker for the direct labeling of the schistosomulum membrane.

Introduction of the fluorescent group lissamine rhodamine B into the surface of schistosomula of S. mansoni was achieved by brief incubation of the worms with liposomes carrying the lipid bound fluorophore in their bilayers. The liposomes were made of egg lecithin (PC) and lissamine-phosphatidylethanolamine (lissamine-PE). The lissamine groups could be directly detected on the parasite membrane by observation of the single worms under a fluorescent microscope. The fluorescent marker was employed to measure the lateral diffusion coefficient (D) of lipids in the schistosomular membrane and as a surface marker during the isolation of the schistosomula surface membrane.

Animals↗
PubMed1986

Cis-platinum(II) complexes of carboxymethyl-dextran as potential antitumor agents. I. Preparation and characterization.

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were demonstrated to form complexes with dextran (dex) substituted with carboxymethyl (CM) groups at an average substitution ratio of 1 mole CM per 2 mole glucose units of dextran. The complexes were formed by reacting each of the two platinum (II) derivatives with carboxymethyl-dextran (CM-dex) at room temperature (RT) or at 37 degrees C in an aqueous solution. The complexing rate depended on temperature, ratio of platinum (II) compounds to CM-dex in the reaction mixture, and time of reaction. Experiments were performed with two CM-dex preparations, derived from dex T-10 (Mr-10,000) and from dex T-40 (Mr-40,000). Soluble cis-DDP and cis-aq complexes formed with CM-dex T-10 and CM-dex T-40 could carry up to 15 mole or 60 mole of the platinum (II) compounds per 1 mole CM-dex, respectively but higher complexing ratios resulted in complex precipitation. Reactivity of cis-aq with CM-dex was higher than that of cis-DDP. NaCl interfered with complex formation, but did not cause dissociation of already formed complexes. The binding of cis-DDP and cis-aq to CM-dex is, however, reversible since the drugs could be exchanged by other acceptors of higher affinity to platinum (II) such as O-phyenlenediamine, or DNA.

Antineoplastic Agents↗
PubMed1986

Cis-platinum (II) complexes of carboxymethyl-dextran as potential antitumor agents. II. In vitro and in vivo activity.

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were complexed to a macromolecular carrier carboxymethyl dextran (CM-dex). Two carriers were used in this study, one derived from dex-T-10 (Mr-10000) and the other from dex-T-40 (Mr-40000). The two platinum (II) drugs formed soluble complexes with both carriers. Uncomplexed and complexed drugs were tested and found to be cytotoxic in vitro against 5 murine and 2 human derived tumor cell lines. The two free platinum (II) drugs were cytotoxic against these cells to a similar extent. In comparison to the free drugs the complexes were somewhat less active, up to 3 fold, against murine 38C-13, L1210, EL-4 and RDM-4 leukemias, as well as against human HeLa and osteogenic sarcoma, and as active as the free drugs against murine F9 embryonal carcinoma. There were no major differences in the in vitro cytotoxic activity between CM-dex T-10 and CM-dex T-40 complexes. Differences due to the molecular size of the carrier were observed in vivo: The CM-dex T-10 complexes were significantly less toxic than the free drugs, whereas the reduction of toxicity by complexing to CM-dex T-40 was less profound. As for the efficacy, when tested in vivo against a cis-DDP sensitive tumor (F9) the T-40 complexes were equally or even more effective than the respective free drugs. The T-10 complexes were less effective than the free drugs at equal drug doses but their effectivity increased at increasing drug levels. These complexes were, however, very effective in inhibiting tumor growth upon repeated injections, leading to 100% survival.

Animals↗
PubMed1985

Priming immunization against cholera toxin and E. coli heat-labile toxin by a cholera toxin short peptide-beta-galactosidase hybrid synthesized in E. coli.

A synthetic oligodeoxynucleotide encoding for a small peptide was employed for the expression of this peptide in a form suitable for immunization. The encoded peptide, namely, the region 50-64 of the B subunit of cholera toxin (CTP3), had previously been identified as a relevant epitope of cholera toxin. Thus, multiple immunizations with its conjugate to a protein carrier led to an efficient neutralizing response against native cholera toxin. Immunization with the resulting fusion protein of CTP3 and beta-galactosidase, followed by a booster injection of a sub-immunizing amount (1 microgram) of cholera toxin, led to a substantial level of neutralizing antibodies against both cholera toxin and the heat-labile toxin of Escherichia coli.

Animals↗
PubMed1985

Specificity and cross-reactivity of synthetic peptides derived from a major antigenic site of influenza hemagglutinin.

A synthetic peptide corresponding to sequence 138-164 of influenza hemagglutinin elicited in rabbits antibodies that recognized different parts of the peptide, namely the loop region (139-146) and the rest of the peptide, region 147-164. This was shown both by direct binding and by competitive-inhibition experiments. Individual antisera differed in their specificity. The contribution of the Asp residue at position 144 to the antigenic specificity was shown in various inhibition assays. These data are in accordance with the reported effect of the exchange Gly----Asp on the serological specificity of influenza virus.

Animals↗
PubMed1985

Effect of carrier on the immunogenic capacity of synthetic cholera vaccine.

In the design of the synthetic antigens and synthetic vaccines, primary consideration should be given to the choice of the carrier. Since small peptides which are being used as the relevant antigenic determinants are likely to be poor immunogens as such, the augmentation of their immunogenic capacity by the carrier or any other means is crucial for the induction of immunity. In the present study, we explored several approaches for the enhancement of the immune response towards synthetic peptides derived from the B-subunit of cholera toxin. The results indicate that the use of tetanus toxoid as a macromolecular carrier, polymerization of the peptide without any external carrier and the conjugation of dipalmityl side chain had comparable effects in enhancing the immune response to several synthetic peptides. This effect was manifested both at the level of antibodies produced and in their capacity to neutralize the biological activity of the cholera toxin. Prior exposure to the carrier resulted in a dose-dependent suppression against the synthetic epitope attached to it.

Animals↗
PubMed1985

In vivo protection against S. mansoni infection by monoclonal antibodies.

A monoclonal antibody of the IgG1 class (27.21), that was previously shown to be cytotoxic in vitro to the schistosomula, conferred partial protection in vivo against challenge infection with S. mansoni. Monoclonal antibodies of the IgE class (54.10) were not effective in these experiments, but were capable of causing specific degranulation of basophilic cells upon contact with the young larva (3-6 h). The relevance of the IgE antibodies to protection observed in immunized mice is discussed.

Animals↗
PubMed1985

Identification of Schistosoma mansoni antigens by means of biologically active monoclonal antibodies.

Two monoclonal antibodies of the IgE class (54.10) and of the IgG1 class (27.21), that were shown previously to possess biological activity against Schistosoma mansoni larvae, were used for identification of surface antigens of the cercariae and schistosomula. This was performed by immunoprecipitation, immunoaffinity chromatography and immunoblotting. The epitope reactive with 27.21 mcIgG1 is present on four polypeptides (60, 50, 27 and 19 kDa) derived from the parasite. The 60 kDa is specific to cercariae, whereas the 50 kDa is a glycoprotein shared both by cercariae and schistosomula. The antigen reactive with the 54.10 mcIgE was isolated by affinity chromatography on 54.10 column, and contained three major peptides of 125, 94 and 30 kDa. The 125 and 94 kDa band probably originate from the same protein, since they yield almost identical peptide maps. The isolated antigen retained its biological activity as demonstrated in the basophils degranulation assay.

Animals↗
PubMed1985

A synthetic vaccine against influenza with built-in adjuvanticity.

In a previous publication we demonstrated that an anti-viral response against influenza can be achieved by immunization with a conjugate of the synthetic peptide corresponding to the sequence 91-108 of the hemagglutinin, when administered in complete Freund's adjuvant. In the present study we compare the adjuvant activity of the synthetic MDP with that of CFA and alum, in the above mentioned immunological system. The level of anti-peptide antibodies raised by the three adjuvants was similar, with only slight variations, yet, only CFA led to significant cross reaction with the virus. Nevertheless, MDP, when linked covalently to the conjugate (91-108)-TT was an efficient substitute for CFA in inducing anti viral protection against in vivo challenge infection. The administration of free MDP in a mixture with the peptide-toxoid conjugate did not lead to a significant protection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

The covalent linking of two nucleotide analogues to antibodies.

Two anticancer drugs, antagonists of nucleic acids, were covalently linked to antibodies specifically reactive with B leukemia cells and thus with a potential possibility of drug targeting to the tumor site. The drugs cytosine 1-beta-D-arabinoside and 5-fluorouridine, competitive inhibitors of enzymes involved in DNA synthesis, were linked to antibodies via a dextran bridge. Cytosine 1-beta-D-arabinoside was linked to periodate-oxidized dextran and fluorouridine to dextran hydrazide. The dextran derivatives were in turn linked to antibodies that recognized a specific membrane IgM on B leukemia cells. The drug-antibody conjugates maintained most of the original antigen-binding capacity of the antibody and the full pharmacological activity of the drugs.

Animals↗
PubMed1985

Biologically active antibodies elicited by a synthetic circumsporozoite peptide of Plasmodium knowlesi administered in saline with a muramyl dipeptide derivative.

A synthetic peptide whose sequence was derived from the circumsporozoite protein of Plasmodium knowlesi coupled to bovine gamma globulin has been shown to be immunogenic when administered with Freund complete adjuvant. The present experiments were designed to test the immunogenicity of the peptide when attached to a tetanus toxoid carrier and administered with alum or murabutide, both acceptable clinical adjuvants. In both cases, the use of an adjuvant increased the levels of circulating anti-peptide antibodies over those observed when no adjuvant was used. However, when the antisera were tested for reactivity with the native protein, animals of the group receiving the conjugate associated with murabutide always had titers greatly exceeding those observed in animals that received the conjugate with alum. Moreover, the sera of the murabutide-treated group were shown to be more active in eliciting shedding of the circumsporozoite protein than were sera of animals of the Freund complete adjuvant-treated group. The use of tetanus toxoid in secondary immunizations could be eliminated when the mice primed with peptide-tetanus toxoid and murabutide were boosted with a polymer of the peptide. The results indicate that the synthetic malarial peptide-tetanus toxoid conjugate is capable of stimulating high levels of biologically active antibodies only when administered with murabutide.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Some properties of the plasma hGH activity in patients with Laron-type dwarfism determined by a radioreceptor assay using human liver tissue.

A radioreceptor assay for human growth hormone (hGH) using the 100,000-g pellet of human liver tissue homogenates obtained from a 13-year-old male donor of a kidney transplantation is described. The dilution curves of the plasma hGH of 6 patients with Laron-type dwarfism (LTD) as well as those of the plasma hGH from 1 normal child and 2 acromegalic patients were all found to be parallel to the standard curve, suggesting that in the LTD syndrome the circulating hGH is biologically active.

Acromegaly↗
PubMed1985

Protective monoclonal antibody against Schistosoma mansoni: antigen isolation, characterization, and suitability for active immunization.

Monoclonal antibodies that bind to the surface of developing schistosomula were generated from the spleens of chronically infected mice that were boosted with cercarial glycoproteins. The two most reactive monoclonal antibodies, denoted 152-66-9B and 152-66-1C, were used for identification of surface antigens. The antigen detected by these monoclonal antibodies persisted on the surface of the developing larva for 72 hr posttransformation. This monoclonal antibody effected complement-mediated killing of schistosomula in vitro as efficiently as infected mouse sera. It was also very efficient in inhibiting the infectivity of both cercariae and schistosomula. The antigen reactive with the 152-66-9B monoclonal antibody contains two major polypeptides (45 and 30 KD). These polypeptide chains might have originated from the same protein, because they have the same isoelectric point in two-dimensional gel electrophoresis. Moreover, the affinity-purified antigen migrated as only one protein band of approximately 200 KD in SDS-PAGE in nonreducing conditions. The 9B antigen was isolated, purified, and used for immunization, resulting in an antigen dose-dependent partial protection against S. mansoni infection.

Animals↗
PubMed1984

Neutralization of heat-labile toxin of E. coli by antibodies to synthetic peptides derived from the B subunit of cholera toxin.

Antibodies elicited by six synthetic peptides corresponding to various fragments of B subunit of cholera toxin (CT) were evaluated for their cross-reactivity with heat-labile toxin (LT) of Escherichia coli. The antiserum directed towards the peptide CTP3 (residues 50-64) was found highly cross-reactive with the LT, in radioimmunoassay and immunoblotting. This peptide was also the most cross-reactive with intact CT. The antiserum against CTP1 (residues 8-20) was also cross-reactive with the two toxins, although to a much lower extent. Antisera to both CTP1 and CTP3, which are inhibitory towards CT, were found equally effective in neutralizing the biological activity of the E. coli LT. This was manifested by inhibition of both adenylate cyclase activity and fluid secretion into ligated ileal loops of rats. These results might indicate the potential of such synthetic peptides as the basis for a general vaccine against several types of infectious diarrhea.

Adenylyl Cyclases↗
PubMed1984

Acetylcholinesterase of Schistosoma mansoni. Molecular forms of the solubilized enzyme.

Several molecular forms of acetylcholinesterase were obtained from Schistosoma mansoni homogenates by extraction in either low-salt buffer, high-salt buffer or detergent buffer. The low-salt soluble form amounts to 25% of the total activity. By contrast, the extract obtained in the presence of Triton X-100 possessed almost almost 3-fold higher enzymatic activity, most of it (86%) being retained in the soluble extract (100 000 X g). High-salt concentration (1 M NaCl) also has a solubilizing effect, but to a lesser extent (50%). Acetylcholinesterase can also be solubilized by treatment with a solution of 1% methylmannoside (40%). In the presence of non-ionic detergents, the enzyme behaves as monodisperse 8 S form. In the absence of detergent the low-salt soluble extract is polydisperse: it contains a 10 S and a 32 S component, the latter could represent high polymers. The molecular form released from tissue homogenate by treatment with alpha-methylmannoside is polydisperse: it contains a major 10 S and a minor 32 S component. Differences in sedimentation coefficient were observed among the enzymes extracted with detergent from the various life cycle stages of the parasite. The enzyme from the cercarial stage sediments as a single 8 S peak. The adult worm exhibits an additional acetylcholinesterase peak of 18 S representing approx. 30% of the total enzymatic activity. The molecular weight of the major 8 S species, as determined by gel filtration, is 450 000.

Acetylcholinesterase↗
PubMed1984

Thymectomy and chronic relapsing experimental allergic encephalomyelitis in guinea pigs.

Chronic relapsing experimental allergic encephalomyelitis (EAE) was induced in young Dunkin Hartley guinea pigs by a single sensitization with guinea pig spinal cord homogenate. The effect of either newborn thymectomy or young adult thymectomy on the clinical course of chronic and relapsing EAE was studied and evaluated statistically by Student's t test. All the animals that underwent thymectomy showed a significant delay in the onset of the disease compared with control groups. In addition, in the young adult guinea pigs in which thymectomy was done, the incidence of clinical disease was decreased. No substantial differences, however, were observed in the severity of the disease and number of remissions or relapses between guinea pigs in which thymectomy was done and in which clinical symptoms developed and controls.

Animals↗
PubMed1984

Acetylcholinesterase of Schistosoma mansoni: antigenic cross-reactivity with Electrophorus electricus and its functional implications.

Acetylcholinesterase (AChE) of the parasite Schistosoma mansoni cross-reacts with rabbit antibodies against AChE from the electric eel. Cross-reactivity was demonstrated by radioimmunoassay with sonicate, as well as soluble, preparations from various stages of the parasite life cycle. On sucrose density gradient, the parasite enzyme migrates as an 7.5 S form, whereas an 9.5 S peak is observed with the enzyme-antibody complex. Immunofluorescence microscopy shows specific staining of intact schistosomula as well as of adult worms. Moreover, the interaction of these antibodies resulted in a marked complement-dependent cytotoxicity towards intact schistosomula, indicating that AChE is an antigen of significance on the surface of the parasite.

Acetylcholinesterase↗