Search PubMed⌕ Search

Biomedical subjects

R Arnon

Publications and source records attributed to R Arnon.

At least 217 records · Page 12Linked to original sources
PubMed1979

Idiotype anti-idiotype complexes in cerebrospinal fluids of multiple sclerosis patients.

The involvement of idiotype-anti-idiotype complexes in multiple sclerosis was approached by ultracentrifuge studies. Specimens of the immunoglobulin G fraction obtained from the cerebrospinal fluids of multiple sclerosis patients which contained distinct oligoclonal bands, were subjected to analytical ultracentrifugation. None of these samples revealed the presence of any detectable amount of oligomeric immunoglobulin G, namely dimer or trimer. By comparison with control mixtures containing known amounts of dimeric immunoglobulin, it was evaluated that the cerebrospinal fluid samples contain less than 5% dimer. These findings indicate that the spinal fluids of multiple sclerosis patients do not contain idiotype-anti-idiotype complexes to an extent that would account for the oligoclonal immunoglobulin bands as representing complementary idiotypes and anti-idiotypes.

Antibodies, Anti-Idiotypic↗
PubMed1979

Enzyme replacement in Tay-Sachs disease.

Enzyme replacement therapy was attempted with two Tay-Sachs-diseased individuals--a 14-month-old child and a 7-week-old infant. Treatment consisted of repeated weekly intrathecal injections of pure hexosaminidase A. Injection of this enzyme resulted in almost complete disappearance of GM2 from the serum, but did not bring about dissolution of the GM2 membranous cytoplasmic bodies in the brain, as detected by electronmicroscopy. Both patients tolerated the treatment without apparent clinical complications, but no clear-cut improvement was noted as a result of prolonged injections of hexosaminidase A. Since this treatment was initiated in both an advanced stage and a very early stage of the disease, we conclude that enzyme replacement treatment by this route is not beneficial for patients with Tay-Sachs disease.

Biopsy↗
PubMed1979

Effect of cyclophosphamide on suppressor cell activity in mice unresponsive to EAE.

Protection against experimental allergic encephalomyelitis (EAE) was induced in susceptible mice of (SJL/J X BALB/c)F1 hybrid, by injection of either mouse spinal cord homogenate, the small mouse basic protein, or Cop 1 in incomplete Freund's adjuvant, before EAE induction. It was demonstrated that the unresponsiveness induced by the three antigens is mediated by suppressor T cells residing in the spleen cell population and can be adoptively transferred to normal syngeneic recipients. Low dose of cyclophosphamide (20 mg/kg) administered 2 days before the encephalitogenic challenge abrogated the unresponsiveness to EAE and reverted the protected mice sensitive to disease induction. Cyclophosphamide was also active on adoptively transferred unresponsiveness, thus donors that had been treated with cyclophosphamide were unable to further transfer unresponsiveness to EAE. These results indicate the elimination by cyclophosphamide of suppressor cells that interfere with the effector mechanisms leading to EAE.

Animals↗
PubMed1978

Biochemical and immunochemical characterization of hexosaminidase P.

Hexasaminidase P, the main isozyme of hexosaminidase in pregnancy serum, was isolated and purified 600--700-fold by a two-step purification procedure--affinity chromatography on Sepharose-bound epsilon-aminocaproyl-N-acetylglucosylamine, followed by ion-exchange chromatography on DEAE-cellulose. The purified enzyme was subjected to biochemical and immunochemical analysis. Its catalytic property, namely, kinetic behavior, is similar to that of the major isozymes of hexosaminidase, A and B. However, it differs from these isozymes in its electrophoretic mobility and in its apparent molecular weight which is around 150 000 compared with 100 000 of the A and B isozymes. Immunochemical analysis indicates that the P isozymes is antigenically cross-reactive with both A and B isozymes, but it does not contain the A-specific antigenic determinants, and exhibits identical antigenic specificity to hexasaminidase B. Two possible structures are suggested that are compatible with the experimental data: (a) a hexosaminidase B like structure with higher extent of glycosylation; (b) a hexameter of beta chain, possibly arranged as three beta2 subunits.

Chemical Phenomena↗
PubMed1978

Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies.

Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.

Animals↗
PubMed1978

Purification, biochemical and immunological characterisation of hexosaminidase A from variant AB of infantile GM2 gangliosidosis.

Variant AB of infantile GM2 gangliosidosis is a fatal disease leading invariably to death within the first few years of life, due to the excessive storage of the glycolipids GM2 and GA2 which occurs in the nervous tissue of the patient. Unlike other variants of this hereditary disease, where a deficiency of hexosaminidase A, the ganglioside-GM2-degrading enzyme, could be demonstrated, the variant AB is characterized by a normal or even elevated level of this enzyme. To examine the possibility of a mutant hexosaminidase A, well capable of hydrolyzing the fluorogenic synthetic substrates but unable to attack the ganglioside, the enzyme was isolated from a patients tissue and characterized biochemically and immunologically in comparison with an enzyme preparation from normal control tissue. No differences between hexosaminidase A from normal and variant AB tissue could be detected indicating that the defect involved in this disease is not at the genetic level of production of either alpha or beta chains of hexosaminidase A.

Child, Preschool↗
PubMed1978

Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies.

The synthetic antigen denoted P2-A--L, comprising the fragment P2 of the coat protein of MS-2 coliphage attached to multichain poly-DL-alanine, served for the immunization of guinea-pigs. Immunization was carried out either in phosphate buffered saline (PBS) or in Freund's incomplete adjuvant (FIA) in the presence or absence of a small molecular weight peptidoglycan prepared from Bacillus megaterium, which was checked for its adjuvant effect. The various antisera were assessed by their capacity to neutralize MS-2 bacteriophage viability. When injected in PBS or FIA, P2-A--L did not elicit any measurable anti-phage activity. Addition of the peptidoglycan by simple mixing did not bring about a significant increase in antibody production. However, when the peptidoglycan was chemically linked to the P2-A--L conjugate, it had a marked adjuvant effect when the material was administered in FIA, almost identical to the extent of the effect of Freund's complete adjuvant.

Adjuvants, Immunologic↗
PubMed1978

Site-directed tumor chemotherapy.

The therapeutic effect of drugs used in cancer chemotherapy has been augmented by their complexing or chemical linking to macromolecular carriers. The role of the carrier should be to deliver the drug preferentially to the tumor site. Potential carriers are either (1) nonspecific macromolecules whose preferential activity is due to the inherently higher permeability and pinocytic activity of tumor cells, (2) lysosomotropic agents such as DNA or liposomes, or (3) the more specific agents--antitumor antibodies. Conjugates of daunomycin to antitumor antibodies, prepared either by direct binding or by binding via dextran, were shown to retain both the antibody and the drug activity. Thus they exert specific cytotoxic activity toward tumor cells that the antibodies recognize. In vivo, these complexes are more active than the free drug in prolongation of survival of mice transplanted with the tumor cells. Conjugates of daunomycin with normal immunoglobulin or with dextran also show higher therapeutic efficacy in vivo, probably due to their capacity to reduce the cytotoxicity of daunomycin and/or to the higher permeability of neoplastic cells. But under certain conditions, mainly at low drug concentrations, the drug-antibody conjugates have an advantage over all others.

Animals↗
PubMed1978

Hexosaminidase A in amniotic fluid of Tay-Sachs fetuses.

Hexosaminidase A is present in relatively low concentrations in cell-free amniotic fluids from pregnancies with Tay-Sachs fetuses. This isoenzyme was determined by an immunological procedure, radial immunodiffusion, by which hexosaminidase A can be directly and specifically detected, even in the presence of excess amounts of hexosaminidase B. No hexosaminidase A could be detected by the same procedure in Tay-Sachs fetal tissues, implying that this isoenzyme in the amniotic fluid originates from the mother.

Amniotic Fluid↗
PubMed1977

Stabilization of human beta-D-N-acetylhexosaminidase A towards proteolytic inactivation by coupling it to poly(N-vinylpyrrolidone).

Human hexosaminidase A was covalently bound to soluble poly(N-vinylpyrrolidone), and the effect of this binding on the enzyme inactivation by various procedures was investigated. Whereas the polymer-bound hexosaminidase underwent inactivation to the same extent as the free enzyme, when exposed to heat or acidic pH, the conjugation to polymer appeared to protect the enzyme towards proteolysis. Thus, the polymer-bound enzyme exhibited considerably higher resistance to treatment of both pronase and macrophage cathepsins. The clearance rate from rabbit blood, of the polymer-bound enzyme (expressed as enzyme activity), was shown to be significantly slower than that of the free enzyme.

Drug Stability↗