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Biomedical subjects

R Arnon

Publications and source records attributed to R Arnon.

At least 235 records · Page 13Linked to original sources
PubMed1977

Experimental allergic neuritis induced by a basic neuritogenic protein (P1L) of human peripheral nerve origin.

Experimental allergic neuritis (EAN) in the peripheral nervous system, without involvement of the central nervous system, was produced in laboratory animals by the injection of a basic neuritogenic protein, P1L, purified from human peripheral nerves. The animals manifested a positive skin test with P1L, and their lymphocytes were found to be transformed in vitro in the presence of this protein several days before the appearance of the clinical signs. Passive transfer of the disease was performed with lymph node cells from donor guinea pigs immunized with P1L protein. EAN, the experimental model for the human disease Guillaain-Barré syndrome, was shown to be a transient disease and could be suppressed by the administration of hydrocortisone.

Animals↗
PubMed1977

Effect of a synthetic polypeptide (COP 1) on patients with multiple sclerosis and with acute disseminated encephalomeylitis. Preliminary report.

Three patients with acute disseminated encephalomyelitis (ADE) and 4 patients in the terminal stages of multiple sclerosis (MS) were subjected to treatment with Cop 1, a synthetic copolymer of amino acids, which had previously been shown to have a beneficial effect in the treatment of experimental allergic encephalomyelitis (EAE). Under the treatment, the ADE patients recovered completely within 3 weeks, but 1 of 2 control cases treated with steroids showed complete recovery as well. The MS patients did not show any significant change in their motor function; however, 2 of them showed some improvement in vision and speech capacity. It is too early to conclude whether this improvement is related to the treatment. No side effect was observed in any of the patients treated with Cop. 1.

Acute Disease↗
PubMed1977

Immunochemical and biochemical investigation of hexosaminidase S.

Hexosaminidase S (HEX S), the residual isozyme found in tissues and body fluids of children with the O variant of GM2 gangliosidosis, was purified from tissues of variant individuals and biochemically and immunochemically characterized. This enzyme has an apparent molecular weight of 103,000 with an isoelectric point of 4.2, is heat labile to the same extent as HEX A, and loses most of its activity following heating for 30 min at 50 degrees C. HEX S reacts immunologically with the antisera against either HEX A or B, but the reaction is considerably stronger with the anti-A serum or with antibody preparations which react exclusively with the A isozyme. Results obtained by a radioimmunoassay using the various antisera indicated that there is no antigenically cross reacting material which lacks enzymatic activity in the variant tissues. These findings are in accord with a suggested molecular structure of two subunits, each composed of two alpha chains (alpha2 alpha2) for HEX S; it also implies that alpha and beta chains have some structural similarity which is manifested in antigenic cross-reactivity.

Antibodies↗
PubMed1977

Viroimmunoassay utilizing a synthetic peptide: a test equivalent to the carcinoembryonic antigen radioimmunoassay.

A recently developed immunoassay which utilizes the synthetic fragment CEA(1-11), corresponding to the N-terminal segment of carcinoembryonic antigen (CEA), was used for the evaluation of human sera. The various sera were tested for their capacity to inhibit the inactivation of the modified bacteriophage preparation CEA(1-11)-T4 by antiserum prepared against the bovine serum albumin (BSA) conjugate CEA(1-11)-BSA. In this immunological system both the free synthetic peptide and a semipurified preparation of intact CEA serve as inhibitors. Sera from a large proportion (85%) of patients with adenocarcinomas of the digestive tract, including the pancrease, gave 50 to 88% inhibition. Sera from patients with other cancers, particularly of breast and ovary, also caused inhibition, although it was less marked in both incidence and level. Most normal sera gave less than 40% inhibition, which was considered as the cutoff point. This assay, like the CEA radioimmunoassay, is not suitable for mass screening nor can it be the primary criterion for diagnosis of cancer, but it might be of value as a follow-up procedure for postoperative diagnosis and prognosis.

Adenocarcinoma↗
PubMed1976

Chemical characterization and subunit structure of human N-acetylhexosaminidases A and B.

Human hexosaminidases A and B were purified from placentae, using two stages of affinity chromatography, to a high degree of purity. Each enzyme was purified 5000-6000-fold, and isolated in 25-40% yield. Enzyme preparations appeared homogeneous in the analytical ultracentrifuge and by acrylamide gel electrophoresis. Hexosaminidase A contained 1.65 residues of sialic acid per molecule, whereas no sialic acid was present in hexosaminidase B. The molecular weights of the A and B isozymes as determined by gel filtration and sedimentation equilibrium are 100 000 and 108 000, respectively. In 5 M guanidine-HCl each of the enzymes yielded a 50 000-dalton species, which can further be dissociated into 25 000-dalton polypeptide chains by reduction and alkylation. The hexosaminidase B yielded one type of polypeptide chain, denoted beta, whereas the product from hexosaminidase A could be separated by ion-exchange chromatography into two species of chains, denoted alpha and beta, in equal amounts. The amino acid compositions of the separated alpha and beta chains were determined, and were found to correlate well with those of the intact enzymes. These findings enable the construction of a plausible model for the molecular structure of both enzymes. According to this model hexosaminidase A is composed of two subunits alpha2 and beta2, in which the two polypeptide chains are linked by a disulfide bridge. The structure of hexosaminidase B is, in parallel, beta2beta2. The suggested model is discussed in view of the accumulated information about the interrelationships between hexosaminidase A and B and the genetic metabolic disorders with which they are involved.

Amino Acids↗
PubMed1976

Antiviral effect on MS-2 coliphage obtained with a synthetic antigen.

The coat protein of bacteriophage MS-2 was cleaved with cyanogen bromide to yield three fragments, possessing the sequence 1-88 (P1), 89-108 (P2), and 109-129 (P3), respectively. The mixture of peptides P2 and P3, which could not be separated, was found capable of inhibiting the neutralization of the phage by antiserum to the whole MS-2. The peptides corresponding to P2 and P3 were therefore synthesized. The synthetic P3 had no capacity to interfere with neutralization of MS-2, not did its macromolecular conjugate with multichain poly(DL-alanine) elicit neutralizing antibodies. On the other hand, the synthetic P2 was very efficient in inhibiting the inactivation of the phage by the antiserum against phage. Furthermore, a synthetic antigen prepared by attachment of P2 to multichain poly(alanine) incuded antiserum in rabbits that was capable of neutralizing MS-2 activity almost as efficiently as the antiserum prepared against the intact coat protein. This inactivation is specific, because it can, in turn, be totally inhibited by P2 peptide.

Antibodies, Viral↗
PubMed1976

Immunological cross-reactivity of antibodies to a synthetic undecapeptide analogous to the amino terminal segment of carcinoembryonic antigen, with the intact protein and with human sera.

A peptide corresponding to the 11 amino acid residues of the NH2-terminal portion in the sequence of carcinoembryonic antigen(CNTHETIC CEA(1-11) peptide was attached by means of a water-soluble carbodiimide reagent to multichain poly(DL-alanine( as well as to bovine serum albumin. Both macromolecular conjugates provoked in rabbit anti-CEA(1-11) peptide antibodies. The specificity of this immunological system and the crossreactivity between the peptide and intact CEA were investigated by two methods--passive hemagglutination and modified bacteriophage inactivation. Hemmagglutination experiments showed that not only anti-CEA(1-11) sera, but also anti-CEA sera, agglutinated CEA(1-11)-coated sheep erythrocytes, and both these reactions were inhibited with CEA(1-11) peptide. In experiments with the chemically modified bacteriophage technique CEA(1-11)-coated phase was efficiently inactivated with antisera against the CEA(1-11) conjugates, and the inactivation reaction could be totally inhibited with the free peptide. The semipure CEA, but not the pure protein, could also inhibit the phage inactivation, even though less efficiently. On the basis of the above results, sera of some cancer patients were tested for their capacity to inhibit the inactivation of CEA(1-11)-coated phage by means of anti-CEA(1-11) antiserum. The results indicate that sera from a large proportion of patients with adenocarcinomas of the digestive tract, pancreas, and breast are capable of inhibiting the above inactivation, whereas most normal sera do not inhibit.

Adult↗
PubMed1976

Fab dimers of antitumor immunoglobulins as covalent carriers of daunomycin.

Fab dimers were prepared by pepsin digestion from the immunoglobulin fraction of a rabbit antiserum towards the Yac Moloney virus lymphoma cells. Daunomycin was attatched to these (Fab)2 by covalent binding. The resultant conjugates exerted pharmacological toxic activity and specificity towards Yac target cells similar to that observed previously with conjugates of intact anti-Yac IgG. The activity was manifested both in vitro by inhibition of RNA synthesis and by the effect of reduction of the growth of the tumor cells in vivo after short exposure to the conjugates. The potential advantage of using an IgG molecule devoid of its Fc portion is discussed.

Animals↗
PubMed1975

Immunochemical studies on tyrosinase induction in Neurospora.

An immunoassay for tyrosinase, using the modified bacteriophage technique, was developed: Tyrosinase of Neurospora was conjugated to bacteriophage T4 using glutaraldehyde as a cross-linking agent. The conjugated phage that survived the coupling process could be inactivated by antiserum raised in rabbits against pure tyrosinase, but not by normal serum. This inactivation was specifically inhibited by pure Neurospora tyrosinase, and the degree of inhibition was proportional to the concentration of tyrosinase within the range of 30-150 ng/ml. Crude mycelial extract possessing tyrosinase activity could similarly inhibit the inactivation of the conjugated phage by the antiserum. To evaluate the tyrosinase content of crude extracts their inhibitory capacity was compared to that of known amounts of pure tyrosinase, and the amounts thus calculated agreed with those predicted from an enzymatic assay. The tyrosinase-bacteriophage immunoassay was used for the quantitation of tyrosinase-antigen in crude extracts of Neurospora cultures that had been induced to form tyrosinase by the addition of ethionine. Enzymatic activity appeared after a lag of several hours, increased for 2-3days and then declined. Immunological assays of these cultures showed: (a) serologically reactive protein started to accumulate upon culture starvation and was evident during the lag period; (b) specific activity (units per mg antigen) was constant throughout induction; (c) at the phase of decrease in mycelial enzyme content, increasing amounts of serologically reactive protein were detected in the medium, indicating that some enzyme was eventually excreted. These results show that the lag is not a qualitatively distinct period, and support the previously forwarded notion that tyrosinase is synthesized de novo upon induction.

Antigen-Antibody Reactions↗
PubMed1975

Inverse relationship between net electric charge on the antigen and that on the sensitized cell in cellular immune response: demonstration with basic encephalitogen of the brain.

An inverse relationship exists between the net-electrical charge of immunogens and the antibodies elicited (1). The cellular basis of the net charge phenomenon has been established for both positively and negatively charged immunogens, by cell separation techniques over columns of opposite charge (7, 8). To establish whether this phenomenon can be extended to include cell-mediated immunity, the response to basic encephalitogenic protein (BE) which induces experimental allergic encephalomyelitis (EAE) was now investigated. Lymph node cells from sensitized strain 13 guinea pigs were fractionated over positively and negatively charged columns and compared to unfractionated cell populations in two assay systems: (a) in vitro response to BE in terms of lymphocyte transformation and (b) the passive transfer of EAE to unsensitized syngeneic recipients. The response was found to be confined to the fraction of cells eluted from glass bead columns, namely, the more negative cells. Cells eluted from poly-L-lysine-coated glass bead columns (i.e., positive cells) were devoid of the capacity to respond to this antigen either in vivo or in vitro. It was previously established that thymocytes rather than bone marrow cells account for the inverse charge phenomenon as assayed by T-helper-cell function in in vivo antibody production (8). We have now extended the inverse charge effect to include cell-mediated immune response of the delayed hypersensitivity type.

Animals↗
PubMed1975

Specific determination of N-acetyl-beta-D-hexosaminidase isozymes A and B by radioimmunoassay and radial immunodiffusion.

The two major isozymes of N-acetylhexosaminidase, namely hexosaminidases A and B were quantitatively determined in tissues and biological fluids of both normal individuals and Tay-Sachs patients. The determination was carried out by two sensitive immunoassays:radial immunodiffusion, using chromogenic substrate, and radioimmunoassay, which were developed in this study. For this purpose [corrected] we used either a cross-reactive antiserum which reacts to a similar extent with both isozymes, or an antiserum reacting exclusively with hexosaminidase A (obtained by selective immunoadsorption). This enabled the quantitisation of the two isozymes separately, or in the presence of each other, in purified enzyme preparations or in tissue homogenates, affording a direct positive determination of hexosaminidase A. The results demonstrated that normal tissues contain the two isozymes in comparable amounts, whereas tissues of Tay-Sachs patients lack hexosaminidase A or any material which carries the A-specific antigenic determinants. The possible applications of these assays and their potential use in diagnosis are discussed.

Acetylglucosaminidase↗
PubMed1975

Cellular immune response to peripheral nerve basic protein in idiopathic facial paralysis (Bell's palsy).

Lymphocytes from patients with Bell's palsy were shown to undergo significant stimulation when cultured in vitro in the presence of a purely neuritogenic basic protein (P1L) isolated from human peripheral nerve myelin. No sensitization was observed to other neural antigens, namely, another periperal nerve myelin basic protein (P2) and the central nerve myelin basic encephalitogenic protein (BE). A similar pattern of response was also demonstrated in patients with Guillain-Barré syndrome (GBS). Lymphocytes from patients suffering from other neuropathies or other diseases involving the face showed no response to any of these antigens. The specific in vitro response to P1L protein in Bell's palsy may suggest that an in vivo sensitization of lymphocytes to such self protein occurs in this condition, and that cell-mediated, probably post-infectious, autoimmune mechanisms may be an important factor in the pathogenesis of the paralysis. Thus, Bell's palsy is immunologically similar to GBS, or may even represent a mononeuritic variant of GBS. In view of these findings the administration of steroids to patients with Bell's palsy seems logical on the basis of their immunosuppressive action.

Adolescent↗
PubMed1975

Neuritogenic and encephalitogenic properties of the peripheral nerve basic proteins.

Two basic proteins, P1 of molecular weight 14,200 and P2 of molecular weight 12,300, purified from bovine peripheral nerve, were assayed for biological activity. The P1 protein is an exclusively neuritogenic agent, capable of producing clinical signs of experimental allergic neuritis (EAN) and histological abnormalities in the peripheral nervous system (PNS) of guinea pigs and rabbits, without any changes in their central nervous system (CNS). P2 protein, like the CNS basic encephalitogenic protein (BE), has combined neuritogenic and encephalitogenic activities, therefore it induces in these animals neurological signs and pathological evidence of EAN, as well as histological characteristics of experimental allergic encephalomyelitis (EAE).

Animals↗