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Biomedical subjects

M Sela

Publications and source records attributed to M Sela.

At least 217 records · Page 12Linked to original sources
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

Determinants of antigenic molecules responsible for genetically controlled regulation of immune responses.

The ability of mice bearing the H-2S haplotype to develop helper responses to the random copolymer of Glu,Ala while they developed suppressor responses to the terpolymer of Glu,Ala,Tyr suggested the crucial role of tyrosine in these peptides. On the basis of various considerations, it was postulated that many of the tyrosine residues in Glu,Ala,Tyr would be localized at the NH2-terminal end of the molecule. To verify this hypothesis, a block terpolymer composed of a short sequence of homopolymer tyrosine covalently bound to the random copolymer of Glu,Ala was synthesized. The present studies, using this block terpolymer, demonstrated that the chemical determinants stimulating helper and suppressor responses are distinct and can be present simultaneously in the same molecule. Thus, addition of COOH-terminal tyrosine residues to the Glu,Ala polypeptide converted this immunogenic molecule to an immunosuppressive molecule in mice bearing the H-2S haplotype. The mechanism by which these short sequences of tyrosine influence H-2-linked immune responses remains to be determined.

Alanine↗
PubMed1976

Genetic control of immune responsiveness to poly (LPro)--poly (LLys)-derived polypeptides by histocompatibility-linked immune response genes in the rat.

In rats responsiveness to branched synthetic polypeptides carrying a Pro--L backbone, such as (T,G)-Pro--L or (Phe,G)-Pro-L and to Pro--L itself is controlled by Ir genes which are linked to the major histocompatibility genes. The level of antibody production to these polypeptides does not fall into strict high or low responder categories but covers the range in between. (T,G)-pro--L and Pro--L elicit a very similar response pattern which, however, differs from that obtained with (Phe,G)-Pro--L. Anti-(T,G),Pro--L antibodies do not cross-react with (T,G)-A--L, but do so extensively with Pro--L. Anti-(Phe,G)-Pro--L antibodies show cross-reactivity to (Phe,G)-A--L only when the antibody-producing strain is a high responder to (Phe,G)-A--L. These results when considered in view of data obtained in mice on genetic control of the immune response to (T,G)-Pro--L suggest that at least two unlinked Ir genes are involved in controlling anti-Pro--L responsiveness.

Animals↗
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

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

Binding of histamine- and other ligand-conjugated macromolecules to lymphocytes.

The presence of histamine receptors on lymphocyte membranes was investigated using conjugates of histamine and macromolecules tritiated or iodinated with I-125. Histamine-RSA conjugate binds to lymphocytes and causes patching and capping of the bound conjugate. It was found, however, that free histamine did not inhibit the binding of histamine-rabbit serum albumin to mouse lymphocytes, nor did His-RSA interfere with the binding of free histamine. In addition conjugates between RSA and other small molecules, such as ethylamine, ethanolamine, tyramine and glycine, were found to bind to the same sites on lymphocyte membrane as did His-RSA. Ethylamine-RSA like His-RSA when coupled to Sepharose, was capable of removing antibody producing cells from spleen cells of mice immunized against sheep red blood cells. In addition, when spleen cells from such immunized mice were passed through ethylamine or histamine-RSA-Sepharose and the unbound cells were subsequently injected into X-irradiated mice, a 1.8 fold increase in the immunological response was noted. We conclude that the selective binding to lymphocytes of the various ligand-macromolecular conjugates may be due to some general properties of the cell membrane and not to any specific receptors. Nevertheless, these conjugates can be used as a tool to remove selectively antibody producing cells as well as some regulatory cells.

Animals↗
PubMed1975

Genetic control of immune response. The dose of antigen given in aqueous solution is critical in determining which mouse strain is high responder to poly(LTyr, LGlu)-poly(LPro)--poly(LLys).

Antibody response to different doses of (T,G)-Pro--L, given in aqueous solution, was investigated in the high responder SJL and low responder DBA/1 strains by measuring hemolytic plaque-forming cells (PFC) in the spleens as well as hemagglutination titers in the sera. The gene responsible for the difference between the two strains in the response to this antigen, given in complete Freund's adjuvant, has been previously denoted Ir-3. This gene is not linked to the major histocompatibility locus. In the response to the optimal dose (1 mug) of antigen, no difference could be shown between the strains. The peak of the response and the numbers of direct and indirect PFC were similar in both strains in the primary and secondary response. After injection of higher doses (10-100 mug) of antigen, both the direct and indirect PFC responses were lower in the low responder than in the high responder strain. Moreover, the peak of the response occurred earlier in the high responder strain in the primary response to the 10 mu dose of antigen. After administration of a suboptimal dose (0.02 mug) of antigen, the low responder strain produced in the primary response 4-20 times more indirect plaques than the high responder strain. Also the number of direct plaques was higher in the low responder than in the high responder strain. The serum antibody responses to the optimal and higher doses of antigen were parallel to the PFC responses. From inhibition of PFC with free antigen, it was concluded that a similar proportion of cells was producing high and low affinity antibodies to (T,G)-Pro--L in both strains. High and low zone tolerance could be induced in the two strains with (T,G)-Pro--L, but no difference could be shown between the strains. It is suggested that the Ir-3 gene plays a role in the regulation of the balance stimulation and suppression according to the dose of antigen given.

Animals↗
PubMed1975

Shape and volume of fragments Fab' and (Fab')2 of anti-poly(D-alanyl) antibodies in the presence and absence of tetra-D-alanine as determined by small-angle x-ray scattering.

The conformation of two fragments derived from anti-poly(D-alanyl) antibodies, the divalent fragment (Fab')2 and the monovalent fragment Fab', was studied by small-angle X-ray scattering before and after interaction with the tetra-D-alanine amide hapten. More than 90% of the combining sites were occupied by the hapten. No significant changes were observed in the volume or in the radius of gyration, with either of the fragments. This contrasts with the significant decrease in these two parameters found upon reacting the hapten with intact anti-poly(D-alanyl) antibodies (I. Pilz, O. Kratky, A. Licht, and M. Sela (1973), Biochemistry 12, 4998). For Fab', the radius of the whole particle was found to be 3.48 nm in the absence of the hapten and 3.46 nm in its presence, the radius of gyration of the cross-section was 1.37 nm without hapten and 1.38 nm in its presence, and the volume of the particle was 98 nm3 in the absence of the hapten and 91 nm3 in its presence. For (Fab')2 the respective values were 5.06 and 5.05, 1.38 and 1.37, and 182 and 182. These results suggest that a conformational change occurs within the antibody molecule, but not within its Fab fragment, upon reaction with the tetraalanine hapten.

Alanine↗
PubMed1975

Oral manifestations of Morquio's syndrome.

The clinical and laboratory findings in two siblings affected with Morquio's syndrome are described. The oral findings, consisting of disturbances in the structure of the enamel in both deciduous and permanent teeth, resemble those of amelogenesis imperfecta, Type 1. Preformed crowns are recommended as the initial treatment, in order to avoid loss of vertical height. The dentist's familiarity with the oral manifestations of Morquio's disease may contribute to the early detection of this condition.

Child↗
PubMed1975

Adaptation of silicate and Adaptic to the margins of cavities. A scanning electron microscope study.

The effects of etching of the enamel, on the adaptation of silicate and Adaptic to the cavity walls was examined with the scanning electron microscope. Replica methods were utilized to ensure that no shrinkage of the filling materials was caused by the vacuum in the instrument. It was shown that following etching of the cavity margins, Adaptic adhered to the enamel with absent, or minimal, fissure formation on one side of the filling, and some on the opposite side. The adaptation of silicate to the margins of the cavities was not improved by etching.

Composite Resins↗
PubMed1975

The effect of local anesthetic solutions on the blood vessels of the rat molars.

The effect of solutions of lidocaine, with and without adrenaline, on the blood vessels of the dental pulp and periodontal ligament in rat molars was examined. The vessels were visualized by intravascular injection of a supension of carbon particles. The results indicate that the anesthetic solution alone does have a local effect on the blood vessels. Local anesthetic solutions containing adrenaline had a more marked effect; in addition, a dose-dependent systemic effect of adrenaline was noted.

Animals↗
PubMed1975

Genetic control of the murine cell-mediated immune response in vivo. II. H-2 linked responsiveness to the synthetic polypeptide poly(Tyr,Glu)-poly(DL-Ala)--poly(Lys).

Cell-mediated immunity in response to (T,G)-A-L was studied with a radioisotopic footpad assay. It appears that in vivo cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was demonstrated previously for specific antibody snythesis. Evidence is presented in this report which indicates that the cell-mediated immunity measured is a function of a population of T cells. The apparent controversy between results obtained by analyzing antibody formation and cell-mediated immunity can be explained by assuming the need for cell cooperation between helper T cell and effector T cell, because efficient purely cellular immunity is analogous to T-B cell cooperation needed for antibody production.

Animals↗
PubMed1975

Lack of inverse relationship between the net charge of T-independent immunogens and the responding spleen cells.

Previous studies have demonstrated an inverse relationship between the net electrical charge of immunogens and the antibodies they elicit. This correlation was found to be expressed at the cellular level. It has been shown that thymus-derived cells may recognize immunogens on the basis of their overall electrical charge. In this study, charged T-independent copolymers composed of tyrosine, glutamic acid, and lysine of the D configuration were prepared in order to find out whether this net charge phenomenon holds also for immunogens which do not require helper T cells for generation of immune response. Spleen cells were fractionated over negatively charged glass bead columns, and their immunocompetence was tested by transferring them into irradiated recipient mice which were immunized with the dinitrophenylated acidic or basic T-independent carrier. No differences in the responsiveness to the dinitrophenyl group on either carrier could be detected in recipients of unfractionated or fractionated cells on the charged columns. Similar results were obtained with the negatively charged T-independent branched polypeptide poly-(DTyr,DGlu)-poly(DPro)--poly(DLys). Filtration of spleen cells through glass bead columns did not affect the immune response potential of the recipient mice. In contrast, a significant reduction was observed in the frequency of positive responses in recipients of filtered cells, which were immunized with the negatively charged T-dependent poly(DTyr,DGlu)-poly(DPro)--poly(DLys). Thus, the inverse net charge phenomenon holds only for T-dependent antigens.

Animals↗
PubMed1975

The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities.

Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity.

Animals↗