Studies on the types of immune responses to synthetic antigens in guinea-pigs.
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Biomedical subjects
Publications and source records attributed to M Sela.
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Guinea pigs injected with 100 micrograms of p-azobenzenearsonate derivatives of hexa-L-tyrosine, tri-L-tyrosine, or N-acetyl-L-tyrosine amide, in complete Freund's adjuvant, developed, after 10 to 19 days, delayed-type hypersensitivity to these substances. This was shown by skin reactions, followed by the formation of circulating antibodies that were detectable by passive cutaneous anaphylaxis. Experiments with p-azobenzenearsonate-hexa-L-tyrosine labeledwith iodine-131 showed that this substance was bound in vitro to proteins of normal guinea pig serum. Binding was similar with the nonantigenic hexa-L-tyrosine and its p-azobenzoate derivative.
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Immunization of CBA and C57 mice with a branched, multichain synthetic polypeptide, poly (tyr,glu)-poly DL-ala--poly lys, ((T,G)-A--L), in Freund's complete adjuvant results in a tenfold or more difference in the antigen-binding capacity of sera from the two strains, although they respond equally to bovine serum albumin. Immunization of CBA x C57 F(1), F(1) x CBA, and F(1) x C57 mice reveals definite genetic control of the response to (T,G)-A--L, which appears to be due to a single major genetic factor, with perhaps one or more modifying factors. Immunization of CBA and C57 mice with (H,G)-A--L, a synthetic polypeptide in which histidine replaces tyrosine, gives the opposite result, CBA's respond and C57's do not. From this, it appears that the genetic control of the response to (T,G)-A--L is specific for the antigenic determinant. The implications of these results are discussed.
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1. Three random linear copolymers composed of two or three of the amino acids d-tyrosine, d-glutamic acid, d-alanine and d-lysine, and a branched multichain copolymer with a poly-d-lysine backbone and polymeric side chains of d-tyrosine and d-glutamic acid, were found to be non-antigenic in rabbits, by precipitin and passive cutaneous anaphylaxis, and in guinea pigs, by delayed hypersensitivity tests. The corresponding four copolymers of l-amino acids were shown to be antigenic by all the three criteria. 2. No immunological cross-reactions were observed between the polypeptides composed of d-amino acids and the corresponding l-amino acid copolymers. 3. Similarly, an azobenzenearsonic acid conjugate of poly-d-tyrosine was shown to be non-antigenic in guinea pigs, in contrast with an analogous conjugate of poly-l-tyrosine. Animals sensitized with the conjugate of poly-l-tyrosine did not exhibit delayed skin reactions, when cross-tested with the d-conjugate. 4. A linear polymer composed of d-tyrosine, l-glutamic acid and l-alanine was found to be immunogenic and to cross-react with the corresponding polymer composed exclusively of d-amino acids.
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We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000 degrees/sec 2 and with a rise time of 1-2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200-2000 Hz; average of 1024 trials), had amplitudes of about 0.5 microV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30-300 Hz; N = 128 trials), with larger amplitudes (about 15 microV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths.(ABSTRACT TRUNCATED AT 250 WORDS)
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The ribose moiety of 5-fluorouridine (FUR) was oxidized with periodate and the product was bound through a poly(L-lysine) bridge to monoclonal antibodies, denoted SF25MAb, reactive with a human colon carcinoma LS180. The antibody was linked via its polysaccharide (previously oxidized with periodate) to the poly(L-lysine)-drug conjugate. The linking of FUR-poly(L-lysine) to the antibody markedly increased the latter's binding to the tumor cells. A relatively lower increase was also observed with conjugates of nonrelated antibodies, such as anti-hepatitis B surface antigen and anti-epidermal growth factor receptor antibodies. The pharmacological activity of the specific conjugate FUR-poly(L-lysine) -SF25MAb was higher than that of the drug-substituted polymer alone. The poly(L-lysine) bridge caused toxic effects in vivo, even though substituted both by FUR and by antibody. Therefore, the additional unreacted lysyl residues were blocked by succinylation. Partial blocking of free amino groups on the conjugate rendered it nontoxic but decreased its cell-binding capacity, though to a level still higher than that of the original unmodified antibody. The pharmacological activity of the specific conjugate after blocking was also reduced and necessitated prolonged incubation periods or higher concentrations. Following periodate oxidation and reduction, FUR was as effective as the clinically preferred compound 5-fluoro-2'-deoxyuridine in vitro and in vivo, against the LS180 colon carcinoma. Experiments in nude mice, with LS180 tumor subcutaneous xenotransplants, showed that FUR-poly(L-lysine)-SF25MAb (blocked by succinylation) was not toxic and was effective in the retardation of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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In 12 chronically ill patients, 14 overdentures were inserted. The status of the retained teeth and the denture-supporting structures was evaluated annually for up to 4 years. The limitations and implications of this therapy as related to specific chronic diseases, medications, and patient behavior are emphasized. Based on short- and long-term follow-up, recommendations for the applicability of overdentures in systemically ill patients are offered.
The prevalence of dental caries and periodontal treatment needs in an institutionalized population with Down syndrome was examined and the relationship between caries prevalence, salivary pH, and salivary levels of Streptococcus mutans was studied. Thirty-two children with Down syndrome, aged 8 to 13, were compared with two control groups of similar age ranges: healthy children and non-Down mentally retarded (MR) children living in the same institution as the Down syndrome population. The gender ratio mixtures in each group also matched the study sample. Caries experience as indicated by decayed, missing, and filled surfaces (DMF-S) showed significantly lower mean scores for the Down syndrome group compared with both control groups. A similar pattern was found when evaluating the mean numbers of decayed surfaces. Streptococcus mutans counts, expressed as number of colony-forming units on mitis salivarius agar plates among the Down syndrome group, were the lowest, although not statistically significant compared with the counts of the healthy children. Both groups had bacterial counts which were significantly lower than those of the MR group. Significant differences between the two institutionalized groups and the healthy group were recorded for the salivary pH levels. The periodontal treatment needs as evaluated by the Community Periodontal Index of Treatment Needs showed significant difference between the MR group versus both the healthy population and the Down syndrome group. On the whole, 84% of the Down syndrome children were cariesfree.