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Presentations des localisations et attributions des 105 niveaux du champ cristallin de Ho 3+ dans ce systeme trigonal. On les localise et attribue a partir des transitions observees dans les spectres d'absorption orthoaxiale a polarisation π et σ et axiale. Ces spectres sont obtenus sur des echantillons monocristallins, entre 5 et 295 K. Les donnees empiriques des niveaux d'energie sont analysees en termes d'un hamiltonien modele pour la configuration electronique 4f 10 supposee etre perturbe par un champ cristallin de symetrie trigonale (D 3 )

SummaryA high capacity, quantitative radioimmunoassay procedure has been developed to measure IgG antibodies to streptokinase (SK) in human serum. Results showed that the use of low concentrations of 125I-SK (100 ng/ml) and ambient temperature incubation conditions minimised degradation of the target labelled antigen and afforded antibody binding values which could be confidently related to the native intact SK protein. SK-complexed to plasminogen was also shown to retain the equivalent antigenic activity of native SK. Comparison of the absolute anti-SK levels with streptokinase resistance titres demonstrated that the two measurements of antibody correlated statistically but afforded quantitatively poor agreements. A survey of IgG levels to SK in sera from 93 normal healthy volunteers showed that all individuals displayed readily measurable anti-SK antibodies, with some 80% having IgG concentration capable of binding in excess of 1 μg SK per ml serum.

Previous studies on histamine release by corticotropin peptides and melittin peptides were extended, leading to the identification of a synthetic peptide intermediate, Lys(Z)-Arg(NO2)-Arg(NO2)OMe, (I) as an active non-cytolytic histamine releaser from rat mast cells. However, significant differences in the releasing capacity of optical isomers of this compound, and of Lys-Lys-Arg-ArgOMe [methyl ester of corticotropin-(15-18)-tetrapeptide; ‘basic core’] were observed, with the L-forms being markedly more active. A study of various analogues of the tripeptide compound (I) indicated that the structural basis for mast-cell triggering by such peptidic agents was highly specific. The relevance of these observations to the immunologically induced histamine-release processes is discussed.

Locations and assignments of 104 crystal-field levels have been made for Ho3+ in the trigonal Na3[Ho(oxydiacetate)3]·2NaClO4·6H2O system. These energy levels span the 0–36100 cm−1 energy region, and they were located and assigned from axial and orthoaxial (σ and π polarized) absorption measurements on single crystals. The assigned levels are analyzed in terms of a 26-parameter hamiltonian in which six of the parameters are defined to represent the 4f-electron-crystal-field interactions for Ho3+ ions located at sites with trigonal dihedral (D3) symmetry. Quantitative line intensities have been determined for 59 individual 4f → 4f (crystal-field) transitions observed in the low-temperature (10 K) absorption spectra, and these intensity data have been analyzed in terms of a general parametric model for 4f → 4f transition intensities in lanthanide systems. The energy and intensity parametrizations provide a basis for calculating the 4f → 4f absorption spectra of Ho3+ in Na3[Ho(oxydiacetate)3]·2NaClO4·6H2O over a wide spectral range, and excellent agreement between calculated and experimentally measured spectra is obtained.

The production of IgE and IgG protein by human peripheral blood mononuclear cells in culture has been examined. Cells obtained from 18 grass-sensitive donors during the grass pollen season and from 11 atopic dermatitis patients (total serum IgE levels greater than 960 ng/ml), spontaneously produced significant amounts of IgE but not IgG with time. Similar results were obtained using B-cell enriched preparations from both groups. Cells from 16 non-atopic donors had mean levels of pre-formed IgE similar to those of grass pollen-sensitive donors, but there was no increase in culture IgE with time. Treatment of mononuclear cells with pokeweed mitogen did not influence the production of IgE but markedly increased the amount of IgG synthesized by non-atopic and atopic donor cells. Slight, but significant increases in culture IgE, but not IgG, were seen following a 7-day mixed lymphocyte reaction involving both unrelated non-atopic donor cells and the lymphoblastoid B-cell line, Raji. Treatment of cells with 50 HA units of influenza A/Hong Kong/1/68 (H3N2) virus or with 0.02% v/v (240 IU/ml) of a purified beta-interferon preparation did not alter IgE or IgG produced.

The activities of streptovaricin complexes, streptovaricins, streptovals, and streptovarinic degradation products were elevated against RNA-directed DNA polymerases of Rauscher leukemia virus, DNA-dependent DNA polymerase of bacterial and mammalian cells, and DNA-dependent RNA polymerases of mammalian origin. The activities of streptovaricins were also listed for comparison purposes. The effects of streptovaricin complexes on viral DNA polymerases varied significantly from lot to lot, and streptovaricin complex lot 7 was the most active. All the streptovals and streptovaricin degradation products except varicinal A showed a marked improvement (twofold to tenfold) in activity against the viral enzyme over the parent streptovaricins. None of these compounds, however, displayed any significant effect on either the DNA polymerase of L1210 leukemia cells and Escherichia coli or the RNA polymerase of isolated nuclei of mouse liver. As a result of tests in these systems, some specific inhibitors of RNA-directed DNA polymerases of Rauscher leukemia virus were selected.

An investigation has been made of the inhibitory activity of the so-called Hamburger pentapeptide, Asp-Ser-Asp-Pro-Arg, in both the human Prausnitz-Küstner and baboon passive cutaneous anaphylaxis systems. With a dose of 6 μg peptide, administered intradermally 24 h prior to diluted allergic serum from a horse-dandruff-sensitive individual, partial inhibition of wealing was observed in three different normal recipients following the pricking in of specific allergen. In one of the recipients, inhibition of flaring was observed at test sites subsequently challenged with timothy grass pollen allergen. A similar dose of pentapeptide, again injected intradermally 24 h prior to passive sensitisation, was shown to inhibit extravasation in a normal baboon on subsequent challenge with horse dandruff (but not grass pollen) allergen by subcutaneous injection into the upper arm. In vivo tests performed in the forearms of grass-pollen-sensitive individuals failed to provide convincing evidence of displacement of mast-cell-bound IgE antibody by the pentapeptide.

The capacity of various N-acyl, O-acyl, amide and ester derivatives of L-tyrosine to promote the induction of antibodies to grass pollen extracts has been studied in guinea pigs. Antibody production was generally found to be enhanced when these derivatised materials were used as adsorbate vehicles compared with either L-tyrosine or simple aqueous presentations. Increases in alkyl chain length were found to parallel increased adjuvant activity. Unlike L-tyrosine, however, these hydrophobic materials tended to produce tissue lesions in experimental animals at concentrations which displayed apparent adjuvant advantages.

The effects have been studied of three different chemical modifications of timothy grass pollen extract on various immunological properties. The ability to induce IgG antibody with specificity for native antigen was least affected by glutaraldehyde treatment; IgE antibody production was reduced to a similar extent by all three modifications; there was no increase in IgM production; delayed reactions were reduced. New antigenic determinants were introduced by all the modifications, but the effect was minimal following glutaraldehyde treatment. The significance of these results and the potential application of modified allergen in hyposensitisation therapy are discussed.

Timothy pollen extracts have been reacted with glutaraldehyde under conditions leading to different degrees of aggregation of the product. Aggregation tends to enhance the previously demonstrated effects of glutaraldehyde in that reactivity with human IgE antibody, and ability to induce IgE antibody in the Bordetella pertussis-treated rat, are further reduced. Ability to induce IgG antibody with specificity for unmodified extract is substantially retained in all aggregated products.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed.

Glutaraldehyde modification was found to reduce the allergenic potency of crude timothy pollen extracts yet even highly substituted materials retained the capability of inducing the formation of allergen-specific antibody in animals. Experiments showed that these antibodies were capable of blocking skin test reactions to native timothy allergens in pollen-sensitive human volunteers. The value of glutaraldehyde-modified allergen extracts for use in desensitization vaccine therapy is discussed.

A procedure utilising the latent activating potential of the 4-(methylmercapto)phenyl ester group has been developed for the controlled, reproducible preparation of macromolecular conjugates. This ester, as part of a succinyl-bridging group, was used to couple the water-soluble, amino acid polymer, poly-(N-methylglycine) (polysarcosine), via its N-terminal secondary amine, with the nucleophilic components of the aqueous extract of a mixture of grass pollens. The products exhibit a reproducible, antigen-specific suppressive effect on the in vivo synthesis of IgE in mice.

On the basis of previous studies on the structure-activity relationship of model polypeptide histamine liberators, a site within the Fc region of immunoglobulin E antibody molecules has been proposed as that responsible for the direct triggering of target mast cells after antigen challenge. Peptides comprising this region of the epsilon-chain have now been synthesized and shown to induce histamine release from normal rat peritoneal mast cells in a selective manner essentially similar to that mediated by anaphylactic antibody-antigen interaction.

The activities of streptovaricin complexes, streptovaricins, streptovals, and streptovarinic degradation products were elevated against RNA-directed DNA polymerases of Rauscher leukemia virus, DNA-dependent DNA polymerase of bacterial and mammalian cells, and DNA-dependent RNA polymerases of mammalian origin. The activities of streptovaricins were also listed for comparison purposes. The effects of streptovaricin complexes on viral DNA polymerases varied significantly from lot to lot, and streptovaricin complex lot 7 was the most active. All the streptovals and streptovaricin degradation products except varicinal A showed a marked improvement (twofold to tenfold) in activity against the viral enzyme over the parent streptovaricins. None of these compounds, however, displayed any significant effect on either the DNA polymerase of L1210 leukemia cells and Escherichia coli or the RNA polymerase of isolated nuclei of mouse liver. As a result of tests in these systems, some specific inhibitors of RNA-directed DNA polymerases of Rauscher leukemia virus were selected.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen allergen extracts, which have been previously shown to suppress murine IgE responses, were examined for their ability to modify lymphocyte activity in vitro. Allergen-specific T lymphocytes obtained from Balb/c mice gave a reduced response to syngeneic accessory cells pulsed with conjugates of polysarcosine-allergen compared with the response found using equivalent concentrations of native extract. Pretreatment of accessory cells with either polysarcosine or polysarcosine-allergen conjugates did not impair their subsequent ability to present grass pollen extract to immune T cells. Incubation of allergen-specific spleen cells with polysarcosine-allergen conjugates, but not with polysarcosine or allergen alone, resulted in specific cell-mediated suppression which significantly reduced proliferation in vitro. This activity was sensitive to treatment of cells with anti-T-lymphocyte antisera plus complement. Spleen cells obtained from animals immunised with allergen and taken 21 days after intravenous treatment with polysarcosine-allergen conjugates, a regimen that suppressed IgE antibody production, did not proliferate in the presence of grass pollen extract and failed to suppress a secondary lymphoproliferative response in vitro. Spleen cells obtained from similarly treated animals 3 days after the final polysarcosine-allergen injection responded to pollen extract in culture and, additionally, impaired a secondary response. The results suggest that the reduced IgE response found in animals treated with polysarcosine-allergen conjugates may be due, in part, to the generation of a short-lived antigen-specific T cell suppression.

Zinc deficiency dermatitis in a patient on long-term total parenteral nutrition (TPN) with trace-element supplementation is reported, and the therapeutic aspects of zinc deficiency are reviewed. A 36-year-old white man was hospitalized and found to have a small-bowel perforation secondary to internal herniation. Small-bowel resection with end-to-end anastomosis was performed, and TPN supplemented with folic acid, multivitamins, trace elements (including elemental zinc 2 mg/day), and fat was begun. Four months later, the patient developed a moist, erythematous, painful groin rash that did not respond to one month of topical antifungal and topical and intravenous antibacterial treatment. At five months after admission, zinc deficiency was suspected; serum zinc concentration was 85 micrograms/dl (normal = 55-150 micrograms/dl). The total daily zinc dose was increased to 60 mg, and within two days the patient's lesions began to improve. The rash healed within two weeks. Six days after increased zinc therapy was begun, lab tests showed: hair zinc content, 185 micrograms/g (normal = 163 micrograms/g); serum zinc content, 90 micrograms/dl; and erythrocyte zinc content, 1058 micrograms/dl (normal = 1100-1400 micrograms/dl). Signs and symptoms of zinc deficiency, zinc disposition in man, predisposing factors to zinc deficiency, laboratory analysis of zinc nutriture, zinc therapy, and zinc toxicity are discussed. Knowledge of drug use, diet, geographic location, underlying disease, and other patient-specific factors is important in recognizing the patient at risk of developing zinc deficiency. Several tests should be performed to document zinc deficiency. Zinc replacement guidelines are outlined.

A series of experiments has been carried out to investigate the adjuvant properties of the amino acid L-tyrosine in laboratory animals. Adsorption of various allergenic materials to L-tyrosine was found to enhance the induction of IgG antibodies, but no unusual propensity to stimulate IgE antibody or delayed hypersensitivity was observed. Administration of the amino acid at a site remote from the allergen was found not to augment antibody production. This, together with evidence of reduced bioavailability of the tyrosine-adsorbed allergen, suggested that the adjuvant activity observed resulted from a short-term depot effect.

Treatment with conjugates of polysarcosine and grass pollen allergen extracts efficiently suppressed the induction of IgE responses in mice. The suppressive activity was shown to be allergen-specific and required covalent linking of the polysarcosine. Inhibitory effects could be overcome by booster injections of native allergen when these were given 3-4 weeks after treatment with conjugates. Administration of conjugates had only marginal effects on established IgE responses. The variance of these results with those of other studies on IgE suppression and the suitability of murine models for investigating reaginic antibody suppression are discussed.

Adsorbed hydrogen on platinum-silica gives infra-red bands at 2040 and 2120 cm–1, and on platinum alumina at 2040 and 2110 cm–1. The 2110–2120 band is much enhanced by treatment by oxygen, and adsorption-desorption behaviour together with deuterium shift establish the band as due to weakly adsorbed hydrogen. It is proposed that the hydrogen is adsorbed on platinum oxide patches, possibly on the Pt4+ surface ions. The effect of oxygen pretreatment is to reduce or remove the 2040 band, which, however, slowly appears in the presence of water, more quickly for hydrogen plus water, in either order, for platinum silica. On platinum alumina the addition of water is not necessary to observe this band. It is suggested that the 2040 band is due to hydrogen atoms chemisorbed on Pt4+ and hydrogen bonded to an adjacent OH. This may be formed by dissociative chemisorption of water, or even by hydroxyl ion diffusing from the adjacent support for alumina. Experiments on carbon monoxide rule out any possible impurity effects due to this gas. While the bands observed agree with the observations of Eischens and Pliskin on platinum-alumina, the new results on the effects of oxygen and water have led us to change considerably their interpretations (which involved hydrogen chemisorbed atomically and interstitially on metallic platinum).