[Assessing language development in children with cochlear implants using the parental questionnaire FRAKIS]. / Der Einsatz des Elternfragebogens FRAKIS zur Erfassung des Sprachstandes bei Kindern mit Cochleaimplantat.

BACKGROUND: The aim of this study was to examine if the parental questionnaire FRAKIS (German CDI questionnaire on early language development) is a valid instrument for assessing linguistic progress in children with cochlear implants (CI). Descriptive statistics on the course of language acquisition in children with CI will also be presented. MATERIALS AND METHODS: Participants were 140 children with CI and language levels were assessed cross-sectionally with the parental questionnaire FRAKIS at 12, 18, 24 and 30 months post-implantation. For a subgroup of 25 children language was assessed longitudinally and additionally by 45 min spontaneous speech samples per data point. RESULTS: Correlational analyses showed high concurrent validity between the questionnaire measures of vocabulary, inflectional morphology, sentence complexity, as well as the subscales of inflectional morphology and the corresponding language measures based on spontaneous speech. Descriptive statistics for the course of language development indicated a wide distribution of children across language levels. CONCLUSIONS: The parental questionnaire FRAKIS is a valid instrument for assessing language levels in children with CI. In assessing these children it is recommended that they are compared with values within this population.

Humanized anti-Lewis Y antibodies: in vitro properties and pharmacokinetics in rhesus monkeys.

ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two Phase I/II trials in relapsed small cell lung cancer and metastatic breast cancer. To improve the effector functions of the antibody, increase its half-life in circulation, and avoid the human antimouse antibody response, two chimeric and several humanized antibodies were constructed for evaluation. The chimeric IgG1 is more potent than the murine IgG3 in tumor cell lysis via activation of human peripheral mononuclear cells (10-fold), but somewhat less effective in complement-dependent lysis (2-3 fold). The chimeric IgG3 is slightly less potent than the IgG1. A humanized IgG1 was constructed by combining the complementarity-determining regions of the ABL 364 antibody with human framework and constant regions. Several additional variants were subsequently constructed to improve the binding affinity and increase expression of the antibody. Two of the variants, designated I and K, differ by a single amino acid at position 75 of the heavy chain. Both variants have affinity within 2-fold of the chimeric IgG1 antibody and retain the cytolytic activities toward tumor cell lines. However, it was possible to express variant K at a significantly higher level (5- 10-fold) than variant I. Pharmacokinetics of the humanized ABL 364 antibody variant K was compared with that of the parent murine antibody in rhesus monkeys. It was shown that the terminal half-life of the humanized antibody in rhesus monkeys is 14-20 days, with a mean of 16.3 days, while that of the parent murine antibody is only 1.9 days.

Affinity labeling of Escherichia coli ribosomes with a covalently binding derivative of the antibiotic pleuromutilin.

Reaction of an alkylating pleuromutilin derivative with E. coli ribosomes led to the binding of the compound to both proteins and RNA. If ribosomes of the E. coli strain MRE600 were used, mainly S18 and L2 became labeled. Ribosomes from E. coli D10 bound the reagent to S18 and frequently to L27 instead of L2. Possibly at slight difference in the structure of these ribosomes exposes different, although closely neighboring, L proteins to the reagent. The simultaneous labeling of L and S proteins seems to reflect the presence of two binding sites for the antibiotic and indicates that the binding sites are located at the interphase region between large and small ribosomal subunits. Analysis of the RNA showed that the affinity label is mainly attached to the 23S species. These data are in good agreement with the known effects of pleuromutilin derivatives on ribosomal functions.

Dog allergy, a model for allergy genetics.

Experimental sensitization in dogs has revealed that the capacity to produce high levels of IgE against a variety of allergens (high IgE responders), an essential characteristic of the atopic state, is a genetic trait inherited in a dominant manner. In high IgE responder dogs spontaneous development of IgE to inhaled allergens, such as house dust mites, on the other hand, represents an apparent phenotype very similar to that observed in human atopic families. The full potential of the high IgE response gene appears to be fulfilled only under some conditions such as early and repeated exposition to allergens. It is therefore quite possible that the true phenotype of human atopy would also be inherited in a dominant fashion but not constantly expressed. This would explain why the increase in the prevalence of allergic diseases started long before the environmental factors currently accused could have been at play. This hypothesis, which can be verified experimentally, has important implications for the future of allergy.