Surface Antigens on Cat Leukemic Cells Induced by Feline Leukemia Virus: Area Density and Antibody-Binding Affinity

The binding of autologous bovine antibody to feline leukemia virus-induced cell surface antigens (FeCSA) on cat leukemia cells was studied by performing certain titration procedures with a mixture of immune and normal sera labeled with different iodine radioisotopes (paired-label technique). By using plots of titration data which conformed to linear equations derived from the mass action law, we determined the following constants. (i) The density of FeCSA was 2.03 x 10(6) sites per cell, or 5,230 sites per mum(2). (ii) The equilibrium constant of the FeCSA-antibody reaction was 2.67 x 10(7), from which the antibody binding affinity or standard free energy of the FeCSA-antibody bond was determined to be - 10.48 kcal (-43,869.28 J) per mol. The use of the techniques described to measure the concentration of antibody in antiserum, in micrograms per milliliter, is discussed.     

Interaction of granulocyte colony-stimulating factor (G-CSF) with its receptor. Evidence that Glu19 of G-CSF interacts with Arg288 of the receptor.

Granulocyte colony-stimulating factor (G-CSF) forms a tetrameric complex with its receptor, comprising two G-CSF and two receptor molecules. The structure of the complex is unknown, and it is unclear whether there are one or two binding sites on G-CSF and the receptor. The immunoglobulin-like domain and the cytokine receptor homologous module of the receptor are involved in G-CSF binding, and Arg288 in the cytokine receptor homologous module is particularly important. To identify residues in G-CSF that interact with Arg288, selected charged residues in G-CSF were mutated to Ala. To clarify whether there are two binding sites, a chimeric receptor was created in which the Ig domain was replaced with that of the related receptor gp130. This chimera bound G-CSF but could not transduce a signal, consistent with failure of dimerization and loss of one binding site. The G-CSF mutants had reduced mitogenic activity on cells expressing wild-type receptor. When tested with the chimeric receptor, all G-CSF mutants except one (E46A) showed reduced binding, suggesting that Glu46 is important for interaction with the Ig domain. On cells expressing R288A receptor, all the G-CSF mutants except E19A showed reduced mitogenic activity, indicating that Glu19 of G-CSF interacts with Arg288 of the receptor.     

Klinefelter's syndrome as a model of anomalous cerebral laterality: Testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed “anomalous dominance,” is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes. Dev. Genet. 23:215–229, 1998. © 1998 Wiley-Liss, Inc.     

Long-term platinum retention after treatment with cisplatin and oxaliplatin

Background  

The aim of this study was to evaluate long-term platinum retention in patients treated with cisplatin and oxaliplatin.