Human IgG Fc receptors

Human IgG receptors constitute a family of glycoprotein complexes consisting of ligand-binding, and associated signaling chains. Three leukocyte classes (Fc gamma RI, II, and III) and one separate endothelial Fc gamma R class (FcRB) are defined which are expressed on hematopoietic and endothelial cells. Upon interaction with IgG, Fc gamma R initiate a plethora of signaling cascades involving receptor signaling motifs, and protein tyrosine kinases and phosphatases. These cascades ultimately culminate in activation or deactivation of effector cells, resulting in initiation or down-modulation of cellular processes. Recent evidence points to a crucial in vivo role of Fc gamma R in both initiation and regulation of inflammatory and cytotoxic responses. These Fc gamma R-mediated immune responses can be exploited to develop novel immunotherapies.     

Oligonucleotide dendrimers: synthesis and use as polylabelled DNA probes

Oligonucleotide dendrimers were synthesized using a novel phosphoramidite synthon, tris-2,2,2-[3-(4,4'-dimethoxytrityloxy) propyloxymethyl]ethyl- N , N -diisopropylaminocyanethoxy phosphoramidite. Label, incorporated using [gamma-32P]ATP and polynucleotide kinase, was increased in proportion to the number of 5'-ends. There was a similar increase in signal when these multiply labelled oligonucleotides were used as probes to oligonucleotide arrays. A dendrimeric oligonucleotide was used successfully as a primer in the PCR. The strand bearing the dendrimer was resistant to degradation by T7 Gene 6 exonuclease making it easy to convert the double-stranded product of the PCR to a multiply-labelled, single-stranded probe.     

The characteristics of the clinical course in individual types of radiation-induced cataracts

Twenty-eight patients exposed to acute and chronic ionizing radiation were followed up. Radiation cataracts were diagnosed in 22 eyes. Localizations of changes in the lens after ionizing and solar radiation are similar. Opacities are localized under the posterior lenticular capsule, round the nucleus, and under the anterior capsule and do not depend on the type of radiation. Opacities caused by solar radiation are notably smaller and look as numerous small dots. Study of cataracts of different origin and assessment of the efficacies of different anticataract drugs were carried out for evaluating the progress of different types of cataracts (cellular, extracellular, and capsular forms).     

Distribution and excretion of radiolabelled tert-butylhydroquinone in Fischer 344 rats

Uniformly 14C-ring-labelled tert-butylhydroquinone (TBHQ) was diluted with non-radioactive TBHQ and administered orally (for excretion studies) to Fischer 344 rats. An average of 72.9% and 10.6% of the administered radioactivity was recovered in the urine and faeces, respectively, of male rats, and 77.3% and 8.2% in the urine and faeces, respectively, of female rats in 4 days. No significant sex-related differences were found in either excretion, tissue distribution or urinary metabolites of TBHQ-derived radiolabel. For distribution studies, intraperitoneal doses were administered to female rats, and tissue levels of radiolabel were determined at various times after dosing. The parent compound quickly disappeared from tissue in vivo. The highest concentrations of radiolabel were found in the liver and kidneys. The urinary metabolites consisted of conjugated TBHQ and unidentified polar substance(s).     

GPI-anchored complement regulatory proteins in seminal plasma. An analysis of their physical condition and the mechanisms of their binding to exogenous cells

We analyzed and compared the properties of three glycosylphosphatidylinositol (GPI)-anchored proteins. CD59, CD55 (both C regulators), and CDw52, and of the transmembrane C regulator CD46 in seminal plasma (SP). We demonstrated previously that anchor-intact SP CD59 is present on the membranes of vesicles (prostasomes) and that cells acquire this protein during incubation with SP. We now report that this acquisition is due partly to adherence of prostasomes to cells and partly to a second mechanism which may involve micellar intermediates. Using fluorescent labeling, ultracentrifugation, and density gradient centrifugation, virtually all CD46 was present on prostasomes whereas CD59, CD55, AND CDw52 were also detected in a form which remained in the 200,000 g supernatant and equilibrated at higher density than prostasomes in gradients. All three GPI-linked proteins eluted at high molecular mass during size exclusion chromatography of this nonprostasome fraction. As documented by videomicroscopy and biochemical analysis, cells acquired new copies of the GPI-linked proteins during incubation with the nonprostasome fraction as well as with prostasomes. These data demonstrate the presence in SP of a stable population of membrane-free, GPI-linked proteins available for transfer to cells. Binding of these proteins to spermatozoa and pathogens in SP may confer new properties on their membranes including increased resistance to C attack. Finally, our data raise the possibility that lipid-associated GPI-linked proteins may be suitable for therapeutic applications.     

Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta

1. The effects of niflumic acid, an inhibitor of calcium-activated chloride channels, were compared with the actions of the calcium channel antagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta. 2. The cumulative concentration-effect curve to noradrenaline (NA) was depressed by both nifedipine and niflumic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 microM) produced by 10 microM niflumic acid (38%) was similar to the effect of 1 microM nifedipine (39%). 3. Contractions to brief applications (30 s) of 1 microM NA were inhibited by 55% and 62% respectively by 10 microM niflumic acid and 1 microM nifedipine. 4. In the presence of 0.1 microM nifedipine, niflumic acid (10 microM) produced no further inhibition of the NA-evoked contractions. Thus, the actions of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contraction induced by 1 microM NA was not inhibited by niflumic acid (10 microM) and therefore this agent does not reduce the amount of calcium released from the intracellular store or reduce the sensitivity of the contractile apparatus to calcium. 6. Niflumic acid 10 microM did not inhibit the contractions produced by KCl (up to 120 mM) which were totally blocked by nifedipine. Contractions induced by 25 mM KCl were completely inhibited by 1 microM levcromakalim but were unaffected by niflumic acid. 7. It was concluded that niflumic acid produces selective inhibition of a component of NA-evoked contraction which is probably mediated by voltage-gated calcium channels. These data are consistent with a model in which NA stimulates a calcium-activated chloride conductance which leads to the opening of voltage-gated calcium channels to produce contraction.     

Hirsutism in the United Arab Emirates: a hospital study

In a study of 102 women (Arabs and Asians) with hirsutism, polycystic ovary syndrome was diagnosed in 93 patients (91%) including 26 cases with hirsutism and regular menstrual periods. In more than half of the cases the diagnosis was made on the basis of transabdominal ultrasonography, which was the single test with the highest yield. Luteinising hormone hyperresponsiveness to gonadotropin-releasing hormone was positive in only seven of 50 patients tested. Late onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency was identified in two cases, thus forming a prevalence of 8% in those who underwent adrenocorticotropin stimulation. In one case, polycystic ovary syndrome was an associated condition. In this study of a population of women with hirsutism and regular menses, the majority had polycystic ovaries. It is suggested that the term 'idiopathic or racial' hirsutism should not be applied unless a thorough evaluation has failed to reveal a diagnosable underlying disorder.