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The number and affinity of glucocorticoid binding sites in peripheral mononuclear cells (MNC) of asthmatic and healthy children were determined by a whole cell (3H)dexamethasone binding assay at 37 degrees C. Using HPLC determination, corresponding serum levels of non-protein-bound (free) cortisol, whole cortisol and cortisone as well as urine excretion of free cortisone and cortisol were assessed. The average number of binding sites (BS) per cell and the dissociation constant (KD) respectively, in atopic asthmatics (7768 +/- 666 BS/MNC resp. KD = 17.2 +/- 2 nM) did not differ from the values measured in our control group (8333 +/- 691 BS/MNC resp. 25.4 +/- 4.8 nM). Within the age range 1 month-15.8 years neither age-dependent changes nor sex-related differences in the number of binding sites or the KD values could be detected. Active or currently inactive asthmatics, and patients under different antiasthmatic drug regimes, had similar binding sites on MNC. No differences in serum levels of cortisol, cortisone and free cortisol or in free cortisol and free cortisone of 24-h urine samples were found between healthy children and asthmatics. After a short course of prednisolone therapy for an acute severe asthmatic attack the number of glucocorticoid binding sites in peripheral MNC decreased to an average of 4632 +/- 421 BS/MNC, whereas the dissociation constant did not change significantly (14.5 +/- 3.6 nM). The corticoid-hormone pattern in the serum, 24-h urine excretion, and the normal number and affinity of glucocorticoid receptors on peripheral MNC suggest that there is no primary, general impairment of glucocorticoid metabolism in asthmatic children.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

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The Escherichia colifhu operon, composed of the fhuA, C, D, and B genes, is essential for the utilization of ferric siderophores of the hydroxamate type and for the uptake of the antibiotic albomycin. We have had difficulty studying the effects of missense mutations in individual plasmid-encoded transport genes because appropriate test strains were not found: all isolated chromosomal mutations in either one of the fhu genes (with a complete loss of function) negatively influenced the expression of other fhu genes in the operon. In order to analyze Fhu mutant proteins in a system free of polar effects, we constructed a plasmid-encoded gene cassette system by introducing unique restriction sites that allowed precise cloning of individual fhu genes. The fhu cassette operon expressed in a chromosomal fhu deletion mutant enabled us to evaluate the transport activity of mutated FhuA, FhuC, FhuD or FhuB derivatives. In addition, we found that transport across the outer membrane (via FhuA, TonB, ExbB, D) rather than transport across the cytoplasmic membrane (via FhuC, D, B) was rate limiting. The stoichiometry of the components involved in the uptake of iron(III) hydroxamates seems to be important for proper functioning. [ABSTRACT FROM AUTHOR]

Defence against oxidative damage by UV-generated free radicals in both guinea pig and human skin has been found to be mediated by the ubiquitous thioprotein, thioredoxin reductase. Human keratinocytes contain approximately 5% thioredoxin reductase in their total acidic protein fraction and also express membrane-associated enzyme activity in cells cultured in synthetic medium. The thioredoxin reductase/thioredoxin system has been shown to reduce superoxide anion radicals through hydrogen peroxide to water. However, both UVA and UVB radiation, below the minimal erythemal dose, generate a sufficiently high concentration of oxygen radicals to deactivate thioredoxin reductase considerably. In albino guinea pigs, enzyme deactivation was up to 70% for UVA and 66% for UVB ( n=10 animals/protocol). The application of sun blockers SPF, SPF and SPF to albino guinea pig skin offered no significant protection for the deactivation of thioredoxin reductase by either UVA or UVB radiation. In the human population ( n=15), thioredoxin reductase was deactivated by 54% with UVA and 36% with UVB radiation, although the degree of enzyme inhibition depended on skin phototype (I-VI, Fitzpatrick Classification). SPF offered considerable protection for thioredoxin reductase against both UVA and UVB for skin types I and II. However, SPF yielded no significant protection with UVA for skin types III-VI, and enhanced the enzyme inhibition with UVB additively. These results indicate that UVB photo-oxidation of oxybenzone (the UVA filter in SPF) may deactivate thioredoxin reductase in more pigmented members of the population by Michael addition of oxybenzone semiquinone to the thiolate active site of this enzyme. [ABSTRACT FROM AUTHOR]

During the last ten years we observed three non-hemophilic patients with factor(F) VIII: C inhibitors (2 women aged 68 and 80 and a man aged 51). In all three cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII: C level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease could be excluded. Therapy with F VIII: C concentrate, cryoprecipitate, or fresh-frozen plasma did not produce the expected increase in F VIII: C. Measurement of F VIII: C inhibitor levels (Bethesda Units, BU) revealed values in the range between 9 and 64 BU. The two patients subjected to long-term therapy with a combination of prednisone (initially 2-3 mg/kg BW) and azathioprine (2-3 mg/kg BW) responded positively; the F VIII: C concentration increased. The third patient, treated only with a low dose of prednisone (30 mg/day), did not show any reaction at all. Since hereditary hemophilia A could be excluded, the inhibitors apparently were acquired. Malignant tumors did not appear. In conclusion, long-term therapy of an acquired F VIII: C inhibitor with a combination of prednisone and azathioprine may lead to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency. [ABSTRACT FROM AUTHOR]