Single-serum diagnosis of recent rubella infection with the use of hemagglutination inhibition test and enzyme-linked immunosorbent assays

Single-serum diagnosis of recent rubella infection was attempted with the use of hemagglutination inhibition (HI) test and two commercially available enzyme-linked immunosorbent assays (ELISAs). The period during which IgM antibody was detectable by IgM capture ELISA was 4 to 30 days after the onset of rash. Rubella IgG ELISA values relative to HI titer were lower in the sera from the patients with recent infection than in the sera from the subjects with remote infection. IgM ELISA and the combined use of IgG ELISA and HI test are two useful methods of single-serum diagnosis of recent rubella infection.     

Drug-binding properties of human alpha-foetoprotein.

The drug-binding properties of human alpha-foetoprotein (alpha FP) were investigated by a fluorescence-spectral method. Human alpha FP was shown to bind to albumin's site I marker (warfarin, phenylbutazone), site II marker (L-tryptophan), but not site III marker (cholic acid, digoxin). The binding of human alpha FP towards lower alcohols was examined, and this binding seems to depend partly on the hydrophobicity of the ligands. The binding of human alpha FP is discussed in comparison with human serum albumin or rat alpha FP.     

High and low affinity binding sites for endothelin on cultured rat glomerular mesangial cells

Endothelin contracts glomerular mesangial cells, thereby influencing glomerular size and filtration rate. Here, we demonstrate the presence of two ET-specific binding sites on cultured rat mesangial cells with Kds of 0.76 and 44.70 nM, and maximal binding capacity (Bmax) values of 6.78 x 10(2) and 27.60 x 10(2) binding sites/cell, respectively. Binding of [125I]-ET was maximal at 120 min at 4 degrees C, stable for the subsequent 60 min, and selective. No competition for binding was observed with greater than 1000-fold concentrations of atrial natriuretic peptide, angiotensin II, arginine vasopressin, nicardipine, or nifedipine. The presence of specific receptors for ET on glomerular mesangial cells suggests a major role for this peptide in the regulation of glomerular filtration rate.     

Isoleucine Accumulation by Regulatory Mutants of Serratia marcescens: Lack of Both Feedback Inhibition and Repression

Double mutants of Serratia marcescens resistant to isoleucine hydroxamate and alpha-aminobutyric acid accumulated large amounts of isoleucine in a salts-sugar medium and lacked both feedback inhibition and repression of the isoleucine biosynthesis.     

Augmented production of platelet-activating factor in human polymorphonuclear leukocytes by ketone bodies

The production of platelet-activating factor (PAF) in A23187-stimulated human polymorphonuclear leukocytes was markedly increased in the presence of 5 mM acetoacetate and beta-hydroxybutyrate. Such an augmentation was observed even at 500 microM but not at 50 microM. The augmented production of PAF by acetoacetate was also observed in the presence of autologous serum and was most prominent in the case of opsonized zymosan-stimulation rather than A23187-stimulation. These observations suggest that increased levels of acetoacetate and beta-hydroxybutyrate in blood may lead to the augmented production of PAF, which would amplify the various PAF-mediated biological reactions.     

Pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines and their tricyclic derivatives as corticotropin-releasing factor 1 (CRF₁) receptor antagonists

To identify structurally novel CRF1 receptor antagonists, a series of bicyclic core antagonists, pyrazolo[1,5-a]pyrimidines, triazolo[1,5-a]pyrimidines, imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a][1,3,5]triazines were designed, synthesized and evaluated as CRF1 receptor antagonists. Compounds 2-27 showed binding affinity (IC(50)=4.2-418 nM) and antagonist activity (EC(50)=4.0-889 nM). Compound 5 was found to show oral efficacy in an Elevated Plus Maze test in rats. Further chemical modification of them led us to discovery of the tricyclic core antagonists pyrazolo[1,5-a]pyrrolo[3,2-e]pyrimidines. The discovery process of these compounds is presented, as is the study of the structure-activity relationship.     

Change of positive selection pressure on HIV-1 envelope gene inferred by early and recent samples

HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo- and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures.