No association of GSK3beta gene (GSK3B) with Japanese schizophrenia.

Several lines of evidence indicate that glycogen synthase kinase-3beta (GSK3beta) is one of the candidates for schizophrenia-susceptibility factor. However, it has not been reported the association analysis between GSK3beta gene (GSK3B) and Japanese schizophrenia based on linkage disequilibrium (LD). We provide an association analysis using relatively large samples (381 schizophrenia, and 352 controls) after determination of "tag single nucleotide polymorphisms (SNPs)." In this LD mapping, we selected and genotyped for eight polymorphisms (seven SNPs and one diallelic (CAA)(n) repeat), which covered the entire region of GSK3B, and determined two "tag SNPs." In the following association analysis using these two "tag SNPs," we could not find association with Japanese schizophrenia. Furthermore, we also include subgroup analysis considering age-at-onset and subtypes, neither could we find associations. Because our samples provided quite high power, these results indicate that GSK3B may not play a major role in Japanese schizophrenia.     

Quantitative analysis for soluble elastin in circulation and cell culture fluids using monoclonal antibody-based sandwich immunoassay

We have newly established 3 distinct murine monoclonal antibodies (MoAbs) against human soluble elastin by using chemically denatured immunogen isolated from human aorta; they are designated as HASG-2, HASG-30, and HASG-61-1. All of these MoAbs were highly reactive with soluble forms of native elastin in normal human serum. HASG-2 and HASG-61-1 MoAbs can recognize soluble bovine elastin as well as human antigen, but HASG-30 cannot. The sandwich enzyme-linked immunosorbent assay (ELISA) for human soluble elastin was developed with HASG-61-1 labeled with peroxidase and HASG-30 immobilized on the microplates. The circulating levels of soluble elastin in human healthy subjects (mean +/- SD; 42.9 +/- 19.9ng/mL; n = 85) could be measured with full accuracy and reproducibility, and gradually increased with aging. The positive correlation between the levels and ages was statistically significant (r = 0.581, p < 0.0001). In addition, we could also determine the concentration of tropoelastin secreted from cultured human dermal fibroblasts accurately by this ELISA. This simple assay can be utilized for the routine clinical laboratory screening of patients with arteriosclerotic vascular diseases or to accurately determine the concentrations of tropoelastin secreted from cultured human cells.     

Experimental production of pulmonary granulomas. IV. Eosinophilic granuloma.

Pulmonary granulomas induced in rabbits by the endobronchial instillation of mycobacterial chemical fractions were re-examined for eosinophilic infiltration. Delayed type hypersensitivity reactions either of tuberculin type or of wax D type did not induce but rather suppressed eosinophilic infiltration in the inflamed area, although some peptidoglycans which are antigenic for the induction of immediate hypersensitivity and fatty acid fractions were weak stimulators of eosinophilic infiltration. Bacterial endotoxin, LPS, was a potent stimulator. It was found that some long chain fatty acids can cause severe eosinophilic infiltration in the induced granulomas. Arachidonic acid was the most active of those examined, so the activity of its metabolites was tested and PGE2 was found to be most active. As the eosinophilic infiltration was markedly suppressed in animals treated with a cyclooxygenase inhibitor (aspirin), the stimulators of eosinophilic infiltration were not fatty acids themselves but their metabolites, PGE2 and some others. The site of permeation of eosinophils from the circulation was found to be arteriolar in the inflamed lung. The granulomatous lesion with eosinophilic infiltration in rabbits is discussed to shed light on the aetiology of eosinophilic granuloma in the human lung.     

Immunohistochemical study of copper-zinc and manganese superoxide dismutases in the lungs of human fetuses and newborn infants: Developmental profile and alterations in hyaline membrane disease and bronchopulmonary dysplasia

To determine the late gestational development of copper-zinc (CnZn) and manganese (Mn) superoxide dismutases (SOD) in human lung, immunohistochemical localization was performed for each SOD. The lung samples were taken from five aborted fetuses, four fetuses in which intrauterine death occurred, one full-term neonate, two premature infants with hyaline membrane disease and one premature infant with bronchopulmonary dysplasia (BPD). Morphometry was performed, and the percent area of positive staining was computed. The bronchial epithelium was intensely stained from the early stages of gestation (i.e. 17 weeks), while the staining intensity for both CuZnSOD and MnSOD in the peripheral airways increased gradually during lung development. The mean percent area of the staining for CuZnSOD and MnSOD from 16 to 38 weeks was increased 30-fold and 8-fold, respectively, and further increases were observed postnatally. CuZnSOD staining was markedly decreased in lungs with respiratory disorders. However, proliferating type II pneumocytes were intensely stained for MnSOD in the BPD lungs, making the staining area 3-fold larger than that in the control lungs. These results clearly depict age-related increases in staining for both CuZnSOD and MnSOD and an alteration in SOD distribution associated with neonatal respiratory disorders.     

Kinetic studies on the reaction of formaldehyde with diphenyl sulfide. Formaldehyde resins. 99

Kinetic studies on the acid-catalyzed reaction of formaldehyde with diphenyl sulfide (DPS) were carried out in acetic acid in the presence of sulfuric acid. The rate of the initial stage of the reaction was found to be in agreement with the following equation. The relative rates of diphenyl sulfide and its homologous compounds in the reaction with formaldehyde gave a good correlation with BROWN -OKAMOTO 's σ^⊕ values and a large ρ value. The polar effects of substituents of the substituted diphenyl sulfides on the rates were found to be considerably large. From these results a plausible mechanism of the reaction has been deduced.     

Enhancing effects of oral adjuvants on anti-HBs responses induced by hepatitis B vaccine.

Hepatitis B (HB) vaccine is very promising for the prevention of HB infection. There exist, however, some non-responders to current vaccination trials. In this study, taurine, parotin and lithium were selected as adjuvants which can be administered orally. The mechanisms of these three materials as adjuvants and their effects on HB vaccine were investigated in mice. For instance, taurine induced polyclonal antibody production and exhibited adjuvant activity. Although taurine did not have any activity on the proliferation of thymocytes nor stimulate IL-2 production, taurine did induce IL-1 production by macrophages. It was considered that taurine-induced IL-1 would play an essential role in the proliferation and differentiation of B cells. Parotin also induced polyclonal antibody production and exhibited adjuvant activity. These effects of parotin were not affected even if macrophages or T cells were depleted, and parotin itself had an IL-1-like activity. Therefore, it was considered that parotin acted directly on B cells by its IL-1-like activity and mitogenic activity, resulting in the proliferation and differentiation of B cells. Lithium induced neither polyclonal antibody production, nor IL-1 or IL-2 production. However, when given with an antigen, lithium activated the humoral immune system, resulting in the augmentation of antibody production. Oral administration of taurine, parotin and lithium were capable of restoring antibody responses to HB surface antigen (HBsAg) in HBsAg-nonresponder mice. Furthermore, taurine, parotin and lithium enhanced the adjuvant effects of aluminium contained in the present HB vaccine. These observations indicate that use of these oral adjuvants may open new perspectives in the field of human HB vaccination.