Therapy with nebulized beta2 agonists (procaterol) in asthmatic children: pulmonary function and plasma levels after inhalation]

BACKGROUND: Relationship between post administrative changes in plasma drug levels and bronchodilation remains unknown. In this study, we measured plasma levels of procaterol, a beta2-agonist, when being inhaled through nebulizers in children with bronchial asthma to examine relationship between improvement of pulmonary function and the plasma levels. METHOD: Six asthmatic children with the mean age of 9.8 years, inhaled 0.3 ml of 0.01% procaterol solution through a nebulizer. We examined changes in pulmonary function and plasma procaterol levels before and after inhalation. RESULTS: Procaterol was detected in the plasma 2 minutes after inhalation when it already rose to the maximum level, and kept the steady until showing a decline in 30 minutes. The measured highest value was 87.8+/-45.1 pg/ml. FEV 1.0 remarkably increased 2 minutes after inhalation and was maintained until 60 minutes after inhalation. Other lung function parameters also improved. There was no significant change in the heart rate, but serum potassium concentrations significantly dropped in all patients 60 minutes after inhalation. CONCLUSION: Plasma procaterol levels promptly rose to the peak at 2 minutes after inhalation and decreased 30 minutes later. Improvement of pulmonary function started promptly at minutes after inhalation and it became a peak 60 minutes later.     

Calcineurin-mediated BAD Ser155 dephosphorylation in ammonia-induced apoptosis of cultured rat hippocampal neurons

We previously reported that ammonia induced apoptosis in cultured rat hippocampal neurons with moderate increases in the intracellular calcium concentration and decreases in phospho-BAD levels. Since this suggested the involvement of calcineurin in the apoptosis, the effects of calcineurin inhibitors, 1 microM cyclosporin A and 1 microM FK506, on the ammonia-induced neuronal apoptosis were tested. Both of the inhibitors abolished the neuronal apoptosis assessed by double staining with Hoechst 33258 and anti-neurofilament antibody, and the ammonia-induced decrease in phospho-BAD Ser(155) level. Thus, calcineurin appeared to be involved in the dephosphorylation of BAD at the sites including Ser(155) in ammonia-induced apoptosis.     

The GOR gene product cannot cross-react with hepatitis C virus in humans

GOR (GOR47--1) is an epitope thought to be a host-derived antigen cross-reactive with hepatitis C virus (HCV) since it was isolated from a cDNA library of host animals reactive with sera of HCV-positive patients. An enzyme immunosorbent assay (ELISA) using this epitope as antigen is of sufficient sensitivity and specificity for screening patients with HCV. However, the relationship between GOR47--1 epitope and autoimmune phenomena associated with HCV infection or autoimmune hepatitis is controversial. Here we isolated the human GOR gene and found that the GOR47--1 epitope was not translated in humans due to a single base replacement from chimpanzee. Furthermore, we found some patients who had antibodies against another epitope, which is translated (GOR1--125) in humans, although there was no correlation between the existence of anti-GOR47--1 or anti-GOR1--125 Ab and autoimmune phenomena. Serum IgG levels did not influence the titres of these antibodies. Taken together with the results of several other studies, our finding that the GOR47--1 epitope cannot be translated into a protein suggests that there is little relationship between autoimmunity and the GOR gene product in human beings. We also discuss here the possible mechanism of cross-reactivity between HCV and the GOR gene product.     

Human T-cell receptor BV6 gene polymorphism in relation to expression level and CD4/CD8 skewness

Using 50 samples of umbilical cord blood lymphocytes from Japanese donors, we analysed two human T-cell receptor beta variable (TCRBV) genes, BV6S4 and BV6S5, for their polymorphism, usage frequencies and CD4/CD8 skewness. They showed contrasting CD4/CD8 skewness, BV6S4 to CD8+ T cells and BV6S5 to CD4+ T cells. Genotyping of the BV6S4 alleles (A1, A2 and A3) revealed two of the six possible BV6S4 genotypes, A1/A2 and A2/A2. Among the two BV6S4 genotypes, no significant difference was detected in usage frequency or CD4/CD8 skewness. On the other hand, genotyping of the BV6S5 alleles (A1 and A2) revealed all three possible BV6S5 genotypes, A1/A1, A1/A2 and A2/A2, and the gene usage frequency was high, in the order A1/A1 > A1/A2 > A2/A2. These results indicate that the amino acid substitutions in BV6S5 (S36R and G70E) are in some way associated with the expression level of this gene. In the analysis of CD4/CD8 skewness, the three BV6S5 genotypes had similar skewness, indicating that A1 alleles are expressed more frequently than A2 alleles in both CD4+ and CD8+ T-cell populations. Although BV6S5 exhibits marked skewness to CD4+ T cells, our results indicate that the higher expression of A1 alleles is not associated with the increased ratio of CD4+ T cells.     

Vacuolated cell mesothelioma of the pericardium resembling liposarcoma: a case report

We report a case of localized pericardial mesothelioma with unusual histological features in a 44-year-old woman. Her radiological imagings showed an 11-cm pericardial tumor, between the heart and aortic arch. Microscopically, the tumor was predominantly composed of vacuolated cells and vaguely reminiscent of well differentiated "lipoma-like" liposarcoma, but only small foci of the tumor showed the papillotubular configuration. Histochemically, the tumor cells contained hyaluronic acid in the vacuoles but no lipids. Immunohistochemically, they showed immunoreactivity for cytokeratin, calretinin, vimentin, and epithelial membrane antigen. Ultrastructural study showed that the vacuoles of the tumor cells were intracytoplasmic lumina. The intracytoplasmic lumina and the surface membranes of the tumor cells had many long and slender microvilli with focal bush-like appearance. Desmosomes between adjacent cells were occasionally observed. To our knowledge, this is the first case report of epithelial type mesothelioma predominantly composed of vacuolated tumor cells, microscopically mimicking liposarcoma.     

Fundamental morphological changes in human olivary hypertrophy.

Morphological features of neurons in human inferior olivary nuclei were studied in 6 autopsied patients with dentato-olivary pathway lesions, who had survived for between 6 days and 15 months. Central chromatolysis-like neuronal enlargements were already present in the acute cases. Electron microscopy revealed round, homogeneous and electron-dense granules, varying in diameter from 0.15 micron to 2.5 microns, occurring frequently within the rough endoplasmic reticulum (ER) in the chromatolytic neurons of all 6 patients. No similar granules were observed in 6 controls. The vacuoles were due to dilatation of the rough ER, and often contained floccular materials. Neurofilamentous hyperplasia in the neurons was more frequently seen in the chronic cases. These findings suggest that the fundamental changes in the neurons in olivary hypertrophy occur within the rough ER.     

Neural progenitor cells lack immunogenicity and resist destruction as allografts

Multipotent, self-renewing stem and progenitor cells isolated from the mammalian central nervous system (CNS) have been shown to survive as allografts following transplantation to sites throughout the neuraxis. However, studies of this type shed little light upon the immunologic properties of the cells themselves, primarily because little is learned about the intrinsic immunogenic properties of a cell when it is grafted into an immune-privileged site. We have therefore investigated the immunogenic and antigenic properties of CNS progenitor cells by grafting them into a conventional (i.e., non-immune-privileged) site, namely, beneath the kidney capsule. Our results indicate that allogeneic CNS progenitor cells survive at least 4 weeks in a conventional site, during which time they neither sensitize their hosts nor express detectable levels of major histocompatibility complex (MHC) class I or II. These in vivo data are in accord with flow cytometric results showing that CNS progenitor cells do not express MHC class I or class II, either at baseline or upon differentiation in 10% serum. Exposure to interferon gamma, however, reversibly upregulates expression of these key transplantation antigens. Together, these results reveal CNS progenitor cells to possess inherent immune privilege. Since CNS progenitor cell allografts were rejected beneath the kidney capsule following specific sensitization of the host, CNS progenitor cells were able to display alloantigens, albeit not in an immunogenic form.