Molecular cloning of a novel gene involved in serotonin receptor-mediated signal transduction in rat stomach

AbstractIn Xenopus oocytes injected with small size mRNAs (500–700 b), obtained from rat stomach by fractionation, application of 10 μM 5-HT induced a substantial Ca2+-activated Cl− current (ICl-Ca). ICl-Ca was not elicited by 5-HT in native oocytes. Consistent results from this assay in the oocyte expression system motivated cDNA cloning experiments. A novel cDNA (named r at s tomach s erotonin receptor-related cDNA: RSS cDNA) which encodes a small protein involved in specific 5-HT receptor-mediated ICl-Ca activation was identified. The molecular weight of RSS protein in the reticulocyte lysate translation system (∼10 kDa) is identical to that calculated from the amino acid sequence. Computer-aided analysis of the predicted protein does not show any obvious sequence homologies (<18%) to any other proteins including G protein-coupled receptors. Northern analysis revealed that RSS mRNA is ubiquitously expressed at varying levels in a number of different tissues. Furthermore, the binding of [3H]spiperone, a 5-HT2 receptor antagonist, was examined in CHO cells, which highly expressed RSS transcripts (named CHO-RSS). Specific binding of [3H]spiperone was not clearly observed in native CHO but was detected in CHO-RSS. The dissociation constant was 10.3 nM in CHO-RSS. These results suggest that RSS protein may be a factor which facilitates 5-HT receptor expression or, alternatively, an enhancer of the affinity of native 5-HT receptor to 5-HT

キカンシ ゼンソク ゾウカ ノ ヨウイン ト サイキン ノ チリョウ ノ トピックス

Increasing asthma prevalence is a major problem in Western countries. Various factors, such as allergic sensitization to indoor allergens, change in incidence in infectious diseases, and increase of air pollutants, are considered to be possible factors for increasing prevalence. Inhaled corticosteroids play an important role in asthma treatment, and its impact on asthma morbidity and mortality has already been established. In addition, recent attention has been focused on molecular targeted therapy in the treatment of bronchial asthma. Promising results of anti-IgE antibody are reported in several clinical trials and anti-CD23 antibody is now introduced in clinical trials

Inhaled steroid therapy and hospitalization for bronchial asthma : trend in Tokushima University Hospital

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean 81.3%) compared to earlier years (mean 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, β2-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean 0.18/patient/year) compared to earlier years (mean 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean 0.043/patient/year) compared to earlier years (mean 0.23/patient/year).In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter

Increased Systemic Th17 Cytokines Are Associated with Diastolic Dysfunction in Children and Adolescents with Diabetic Ketoacidosis

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA