Prevalence of asthma in adults in Menda town rural-mountain area in Japan]

Several reports have suggested that the prevalence of asthma in adults is currently increasing. However, recent prevalence of asthma has not reported in Japan, especially in rural-mountain areas. To investigate the prevalence of asthma in adults in Japan, we conducted clinical epidemiological research on 5066 inhabitants of Menda town, in a rural-mountain area of Japan. The study population comprised 98.7% of adults in the town, including senior high school students whose age were more than 15 years old. The prevalence of asthma among adults was 3.6%. The ratio of prevalence in males to prevalence in females was 1.44. Peaks prevalences were observed in the age ranges of 15-19 and > 70 years old in males, and 15-19, 40-49 and > 70 years old in females.     

New method to determine oxygen cost for contractility

We developed a new method to determine the oxygen cost for myocardial contractility and applied it to epinephrine in the excised cross-circulated dog heart. We utilized the relation between myocardial oxygen consumption (VO2) and the systolic pressure-volume area (PVA) which represents the total mechanical energy generated by contraction. We first obtained a reference VO2-PVA relation in a baseline contractile state. Then, the end-diastolic and stroke volumes were fixed constant and a global index of ventricular contractility, Emax, was enhanced by infusing epinephrine. The VO2-PVA data point was shifted linearly right-upward with the increases in Emax. From the slopes of both the reference VO2-PVA relation line and the regression line of VO2 on PVA during the gradually increased Emax, we calculated the oxygen cost for contractility, i.e., the ratio of the elevation of the VO2-PVA relation to enhanced Emax in each heart. The ratio was 0.00095 +/- 0.00013 ml O2.ml.mmHg-1.beat-1.100 g LV-2. The result indicates that the oxygen cost for contractility can be reliably and efficiently determined by this new method.     

Evolution of interleukin-18 binding proteins and interleukin-1 receptor, type II proteins

Interleukin-18 (IL-18) is one of the pivotal cytokines controlling the defense mechanism called inflammation. As a first step to develop proteins for controlling the IL-18 level, we initiated a study of IL-18-binding proteins (IL-18BPs). Twenty-four IL-18BP family members, 11 from vertebrates and 13 from chordopoxviruses, were picked from the NCBI database. Eight of these vertebrate IL-18BPs and two of the chordopoxvirus IL18-BPs were identified here and characterized as new members of the IL-18BP family. Their IL-18 binding domains were aligned and the distribution of highly conserved critical amino acid residues was analyzed and used to construct a phylogenetic tree. From this tree it was inferred that at least two independent events created two different ancestral viral IL-18BP genes by retroposition of IL-18BP genes from the vertebrate lineage. These two events are estimated to have occurred after an ancient mammalian IL-18BP gene diverged from birds, and before the mammalian IL-18BP gene diverged into human, ungulate and rodent IL-18BP genes. Moreover, our results suggest that IL-18BP and interleukin-1 receptor, type II (IL-1R2) had a common ancestral gene and diverged from the ancestral gene into IL-18BP and IL-1R2 genes in the fish period.     

A case with multiple myeloma in which serum forms gel precipitation upon exposure to air

We present the case of a 69-years-old man who was admitted to hospital with multiple myeloma. IgG-kappa type monoclonal protein was detected in the serum. When we separated the serum obtained from blood sample of the patient and the lid of the collecting tube was opened, the patient's serum became gelled immediately. When the lid of the collecting tube remained closed, the patient's serum did not become gelled even at 4 degrees C. Moreover, the gelled serum of the patient did not resolve at 56 degrees C. Taken together, these results indicated that gel formation of the patient's serum may not be due to cryoglobulin. It was found that the pH of the patient's serum elevated to pH 8.0 quickly after exposed to air. It was also found that the patient's serum, but not the sera of other IgG-kappa multiple myeloma patients, became gelled as soon as PBS of pH 8.0 was added. These results highly suggest that the patient's serum becomes gelled at pH 8.0. However, the isoelectric focusing of isolated precipitation in the patient showed fractions around the pH 8.5-8.7 zone, which was different from the pH at which the precipitation began to form. We think that this may be the first report of a multiple myeloma patient whose serum becomes gelled after exposed to air.     

Dissociation of pressure-rate product from myocardial oxygen consumption in dog

Although the pressure-rate product (double product; DP) is generally recognized as a good index of myocardial oxygen consumption (VO2), catecholamines are reported to change the VO2-DP relationship. However, the separate influences of chronotropism and inotropism on the VO2-DP relation have not been studied. Therefore, we examined these influences in anesthetized open-chest dogs by cardiac pacing and dobutamine infusion. We observed two different VO2-DP lines under the separate chronotropic and inotropic changes. We interpreted such VO2-DP relations by the concept of the pressure-volume area (PVA). PVA is a measure of total mechanical energy for ventricular contraction and is a specific area in the ventricular pressure-volume (P-V) diagram circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V trajectory. The empirical VO2-PVA relation that had been obtained in our previous studies reasonably simulated the dissociation of DP from VO2 under separate changes in chronotropism and inotropism.     

Anti-allergic activities of a new benzopyranopyridine derivative Y-12,141 in rats.

Passive cutaneous anaphylaxis (PCA) mediated in rats by IgE-like antibodies against egg albumin or the benzylpenicilloyl determinant was inhibited in a dose-dependent manner by intravenous treatment with Y-12,141; the ED50 was 0.09--0.2 mg/kg. The inhibitory effect of Y-12,141 ON PCA was about 5 times as potent as that of disodium cromoglycate (DSCG). Oral treatment with Y-12,141 resulted in the inhibition of PCA, showing an ED50 of 2.5 mg/kg. This action of Y-12,141 on PCA was considered to be due to the inhibition of the release of allergic mediatros from mast cells in a manner similar to DSCG. The results suggest that Y-12,141 may have an anti-allergic activity.     

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.     

Expression and localization of chromogranin A gene and protein in human submandibular gland

Human saliva chromogranin A (CgA) is clinically promising as a psychological stress marker. However, expression of CgA is poorly understood in humans, although salivary gland localization of CgA in other mammals, such as rodents and horses, has been demonstrated. In the present study, we investigated the expression and localization of CgA in the human submandibular gland (HSG) using various methods. CgA was consistently localized in serous and ductal cells in HSG, as detected by immunohistochemistry and in situhybridization. Reactivity was stronger in serous cells than in ductal cells. In addition, strong immunoreactivity for CgA was observed in the saliva matrix of ductal cavities. Western blotting gave one significant immunoreactive band of 68 kDa in the adrenal gland, HSG and saliva. Finally, CgA was detected in secretory granules of serous and ductal cells by immunoelectron microscopy. In conclusion, CgA in humans is produced by HSG and secreted into saliva.