Search PubMed⌕ Search

Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 505 records · Page 28Linked to original sources

Comparison between the fluorometric HPLC method and the conventional method for determining urinary delta-aminolevulinic acid and coproporphyrin as indices of lead exposure.

Fluorometric methods for determining delta-aminolevulinic acid (ALA) and coproporphyrin (CP) in urine have been recently developed by using high-performance liquid chromatography (HPLC). In the present study, urinary ALA and CP in lead-exposed workers were determined with these fluorometric HPLC methods and the conventional methods, and the results obtained were compared. In lead workers with a urinary ALA greater than or equal to 5 mg/l, the values obtained with the fluorometric HPLC method corresponded well with those measured with the conventional colorimetric method. In contrast, in lead workers with ALA less than 5 mg/l, ALA values obtained with the fluorometric HPLC method were lower than those measured with the conventional method, suggesting the possibility of matrix interference in urine. The urinary CP values obtained with the conventional method of Rimington (1971) were higher than those measured with the fluorometric HPLC method, though the correlation was good.

Adult↗

Effects of inositol phosphates on the membrane activity of smooth muscle cells of the rabbit portal vein.

The effects of intracellular perfusion of inositol 1,4,5-trisphosphate (InsP3) or inositol 1,3,4,5-tetrakisphosphate (InsP4) on electrical responses of smooth muscle cell membranes of the rabbit portal vein were studied using the whole cell voltage clamp technique. Depolarisation to 0 mV from a holding potential of -60 mV, evoked inward Ca (Ica), transient outward (ISO), oscillatory outward (IOO) and sustained outward (ISO) currents. Generation of IOO was dependent on the [Ca]o, but it was also generated in 0 mM Ca solution for over 10 min. From amplitude histograms, IOO was divided into two components. Reduction in [Ca]o inhibited the appearance of but not the amplitudes of both IOO components. However, the larger component of IOO was more resistant to a reduction in [Ca]o than the smaller one. InsP3 (10 microM) increased the frequency of both IOO components to a greater extent than their amplitude, but the larger component was more sensitive to InsP3 than the smaller one. The increase in the occurrence of IOO induced by InsP3 did not occur following pretreatment with 3 mM caffeine or 1 nM A23187. In normal PSS, InsP3 was evoked by a depolarising pulse positive to -40 mV, whereas following perfusion with InsP3 (10 microM), IOO was evoked at -60 mV. In normal PSS, intracellular perfusion with 10 microM InsP4 changed neither the frequency nor the amplitude of IOO, and the amplitudes of ICa, ITO and ISO were also unchanged. However, in 10 mM Ca solution, 10 microM InsP4 generated IOO at a membrane potential of -60 mV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Lead levels in ancient and contemporary Japanese bones.

During the past few centuries, lead production, consumption and emissions, to our total environment have increased remarkably. We have determined the concentrations of lead in 41 well-preserved ancient and 11 contemporary rib bones of a mature age (40-60 y), with a view of historically evaluating lead exposure in humans. The oldest Japanese bones (1000-300 B.C.) were found to contain a mean of 0.58 microgram Pb/g dry wt and a mean molar ratio of lead to calcium of 0.6 x 10(-6), compared with 4.7-5.2 x 10(-6) in the bones of the Edo era (1600-1867 A.D.) and contemporary residents in Japan. The mean molar ratios of female bones were always higher than those of male bones for each era. From this fact we may assume that facial cosmetics were one of the main routes of lead exposure among the ancient Japanese, especially those who lived during the Edo era.

Adult↗

A comparison of the carcinogenicity of N-nitrosodiethylamine and N-nitrosodimethylamine after intratracheal instillation into Syrian golden hamsters.

N-Nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) were instilled intratracheally into male Syrian golden hamsters once a week for 15 wk. The total dosages were 1.5 mg and 7.5 mg of NDEA and 0.75 mg and 1.5 mg of NDMA. A control group simultaneously received phosphate buffer vehicle. Tumours related to instillation appeared principally in the respiratory tract and the liver. Over the entire lifespan of the animals tumour incidence rates in the respiratory tract were 100% in both the NDEA groups, 6% in both NDMA groups and 8% in the control group. The total incidences of liver tumours were 6% in the 0.75 mg NDMA group, 19% in the 1.5 mg NDMA group, zero in the NDEA groups, and 4% in the control group. These results indicate that, when administered by this route, NDEA is a much more potent carcinogen in the respiratory tract than is NDMA but NDMA alone seems to be carcinogenic to the liver, at a total dosage of 1.5 mg.

Animals↗

Studies on scavengers of active oxygen species. 1. Synthesis and biological activity of 2-O-alkylascorbic acids.

A novel series of 2-O-alkylascorbic acids (5a-u) was synthesized, and their scavenging activities against active oxygen species as well as their suppressive effects on the arrhythmias in rat heart ischemia-reperfusion models were evaluated. Some 2-O-alkylascorbic acids (5e-1) exhibited potent inhibiting activities against lipid peroxidation in rat brain homogenates and in alleviating effects in the ischemia-reperfusion models. Studies on the structure-activity relationship demonstrated that a free 3-enolic hydroxyl group and the longer alkyl chains substituted on the 2-hydroxyl group of ascorbic acid were beneficial for the biological and pharmacological activities. 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats.

Animals↗

Serological evaluation of ultrasound examination for chronic schistosomiasis japonica in a previously endemic area--the Chikugo River Basin, Japan.

Ultrasound diagnosis of chronic schistosomiasis japonica was assessed by comparison with the results of serological tests using enzyme-linked immunosorbent assay (ELISA) with egg and adult worm antigen, and the circumoval precipitation test. The subjects were persons resident in the Chikugo River Basin in Kyushu, southwest Japan, where schistosomiasis used to be highly prevalent. Of 93 individuals with a past history of infection, 37 (39.8%) presented the characteristic echo pattern of the disease (network, sieve, mottled or mixed pattern). In the serological tests, the ultrasound (US)-positive subjects showed a significantly higher IgG antibody-positive rate in ELISA (81.1% for egg-ELISA), than the US-negative subjects (37.5% for egg-ELISA). Individuals bearing dead Schistosoma japonicum eggs proven by tissue biopsy showed a similar antibody-positive rate (76.5% for egg-ELISA) to that of the US-positive subjects. Sera of a group which had no schistosomiasis characteristic echo pattern, but had liver fibrosis, hepatomegaly or liver cirrhosis as shown by US, were also highly positive (71.4% for egg-ELISA). The present serological studies thus confirmed the usefulness of ultrasound diagnosis for chronic schistosomiasis japonica. Furthermore, we were able to determine certain indications of liver abnormality currently undefined in the normally utilized US classifications.

Adult↗

Comparative study on the carcinogenicity of N-nitrosodiethylamine, N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopyrrolidine and N-nitrosodi-n-propylamine to the lung of Syrian golden hamsters following intermittent instillations to the trachea.

N-Nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), N-nitrosopyrrolidine (NPYR) and N-nitrosodi-n-propylamine (NDPA) were instilled into the lungs of male Syrian golden hamsters by intratracheal instillations once a week for 15 weeks. The total doses given were 1.5 mg of each drug. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the total lifespan, tumor incidence rates in the respiratory organs were 100% in the NDEA group, 6% in the NDMA group, 43% in the NMOR group, 0% in the NPYR group, 72% in the NDPA group and 4% in the control group. The incidence rates in the liver were 19% in the NDMA group and 4% in the NPYR group. No liver tumors developed in the other groups. The carcinogenic potencies of these N-nitroso compounds to the respiratory organs was provisionally estimated to be in the following order: NDEA greater than NDPA greater than NMOR greater than NDMA = NPYR, at the 1.5 mg dosage level. However, the difference in the rates of tumor incidence between the NDMA or NPYR group and the control group was not significant.

Adenoma↗

Effects of nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides on cGMP.

The interactions of the nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides with cGMP synthesis have proved to be useful and important leads to the functions of cGMP and signal transduction mechanisms. Although considerable progress has been made, many important questions remain to be answered. Nevertheless, the guanylate cyclase-cGMP system clearly represents an important second-messenger system that mediates the effects of numerous agents.

Atrial Natriuretic Factor↗

Identification of Re lipopolysaccharide-binding protein on murine erythrocyte membrane.

Our recent studies have suggested that bacterial lipopolysaccharide (LPS) attaches to Pronase-sensitive proteins on the murine erythrocyte membrane. In the present study, in order to identify the LPS-binding protein on the murine erythrocyte membrane, a unique method to detect LPS-binding protein on a nitrocellulose membrane was developed. Murine erythrocyte membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, then transferred electrophoretically onto a nitrocellulose membrane. The membrane was incubated with LPS of Salmonella minnesota R595 (Re LPS) in phosphate-buffered saline (PBS), after the remaining sites were blocked with gelatin in PBS. We were able to obtain a non-background stain by adding the nonionic detergent octylglucoside at the low concentration of 0.1% to the Re LPS solution. The Re LPS bound to the protein on the nitrocellulose membrane was exposed to affinity purified anti-Re LPS antibodies (IgG) and then to alkaline phosphatase-conjugated anti-IgG. The alkaline phosphatase was detected on the membrane by an enzymatic reaction. This method demonstrated that Re LPS was bound to an erythrocyte protein of 96 kDa. Treatment of erythrocytes with Pronase led to disappearance of the Re LPS-binding protein on the erythrocyte membrane. There was no difference between LPS-responder and LPS-nonresponder murine erythrocyte membranes in amount and molecular weight of the Re LPS-binding protein.

Animals↗

Characterization of [3H]nifedipine binding to intact vascular smooth muscle cells.

Specific binding of the dihydropyridine Ca2+ antagonist [3H]nifedipine to dispersed smooth muscle cells of the porcine coronary artery was investigated and the findings were compared with the binding to microsomes of smooth muscles. Specific binding to intact cells was saturable and reversible. The dissociation constant was 1.93 +/- 0.42 nM and the maximal binding capacity was 59.6 +/- 12.4 fmol/10(6) cells, as assessed by Scatchard analysis of the equilibrium binding at 25 degrees C. The Kd value with intact cells was slightly higher than that observed with microsomes. Specific binding of [3H]nifedipine to intact cells was completely displaced by unlabeled dihydropyridine derivatives. Among other Ca2+ antagonists, verapamil and d-cis-diltiazem partially and flunarizine completely inhibited the binding. In the case of microsomes, d-cis-diltiazem stimulated the binding of [3H]nifedipine. These results suggest that there may be multiple binding sites for different subclasses of Ca2+ antagonists. Polyvalent cations had no effect on the binding to intact cells. In the case of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-treated microsomes, the addition of CaCl2 and BaCl2 increased the Bmax, but the Kd value remained unchanged. MnCl2 and CdCl2 had stimulatory or inhibitory effects, depending on the concentrations, whereas LaCl3 had no effect. The effect of membrane depolarization on the binding was also examined. When the intact cells were incubated in high [K+]o solution for 60 min, the Kd was lowered to 1.4 nM from the control value of 2.0 nM, thereby indicating that [3H]nifedipine binds to Ca2+ channels, with a higher affinity, at depolarized states.

Animals↗

Effect of beta-lactam antibiotics on hepatocellular glutathione levels in vitro and in vivo.

Incubation of isolated rat hepatocytes with high concentration of beta-lactam antibiotics, cephaloridine (CER), flomoxef (FMOX) or cephamandole (CMD), resulted in significant reduction of cellular glutathione (GSH) levels, though cell viability was not affected during the incubation period. I.v. injection of a large dose, 300 mg/kg, of these beta-lactam antibiotics to rats did not affect the hepatic GSH levels. The concentration of beta-lactam antibiotics in the body fluid of the rats were found to be much lower than the amounts which causes GSH depletion in vitro.

Animals↗