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Biomedical subjects

K Hirano

Publications and source records attributed to K Hirano.

At least 253 records · Page 14Linked to original sources

Clinical evaluation of a portable digital hearing aid with narrow-band loudness compensation.

A new portable digital hearing aid referred to as CLAIDHA (Compensate for Loudness by Analyzing Input-signal Digital Hearing Aid), which employs frequency-dependent amplitude compression based on narrow-band loudness compensation, was clinically evaluated in 159 subjects with hearing loss. The results of speech tests revealed better intelligibility compared with the subject's own hearing aids; the advantage of using CLAIDHA in daily life was also indicated by the results of a questionnaire completed by the subjects. In about 64% of the subjects with a flat, gradually sloping type of hearing loss, CLAIDHA was satisfactorily adopted for daily use. However, in the subjects with a steeply sloping type of hearing loss and subjects with losses mainly at high and low frequencies, with near-normal mid-frequency hearing. this loudness compensation scheme seems to be slightly less effective.

Aged↗

The expression pattern of the gene for NPK1 protein kinase related to mitogen-activated protein kinase kinase kinase (MAPKKK) in a tobacco plant: correlation with cell proliferation.

Mitogen-activated protein kinase (MAPK) cascades consist of members of three families of protein kinases: the MAPK family, the MAPK kinase family, and the MAPK kinase kinase (MAPKKK) family. Some of these cascades have been shown to play central roles in the transmission of signals that control various cellular processes including cell proliferation. Protein kinase NPK1 is a structural and functional tobacco homologue of MAPKKK, but its physiological function is yet unknown. In the present study, we have investigated sites of expression of the NPK1 gene in a tobacco plant and developmental and physiological controls of this expression. After germination, expression of NPK1 was first detected in tips of a radicle and cotyledons, then in shoot and root apical meristems, surrounding tissues of the apical meristems, primordia of lateral roots, and young developing organs. No expression was, however, observed in mature organs. Incubation of discs from mature leaves of tobacco with both auxin and cytokinin induced NPK1 expression before the division of cells. It was also induced at early stages of the development of primordia of lateral roots and adventitious roots. Thus, NPK1 expression appears to be tightly correlated with cell division or division competence. Even when an inhibitor of DNA synthesis was added during the germination or the induction of lateral roots by auxin, NPK1 expression was detected. These results showed that the NPK1 expression precedes DNA replication. We propose that NPK1 participates in a process involving the division of plant cells.

Base Sequence↗

Increased expression of sucrase and intestinal-type alkaline phosphatase in human gastric carcinomas with progression.

The activities of sucrase, total alkaline phosphatase (total ALP) and intestinal-type alkaline phosphatase (I-ALP) were assayed in gastric carcinomas and in their surrounding mucosae from 57 patients with advanced cancers, and the localization of sucrase in 203 carcinomas, including 86 early cancers, was examined immunohistochemically using polyclonal anti-sucrase antibody. All three enzymes were active in the 57 carcinomas as well as in their surrounding mucosae, but the levels were fairly low as compared to those in normal jejunum mucosa. A considerable part of the total ALP activity in tumor specimens was assumed to be due to I-ALP itself. Increased sucrase and I-ALP were found with greater depth of invasion by undifferentiated-type carcinomas. The pattern of immunohistochemical localization of sucrase in the 203 carcinomas also clearly indicated increased expression with greater depth of invasion even in differentiated-type carcinomas.

Adenocarcinoma↗

Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease.

Allantoin, the oxidation product of uric acid (UA), can be used as an in vivo marker of free radical generation. The aims of the present study were to evaluate the allantoin changes in plasma and bronchoalveolar lavage fluid (BALF) as well as to examine plasma levels of ascorbic acid (AA) and its oxidation product, dehydroascorbic acid (DHAA), in infants with or without chronic lung disease (CLD) during the first week of life. The study population was 20 infants of 24-30 weeks gestation, comprising 10 who subsequently developed CLD and 10 without CLD. In the CLD infants, the plasma allantoin/UA ratio showed a significant increase after day 1 and continued to increase gradually to reach a peak on day 6 (6.5 +/- 4.1% for CLD and 2.1 +/- 0.9% for non-CLD infants). The allantoin/UA ratio in BALF was also higher in CLD infants and the difference reached significance on days 4-6 (41.2 +/- 15.8% for CLD and 11.7 +/- 9.9% for non-CLD infants). In contrast to allantoin, the plasma DHAA/AA ratio did not differ between the 2 groups throughout the study period. Our findings that the allantoin/UA ratios were significantly higher in CLD than non-CLD infants not only in plasma but also in BALF, and that the intergroup differences of this ratio in both plasma and BALF was more prominent in the latter half of the first week of life further confirm our previous speculation that oxygen radicals are involved in the development of neonatal CLD.

Allantoin↗

Changes in the heparin affinity of extracellular-superoxide dismutase in patients with coronary artery atherosclerosis.

Extracellular-superoxide dismutase [EC 1.15.1.1] (EC-SOD) is a secretory glycoprotein with high affinity for heparin. This enzyme locates in blood vessel walls at a high enough level to suppress oxidative stress under normal conditions. EC-SOD is the major SOD isozyme in plasma, anchored to heparan sulfate proteoglycans in the glycocalyx of endothelial cell surfaces. Plasma EC-SOD is heterogeneous in heparin affinity and can be divided into five fractions, I to V, by heparin-HPLC. It has been suggested that EC-SOD form V is the primary form synthesized in the body and that EC-SOD forms with reduced heparin affinity are the result of proteolytic truncation of the C-terminal end of EC-SOD form V which is responsible for the binding with heparin. Recently, we reported that only plasma EC-SOD form V, with the highest heparin affinity, was increased by intravenous injection of heparin. The heparin affinity of plasma EC-SOD in patients with coronary atherosclerosis (CA+ patients) was compared in this study. The increase of plasma EC-SOD form V after heparin injection in CA+ patients was significantly less than that in subjects without evidence of stenosis in their major coronary arteries (CA- subjects). On the other hand, in CA+ patients, EC-SOD forms I to III, with low heparin affinity, were significantly increased compared to those in CA- subjects. EC-SOD in plasma apparently forms an equilibrium between the plasma phase and endothelial cell surface, and EC-SOD on the endothelial cell surface contributes to protecting the vessel wall against oxidative stress. These findings suggest that the quantitative and qualitative changes of EC-SOD, i.e., the decrease of bound EC-SOD on the endothelial cell surface, might suppress the defense systems against oxidative stress, which causes in part the development of coronary artery atherosclerosis.

Aged↗

A rapid assay of granisetron in biological fluids from cancer patients.

A convenient high-performance liquid chromatography (HPLC) was developed for the rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase extraction. HPLC was carried out using a LiChroCART cartridge column packed with Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5) and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365 nm for emission was used. The standard curve was linear over the range of 2 to 100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation (C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the between-day assay, respectively. GRN was well separated on the HPLC chromatogram from drugs such as etoposide, metclopramide, ondansetron, and domperidone which are often used together with GRN. It was suggested that the present method is useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion of patients undergoing cancer chemotherapy.

Antiemetics↗

The effect of ethanolamine on acute carbon tetrachloride intoxication.

The effects of ethanolamine on injured liver were investigated by oral administration of ethanolamine to male ddY mice 24 h after carbon tetrachloride (CCl4) injection. The serum aminotransferase activities in mice with liver injury were reduced by ethanolamine treatment (10-30 mg/kg body weight). Drastically increased regenerative reaction of ethanolamine treated-CCl4 injured liver was also observed through an increase in 5-bromo-2'-deoxyuridine uptake. ATP concentration in liver tissue was recovered by administration of ethanolamine. These results suggest that oral administration of ethanolamine accelerates recovery from CCl4-induced liver injury.

Adenosine Triphosphate↗

Lipoxygenase-1 from soybean seed inhibiting the activity of pancreatic lipase.

There are some similar characteristics in protein nature between the lipase inhibitor from soybean seed and soybean lipoxygenase-1 (LOX-1). Thus, the inhibiting protein for pancreatic lipase was prepared from defatted soybean meal by the procedure for the isolation of LOX-1 [Axelrod et al., Methods in Enzymology, 71, 441-451 (1981)]. The LOX-1 from soybean seed dose-dependently inhibited the release of fatty acid from a soybean oil emulsion, and the concentration of LOX-1 to cause half inhibition of the lipase activity was 3.2 x 10(-7) M. The LOX-1 obtained from E. coli transfected with a plasmid carrying the soybean LOX-1 gene also inhibited the lipase activity. However, the lipase-inhibiting activity by the LOX-1 was not affected by the presence of nordihydroguaiaretic acid, an inhibitor for LOX, in the reaction mixture. These results show that the soybean LOX-1 inhibits lipase activity regardless of its lipoxygenase activity.

Chromatography, Gel↗

Cerebral mycotic aneurysm treated with endovascular occlusion--case report.

A 56-year-old male with two mycotic aneurysms associated with infective endocarditis was treated by endovascular surgery before mitral valve replacement. Angiography revealed a ruptured proximal aneurysm and an unruptured distal aneurysm on the right middle cerebral artery. The ruptured aneurysm was successfully treated with an interlocking detachable coil, and patency of the parent artery was preserved. The unruptured distal aneurysm disappeared as a result of antibiotic therapy. Endovascular surgery of the mycotic aneurysm is less invasive and more effective than craniotomy under general anesthesia for patients with infective endocarditis.

Aneurysm, Infected↗

Blood flow rate in normal and tumor-bearing rats in conscious state, under urethane anesthesia, and during systemic hypothermia.

The blood flow rates of 14 tissues in the body were determined by microsphere method using normal and tumor-bearing rats kept conscious or under urethane anesthesia. The effects on the blood flow rate in the tissues were assessed for multimodal therapy, systemic hypothermia for ischemic brain injury, and local hyperthermia and angiotensin II-induced hypertensive chemotherapy for cancer. Urethane anesthesia showed no effect on cardiac output, while there was a tendency of decrease of blood flow rate and % of cardiac output in each tissue other than muscle tissue, in which they increased as a counterbalance, in normal and tumor-bearing rats. Systemic hypothermia gave results similar to those of urethane anesthesia in normal rats, but for tumor-bearing rats, it decreased cardiac output, and consequently the blood flow rate in most tissues. Brain blood flow rate was about half of that in the conscious rats. Local hyperthermia also decreased the cardiac output and blood flow rate in each tissue, including the tumor tissue. Angiotensin II-induced hypertension showed no effect on cardiac output, had various effects on blood flow rate in each tissue, and led to no increase in the tumor blood flow rate. Simulations based on the physiological pharmacokinetic modeling suggested that intramuscular injection of a lung-specific derivative of ceftazidime would provide the ideal biodistribution to ensure its optimal therapeutic efficacy during systemic hypothermia. This methodology, namely the pharmacokinetic simulation based on the physiological values of the body, will provide a useful piece of information on drug delivery systems under various conditions.

Anesthesia, Intravenous↗

Effect of composition on biological fate of oil particles after intravenous injection of O/W lipid emulsions.

Plasma concentrations of oil particles after intravenous injection of oil-in-water (O/W) lipid emulsions were monitored based on the plasma concentration of phospholipids (PL) and triglycerides (TG), and the light scattering intensity (LSI) of plasma. Previously, we found that their time profiles after injection of the standard O/W lipid emulsion composed of soybean oil (SO) and egg yolk phosphatides (EYP) were similar and suggested that the oil particles with diameter of about 200 nm were entrapped by reticuloendothelial system (RES). Herein, in order to develop a delivery system to avoid the RES uptake by using the lipid emulsions, biological fate of lipid emulsions with oil particles of various sizes or those emulsified by surfactants with polyoxyethylene segments were subjected to the investigations. Lipid emulsions with oil particles of various sizes (about 150-550 nm) were prepared by altering EYP content. The oil particles were stable in plasma in vitro, but oil particle size decreased time-dependently after intravenous injection. Plasma clearance of oil particles depended on their initial size and was decreased by pretreatment with dextran sulfate 500 (DS500), a known RES suppressor. These results suggested that oil particles are still entrapped by RES, even for small-sized oil particles (about 150 nm). Lipid emulsion with small-sized oil particles was also prepared using medium chain triglycerides. The oil particles were stable in vitro, but the time profiles of plasma concentrations of PL and TG, and LSI of plasma were different, and oil particle size decreased time-dependently after intravenous injection. Plasma clearance of the oil particles also depended on their initial size and was decreased by DS500, suggesting that in vivo instability could be due to RES-mediated processes. Artificial surfactants with polyoxyethylene segments, HCO-60 (HCO60) and polysorbate 80 (PS80), were used for RES avoidance. HCO60 resulted in drastic reduction of the plasma clearance of the oil particles for both lipid emulsions composed of soybean oil and medium chain triglycerides. The time-dependent decrease of oil particle size after intravenous injection was marginal. In contrast, PS80 could not prolong the circulation time of the oil particles, and their size decreased time-dependently after intravenous injection.

Animals↗

O/W lipid emulsions for parenteral drug delivery. III. Lipophilicity necessary for incorporation in oil particles even after intravenous injection.

The potential usefulness of oil-in-water (O/W) lipid emulsions as injectable drug delivery systems was examined. Plasma concentrations of oil particles after intravenous injection of a standard lipid emulsion composed of soybean oil and egg yolk phosphatides were monitored based on the plasma concentrations of phospholipids and triglycerides, and the light scattering intensity of the plasma. Their time profiles were similar to each other, and the oil particle size decreased time-dependently. Pretreatment with dextran sulfate, a known reticuloendothelial system (RES) suppressor, resulted in marked reduction of the plasma clearance of the oil particles and of the time-dependent alteration of oil particle size, suggesting that oil particles were trapped by RES. The lipophilicity of the drug needed for its incorporation in the oil particles even after intravenous injection was found to be clog P > 8, where clog P is the calculated logarithm of the partition coefficient between n-octanol and water. In the case of sudan II (clog P = 5.4), the release from the oil particles was very quick after intravenous injection, resulting in slight alteration in biodistribution when compared with its micellar solution. In contrast, menatetrenone (clog P = 9.5) was selectively delivered to the liver, lungs and spleen, being consistent with the oil particles taken up by RES.

Anesthesia↗

O/W lipid emulsions for parenteral drug delivery. IV. Changes in the pharmacokinetics and pharmacodynamics of a highly lipophilic drug, menatetrenone.

The pharmacokinetics and pharmacodynamics of antihemorrhagic vitamin, menatetrenone after intravenous injection as the lipid emulsion, were compared to those as the micellar solutions. Menatetrenone was selectively delivered to the liver, lungs and spleen and retained in them. Hepatic and splenetic concentration at 6 h (C6h) increased 21.6- and 27.1-fold, respectively, and the area under the tissue concentration-time curve up to 6 h (AUC(0-6h)) were 2.3- and 11.4-fold, respectively, when compared with its micellar solution. Antihemorrhagic effect of menatetrenone was assessed using warfarin-induced hypoprothrombinemic rats. The lipid emulsion of menatetrenone decreased the prothrombin time at 6h after intravenous injection more effectively than micellar solution. The dose response curves indicated that the efficacy of the lipid emulsion was 2.4-2.9 times that of a micellar solution, and this was correlated with AUC(0-6h) rather than C6h. The plasma level of clotting factor VII and the hepatic level of descarboxyprothrombin were also recovered more effectively, while no significant differences were noted between the two formulations for the plasma level of factor II or descarboxyprothrombin at the dose levels examined. Although selective delivery of menatetrenone in the liver by the lipid emulsion was due to phagocytosis by non-parenchymal cells, menatetrenone in the whole liver appeared to contribute to recovery from hypoprothrombinemia.

Analysis of Variance↗

The recovering effect of betaine on carbon tetrachloride-induced liver injury.

The recovering effect of betaine (derivative of choline) on carbon tetrachloride (CCl4)-injured liver was investigated by oral and intraperitoneal administration of betaine at 24 h after acute CCl4 intoxication. The effect of betaine was estimated by the activity of alanine aminotransferase (ALT) released into the serum, histological score, and the incorporation of S-phase indicator (5-bromo-2-deoxyuridine/5-fluoro-2'-deoxyuridine; BrdU/FdU). A significant decrease in the activity of serum ALT was observed by the intraperitoneal (3 mg/kg body) or oral (15 mg/kg body) administration of betaine. Furthermore, an increase in the uptake of BrdU into the hepatocyte nuclear DNA and a reduction in liver necrosis after the oral treatment of betaine (15 mg/kg body) was observed. From these results, the administration of betaine showed a significant effect in recovering CCl4-injured liver.

Alanine Transaminase↗

Mechanism of hypocholesterolemic action of S-8921 in rats: S-8921 inhibits ileal bile acid absorption.

The mechanism of the hypocholesterolemic action of S-8921, methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)- 4-hydroxy-6,7,8-trimethoxy-2-naphthoate, was examined in rats. In diet-induced hypercholesterolemic rats, 2 weeks oral administration of S-8921 dose- and time-dependently decreased plasma cholesterol level in the daily dose range of 0.1 to 10 mg/kg. Results with the dual-isotope plasma ratio method indicated that S-8921 inhibits cholesterol absorption from the intestine and enhances its elimination from the body. The in situ loop method showed that S-8921 does not inhibit the absorption of cholesterol from rat jejunum, clearly inhibits active absorption of taurocholic acid (TCA) and glycocholic acid (GCA) from rat ileum and does not inhibit passive absorption of cholic acid (CA) from the rat jejunum. In rat ileal brush-border membrane vesicles, S-8921 inhibited the sodium-dependent uptake of TCA in a concentration-dependent manner with IC50 of 2.1 microM, not the Na(+)-dependent D-glucose and L-alanine uptake. These results suggest that S-8921 is a potent, selective inhibitor of the Na(+)-dependent bile acid transport system in the ileal mucosal cell brush-border membrane, and this inhibition is the mechanism by which this drug decreases intestinal bile acid reabsorption to result in a significant decrease of plasma cholesterol.

Animals↗

[The impact of low calcium dialysate (1.25 mmol/l; LCD) on bone metabolism in CAPD patients].

The aim of this study was to evaluate the influence of LCD on bone metabolism, and assess the indication of LCD. Fourteen patients on CAPD (m = 8, f = 6) were converted to LCD following over 1 year on standard calcium dialysate (1.75 mmol/l; SCD) treatment, and followed for 1 year. The biochemical measurements included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD) was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol were administered to maintain plasma Ca levels within the normal range. The patients were divided into three groups on the basis of the i-PTH levels just before the conversion to LCD. Group 1; n = 5, i-PTH < 65. Group 2; n = 5, 65 < or = i-PTH < 200. Group 3; n = 4, 200 < or = i-PTH (pg/ml). Mean BMD Z scores decreased significantly in group 3. Mean serum i-PTH significantly increased in all groups. These results suggest that LCD is effective for treating adynamic bone disease, which is seen in high frequency in patients undergoing peritoneal dialysis. However, these results also pointed to the disadvantage of worsening the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in patients whose i-PTH levels are high, because of the possibility of bone mineral loss.

Adult↗

Troglitazone action is independent of adipose tissue.

We have investigated the antidiabetic action of troglitazone in aP2/DTA mice, whose white and brown fat was virtually eliminated by fat-specific expression of diphtheria toxin A chain. aP2/DTA mice had markedly suppressed serum leptin levels and were hyperphagic, but did not gain excess weight. aP2/DTA mice fed a control diet were hyperlipidemic, hyperglycemic, and had hyperinsulinemia indicative of insulin-resistant diabetes. Treatment with troglitazone alleviated the hyperglycemia, normalized the tolerance to intraperitoneally injected glucose, and significantly decreased elevated insulin levels. Troglitazone also markedly decreased the serum levels of cholesterol, triglycerides, and free fatty acids both in wild-type and aP2/DTA mice. The decrease in serum triglycerides in aP2/DTA mice was due to a marked reduction in VLDL- and LDL-associated triglyceride. In skeletal muscle, triglyceride levels were decreased in aP2/DTA mice compared with controls, but glycogen levels were increased. Troglitazone treatment decreased skeletal muscle, but not hepatic triglyceride and increased hepatic and muscle glycogen content in wild-type mice. Troglitazone decreased muscle glycogen content in aP2/DTA mice without affecting muscle triglyceride levels. The levels of peroxisomal proliferator-activated receptor gamma mRNA in liver increased slightly in aP2/DTA mice and were not changed by troglitazone treatment. The results demonstrate that insulin resistance and diabetes can occur in animals without significant adipose deposits. Furthermore, troglitazone can alter glucose and lipid metabolism independent of its effects on adipose tissue.

Adipose Tissue↗