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Biomedical subjects

N Miyazawa

Publications and source records attributed to N Miyazawa.

At least 37 records · Page 2Linked to original sources
PubMed1998

The choleretic effects of N-acetylglucosaminides, major urinary metabolites of ursodeoxycholic acid, in bile fistula rats.

We investigated the effects of three bile acids conjugated with N-acetylglucosamine, ursodeoxycholate N-acetylglucosaminide, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, on bile flow and biliary excretion of various markers in comparison with ursodeoxycholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid in bile fistula rats. These bile acids were infused intravenously at a constant rate of 0.3 or 0.6 micromol/min/100 g b.w. for 2 h. All bile acids examined increased bile flow in a dose-dependent manner. In particular, ursodeoxycholate N-acetylglucosaminide has a longer-lasting effect after its infusion on bile flow than the other bile acids. Furthermore, these bile acids markedly increased biliary total bile acid excretion. At a higher dose level, the coefficient of determination (r2) between the biliary total bile acid excretion and bile flow for ursodeoxycholate N-acetylglucosaminide (r2 = 0.39) was lower than that for the other bile acids (r2 = 0.75-0.92). The ursodeoxycholate N-acetylglucosaminide, as well as tauroursodeoxycholic acid, glycoursodeoxycholic acid, tauroursodeoxycholate N-acetylglucosaminide and glycoursodeoxycholate N-acetylglucosaminide, was mostly excreted in an unchanged form in bile, whereas ursodeoxycholic acid was excreted as a conjugate with taurine. The three N-acetylglucosaminides as well as ursodeoxycholic acid, tauroursodeoxycholic acid and glycoursodeoxycholic acid significantly increased the biliary excretion of cholesterol, phospholipid, bilirubin and total Ca2+. In contrast, the N-acetylglucosaminides significantly decreased in biliary bicarbonate concentration, whereas ursodeoxycholic acid significantly increased biliary bicarbonate concentration. However, tauroursodeoxycholic acid and glycoursodeoxycholic acid did not significantly change the biliary bicarbonate concentration. The results indicate that N-acetylglucosaminides have a choleretic effect in bile fistula rats. Our present study also demonstrates that N-acetylglucosaminides, but not ursodeoxycholic acid, tauroursodeoxycholic acid or glycoursodeoxycholic acid, can significantly reduce the biliary bicarbonate concentration. Furthermore, our findings suggest that ursodeoxycholate N-acetylglucosaminide may partly exert a choleretic effect via mechanisms different from those of the other bile acids.

Animals↗
PubMed1998

Specific detections of the early process of the glycation reaction by fructose and glucose in diabetic rat lens.

The glycation reaction by fructose, as well as that by glucose, in control and diabetic rat lens was analyzed by using antibodies which specifically recognize adducts of lysine with fructose and with glucose. Levels of fructose adducts in diabetic rat lens were 2.5 times that of the control, and correlated with sorbitol levels. This was mainly due to enhanced glycation of beta- and gamma-crystallins by fructose under diabetic conditions. These data suggest that glycation by fructose may also play a role in cataract formation under conditions of diabetes and aging.

Animals↗
PubMed1998

Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening.

Vascular smooth muscle cell migration to the intima from the media and proliferation in the intima play key roles in atherosclerosis and restenosis after coronary angioplasty. Histamine released from adherent platelets at the injured artery and from mast cells in atheromas has stimulant actions on both smooth muscle cell migration and proliferation, and histamine receptor antagonists abolish the effect of histamine in vitro. The aim of this study was to examine the effect of histamine receptor antagonists on intimal thickening. Endothelial injury in the mouse femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. The histamine H1 receptor antagonist, diphenhydramine, at a dose of 30 mg/kg or the histamine H2 receptor antagonist, cimetidine, at a dose of 200 mg/kg was intraperitoneally administered to mice for 21 days after endothelial injury. Twenty-one days after endothelial injury, morphometric analysis was performed to measure the cross-sectional areas of the intima and media. Diphenhydramine significantly reduced the intimal area to 1.1 +/- 0.3 (x 10(-3) mm2) compared with the value in the control group, which was 6.2 +/- 1.4 (x 10(-3) mm2), but cimetidine (5.5 +/- 1.9, x 10(-3) mm2) did not. Similarly, the ratio of intimal area to medial area in the diphenhydramine-treated group but not in the cimetidine-treated group was significantly reduced (83%). In the in vitro study, cimetidine inhibited neither proliferation nor migration of mouse vascular smooth muscle cells stimulated by platelet-derived growth factor (PDGF). In contrast, diphenhydramine significantly (P < 0.05) inhibited proliferation in a dose-dependent manner, but did not inhibit migration. These results suggest that diphenhydramine, a histamine H1 receptor antagonist, reduced the formation of intimal hyperplasia, at least in part due to inhibition of cell proliferation. However, cimetidine, a histamine H2 receptor antagonist, was ineffective. Histamine may play a key role in intimal thickening, in part via histamine H1 receptors in this model.

Animals↗
PubMed1998

Immunological detection of fructated proteins in vitro and in vivo.

An antibody has been raised against fructated lysine in proteins by immunizing fructated lysine-conjugated ovalbumin in rabbits. The affinity-purified antibody specifically recognized proteins incubated with fructose but not with other reducing sugars such as glucose, galactose or ribose, as judged by immunoblotting and ELISA techniques. Competitive binding to this antibody was observed specifically by fructated lysine but not by glucated lysine, glucose, fructose or lysine. The antibody binds specifically to fructated lysine residues in the protein but not to borohydride-reduced material or advanced glycation end products, indicating that the antibody recognizes only the reducing, carbonyl-containing forms produced in the early stage of the fructation reaction. When BSA was incubated with various concentrations of fructose, the reactivity of the antibody increased in a dose- and time-dependent manner. When soluble proteins prepared from either normal or streptozotocin-induced diabetic rat eyes were analysed by ELISA with this antibody, an increase in the reactive components was observed as a function of aging as well as under diabetic conditions. Western blotting analysis showed that lens crystallin reacted highly with this antibody. Because fructose is biosynthesized largely through the polyol pathway, which is enhanced under diabetic conditions, and lens is known to have a high activity of enzymes in this pathway, this antibody is capable of recognizing fructated proteins in vivo. Thus it is a potentially useful tool for investigating two major issues that seem to be involved in diabetic complications, namely the glycation reaction and the polyol pathway.

Animals↗
PubMed1998

Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs.

Nitric oxide (NO) is produced by inducible NO synthase (iNOS) after LPS stimulation, and reacts with superoxide to form peroxynitrite. We hypothesize that in LPS-induced lung injury, NO generated by iNOS plays a key role through the formation of peroxynitrite. We developed an acute lung injury dog model by injecting LPS, and examined the effects of selective iNOS inhibitors, aminoguanidine (AG) and S-methylisothiourea sulfate (SMT), on the LPS-induced lung injury. At 24 h after LPS injection, arterial oxygen tension and mean arterial pressure decreased, and shunt ratio and lung wet-to-dry weight ratio increased. On histology, the LPS group had marked neutrophil infiltration and widening of the alveolar septa. On immunohistochemistry, iNOS and nitrotyrosine, a major product of nitration of protein by peroxynitrite, were observed in the interstitium, capillary wall, and neutrophils in the airspaces of the LPS group. Treatments with AG and SMT prevented worsening of gas exchange, hemodynamics, and wet-to-dry weight ratio. On histology, AG and SMT treatments markedly suppressed lung injury, iNOS protein, and nitrotyrosine production. We conclude that NO released by iNOS may play a critical role in the pathogenesis of LPS-induced acute lung injury. This study suggests that iNOS inhibitors may have potential in the treatment of LPS-induced acute respiratory distress syndrome.

Animals↗
PubMed1998

[Huge localized mesothelioma of the diaphragm in a 17-year-old female--a case report with calculated tumor volume doubling time].

An operative case of localized mesothelioma of the pleura developed in a 17-year-old female was reported. She was admitted to our hospital complaining of right chest pain. A chest X-ray film showed a huge mass in the right lower field of the lung. After the embolization of the right inferior phrenic artery, which was the main feeder to the tumor, it was then successfully resected combined with the right diaphragm and the right lower lobe of the lung. Histologically, the tumor was diagnosed as benign localized mesothelioma (solitary fibrous tumor of the pleura). Further histological and immunohistochemical study revealed that it had developed from the connective tissue under the parietal mesothelium of the diaphragm. As chest roentgenograms had been undertaken during past two years, the tumor volume doubling time was calculated at 153 days. Despite the short tumor volume doubling time as like primary lung cancer, she is alive without recurrence 5 years after the operation.

Adolescent↗
PubMed1998

Assessment of the peripheral benzodiazepine receptors in human gliomas by two methods.

This study was designed to evaluate the density of peripheral benzodiazepine receptor (PBR) sites as a function of tumor malignancy in human gliomas, and to compare the results obtained with autoradiographic and liquid scintillation measurements performed on the same tissue specimens. In vitro binding of [3H]PK-11195[1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoguinol ine carboxamide] to human gliomas in radioligand binding studies revealed a significantly higher level (about 3 fold) of PBR binding sites in both low grade and high grade gliomas as compared to normal cortex. The Bmax (mean +/- SD) of high and low grade gliomas, when entire tissue sections were measured by autoradiography, was 5.5 +/- 0.3 pmol/mg-tissue (n = 5) and 1.8 +/- 0.9 pmol/mg-tissue (n = 6), respectively, although it was evident that there was area of hot spots in the high grade tumors. This difference was significant (p < 0.05; two-tailed t-test). Similarly, the KD values (dissociation constant; nM) between the high (KD = 20.4 +/- 1.3 nM) and low (KD = 14.3 +/- 2.1 nM) grade gliomas were significantly different. A significant difference in binding site density (Bmax) between the two types of gliomas was also obtained in liquid scintillation measurements. The hot spot areas which showed the most intense binding of [3H]PK-11195 had KD of 24.5 +/- 1.0 nM and Bmax of 6.2 +/- 0.42 pmol/mg-tissue, values significantly higher (p < 0.05, two-tailed t-test) than those obtained when the entire tissue section was measured. The data on the Bmax/KD ratios presented here suggest that it might be possible to differentiate high from low grade gliomas in human by in vivo imaging with 11C-labelled PK-11195.

Astrocytoma↗
PubMed1998

Discrepancies in brain perfusion SPECT findings between Tc-99m HMPAO and Tc-99m ECD: evaluation using dynamic SPECT in patients with hyperemia.

Discrepancies have been reported between the findings of Tc-99m HMPAO and Tc-99m ECD brain perfusion SPECT imaging. This study investigated the discrepancies in the accumulation of these tracers using dynamic SPECT to detect the super early phase of distribution. Thirteen patients with luxury perfusion or high flow states were studied with both dynamic and standard SPECT using Tc-99m HMPAO and Tc-99m ECD within 1-3 days. Standard SPECT showed discrepancies in 6 of 13 patients. Patients with meningioma and cerebral thrombosis had increased accumulation of Tc-99m HMPAO and decreased uptake of Tc-99m ECD. Patients with arteriovenous malformation, subarachnoid hemorrhage, and cavernous angioma had decreased accumulation of both tracers, but to different degrees. Dynamic SPECT showed increased or normal accumulation (i.e., essentially no discrepancy) in the first few minutes. However, Tc-99m HMPAO had a longer retention time than Tc-99m ECD in the ensuing 5-10 minutes. Dynamic SPECT revealed a similar accumulation pattern but different washout rates for the two tracers. Tc-99m HMPAO might be a more suitable tracer to detect high flow states or luxury perfusion because the findings on standard SPECT were more in agreement with those of dynamic SPECT using this tracer.

Adult↗
PubMed1998

Technical points to improve surgical results in cases with basilar tip aneurysms.

Surgical results in 82 cases with aneurysm (61 ruptured and 21 unruptured) of the bifurcation of the basilar artery were analyzed and the causes of unfavorable outcome and its measures were discussed. Operation was performed in grade I, II, III, or IV of the Hunt and Kosnik's classification for the patients with ruptured aneurysm. Both in ruptured and unruptured cases, patient's age was not considered. As it turned out, 10 elderly (70 years old or older) cases (8 ruptured and 2 unruptured) were included in this study. Unilateral pterional approach was adopted for all but one case, and temporary clip and/or division of the hypoplastic posterior communicating artery was actively used. Surgery was completed with clipping of the aneurysm in all but six cases and overall surgical result consists of 70% of favorable outcomes. The main causes of unfavorable outcome were surgical procedures and primary brain damage due to subarachnoid hemorrhage. And the factors influenced to increase surgical technical damage to the brain were the patient's age, size of the aneurysm, and/or height of the neck from biclinoids line. The outcome of the higher grade (grade III or IV) in elderly cases was miserable, whereas it was not different from anterior circulation aneurysms in younger cases. From the result we concluded that the surgical indication for elderly cases should be limited in cases with lower grade (grade I or II) without large and/or high-positioned aneurysm. To obtain further improvement of the surgical result in younger cases, additional surgical techniques have to be considered to avoid the injury of perforating arteries from P1 and to reduce the pressure of the brain retraction which are the most important hazards for aneurysm surgery in this area.

Aged↗
PubMed1998

Serum level of eosinophil cationic protein in patients with chronic cough: relationship to blood eosinophils and airway hyperresponsiveness.

We measured the serum level of eosinophil cationic protein (ECP), determined the blood eosinophil count, and assessed pulmonary function by spirometry and airway responsiveness to methacholine in 80 patients with a cough lasting longer than 3 weeks without an obvious cause. The serum level of ECP was above the cutoff value of 15.7 ng/mL (mean + 2 SD in 105 healthy control adults) in 30 (37.5%) of 80 patients (high-serum-ECP group). The blood eosinophil count was significantly higher in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.01). The cumulative dose of methacholine causing a 35% decrease in respiratory conductance (PD35Grs) was significantly lower in the high-serum-ECP group than in the normal-serum-ECP group (p < 0.001). The serum concentration of ECP was correlated with the blood eosinophil count and the PD35Grs (r = 0.59, p < 0.001 and r = -0.48, p < 0.001, respectively). These findings suggest a possible role for serum level of ECP in management of patients with chronic cough.

Adult↗
PubMed1998

Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT.

BACKGROUND AND PURPOSE: The prevalence and clinical features of relative focal hyperperfusion were investigated in 165 consecutive patients with intracerebral hemorrhage. METHODS: Contrast-enhanced xenon CT was used to observe regional cerebral blood flow in all patients (86 men and 79 women ranging in age from 25 to 89 years; mean age, 66 years). The clinical data of patients with and without relative focal hyperperfusion were compared to define distinguishing characteristics. RESULTS: Relative focal hyperperfusion was observed in 24 (23.5%) of 102 patients in the acute stage but in no patient in the subacute or chronic stages. Relative focal hyperperfusion was associated significantly more often with putaminal and subcortical hemorrhage than with thalamic and cerebellar hemorrhage. We found that patients with relative focal hyperperfusion had a lower mean age than those without it; a male dominance; and a more common history of intracerebral hemorrhage. CONCLUSION: Relative focal hyperperfusion occurs in the acute stage after intracerebral hemorrhage and does not persist for more than 30 days. The most common locations are the putamen and subcortical areas. Risk factors include male sex and previous bleeding in the same area.

Adult↗
PubMed1997

Effect of sodium tauroursodeoxycholate (UR-906) on liver dysfunction in bile duct-ligated rats.

We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.

Animals↗
PubMed1997

The biochemical studies on phalloidin-induced cholestasis in rats.

We investigated sequential changes in bile flow, serum and biliary biochemical parameters in phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration with phalloidin (500 microg/kg) for 7 days, and then the animals were allowed to survive for 1, 2, 4, 7, 14 and 28 days after the last treatment. In phalloidin-treated rats, bile flow significantly decreased up to 4 days of recovery, compared with the control animals. In contrast, serum ALP activity, LAP activity, cholesterol concentration and phospholipid concentration exhibited a marked elevation throughout the recovery periods. For biliary parameters, bilirubin excretion rate was unchanged but, cholesterol excretion rate showed a marked decrease throughout the recovery periods. These results demonstrate that some parameters, particularly important indexes of cholestasis (serum ALP, cholesterol, bile flow and so on), continued significant changes at least 4 days after the last administration of phalloidin. These results demonstrate that successive treatment with phalloidin can cause damage in most of serum and biliary parameters at a chronic stage of cholestasis. Thus, our findings may provide useful information for diagnosis of drug-induced cholestasis and help to further elucidate the biochemical mechanisms of drug-induced cholestasis in humans.

Animals↗
PubMed1997

Effects of pemirolast and tranilast on intimal thickening after arterial injury in the rat.

We previously reported that tranilast, an antiallergic agent, reduced intimal thickening after endothelial injury in rats. In this study, to verify whether or not antiallergic agents inhibit intimal thickening, we investigated the effect of pemirolast on intimal thickening after endothelial injury and compared its effect with that of tranilast. Administration of two antiallergic agents, pemirolast (0.1, 1, and 10 mg/kg, p.o.) and tranilast (300 mg/kg, p.o., daily), was begun 2 days before endothelial injury and continued until the animals were killed. Endothelial injury in the rat femoral artery was induced by a photochemical reaction between localized irradiation by green light and intravenously administered rose bengal. To evaluate intimal hyperplasia, we measured the cross-sectional area of the intima 21 days after endothelial damage. Pemirolast at doses of 0.1, 1, and 10 mg/kg reduced the intimal area to 2.10 +/- 0.33, 1.36 +/- 0.19, and 1.35 +/- 0.18 (x0.01 mm2), respectively, and tranilast showed a tendency to reduce the intimal area, which was 1.86 +/- 0.35 x 0.01 mm2, compared with findings for controls (2.83 +/- 0.49 x 0.01 mm2). In rat A10 vascular smooth-muscle cells, we investigated the effects of antiallergic agents on migration by using a modified Boyden chamber assay and on proliferation by using the bromodeoxyuridine-incorporation assay. Two antiallergic agents inhibited in a concentration-dependent manner both migration and proliferation of smooth muscle cells stimulated by platelet-derived growth factor. These results suggest that antiallergic agents directly inhibit migration of smooth-muscle cells to the intima from the media and proliferation in the intima, and that pemirolast has more potent antihyperplastic action than does tranilast. Antiallergic agents may be effective in preventing restenosis after coronary angioplasty.

Animals↗
PubMed1997

Xenon contrast CT-CBF measurements in high-intensity foci on T2-weighted MR images in centrum semiovale of asymptomatic individuals.

BACKGROUND AND PURPOSE: White matter lesions (WMLs) on T2-weighted MR images occurring in the centrum semiovale of normal individuals are a subject of great clinical interest. We therefore investigated regional cerebral blood flow (rCBF) of the centrum semiovale among neurologically normal individuals. METHODS: One hundred thirty-five neurologically normal subjects were divided into four grades of WML on the basis of their MR images. rCBF values in the centrum semiovale were measured by xenon contrast CT methods. RESULTS: Advanced age and associated hypertension were significant risk factors for higher grade WMLs. Centrum semiovale rCBF values on the left side were 24.27 +/- 2.60 mL.100 g-1.min-1 in grade 0, 23.52 +/- 2.78 in grade I, 19.35 +/- 2.81 in grade II, 15.82 +/- 2.05 in grade III, and 11.31 +/- 2.56 in grade IV. Differences were significant between grades (P < .005 between grade 0 and grades II, III, and IV; between grade II and grades III and IV; and between grades III and IV). Patients with hypertension had lower rCBF values than those without in grades 0, I, II, and III, with significant difference in grade I (P < .005). Age-matched studies between patients 61 to 70 years old confirmed a significant difference between WML grades. CONCLUSIONS: WMLs in centrum semiovale are associated with greater age, hypertension, and reduced rCBF values.

Adult↗
PubMed1997

[Effect of amrinone and vagotomy on airway constriction in dogs: analysis by respiratory system impedance method].

Amrinone, a selective phosphodiesterase III inhibitor, is a positive inotropic agent with vasodilating effect which is attributable to an increase in cyclic AMP in vascular smooth muscle. Little is known about the effect of amrinone on airway mechanics. The purpose of this study was to clarify the bronchodilating effect of amrinone in dogs, when bronchoconstriction was induced by methacholine infusion. We also evaluated the effect of amrinone on bronchoconstriction in vagotomized dogs. To evaluate the effect of amrinone on respiratory function, the total respiratory system impedance was measured using forced oscillation method by imposing a random noise. The analysis was performed by dynamic models and a second-order system curve fitting. From the study, we conclude that amrinone 0.5 mg.kg-1.1.0 mg.kg-1 or 2.0 mg.kg-1 attenuates methacholine-induced bronchoconstriction in a dose-related manner. In vagotomized dogs, amrinone also had the same effect on methacholine induced bronchoconstriction.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress through the glycation reaction.

Several reducing sugars brought about apoptosis in isolated rat pancreatic islet cells and in the pancreatic beta-cell-derived cell line HIT. This apoptosis was characterized biochemically by inter-nucleosomal DNA cleavage and morphologically by nuclear shrinkage, chromatin condensation and apoptotic body formation. N-Acetyl-L-cysteine, an antioxidant, and aminoguanidine, an inhibitor of the glycation reaction, inhibited this apoptosis. We also showed directly that proteins in beta-cells were actually glycated by using an antibody which can specifically recognize proteins glycated by fructose, but not by glucose. Furthermore, fluorescence-activated cell sorting analysis using dichlorofluorescein diacetate showed that reducing sugars increased intracellular peroxide levels prior to the induction of apoptosis. Levels of carbonyl, an index of oxidative modification, and of malondialdehyde, a lipid peroxidation product, were also increased. Taken together, these results suggest that reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress mainly through the glycation reaction, which may explain the deterioration of beta-cells under conditions of diabetes.

Acetylcysteine↗