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Biomedical subjects

S Yamagata

Publications and source records attributed to S Yamagata.

At least 55 records · Page 3Linked to original sources
PubMed1999

Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs.

We investigated the role of peroxynitrite, which is formed by a rapid reaction between nitric oxide (NO) and superoxide anion (O(2)(-)), in the airway microvascular hyperpermeability during the late allergic response (LAR) in sensitized guinea pigs in vivo. The occurrence of LAR was assessed as a 100% increase in the transpulmonary pressure, which was monitored by the esophageal catheter technique. Airway microvascular permeability was assessed by Monastral blue dye trapping between the endothelium using an image analyzer. In the LAR phase (4 to 6 h after antigen inhalation), microvascular hyperpermeability and eosinophil infiltration within the airway wall were observed. NO production and xanthine oxidase (XO)/xanthine dehydrogenase activity, which are responsible for O(2)(-) production, were enhanced during the LAR. Peroxynitrite formation assessed by nitrotyrosine immunostaining was also exaggerated at that time. The microvascular hyperpermeability during the LAR was largely reduced by NO synthase inhibitor (L-NAME, 72.7% inhibition; p < 0.05), XO inhibitor (AHPP, 60.8% inhibition; p < 0. 05) and peroxynitrite scavenger (ebselen, 81.0% inhibition; p < 0. 05). L-NAME had a small but significant inhibitory effect on airway eosinophil accumulation, but AHPP and ebselen had no effect. These results suggest that excessive production of O(2)(-) and NO occurs in the LAR. These two molecules appear to cause airway microvascular hyperpermeability via peroxynitrite formation.

Animals↗
PubMed1999

Temperature-dependence of the mechanical properties of FRP orthodontic wire.

The temperature-dependence of the mechanical properties of a new esthetic orthodontic wire with fiber-reinforced plastic (FRP) structure was investigated. The new FRP wire, fabricated by a hot drawing method, is 0.5 mm in diameter and has a multiple fiber structure composed of biocompatible CaO-P2O5-SiO2-Al2O3 glass fibers of 20 microns in diameter and a polymethyl methacrylate matrix. The flexural load at a deflection of 1 mm and Young's modulus at 24, 37, and 50 degrees C under wet conditions showed similar fiber fraction dependence to those under dry conditions for a fiber fraction of 40-51%. The flexural load and Young's modulus tended to decrease slightly with increases in temperature. This tendency was larger for the lower fiber fraction. However, the difference in flexural load for a temperature difference of between 24 degrees C and 50 degrees C was at most 10 gf. This is negligibly small, and a constant orthodontic force regarding temperature change would be advantageous from a clinical point of view.

Elasticity↗
PubMed1999

[Analysis of dynamic CT functional imaging parameters in patients with acute basilar artery occlusion].

It is very important to make a prompt and accurate diagnosis and to commence pertinent treatment for patients suffering from acute cerebrovascular occlusive disease. Thirteen patients (mean age: 67.1 years) with basilar artery occlusion (BAO) were enrolled in this study. Dynamic computed tomography functional images (FID-CT) were analysed to determine whether this method could diagnose BAO in the acute phase. The functional images were categorized into 3 groups: (1) group A (n = 5) showed abnormalities on corrected mean transit time (cMTT) images and time-to-peak (TP) images in the territory of the posterior cerebral artery (PCA) and in the thalamus, (2) group B (n = 6) only showed abnormalities on TP images, and (3) group C (n = 2) had no abnormalities on either cMTT or TP images. The group C patients had poor time-density curves because of heart disease. Although the results may sometimes be false negative and this limitation should be kept in mind, FID-CT seem to be useful not only for defining patients who need angiography but also those who need thrombolytic therapy for acute BAO.

Aged↗
PubMed1999

[Self-expanding stent (Wallstent) supported angioplasty for carotid artery stenosis].

We reported the preliminary results of percutaneous transluminal angioplasty (PTA) supported with a self-expanding stent (Wallstent) for the cervical internal carotid artery (i.c.) stenosis in 6 patients (7 lesions). All were male aged from 60 to 79 (mean 70.8). Three patients were symptomatic and 3 were asymptomatic. The procedure was attempted in patients with severe i.c. stenosis according to criteria of NASCET, ECST or ACAS studies and with high risk if carotid endarterectomy (CEA) were performed. In all cases, vascular access was from the femoral artery and angioplasty was performed without cerebral protection. Successful angioplasty was obtained in all cases with no mortality. Stenosis was improved from 82.7% (74-90%) to 17.4% (10-33%). Perioperative complications were seen in only one case with TIA during the postdilatation period, which was supposed to be due to a distal embolism. The preliminary results of PTA supported with self-expanding stent for severe i.c. stenosis were excellent. These results suggested that some patients with severe i.c. stenosis can be treated safely and effectively by stent-supported PTA. However, it is necessary to mark the indications clear and strict, and to follow up these lesions after the procedure, because of the possibility of perioperative ischemic complications and restenosis.

Aged↗
PubMed1998

Genomic organization and mutational analysis of KVLQT1, a gene responsible for familial long QT syndrome.

To elucidate the role of the KVLQT1 gene in the pathogenesis of long QT syndrome (LQTS), we have established a screening system for detecting KVLQT1 mutations by the polymerase chain reaction-single strand conformation polymorphism technique (PCR-SSCP). We first determined exon/intron boundaries and flanking intronic sequences, and found that the KVLQT1 gene consists of 17 coding exons. Subsequently, we synthesized oligonucleotide primers to cover the coding region and the flanking intronic sequences, and searched for mutations in 31 Japanese LQTS families. When genomic DNA from each proband was examined by PCR-SSCP followed by direct DNA sequencing, mutations were detected in five families; two independent families carried the same mutation and three of the four were novel. Each mutation was present in affected relatives of the respective proband. This work will enable us to search more thoroughly for LQTS mutations associated with KVLQT1, and eventually will help us in finding genotype/phenotype relationships.

DNA Mutational Analysis↗
PubMed1998

Mechanical properties and aesthetics of FRP orthodontic wire fabricated by hot drawing.

The FRP wires 0.5 mm in diameter with a multiple fiber structure were fabricated by drawing the fiber polymer complex at 250 degrees C for an esthetic, transparent orthodontic wire. Biocompatible CaO-P2O5-SiO2-Al2O3 (CPSA) glass fibers of 8-20 microm in diameter were oriented unidirectionally in the longitudinal direction in PMMA matrix. The mechanical properties were investigated by 3-point flexural test. The FRP wire showed sufficient strength and a very good elastic recovery after deformation. Young's modulus and the flexural load at deflection 1 mm were nearly independent of the fiber diameter and linearly increased with the fiber fraction. The dependence on fiber fraction obeys well the rule of mixture. This FRP wire could cover the range of strength corresponding to the conventional metal orthodontic wires from Ni-Ti used in the initial stage of orthodontic treatments to Co-Cr used in the final stage by changing the volume ratio of glass fibers with the same external diameter. The estheticity in external appearance was excellent. Thus the new FRP wire can satisfy both mechanical properties necessary for an orthodontic wire and enough estheticity, which was not possible for the conventional metal wire.

Biocompatible Materials↗
PubMed1998

Effects of gonadal hormones on the zonal expression of rat hepatic phenol sulfotransferases.

Estradiol benzoate (EB) and testosterone propionate (TP) were administered to male and female Wistar rats, and their effects on the zonal expression of hepatic phenol sulfotransferase (P-ST) activities were determined at pH 5.5 and 7.4. Cytosolic fractions from periportal (PP) and perivenous (PV) hepatocytes were prepared by the dual-digitonin-pulse perfusion technique. In control rats, P-ST activities assayed at pH 5.5 and 7.4 were higher in males than in females, and were higher in the PV fraction than in the PP fraction in both sexes. P-ST activities were increased by the administration of TP in the PP and PV fractions of females, whereas the same treatment diminished the enzyme activities in both fractions of the males. EB administration gave reduced P-ST activity at pH 5.5 of both fractions, irrespective of sex, but not a marked difference at pH 7.4. Chromatofocusing of PP and PV fractions revealed the presence of P-ST isoforms eluted at approx. pH 8.0 (peak 1), 7.5 (peak 2), 7.0 (peak 3) and 6.0 (peak 4). In male rats, peak 3, which showed high enzyme activity at pH 5.5 in the PP and PV fractions, was markedly decreased by EB treatment, whereas in females, peak 3 was present only in the PV fraction and was not affected by EB administration. TP treatment did not show remarkable changes in P-ST peaks in the males, while peaks 2 and 3 were increased in the females. Immunoblot analysis revealed the presence of multiple P-ST isoforms which showed different immunoreactivity and electrochemical properties.

Animals↗
PubMed1998

Novel phosphodiesterase 4 inhibitor T-440 reverses and prevents human bronchial contraction induced by allergen.

To study the roles of phosphodiesterase (PDE) 4 in the human airways, we examined the effect of the novel PDE4 inhibitor T-440 in the isolated human bronchus. T-440 inhibited PDE4 extracted from human bronchial smooth muscle. IC50 values for the effect of T-440, rolipram (a PDE4 inhibitor) and theophylline on PDE4 activity of the bronchial tissues were 0.08 microM, 2 microM and > 100 microM, respectively. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-5) M histamine-induced contraction, the efficacy of 10(-6) M T-440 being almost the same as that of 3.3 x 10(-5) M aminophylline. T-440 (10(-6) M to 10(-5) M) and aminophylline (3.3 x 10(-5) M) significantly reversed the 10(-4) M ACh-induced contraction. But their reversal effects on the ACh-induced contraction were weaker than those on the histamine-induced contraction. T-440 (10(-5) M) significantly reversed the contraction induced by allergen in passively sensitized bronchi. The efficacy of the reversal effect of T-440 (10(-5) M) was significantly higher than that of aminophylline (10(-5) M). T-440 and aminophylline significantly relaxed the basal tension, but pretreatment with T-440 or aminophylline did not significantly prevent histamine- or ACh-induced contraction. In contrast, both T-440 (10(-5) M) and aminophylline (3.3 x 10(-5) M) prevented the contraction induced by allergen, which suggests that PDE4 inhibitor inhibits the release of chemical mediators probably from bronchial mast cells in the allergic response. T-440 (10(-6) M to 10(-5) M) caused the accumulation of cAMP at the concentration that relaxed histamine-induced contraction. Thus selective PDE4 inhibitor is a candidate for the treatment of asthma.

Acetylcholine↗
PubMed1998

Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes to dacarbazine N-demethylation.

The N-demethylation of dacarbazine in liver microsomes was significantly increased by treatment of rats with beta-naphthoflavone, dexamethasone, or phenobarbital. However, the extent of increase in the N-demethylation observed in beta-naphthoflavone-treated rats was much greater than that observed in dexamethasone-treated rats. A good correlation between N-demethylation of dacarbazine and O-deethylation of phenacetin was observed when a low concentration of phenacetin was used. Furthermore, the activity of dacarbazine N-demethylase in rat liver microsomes was highly correlated with the amounts of CYP protein immunochemically determined with anti-rat CYP1A2 antibodies. In addition, antibodies to rat CYP1A2, and furafylline and alpha-naphthoflavone, which are known inhibitors of CYP1A enzymes, exhibited inhibitory effects on dacarbazine N-demethylation. These results indicated that CYP1A enzymes may be responsible for N-demethylation of dacarbazine in rat liver microsomes.

Animals↗
PubMed1997

Difference of hyaluronidase produced by human tumor cell lines with hyaluronidase present in human serum as revealed by zymography.

Human carcinoma cells cultured in serum free medium produced an enzyme present as two different isoforms of 62 and 59 kDa which was found to degrade hyaluronan and chondroitin sulfate, with optimum activity at pH 4.0 and 0.03 M NaCl. The activity was suppressed by treatment with 250 mM apigenin and 1 mM DTT. The one-dimensional and two-dimensional gel patterns of tumor hyaluronidase differed from those of human serum hyaluronidase. Deglycosylation of tumor hyaluronidase caused nearly complete elimination of activity, suggesting the importance of sugar chains in enzymatic function. The results of treatment with neuraminidase, in addition to the findings for the enzyme mentioned above, suggest hyaluronidase from carcinoma cells and serum hyaluronidase to differ in sugar chains and/or the core protein. Tumor hyaluronidase was shown to be endo-beta-N-acetyl-D-hexosaminidase and tetrasaccharide was identified as the major product, thus indicating the tumor hyaluronidase to be a testis-type hyaluronidase.

Blood Proteins↗
PubMed1997

Positive correlation between inhibitors of matrix metalloproteinase 1 and matrix metalloproteinases in malignant ovarian tumor tissues.

To investigate the relation between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in malignant ovarian tumor, MMP and TIMP activities in conditioned media of 16 malignant ovarian tumor tissues and six normal ovaries were detected by zymography and reverse zymography, respectively and were quantitated with a densitometer. TIMP-1 and TIMP-2 were detected in all normal and malignant ovarian tumor tissues by reverse zymography. In normal ovaries, the intensity of TIMP-2 bands was stronger than TIMP-1, but in malignant tumor tissues those of TIMP-1 were stronger. The ratios of TIMP-1 to TIMP-2 and MMP-9 to MMP-2 were significantly higher in malignant tumor tissues than in normal ovaries (P < 0.001). TIMP activity consisting of TIMP-1 and TIMP-2 correlated significantly to MMP activity of MMP-2 and MMP-9 (r = 0.67, P < 0.005). There was a significant correlation between TIMP-1 activity and MMP activity (r = 0.72, P < 0.001), but no correlation was observed between TIMP-2 activity and MMP activity. The high level of TIMP-1 appeared to be related to malignant phenotype in ovaries as well as the high level of MMP-9.

Adolescent↗
PubMed1997

Heterogeneous zonal distribution of sulfotransferase isoenzymes in rat liver.

By employing dual-digitonin-pulse perfusion technique, the cytosolic fractions were prepared from periportal (PP) and perivenous (PV) hepatocytes of male and female rat livers. Sulfotransferase (ST) activities toward 2-naphthol (2NAP) (at pH 5.5 and 7.4), 4-nitrophenol, dehydroepiandrosterone (DHEA), and cortisol were measured in each fraction. DHEA-ST activity was mainly localized in PP fraction in males, while in females it was slightly higher in PP fraction than in PV samples. In contrast, phenol ST activities were higher in PV fraction in both sexes. With anti-HS-ST and anti-P-ST antisera, the levels of immunoreactive ST polypeptides were compatible with the levels of ST activities except that in female PP fraction the level of immunoreactive P-ST polypeptide was low in spite of comparatively high levels of P-ST activities. Chromatofocusing of PP and PV fractions separated P-ST activities into three major fractions (I-III), which have distinct catalytic and electrochemical properties. Fraction I was localized only in the PP samples in both sexes and revealed ST activities toward 2NAP at pH 5.5 and 7.4, while fraction II was localized in the PP and PV samples in both sexes with 2NAP-ST activity only at pH 7.4. Fraction III which had ST activities at pH 5.5 and 7.4 was present only in the PV samples in female rats, whereas in male rats it was present in both PP and PV samples. With anti-P-ST antiserum, the immunoreactive polypeptide was present in fraction III, but no immunoreactive band was detected in fractions I and II, suggesting the presence of immunochemically and electrochemically different P-ST(s) in these fractions.

Age Factors↗
PubMed1997

Inhibition of highly metastatic FBJ-LL cell migration by ganglioside GD1a highly expressed in poorly metastatic FBJ-S1 cells.

For clarification of the functions of gangliosides on tumor metastasis, examination was made of the ganglioside patterns of poorly metastatic FBJ-S1 and highly metastatic FBJ-LL cells. FBJ-S1 cells expressed GM3 and GD1a, whereas FBJ-LL cells expressed GM3 and slightly expressed GD1a. The capacity for FBJ-LL cells to migrate was ten times that of FBJ-S1 cells, but decreased by a half by pretreatment with GD1a. GD1b or GT1b had the same effect as GD1a, and synthetic sialyl compounds to a lesser extent, suggesting that gangliosides contain more than two sialyl residues to inhibit the migration of FBJ-LL cells.

Animals↗
PubMed1997

Hyaluronidase activity in gynaecological cancer tissues with different metastatic forms.

We investigated hyaluronidase activity in gynaecological normal and malignant tissues. Hyaluronidase activity in culture medium of tissue specimens was detected by hyaluronic acid zymography and quantified by densitometry. Hyaluronidase activity was shown as one dominant band (molecular weight 65 kDa) at pH 3.5. Hyaluronidase activity was significantly higher in normal ovary (P < 0.05) and normal endometrium (P< 0.05) than in normal cervix. One dominant 65-kDa hyaluronidase was expressed in 100% (14 out of 14) of ovarian cancer tissues and in 91% (10 out of 11) of endometrial cancer tissues. However, hyaluronidase activity was not observed in cervical cancer tissues. Hyaluronidase activity was significantly higher in ovarian (P < 0.001) and endometrial (P < 0.01) cancer tissues than in cervical cancer tissue and was significantly higher in ovarian cancer tissue than in endometrial cancer tissue (P < 0.05). These facts suggest that the cancer cells make use of the original characteristic of the organ to invade and metastasize. Moreover, these results reflect the difference in metastatic forms and are suggestive of a strong relationship between hyaluronidase activity and invasion and metastasis of ovarian and endometrial cancers compared with cervical cancer.

Adult↗
PubMed1997

Bioactivation of monocrotaline by P-450 3A in rat liver.

Monocrotaline (MCT) is bioactivated in liver cytochrome P-450s to MCT pyrrole (MCTP), which primarily injures the lung endothelium to result in the development of pulmonary hypertension (PH) in rats. However, whether there is a relation between the degree of PH and the activity of liver cytochrome P-450 to convert MCT to MCTP remains unclear. To examine the relation between these physiological and biochemical changes, we first measured the severity of MCT-induced (20 mg/kg) PH in male, female, castrated male, and phenobarbital (PB, liver P-450s inducer)-pretreated male rats. The degree of right ventricular hypertrophy was more severe in PB-pretreated male than in control male rats. It was also more severe in male than in either female or castrated male rats, suggesting that sex-specific P-450s could be involved in the metabolic pathways of MCT in the liver. Further to explore which of the isozymes (2A2, 2C11, and 3A) of P-450s in the liver is responsible for the bioactivation of MCT, we measured the rate of MCTP production in hepatic microsomes by a modified Mattock's method. Treatment of male rats with PB and pregnenolone 16alpha-carbonitrile (PCN), which is the specific inducer of P-450 3A, increased the rate of MCTP production, suggesting that P-450 3A may contribute to the conversion to pyrrole. Therefore we measured the amount of P-450 3A protein by immunoblotting and attempted to inhibit MCT metabolism by using antibodies to P-450 3A. P-450 3A was significantly induced by PCN (6.5-fold) and PB (4.6-fold) treatment and reduced by castration (0.38-fold). The amount of P-450 3A was closely correlated with the production of MCTP, and the conversion of MCT to MCTP was strongly inhibited by antibodies against P-450 3A. These results indicated that P-450 3A was predominantly responsible for the metabolism of MCT to MCTP in rat liver and suggested a tight linkage between the degree of PH and the activity of liver P-450 3A.

Animals↗
PubMed1997

Poststroke apathy and regional cerebral blood flow.

BACKGROUND AND PURPOSE: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there have been no studies on regional cerebral blood flow (rCBF) in patients with apathy. In this study we estimated the severity of apathy using the Apathy Scale and examined its relationship to rCBF in 40 stroke patients (mean age, 71.4 years). METHODS: Neuropsychiatric batteries were performed including the Apathy Scale, verbal intelligence and frontal function tests, a depression scale, and an assessment of activities of daily living. The cortical rCBFs were measured by the 133Xe inhalation method. RESULTS: Twenty patients (50%) showed apathy. These patients showed significantly lower scores on verbal intelligence and frontal function tests and a significantly higher depression score than the nonapathetic group. On MRI images there was no relationship between the apathy score and specific regional distribution of lesions. The rCBFs of the bilateral hemisphere were significantly lower in the apathetic group than in the nonapathetic group. The apathetic group showed a significantly reduced rCBF in the right dorsolateral frontal and left fronto-temporal regions. Furthermore, the apathy score for all patients was significantly negatively correlated with rCBF in the same regions. CONCLUSIONS: These findings demonstrate that apathy is a frequent symptom among elderly stroke patients and may be accompanied by cognitive impairments, depressive state, and frontal dysfunction. The hypoactivity in the frontal lobe and anterior temporal regions may contribute to symptoms of apathy after stroke.

Activities of Daily Living↗
PubMed1997

Bronchial anti-spasmogenic effects and selectivity of T-440, phosphodiesterase type 4 inhibitor, in the dog.

We investigated the selectivity of T-440 for the inhibition of phosphodiesterases (PDEs) in vitro and for bronchial anti-spasmogenic effects in vivo. Using a fast protein liquid chromatography system, five PDE isozymes, PDE 1, PDE 2, PDE 3, PDE 4 and PDE 5 were prepared from guinea pig and dog tissues. T-440 selectively inhibited PDE 4 with an IC50 of 0.071 microM and 0.13 microM for guinea pig lung and dog trachea, respectively. The IC50 values for all other PDE isozymes were over 20 microM. In contrast, theophylline nonselectively inhibited all the tested PDE isozymes, and the inhibition did not exceed 50%, even at 100 microM. T-440 inhibited the histamine-induced bronchoconstriction of anesthetized dogs in a dose-dependent manner with an ED50 of 0.029 mg/kg, indicating that T-440 is 600 times more potent than theophylline. Both T-440 and theophylline increased LV dp/dt/P (LVP; left ventricular pressure) in anesthetized dogs with ED50 values of 3.6 mg/kg and 4.4 mg/kg, respectively. This potency was 1/125 times the bronchial anti-spasmogenic effects for T-440 and 4.2 times that of theophylline. Rolipram, a PDE 4 inhibitor, also showed selective bronchial anti-spasmogenic effects in anesthetized dogs. These results suggest that T-440, which specifically inhibits PDE 4 activity, has potent and selective bronchial anti-spasmogenic effects.

Animals↗