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Biomedical subjects

I Yamamoto

Publications and source records attributed to I Yamamoto.

At least 109 records · Page 6Linked to original sources
PubMed1999

Endovascular irradiation prevents smooth muscle cell proliferation and neointimal hyperplasia in rabbits.

The present study examined the temporal responses and the efficacy of 192Ir-HDR endovascular irradiation for preventing smooth muscle cell proliferation of rabbit iliac arteries after PTA with a cutting balloon catheter. Endovascular irradiation with 12 Gy was randomly performed on the one side of iliac arterial segment with the unirradiated side serving as a control. Animals were euthanatized 1, 2, 3, 4, 8 and 12 week(s) after angioplasty. Histopathological and immunohistochemical studies were carried out. Histopathology showed repair of the dissection by cellular accumulation and a striking reduction in the amount of neointimal hyperplasia in the irradiated arteries as compared with control vessels. A peak of PCNA-positive ratio was in neointima of the control arterial segments at a week. 2-4 weeks after irradiation, the neointimal PCNA-positive ratio was still significantly increased in the control arterial segments compared with the irradiated arterial segments. After 8 weeks, PCNA-positive ratio was below 1% in both irradiated arterial segments and the control. Our results showed that the 192Ir-HDR afterloading irradiation with a dose of 12 Gy can be considered sufficient for inhibiting neointimal hyperplasia in angioplastized rabbit iliac arteries with cutting balloon catheter.

Angioplasty, Balloon, Coronary↗
PubMed1999

CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin.

OBJECTIVES: Omeprazole is metabolized mainly by CYP2C19 which has two major mutations (CYP2C19*2 in exon5 and CYP2C19*3 in exon4) associated with the poor metabolizer (PM) phenotype. The aim of this study was to examine the relationship between genetic polymorphism of CYP2C19 and metabolism of omeprazole administrated as a single dose or as repeated-doses, which were in both cases co-administered with clarithromycin. METHODS: Twelve healthy Japanese subjects were typed for CYP2C19 polymorphism. In the single-dose study, plasma levels of omeprazole and its metabolites were measured for 24 h after administration of 20 mg omeprazole and 400 mg clarithromycin to six healthy Japanese subjects. In the repeated-dose study, plasma levels of omeprazole and its metabolites were measured after repeated oral administration of 20 mg omeprazole and 400 mg clarithromycin twice daily for 6 days and then after 20 mg omeprazole and 400 mg clarithromycin once on the 7th day to the other 6 healthy Japanese subjects. RESULTS: In the single-dose study, the areas under the plasma concentration-versus-time curve (AUCs) of omeprazole of homozygotes for the wild-type allele (*1/*1 n = 2), heterozygotes (n = 3) for the CYP2C19*2 (*1/ *2) or for the CYP2C19*3 (*1/*3) and heterozygote (n = 1) for the two defects (*2/*3) were on average 450, 1007 and 6710 ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, *1/*2 or *1/*3 and *2/*3 were 1, 2 and 30, respectively. In the repeated-dose study, the AUCs of omeprazole for * 1/ *1, *1/*2 or *1/*3 and *2/*3 were 4041 (n = 2), 3149 (n = 3) and 6684 (n = 1) ng x h(-1) x ml(-1), respectively. The ratios of AUCs of omeprazole/5-hydroxyomeprazole for *1/*1, * 1/*2 or * 1/*3 and *2/*3 were7, 11 and 30, respectively. In the repeated-dose study, the AUC of omeprazole of * 1/*1 genotypes was nine-fold higher, that of *1/*2 and *1/*3 genotypes was three-fold higher, and the Cmax value of omeprazole was three-fold higher compared with subjects with the same genotype in the single-dose study. However, there were few differences in the AUC and Cmax of omeprazole between the *2/*3 genotype in the single-dose study and the homozygote for the CYP2C19*2 (*2/*2) in the repeated-dose study. CONCLUSION: Subjects with *1/*1, *1/*2 and *1/*3 genotypes in the repeated-dose study had lower CYP2C19 activity than subjects of the same genotype in the single-dose study. The difference in omeprazole metabolism between subjects with different genotypes observed on day 1 seemed to disappear after 7 days of repeated-dose administration.

Adult↗
PubMed1999

Effects of peritumoural oedema on cerebral blood flow and cerebrovascular reactivity in patients with alert consciousness.

The effects of peritumoural oedema on cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were studied in 18 patients with alert consciousness. Hemispheric mean CBF was measured by performing first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after acetazolamide administration. Patients were classified into three groups according to the severity of peritumoural oedema. The mean CBF of both hemispheres in each group was not significantly different from that of age-matched controls. CVR was preserved in patients with mild peritumoural oedema (n=6), but was significantly (P<0.01) reduced in patients with moderate (n=7) and severe peritumoural oedema (n=5). No significant correlation was found between the degree of midline shift and the mean CVR of both hemispheres (P=0.09). Surgical removal of the tumour significantly (P<0.05) improved the impaired CVR, although the mean CBF did not change. Administration of glucocorticoid improved the impaired CVR, without a change in the mean CBF, in a patient with a metastatic brain tumour. We conclude that CVR is impaired by the development of peritumoural oedema prior to changes in mean CBF.

Acetazolamide↗
PubMed1999

Fracture simulation of the femoral bone using the finite-element method: how a fracture initiates and proceeds.

Structural analysis of bones is now actively studied by many researchers using the finite-element method (FEM) to better understand the mechanism of bone fractures. Most previous studies, however, only obtained distribution patterns of stress or strain, and did not show how a fracture initiates and proceeds or how a fracture line grows. The purpose of this study was to simulate a fracture procedure using FEM and to assess its usefulness. Correlation of the strain value of the simulation and of the experiment was satisfactory (r = .81). The simulated fracture process and the consequent fracture lines were quite compatible with the experimental fracture. Quantitatively, however, there was a difference of yield load between the simulation and the experiment, i.e., 2000N and 8400N, respectively, likely caused by inaccuracies of material properties of the elements of the finite-element model.

Aged↗
PubMed1999

Urinary pyridinoline and deoxypyridinoline as bone metabolic markers in predicting therapeutic effects of estrogen and alfacalcidol in women with osteoporosis.

The purpose of the present study was to evaluate the clinical usefulness of urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) in predicting therapeutic effects of estrogen and alfacalcidol (1alpha-D3) in patients with postmenopausal osteoporosis. We measured urinary excretion of Pyr and Dpyr, and determined bone mineral density (BMD) using a dual-energy x-ray absorptiometry in 48 women with osteoporosis (average age, 55.9+/-8.4 years). Patients were treated with estrogen (HRT, n = 13), 1alpha-D3 (n = 20), or calcium alone (n = 15). Baseline mean levels of urinary Pyr and Dpyr were significantly higher in the 48 patients compared to those in the age-matched postmenopausal women. The levels of urinary Pyr and Dpyr were inversely correlated with BMD. After treatment with estrogen or 1alpha-D3, a significant decrease of urinary Pyr and Dpyr was observed, and elevated urinary Pyr and Dpyr were reduced to the level in premenopausal women. A significant inverse correlation was found in Pyr and Dpyr at 6 months and in lumbar BMD after 24 months of treatment (r = -0.43 to -0.52; P < 0.01). We concluded that urinary Pyr and Dpyr have clinical utility for predicting response to estrogen and 1alpha-D3 therapy of osteoporosis patients.

Absorptiometry, Photon↗
PubMed1999

Comparison of bone mineral density at various skeletal sites with quantitative ultrasound parameters of the calcaneus for assessment of vertebral fractures.

This study investigated the role of quantitative ultrasound (QUS) for evaluation of fracture risk in comparison with bone mineral density (BMD) measurement. Our subjects were postmenopausal Japanese women (n = 260; age, 67 +/- 6.1 years) who were examined for bone densitometry, QUS, and spinal X-ray examination at our department between 1992 and 1996. The subjects were categorized into three groups by the number of atraumatic fractured vertebrae: NF, no vertebral fractures: F1, one vertebral fracture; F2, two or more vertebral fractures. We compared the measured parameters to determine their association with the number of fractured vertebrae. Differences among groups were compared and analyzed by Student's t-test. Odds ratios were also calculated after age adjustment, as well as age and lumbar or calcaneal parameters. Between NF and F1, lumbar BMD and BMD of the Ward's triangle showed more significant differences than other values, while between F1 and F2, whole-body BMD and QUS parameters showed more significant differences. Lumbar BMD also showed the highest age-adjusted odds ratio in differentiating F1 from NF. Although QUS parameters showed no power to differentiate between NF and F1, these values showed higher odds ratios than other measurements for discriminating between F1 and F2. Adjustment for bone density did not totally abolish the association between QUS parameters and vertebral fracture. Additionally, the combination of lumbar BMD and QUS ("stiffness") clearly showed a high power to discriminate NF from F1 + F2. In conclusion, we showed that QUS measurement is effective in evaluating fracture risk in advanced osteoporosis, while lumbar dual X-ray absorptiometry is effective in evaluating risk in early osteoporosis.

Aged↗
PubMed1999

Structure-activity relationship of HIV-1 protease inhibitors containing alpha-hydroxy-beta-amino acids. Detailed study of P1 site.

The structure-activity relationship of HIV-1 protease (HIV-1 PR) inhibitors containing alpha-hydroxy-beta-amino acids is discussed. We demonstrated that substituent groups on the P1 aromatic rings of the inhibitors exert significant influence on their biological activity. Inhibitors bearing an alkyl or a fluorine atom at the meta and para position on their P1 benzene ring were found to be good inhibitors. We also discovered that the substitution positions of the P2 benzamides were crucial for good antiviral potency. In this study, inhibitor 48 was the most potent [IC90 (CEM/HIV-1 IIIB) 27 nM] and showed good pharmacokinetics in rats.

Amino Acids↗
PubMed1999

Correlation of clinical features and telomerase activity in human gliomas.

Telomerase is a ribonucleoprotein containing an RNA template that synthesizes telomeric DNA. The expression of telomerase activity is concomitant with the attainment of immortality in tumor tissues and cells. In this report, we analyzed telomerase activity in 39 human gliomas with different histological, and in 10 meningiomas, 3 neurinomas, and 2 normal brain tissues by using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detectable in almost all of the gliomas (36 of 39), but not in any of the meningiomas, neurinomas, or normal brain tissues. In addition, we also analyzed the level of telomerase activity in the 36 gliomas with positive telomerase activity. The relative telomerase activity of the glioma showed a clear association with the pathological grade of glioma; i.e., most of the tumors with high telomerase activity were pathologically of high grade. And also the relative level of telomerase activity could be correlated with the survival time of the patients. These results suggest that the level of telomerase activity in brain tumors is a diagnostic marker indicating the prognosis of the patient as well as the malignant potential of the tumor.

Astrocytoma↗
PubMed1999

Effect of the CYP2D6*10 genotype on venlafaxine pharmacokinetics in healthy adult volunteers.

AIMS: Interindividual differences in the pharmacokinetics of venlafaxine, a new antidepressant, were shown during early clinical trials in Japan. Venlafaxine is metabolized mainly by CYP2D6 to an active metabolite, O-desmethylvenlafaxine (ODV). Therefore, the influence of the CYP2D6 genotypes on venlafaxine pharmacokinetics was examined in a Japanese population. METHODS: Twelve adult Japanese men in good health participated in this study. Genomic DNA was isolated from peripheral lymphocytes, and the CYP2D6 genotypes were determined by codon 188C/T, 1934G/A, 2938G/A and 4268G/C mutations using endonuclease tests based on PCR and by Xba I-RFLP analysis. Subjects were categorized into the following 3 groups (n=4 in each group); Group1: CYP2D6*10/*10, *5/*10, Group2: CYP2D6*1/*10, *2/*10 and Group3: CYP2D6*1/*1, CYP2D6*1/*2. Venlafaxine (25 mg, n=6; 37.5 mg, n=6) was administered orally at 09.00 h following an overnight fast. Plasma concentrations of venlafaxine and ODV were monitored by h.p.l.c. for 48 h. RESULTS: The Cmax and AUC of venlafaxine were 184% and 484% higher in the group 1 subjects than in the group 3 subjects, and 101% and 203% higher in the group 1 than in the group 2, respectively. CONCLUSIONS: These results suggest that CYP2D6*10 influences the pharmacokinetics of venlafaxine in a Japanese population.

Adult↗
PubMed1999

Motor activity of vascularly perfused rat duodenum. 1. Characteristics of spontaneous movement.

We developed an ex vivo model of arterially perfused rat duodenum to examine the motor activity of intestine. In this preparation, spontaneously occurring pressure waves with regular rhythm were observed. The oxygen consumption and motor activity of the intestine were compared at different arterial perfusion rates to determine the degree of oxygenation required to elicit spontaneous motility. Pressure waves with regular rhythm occurred at a frequency of 1 min-1 when the arterial perfusion was 3-5 mL min-1, and stopped when the perfusion rate fell below 2 mL min-1. Atropine and hexamethonium reduced the percentage motor index/10 min of pressure waves in a dose-dependent manner, and tetrodotoxin completely blocked motor activity. Acetylcholine stimulated motor activity, and this effect was not antagonized by TTX. These findings suggest that spontaneous contraction in the ex vivo perfused rat duodenum might be mediated by a cholinergic mechanism via muscarinic receptors on smooth muscle, but that noncholinergic mechanisms may also participate in this response.

Animals↗
PubMed1999

Involvement of 5-HT3 and 5-HT4 receptors in the motor activity of isolated vascularly perfused rat duodenum.

The involvement of serotonin (5-HT) receptor subtypes in motor activity of the ex vivo vascularly perfused rat duodenum was investigated. Clusters of phasic contractions (CPCs), migrating in an oral to anal direction, were obtained without any stimulation. Drug effects were evaluated by changes in different components of the pressure waves, such as motor index (MI), frequency, amplitude and duration of the CPC. The effect of 5-HT depletion on motor activity was examined in animals treated with p-chlorophenylalanine (PCPA). The MI, frequency and duration of CPC were decreased by PCPA, but the amplitude was not affected, suggesting that endogenous 5-HT may play an important role in regulation of the motor activity of the rat intestine. The importance of the 5-HT receptor subtypes in the regulation of motor activity was examined. Neither the nonselective 5-HT1 and 5-HT2 receptor antagonist, methysergide, nor the 5-HT2 receptor antagonist, ketanserin, affected motor activity. However, the 5-HT3 receptor antagonists, granisetron and azasetron, decreased percentage MI, frequency, percentage amplitude and percentage duration of CPC. The 5-HT4 receptor antagonist, SB204070, exerted both excitatory and inhibitory actions, with a higher dose (10 nM) stimulating percentage MI, frequency, percentage amplitude and percentage duration, and a lower dose (0.1 nM or 1 nM) decreasing percentage MI and percentage duration of CPC. These results suggest that endogenous 5-HT regulates the motor activity of the rat duodenum through 5-HT3 and 5-HT4 receptors, with the former mediating the stimulatory influence and the latter mediating both stimulatory and inhibitory influences.

Animals↗
PubMed1999

Long-term follow up of pure myxoid liposarcomas with special reference to local recurrence and progression to round cell lesions.

Myxoid and round cell liposarcomas cytogenetically share the t(12;16)(q13;p11) translocation, and represent a continuous morphological spectrum including pure myxoid liposarcoma (PML), mixed (myxoid/round cell) liposarcoma (MXL) and pure round cell liposarcoma (RCL). It has been documented that a critical amount of RC lesion in low-grade, MXL is associated with poor prognosis. The present long-term follow-up study examined the factors that influence the progression of PML to RCL and several other prognostic factors and compared the results with those of liposarcomas initially diagnosed as MXL. Using 34 primary PML and their local recurrences after curative resection, and two initially diagnosed MXL, the appearance of RC lesion in PML was examined, and the prognostic significance of the local recurrence rate (times/month), tumor size, infiltrative proliferation (defined as entrapping of striated muscle fibers in the tumor), tumor necrosis and mitotic figures. The follow-up period ranged from 19 to 378 months (mean, 173.4 months). Based on Cox's proportional hazards regression model, a recurrence rate >/= 0.01 in 24 PML with recurrences (P = 0.037) and the presence of infiltrative proliferation in 34 PML (P = 0.043) were significant independent factors associated with poor prognosis. Round cell lesions were detected in the last recurrences of two surviving PML. These results indicate that through their recurrence, PML might potentially become malignant, independent of the proportion of RC lesions in the tumor. The appearance of RC lesions in subsequent recurrences may indicate a progression from PML to MXL.

Adult↗
PubMed1999

Effects of bilateral jugular vein ligation on local cerebral blood flow.

The authors examined the effect of bilateral jugular vein ligation (JVL) on local cerebral blood flow (CBF). Local CBF was measured in the neocortex of the frontal lobe over a 1-week period in 10 freely moving male rats. Measurements were taken with the hydrogen clearance method before and after the rat underwent either an operation of bilateral JVL or a sham operation. After the sham operation, blood flow values did not change significantly compared with preoperative values. Blood flow values decreased rapidly in rats with JVL. For 3 hours after surgery, JVL values were significantly lower (p <0.05) than preoperative values were, then gradually they recovered and reached preoperative values within 48 hours. Histopathologic study showed no remarkable parenchymal damages in the brain of rats with JVL. These results show that bilateral JVL produces a reversible decrease in the CBF and does not cause histopathologic brain damages.

Journal Article↗
PubMed1999

1,2-dotriacontanedioyl-sn-glycero-3-phosphocholine: A cyclic lipid used for phospholipase A2-catalyzed modulation of the liposome surface charge.

An aqueous suspension of liposomes, which were made of cyclic 1, 2-dotriacontanedioyl-sn-glycero-3-phosphocholine (dTPC) and 1, 2-diphytanyl-sn-glycero-3-phosphocholine, was incubatedwith phospholipase A2 (Naja mossambica mossambica) in 0.05 M Tris-HCl, pH 7.7-7.8. At 25 degrees C, approximately 30% of the cyclic lipids was digested into 1-(omega-carboxyhentriacontanoyl)-sn-glycero-3-phosphocholine (lyso-dTPC), the original morphology being preserved but with a decrease in the zeta-potential of the membrane from ca. +2 to -1 mv. At 38 degrees C in 30 min, as much as 45% of the cyclic lipids was attacked by the lipase, which resulted in lowering of the potential to -2.5 to -3 mV. The enzymatic surface-charge modulation was discussed in conjunction with a side-selective attack of the phospholipase on the lipid bilayer.

Catalysis↗
PubMed1999

Differential light regulation of the rbcS gene expression in two cell lines of the liverwort Marchantia paleacea var. diptera.

A cDNA of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) gene (rbcS) was isolated from cells of the liverwort Marchantia paleacea var. diptera. The rbcS was expressed light-independently in a green line, but light-dependently in a yellow line. The accumulation of the large subunit of RuBisCO was regulated cooperatively with that of the small subunit.

Amino Acid Sequence↗
PubMed1999

Reverse U-shaped split temporalis musculofascial flap in cranial base reconstruction.

To extend the versatility and range of the temporalis muscle, a new type of temporalis musculofascial flap was developed. This was achieved by dividing the muscle into two portions--anterior and posterior-while maintaining vascular communication between the deep and the middle temporal arteries. This flap is reverse U-shaped with one of the arms of the "U" corresponding to a pedicle, which supplies the blood, and the other corresponding to the recipient region. The bottom of the U corresponds to continuity between the anterior and posterior portions of the muscle, which contains the vascular communication. In two patients with meningioma, the flap was applied to occupy the extradural dead space combined with a pericranial flap to prevent leakage of cerebral spinal fluid to the dural defect. The reverse U-shaped split temporalis musculofascial flap has some advantages for intracranial reconstruction: sufficient rotational arc, adequate thickness, and rich vascularity. A reverse U-shaped split temporalis musculofascial flap is useful and of benefit, especially for reconstruction at the region of the anterior midline skull base.

Aged↗