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H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 55 records · Page 3Linked to original sources
PubMed2000

Movement-related desynchronization of the cerebral cortex studied with spatially filtered magnetoencephalography.

Event-related desynchronization (ERD) within the alpha and beta bands on unilateral index finger extension and hand grasping was investigated on six normal volunteers with magnetoencephalography (MEG). A novel spatial filtering technique for imaging cortical source power, synthetic aperture magnetometry (SAM), was employed for the tomographic demonstration of ERD. SAM source image results were transformed into statistical parametric images. On the same hand grasping task, a functional MRI (fMRI) study was conducted on two subjects and compared with the ERD result. When the MEG data were analyzed with the fast Fourier transformation, power attenuation within the alpha and beta bands was evident on the contralateral sensorimotor area just prior to movement onset. The tomographic distribution of ERD was clearly obtained with SAM statistical imaging analysis. The equivalent current dipole (ECD) for the signal-averaged motor field was localized to the hemisphere contralateral to the hand movement, roughly at the center of the region displaying beta-band ERD. The signal increase on fMRI roughly colocalized with the ERD on the contralateral sensorimotor area. In conclusion, with the novel spatial filtering technique for the brain magnetic field, SAM, cortical regions contributing to ERD on finger movement were successfully demonstrated in a tomographic manner. The relative colocalization of the contralateral SAM ERD with ECD as well as the fMRI activation suggests that SAM is a practically useful technique to extract event-related signals from brain noise.

Adult↗
PubMed2000

Whole-genome analysis of human astrocytic tumors by comparative genomic hybridization.

Frozen sections of 35 astrocytic tumors of various histologic malignancies were analyzed by comparative genomic hybridization in an attempt to characterize the profile of genetic aberrations. Over 94% of the samples revealed DNA copy number aberrations, which increased with higher histological malignancy grades, and also involvement of more than one chromosome was seen in 85% of instances. The aberrations observed were mainly deletions and most frequently incorporated chromosomes 1p, 10, 19q, and 22q. On the other hand, gains or amplifications were detected only in glioblastomas. Additionally, such gains or amplifications were present in all tumor samples where the initial histopathological diagnosis was glioblastoma and immunohistochemical study disclosed p53 tumor suppressor protein negative and epidermal growth factor receptor positive immunoreactivity; such glioblastomas possessing p53 tumor suppressor protein positive and epidermal growth factor receptor negative immunoreactivity seldom displayed any gain. Thus, glioblastomas exhibiting two different profiles of genetic aberrations were recognized--one with and the other without any gains/ amplifications. We speculate that the former variety is de novo glioblastoma.

Adult↗
PubMed2000

Induction of the activation-related antigen CD69 on human eosinophils by type IIA phospholipase A2.

OBJECTIVE: High levels of human type IIA phospholipase A2 (PLA2-IIA) have been found in the eosinophil-mediated inflammation sites, although the pathophysiological role of PLA2-IIA in the eosinophil activation has remained poorly understood. We investigated the effects of PLA2-IIA on eosinophil activation. METHODS: Eosinophils were incubated with recombinant human PLA2-IIA or other stimuli, and then eosinophil peroxidase (EPO) (by colorimetric assay) and leukotriene C4 (by enzyme immunoassay) released in the incubation buffer were measured. Expression of CD11b and CD69 on the cell surface was also measured by flow cytometry (by mean fluorescence intensity (MFI)). EPO, LTC4, and CD11b are thought to be markers for early phase activation (occurred in an hour after stimulation), and CD69 is to be a marker for late phase activation (occurred after several hours). RESULTS: While PLA2-IIA (5 microg/ml) did not induce any early phase activation, it induced significant expression of an activation-related antigen, CD69, on human blood eosinophils. The PLA2-IIA, when enzymatically inactivated by either p-bromophenacyl bromide or EDTA, lost its effect on the CD69 induction. Similarly to PLA2-IIA, several lysophospholipids (1 microg/ml) also induced CD69 on eosinophils significantly (control, 0.71 +/- 0.11; PLA2-IIA, 3.29 +/- 0.37*; lysophosphatidic acid, 2.57 +/- 0.43*; specific MFI +/- S.E.M., n = 4, * indicate p < 0.05 vs. control). CONCLUSIONS: PLA2-IIA induces CD69 expression on the eosinophils through its catalytic activity at least partly via the enzymatic products such as several lysophospholipids from the eosinophil membrane phospholipids. PLA2-IIA may contribute to the eosinophilic inflammation synergistically with other factors.

Antigens, CD↗
PubMed2000

Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS; MIM #154700) is a connective tissue disorder characterized by cardiovascular, skeletal, and ocular abnormalities. The fibrillin-1 gene (FBN1; MIM no. 134797) on chromosome 15 was revealed to be the cause of Marfan syndrome. To date over 137 types of FBN1 mutations have been reported. In this study, two novel mutations and a recurrent de-novo mutation were identified in patients with MFS by means of single-strand conformational polymorphism (SSCP) analysis. The two novel mutations are a 4-bp deletion at nucleotide 2820-2823 and a G-to-T transversion at nucleotide 1421 (C474F), located on exon 23 and exon 11, respectively. A previously reported mutation at the splicing donor site of intron 2 (IVS2 G + 1A), which is predicted to cause exon skipping, was identified in a sporadic patient with classical MFS.

Amino Acid Substitution↗
PubMed2000

A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome.

We identified a novel interstitial deletion that spanned from exons 5 to 10 of KAL1 in two Japanese brothers with X-linked Kallmann syndrome (KS; MIM no. 308700). Both brothers had hypogonadism, unilateral renal agenesis, and disturbance of the sense of smell, but they had no other neurological manifestations, including mental disturbance. Their mother was confirmed to be an asymptomatic carrier, by use of a comparative multiplex polymerase chain reaction (PCR) analysis. The present patients are further examples of patients with KS without mental disturbance caused by a mutation confined to KAL1.

Adult↗
PubMed2000

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein.

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. METHODS AND RESULTS: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.

Actins↗
PubMed2000

The effect of interstimulus intervals and between-block rests on the auditory evoked potential and magnetic field: is the auditory P50 in humans an overlapping potential?

OBJECTIVE: The human auditory P50 may consist of overlapping potentials. To test this hypothesis, we manipulated interstimulus intervals (ISIs) and between-block rests, and recorded the P50, P50m, N100 and the N100m simultaneously. METHODS: Subjects were 12 right-handed healthy adults. Four conditions included: (1) 1.5 s/rest, (2) 1.5 s/successive, (3) 0.5 s/rest, and (4) 0.5 s/successive. Auditory stimuli were presented a total of 880 times for each condition. Auditory evoked potentials and magnetic fields were recorded. We examined the P50, N100, P50m, N100m and dipoles of the P50m and the N100m. RESULTS: There was no significant effect of the ISI on the P50 amplitudes, but the P50m amplitudes in the 0.5 s ISI conditions were significantly smaller than those in the 1.5 s ISI conditions. The N100 and the N100m amplitudes in the 0.5 s ISI conditions were significantly smaller than those in the 1.5 s ISI conditions. The N100 and the N100m amplitudes in the resting conditions were significantly larger than those in the successive conditions. The P50m dipoles were slightly deeper and more anterior than those of the N100m in primary auditory cortex. CONCLUSIONS: Central structures other than supratemporal cortex contribute to the P50 and that the P50 in humans represents overlapping potentials.

Acoustic Stimulation↗
PubMed2000

Inhibition of complement-mediated haemolysis in paroxysmal nocturnal haemoglobinuria by heparin or low-molecular weight heparin.

Complement (C')-mediated haemolysis in paroxysmal nocturnal haemoglobinuria (PNH) is mainly due to the deficiency of glycosyl phosphatidylinositol-anchored membrane proteins with C'-regulatory activities CD55 and CD59 in PNH-affected red blood cells (RBCs). Hydrophobic insertion of C5b-7 to RBC membranes, initiating the formation of a membrane attack complex, readily results in lysis of PNH RBCs due to the deficiency of CD59. We studied the significance of the electrostatic interactions between C5b-6 and RBC membranes preceding the insertion of C5b-7. In vitro, C'-mediated lysis of PNH RBCs (assessed by sucrose haemolytic assay) was inhibited by heparin, low-molecular weight heparin (LMWH) or protamine, indicating the significance of the electrostatic interactions between C' components and RBC membranes in the process of C'-mediated haemolysis. Neuraminidase-treated PNH RBCs became resistant to C' activation, suggesting that the sialic acid moieties on RBC membranes are involved in the interactions of RBC with C' components. By using biotin-labelled C7, we demonstrated that LMWH as well as heparin inhibited the insertion of C5b-7 to RBCs, although they did not inhibit the incorporation of C7 into membrane-associated C5b-6. Neither heparin nor LMWH could inhibit the procoagulant alteration of PNH RBC membranes induced by C' activation even at concentrations which inhibited the haemolysis completely. Because LMWH inhibited the C'-mediated lysis of PNH RBCs in vitro at the range which induced a limited prolongation of activated partial thromboplastin time of normal plasma, we consider that LMWH may be useful for both the inhibition of haemolysis and the prevention of thrombosis, which often follow a haemolytic attack in PNH.

Anticoagulants↗
PubMed2000

The vascular bed in the rabbit ear: microangiography and scanning electron microscopy of vascular corrosion casts.

The vascular bed of the rabbit ear has been studied with light microscopy, microangiography and scanning electron microscopy of resin casts in a series of 20 ears. The major arteries supplying the ear were the central and rostral auricular branches of the caudal auricular artery. The caudal auricular branch was not observed, except as a small vessel supplying the rostral auricular base. The central auricular branch supplied blood to most of the auricular integument and was surrounded by capillaries extended from those supplying the skin. The periarterial capillaries formed a fine, compact network in the tunica media and were closely related to the central auricular branch. Evidence is presented suggesting that this vascular mechanism has a counter-current heat-exchange function for regulating body temperature. The artery had the well-developed internal elastic lamina and intimal cushions that regulate blood flow at the branching sites. A number of arteriovenous anastomoses were also observed between arterioles and venules, particularly in marginal regions of the ear. The intimal cushions and arteriovenous anastomoses might play an additional role in thermoregulation by regulating local blood flow in the ear.

Angiography↗
PubMed2000

Auditory P50 obtained with a repetitive stimulus paradigm shows suppression to high-intensity tones.

We manipulated stimulus intensity and number of frequency bands in auditory stimuli in order to investigate the nature of P50 in human auditory evoked potentials. Pure-tone and mixed-tone conditions were examined. For each condition, four stimulus intensities were used: 55, 70, 85 and 100 dB sound pressure level (SPL). The P50s were obtained at Cz using a repetitive stimulus paradigm. P50 amplitudes increased as stimulus intensities increased up to 85 dB; with 100 dB stimulation amplitudes decreased. The number of frequency bands in the stimulus did not affect P50 amplitude. Considered in terms of P50 suppression under a conditioning/testing paradigm, the results suggest that the P50 wave reflects activity of the sensory gating mechanism in humans.

Adult↗
PubMed2000

A demand valve device decreases exhaust nitric oxide and nitrogen dioxide by nitric oxide inhalation with a nasal cannula in the human.

To improve patients' quality of life and decrease pollution risks to medical personnel, we tested the usefulness of a nitric oxide (NO) inhalation system consisting of a nasal cannula and a demand valve in an open circuit system. To estimate the content of NO entering the lung with the open system, concentrations of NO and nitrogen dioxide (NO2) were measured in a mechanical lung model, and then nitrocylhaemoglobin (NO-Hb), methaemoglobin (Met-Hb), and nitrite (NO2-) + nitrate (NO3-) concentrations in venous blood were measured in eight healthy subjects. Exhaust NO and NO2 in the open system were also observed in 14 healthy subjects. In the lung model, NO concentration delivered with the open system was approximately 1/11 of that in the gas tank. Increases in Met-Hb and NO2- + NO3- with the open system showed that the concentration of delivered NO was approximately 1/9 of that in the gas tank. The open system reduced exhaust NO to 1/10 in human subjects. These data suggest that this NO inhalation system delivers sufficient NO to spontaneously breathing patients. In addition, these findings indicate that there is little environmental toxicity associated with the open circuit system.

Adult↗
PubMed2000

Effectiveness of spray application of ACNU in the local control of malignant gliomas: report of two cases.

Malignant gliomas encompassing the eloquent areas cannot be removed totally and their surgical extirpation is followed by adjuvant therapy for the residual tumor. Recently, we have employed fibrin glue as a vehicle for the sustained release of ACNU (nimustine hydrochloride) by spray application following subtotal tumor removal in two patients with recurrent malignant gliomas. Follow-up MRI at six months demonstrated no neuroradiological evidence of tumor recurrence in the site of operation. We conclude, this novel mode of intra-operative local chemotherapy by spray application of fibrin glue containing antineoplastic agent is effective in the control of residual tumor progression and may also prevent local recurrence and hence suggests its possible role as an adjuvant therapy in the management of malignant gliomas.

Aerosols↗
PubMed2000

Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication.

The authors report on a Japanese adult male patient with a long history of partial seizures that were poorly controlled by conventional doses of phenytoin and other drugs. His treatment was complicated by toxic symptoms and an excessive serum phenytoin concentration, 32.6 microg/mL at a dose of 187.5 mg/day. Polymerase chain reaction-restriction fragment length polymorphism analysis disclosed heterozygosity involving cytochrome P450 subfamilies 2C9 (*1/*3) and 2C19 (*1/*3). Currently, it is generally accepted that the former mutation is responsible for the CYP2C9 poor metabolizer phenotype. Pharmacokinetic parameters were estimated by a kinetic analysis, MULTI, using 17 observed dose-concentration data sets: a lower Vmax (5.6 mg/kg/day) and a higher Km (11.5 microg/mL) were observed. Although phenytoin is metabolized predominantly by CYP2C9 with a minor contribution of CYP2C19, patients with the Leu359 variant should be monitored closely when treated with a moderate to high daily dose of phenytoin.

Adult↗
PubMed2000

Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis.

This study evaluated the catalytic activity of three variants (Ile, Leu, and Thr) at codon 359 of CYP2C9 enzymes expressed in a yeast cDNA expression system, and then established single-strand conformation polymorphism (PCR-SSCP) analysis for simultaneous detection as a screening method. Diclofenac was used for the in vitro experiment, and its hydroxy metabolite (4'-hydroxydiclofenac) was measured by HPLC. To discuss the in vivo effect of the Thr359 variant on the pharmacokinetics of phenytoin, a case report is presented. The efficiency of the SSCP method was evaluated by analyzing DNA samples from a homozygote for Ile359 and a heterozygote for Leu359 or Thr359. To evaluate the interaction between the P450 level and reductase activity, two batches of the Thr359 variant with a different P450:reductase activity ratio (1:4.0 and 1:1.4) were used. The in vitro study revealed that recombinant Ile359, Leu359, and Thr359 (2 batches) possessed a mean Km of 2.0, 16.5 and (3.8 and 2.9) micromol and Vmax of 12.4, 17.9 and (4.4 and 5.1) nmol/min/nmol P450, respectively. Although the magnitude of the change in catalytic efficiency for the Thr359 variant was close to that of the Leu359 variant, the effect of the two variants on diclofenac 4'-hydroxylation appears to be different because Leu359 variant was associated with a high Km, and Thr359 with a low Vmax. No significant differences in the kinetic data were observed between the two Thr359 enzymes, suggesting that low reductase activity in the Thr359 enzyme was not a major determinant in the present in vitro experiment. Estimated pharmacokinetic parameters of phenytoin obtained by the Bayesian method in an epileptic patient who was a heterozygote carrier for Thr359 variant were: Km = 6.45 microg/mL, Vmax = 5.77 mg/kg/d, and Vmax/Km = 0.89 L/kg/day. The Vmax/Km value in this patient was similar to the population mean value (0.90 L/kg/day) in Japanese heterozygotes for the Leu359 variant. Results for PCR-SSCP were in complete agreement with those obtained using established methods. Thus, the PCR-SSCP approach is useful for identifying these three variants of the CYP2C9 gene.

Adult↗
PubMed2000

Microvasculature of hydronephrotic kidneys in KK-A(Y) mice.

Spontaneous hydronephrosis in KK-A(Y) mice was studied using light and electron microscopy and scanning electron microscopy of resin casts to evaluate micro vascular changes in the kidney. The renal parenchyma was extremely thin as a result of tubular atrophy. Histologically, varying degrees of glomerulosclerosis were observed. Ultrastructurally, marked thickenings of the glomerular basal lamina, an increase in mesangial cells and matrix, and marked effacement of foot processes were observed. In resin casts, a marked reduction in number of glomeruli was evident. The capillaries were thin, strangulated and tom-off to varying degrees in severely affected glomeruli. In the medulla, the three-dimensional capillary network running along the tubules was lost and changed to a two-dimensional vascular bed. Despite severe hydronephrosis, the glomerular capillary network was relatively well preserved, being either slightly or moderately injured in approximately 60% of surviving glomeruli.

Animals↗
PubMed2000

Influence of castration on development of the thymus in neonatal male rats.

The influence of castration on the development of the thymus in neonatal rats was studied to elucidate when after birth the thymus comes under inhibitory regulation by the testis in rats. The relative and absolute weights of the thymus were measured five days after castration these cases. No excessive changes in the weights of the thymus with castration were observed by 31 days after birth. Significant changes in the thymus appeared in the relative weight at 36-day-castration. The absolute weight of the thymus was also significantly increased after 41-day-castration. These findings suggest that in rats the inhibitory regulation of the thymus by testis development does not appear before at least 31 days of age.

Aging↗