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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 19 recordsLinked to original sources
PubMed2000

Asymmetry of the human visual field in magnetic response to apparent motion.

Predominance of the lower visual field has been shown in various visual tasks, but whether the upper visual field is involved in a specific neural process is unknown. We used magnetoencephalography to study the effect of orientation and direction on the responses of five subjects to apparent motion from the human extrastriate cortex. The first magnetic response always was the largest, and the peak latency of about 200 ms did not change with the stimulus conditions. Amplitudes of the first responses were highest when motions were oriented at the horizontal meridian, decreasing with the degree of the angle between motion orientation and the horizontal meridian. There was no difference in amplitude between the two directions in the lower visual field, whereas the value of the response to downward motion in the upper visual field was significantly larger than that to upward motion. These amplitude changes are not due to differences in the anatomical distribution of neural activities because the estimated origins for the first responses always were in the same cortical area (around the occipito-parieto-temporal region) and the directions of the current vectors did not change with the stimulus conditions, and the estimated current strength changed with the stimulus conditions as did the response amplitude. These findings suggest that the human extrastriate cortex has a directional preference for downward versus upward motion in the upper visual field.

Adult↗
PubMed2000

Stereocontrol in solid-phase radical reactions: radical addition to oxime ether anchored to polymer support

A high degree of stereocontrol in solid-phase radical reactions was achieved by using triethylborane and diethylzinc as a radical initiator at low reaction temperature. Alkyl radical addition to Oppolzer's camphorsultam derivatives of oxime ether anchored to polymer support proceeded smoothly to give the alpha-amino acid derivatives with excellent diastereoselectivities.

Journal Article↗
PubMed2000

Doxapram accentuates white matter injury in neonatal rats following bilateral carotid artery occlusion.

The effect of the respiratory stimulant, doxapram, on white matter damage was investigated in neonatal rats under cerebral ischemia. Five-day-old rats underwent bilateral carotid artery occlusion with or without 50 mg/kg i.p. of doxapram. Their brains were neuropathologically examined 48 h later. Doxapram induced about a 20% decrease of PCO(2) for 90 min, but did not cause any neuropathological abnormalities. Bilateral carotid artery occlusion resulted in mild cerebrocortical lesions in 67% of pups, and white matter lesions in the internal capsule in 44%. Doxapram, in addition to bilateral carotid artery occlusion, produced more severe white matter injury in the internal capsule (injury score; 0.67+/-0.87 vs. 1.70+/-0.48, P<0.05) and in the subcortical white matter (0.33+/-0. 67 vs. 1.10+/-0.54, P<0.05). These results demonstrated that the use of doxapram under an ischemic condition accentuates white matter damage in neonatal rats.

Animals↗
PubMed2000

Increase in receptor binding affinity for nimodipine in the rat brain with permanent occlusion of bilateral carotid arteries.

The permanent occlusion of bilateral common carotid arteries (2VO) in rats has been shown to cause progressive and long-lasting cognitive deficits which may be due to impairment of memory retention and/or memory recall process. To clarify the function of voltage dependent calcium channels and the receptor binding of nimodipine by chronic cerebral ischemia, we examined specific (+)-[3H]PN 200-110 binding and the effect of oral administration of nimodipine in brain regions and hearts of rats, at 2 weeks to 4 months after permanent 2VO. There was no significant difference in either dissociation constant (Kd) or maximal number of binding sites (Bmax) for (+)-[3H]PN 200-110 in the cerebral cortex, hippocampus, corpus striatum and thalamus between 2VO and sham rats. In addition, in vitro inhibitory effect of nimodipine on cerebral cortical (+)-[3H]PN 200-110 binding in 2VO rats was similar to that in sham rats. Compared to control rats, oral administration of nimodipine to both 2VO and sham rats at 2 months after permanent 2VO brought about a significant increase in Kd values of specific (+)-[3H]PN 200-110 binding in the cerebral cortex, hippocampus, thalamus and myocardium, and the increase in Kd values was much larger in brain regions of 2VO rats than sham rats. However, the increase in Kd values in the myocardium did not differ between 2VO and sham rats. This observation suggests an increased in vivo binding affinity for nimodipine in chronic ischemic brain. In conclusion, the present study has shown that oral administration of nimodipine may cause a greater occupation in vivo of 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in brains of permanent 2VO rats than in sham rats. Thus, nimodipine may be pharmacologically effective in preventing brain dysfunction due to cerebral ischemia in vivo.

Animals↗
PubMed2000

Asymmetric synthesis of alpha-amino acids based on carbon radical addition to glyoxylic oxime ether

The first asymmetric synthesis of alpha-amino acids based on diastereoselective carbon radical addition to glyoxylic imine derivatives is reported. The addition of an isopropyl radical, generated from i-PrI, Bu(3)SnH, and Et(3)B in CH(2)Cl(2) at 25 degrees C, to achiral glyoxylic oxime ether 1 proceeded regioselectively at the imino carbon atom of the oxime ether group to give an excellent yield of the C-isopropylated product 2. The competitive reaction using glyoxylic oxime ether 1 and aldoxime ether 4 showed that the reactivity of the glyoxylic oxime ether toward nucleophilic carbon radicals was enhanced by the presence of a neighboring electron-withdrawing substituent. Thus, the alkyl radical addition to glyoxylic oxime ether 1 proceeded smoothly even at -78 degrees C, in contrast to the unactivated aldoxime ether 4. A high degree of stereocontrol in the carbon radical addition to the glyoxylic oxime ether was achieved by using Oppolzer's camphorsultam as a chiral auxiliary. The stannyl radical-mediated reaction of the camphorsultam derivative 6 with an isopropyl radical at -78 degrees C afforded a 96:4 diastereomeric mixture, 7a, of the C-isopropylated product. The reductive removal of the benzyloxy group of the major diastereomer (R)-7a, by treatment with Mo(CO)(6) and the subsequent removal of the sultam auxiliary by standard hydrolysis, afforded the enantiomerically pure D-valine (R)-12 without any loss of stereochemical purity. To evaluate the new methodology, a variety of alkyl radicals were employed in the addition reaction which gave the alkylated products 7 with excellent diastereoselectivity, allowing access to a wide range of enantiomerically pure natural and unnatural alpha-amino acids. Even in the absence of Bu(3)SnH, treatment of 6 with alkyl iodide and Et(3)B at 20 degrees C gave the C-alkylated products 7 with moderate diastereoselectivities. The use of Et(2)Zn as a radical initiator, instead of Et(3)B, was also effective for the radical reaction. The enantioselective isopropyl radical addition to 1 using (R)-(+)-2, 2'-isopropylidenebis(4-phenyl-2-oxazoline) and MgBr(2) gave excellent chemical yield of the valine derivative 2 in 52% ee.

Journal Article↗
PubMed2000

Heterologous enzyme immunoassay for serum androstenediol.

A heterologous enzyme immunoassay for serum androstenediol (Adiol: 3beta, 17beta-dihydroxy-androst-5-ene) was established. The combination of anti-Adiol antiserum raised in rabbit against Adiol 7-O-(carboxymethyl)oxime (Adiol 7-CMO) conjugated bovine serum albumin (Adiol 7-CMO-BSA) and Adiol 7-iminomethylcarboxylic acid conjugated alkaline phosphatase was used for the assay. The sensitivity of the heterologous assay system was superior to that of a homologous assay system in which an antibody raised in rabbit against Adiol 7-CMO-BSA and enzyme labeled antigen, Adiol 7-CMO conjugated alkaline phosphatase, were used. The minimal amount of Adiol detected was 0.4 ngml(-1) and the measurable range was from 0. 4 to 150 ngml(-1). Intra-assay coefficients of variation (C.V.) were 8.6% (1.52+/-0.13 ngml(-1), mean+/-S.D., n=10) and 6.7% (13.4+/-0.9 ngml(-1), n=10). Inter-assay C.V. were 12.9% (1.63+/-0.21 ngml(-1), n=8) and 11.5% (12.2+/-1.4 ngml(-1), n=8). A linear relation was observed between the serum sample dilution and the Adiol concentration. For recovery study, authentic Adiol was added to serum sample (original concentration: 1.43 ngml(-1)). The calculated final Adiol concentration was 2.99 ngml(-1). The recovery was 98.6% (n=5). The Adiol concentrations in healthy subjects measured by the proposed assay (male: 1.1+/-0.3 ngml(-1) (mean+/-S.D.), range: 0.7-1. 7 ngml(-1), age: 22-50, n=10; female: 0.6+/-0.4 ngml(-1), range: 0. 2-1.6 ngml(-1), age: 23-48, n=20) were consistent with reported values.

Adult↗
PubMed2000

Brain distribution of 6-mercaptopurine is regulated by the efflux transport system in the blood-brain barrier.

6-mercaptopurine (6-MP) has been used clinically for 40 years to maintain remission in patients with acute lymphoblastic leukemia (ALL). However, central nervous system (CNS) relapses frequently occur in patients with ALL who continuously receive anticancer drugs, including 6-MP, during remission maintenance therapy. The cause of such CNS relapse is not well understood. One possible reason may involve the restricted distribution of 6-MP in the brain. This study, therefore, investigates the blood-brain barrier (BBB) transport which largely regulates 6-MP distribution in the brain using a quantitative microdialysis technique and centers on the efflux transport of 6-MP across the BBB. The brain tissue, cerebrospinal fluid (CSF), or hippocampal interstitial fluid (ISF) concentration of 6-MP was very low compared with the unbound plasma concentration, suggesting that 6-MP distribution in the brain is highly restricted. Kinetic analyses of this BBB transport showed that the efflux clearance from brain ISF to plasma across the BBB (CLout) is approximately 20-times greater than the influx clearance from plasma to brain (CLin). The CLout was significantly reduced by 1mM N-ethylmaleimide (NEM), a sulfhydryl-modifying agent, suggesting the participation of transport protein in the efflux of 6-MP across the BBB. In addition, efflux transport was inhibited by an intracerebral infusion of probenecid (1.5 mM), p-aminohippuric acid (PAH, 3.0 mM), benzoate (3.6 mM), or salicylate (3.7 mM) administered through a microdialysis probe, but neither choline (0.8 mM) nor tetraethylammonium (TEA, 0.7 mM) had any effect. These data suggest that the restricted 6-MP brain distribution may be ascribed to efficient efflux from the brain, possibly via both the organic anion transport system, shared with probenecid and PAH, and the monocarboxylic acid transport system, shared with benzoate and salicylate.

Animals↗
PubMed2000

Magnetic response of human extrastriate cortex in the detection of coherent and incoherent motion.

Although direction selectivity is a cardinal property of neurons in the visual motion detection system, movement of numerous elements without global direction (incoherent motion) has been shown to activate human and monkey visual systems, as does coherent motion which has global direction. We used magnetoencephalography to investigate the neural process underlying responses to these types of motions in the human extrastriate cortex. Both motions were created using a random dot kinematogram and four speeds (0, 0.6, 9.6 and 25 degrees /s). The visual stimuli were composed of two successive motions at different speeds; a coherent motion at a certain speed that changed to incoherent motion at another speed or vice versa. Magnetic responses to the change in motion consisted of a few components, the first of which was always largest. The peak latency of the first component was inversely related to the speed of the preceding motion, but for both motions it was not affected by the speed of the subsequent motion. For each subject, the estimated origin of the first component was always in the extrastriate cortex, and this changed with the speed of the preceding motion. For both motions, the location for the slower preceding motion was lateral to that for the faster preceding motion. Although the latency changes of the two motions differed, their overall response properties were markedly similar. These findings show that the speed of incoherent motion is represented in the human extrastriate cortex neurons to the same degree as coherent motion. We consider that the human visual system has a distinct neural mechanism to perceive random dots' motion even though they do not move in a specific direction as a whole.

Adult↗
PubMed2000

Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor.

PURPOSE: This study was carried out to examine the blood-brain barrier (BBB) transport of human basic fibroblast growth factor (bFGF) and investigate its mechanism. METHODS: The BBB transport of 125I-bFGF was measured by several in vivo methods including intravenous administration, in situ internal carotid artery perfusion, and intracerebral microinjection. The in vitro binding of 125I-bFGF was characterized using freshly prepared bovine brain capillaries. RESULTS: The distribution volume of 125I-bFGF in the postvascular supernatant increased with the perfusion time, and exceeded the space occupied by the brain microvasculature and its trichloroacetic acid (TCA) precipitability was more than 90%. 125I-bFGF avidly bound to isolated bovine brain capillaries with a Bmax of 206 +/- 48 pmol/mg protein, and a Kd of 36.5 +/- 15.7 nM. This binding was significantly inhibited by unlabeled bFGF and heparin in a concentration-dependent manner. The cationic peptides, protamine and poly-L-lysine (each 300 microM), produced over 85% inhibition of 125I-bFGF binding to brain capillaries. Furthermore, glycosaminoglycans with a sulfate residue, chondroitin sulfate B and C (each 10 microg/mL) also inhibited the binding of 125I-bFGF The in vivo transcytosis of 125I-bFGF from the luminal side to the brain was also inhibited by the presence of heparin (10 microg/mL) and poly-L-lysine (300 microM), whereas neither hyaruronic acid (10 microg/mL) nor insulin (10 microM) had any effect. In addition to these results, the brain efflux index method was used to confirm that the transcytosis of 125I-bFGF from brain to blood across the BBB was negligible. CONCLUSIONS: These results suggest that 125I-bFGF is transported across the BBB, possibly by an adsorptive-mediated transcytosis mechanism that is triggered by binding to negatively charged species on the luminal membrane surface of the brain microvasculature, such as heparan sulfate proteoglycans.

Animals↗
PubMed2000

Left ventricular mass and global function in essential hypertension after antihypertensive therapy.

This study compares left ventricular global function in 55 patients (25 with hypertrophy and 30 without hypertrophy) with essential hypertension, whose blood pressure had been stable for longer than 1 year, with that in 35 healthy subjects. Left ventricular global function was calculated using the echocardiographic Doppler index as described by Tei et al. (Tei index). No significant differences were observed in echocardiographic left ventricular systolic function between the three groups. Left ventricular global function differed significantly between the three groups, however, suggesting impaired left ventricular global function even in the absence of left ventricular hypertrophy. Similar changes were observed in the ratio of peak velocity of atrial systole to peak velocity of early diastole during left ventricular inflow waveform (A/E), indicating that this disorder mainly reflects impaired left ventricular diastolic function. Unlike A/E, the Tei index is not affected by increasing age, and, therefore, is appropriate for evaluating left ventricular global function in hypertensive patients, most of whom are middle-aged or older. This index may be useful for determining treatment strategy and evaluating treatment effects.

Adrenergic beta-Antagonists↗
PubMed2000

Cardiac function in dialysis patients evaluated by Doppler echocardiography and its relation to intradialytic hypotension: a new index combining systolic and diastolic function.

AIM, PATIENTS AND METHODS: Cardiac function of 40 patients on maintenance dialysis was examined using a new Doppler index combining systolic and diastolic function. Immediately before dialysis, ultrasonic pulsed Doppler was used to measure right and left ventricular inflow and outflow waveforms. The sum of the isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) was calculated by subtracting the ejection time from the interval between the end of an inflow waveform and the start of the next inflow waveform. The new index was obtained by dividing the sum of the two isovolumetric times by the ejection time. Cardiac function was evaluated in dialysis patients and healthy controls using new indices of the right and left heart systems. RESULT: Indices of the right and left heart systems in dialysis patients were significantly higher than those in healthy controls. With respect to hypotension during dialysis, patients were divided into two groups, a group with decreased blood pressure (group A: 27 patients) and a group with normal blood pressure (group B: 13 patients). Only the left heart system index in group A was significantly higher. There were no significant differences in other M-mode Doppler indices between the two groups. CONCLUSION: The new index was a more sensitive evaluator of cardiac function and predictor of hypotension during dialysis compared to standard echocardiographic indices.

Adult↗
PubMed2000

Identification of 7-hydroperoxycholesterol in human liver by liquid chromatography-mass spectrometry.

BACKGROUND: A liquid chromatography-mass spectrometry with an atmospheric chemical ionization interface has been developed to identify simultaneously various oxygenated cholesterols in lipid extracts from alcoholic fatty liver. METHODS: We collected human liver tissues from alcoholic and control subjects at autopsy. We purified the lipid extracts with solid phase extraction and injected them onto a spherisorb ODS column, by using methanol that contained 10 mM ammonium acetate as a mobile phase and a flow rate of 0.7 ml/min. RESULTS: We found the presence of 7-hydroperoxycholesterol and other oxysterols (5-cholesten-3beta-ol-7-one, cholest-5-ene-3beta, 7-diol, and 5, 6beta-epoxy-5beta-cholestan-3beta-ol) in alcoholic fatty liver tissues. CONCLUSIONS: We assume that long-term ethanol ingestion leads to excessive oxidative stress and to the accumulation of cholesterol-derived hydroperoxides and oxysterols in alcoholic fatty liver.

Adult↗
PubMed2000

A case of CREST syndrome and myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis.

We report the first case of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated glomerulonephritis in a patient with CREST syndrome. A 74-year-old Japanese man with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia) developed rapidly progressive renal failure without elevation of blood pressure. Renal biopsy revealed glomerular sclerosis and fibrous crescents. The MPO-ANCA titer was elevated to 145 EU/ml. When patients with collagen diseases develop rapidly progressive glomerulonephritis, the possibility of MPO-ANCA-associated glomerulonephritis should be kept in mind.

Aged↗
PubMed1999

Sequence analysis of RNA-2 of different isolates of broad bean wilt virus confirms the existence of two distinct species.

The complete nucleotide sequence of RNA-2 from a Japanese isolate IP of broad bean wilt virus (BBWV) was determined. The sequence encodes a single large polyprotein, which contains a putative movement protein and two coat proteins (CPs). The 3'-terminal sequences of RNA-2 were also determined for three other Japanese isolates and two ATCC isolates (PV132 and PV176) of BBWV. The CPs of the four Japanese isolates share 86.8-98.0% amino acid sequences homology with one another and 88.3-96.5% with those reported for the isolate PV131 (BBWV-2). However, they have only 57.9-66.2% homology with those of PV132 and PV176 (BBWV-1).

3' Untranslated Regions↗
PubMed1999

Effects of cholestyramine on hepatic cholesterol 7alpha-hydroxylase and serum 7alpha-hydroxycholesterol in the hamster.

Cholestyramine increases activities of hepatic cholesterol 7alpha-hydroxylase and serum levels of 7alpha-hydroxycholesterol. To examine if serum 7alpha-hydroxycholesterol levels parallel with enzyme activity, 0, 0.5, 1, 2, 4, and 10% of cholestyramine was administered to female golden Syrian hamsters for 28 d in the dose-dependent study, and 2% cholestyramine for 0, 1, 3, 7, 14, 21, and 28 d in the time-dependent study. In the dose-dependent study, hepatic and serum cholesterol levels were significantly decreased dose-dependently when more than 0.5% of cholestyramine was fed for 28 d. Cholestyramine increased the cholesterol 7alpha-hydroxylase activity in a dose-dependent manner, while the serum 7alpha-hydroxycholesterol level was essentially unchanged. No correlation was found between the serum level and the hepatic enzyme activity. In the time-dependent study, hepatic and serum cholesterol levels markedly decreased when 2% cholestyramine was fed for longer than 3 d. The serum triglyceride level increased significantly for the first 7 d and then decreased. Cholesterol 7alpha-hydroxylase activity increased significantly as early as day 1, reached maximum activity level on day 7, and then kept the significantly high values until day 28. The serum 7alpha-hydroxycholesterol level significantly increased for the first 7 d and decreased to the pretreatment level thereafter. 7Alpha-hydroxycholesterol levels significantly correlated with serum cholesterol and triglyceride levels. We conclude that the serum 7alpha-hydroxycholesterol level does not always reflect the activity of hepatic cholesterol 7alpha-hydroxylase, when cholesterol metabolism is severely disturbed by cholestyramine.

Animals↗
PubMed1999

Cell-dependent replication potentials of HIV-1 gag mutants.

An infectious molecular clone of human immunodeficiency virus type 1 (HIV-1), designated pNLaiKH, which is tropic for both lymphocytic and monocytic cells, was constructed. To study the early function of HIV-1 Gag proteins in two types of cells, the mutations known to give host cell-dependent early defects were introduced into pNLaiKH, and the replication potentials and defective replication sites in the cells of the resultant mutants were monitored. All mutants grew in some lymphocytic cells, but not at all in monocytic cells. A nucleocapsid mutant was found to be defective at an early replication phase in all the cell lines to various extent, as expected. In contrast, a matrix mutant and a capsid mutant displayed a replication defect in a producer-cell-dependent manner. These results demonstrated that complex interactions of cell factors and Gag proteins are involved in an early process of HIV-1 replication.

Cell Line↗