Biomedical subjects

A Miki

Publications and source records attributed to A Miki.

At least 19 recordsLinked to original sources

PubMed2001

Simultaneous determination of selegiline-N-oxide, a new indicator for selegiline administration, and other metabolites in urine by high-performance liquid chromatography-electrospray ionization mass spectrometry.

In order to discriminate selegiline (SG) use from methamphetamine (MA) use, the urinary metabolites of SG users have been investigated using high-performance liquid chromatography (HPLC)-electrospray ionization mass spectrometry (HPLC-ESI-MS). Selegiline-N-oxide (SGO), a specific metabolite of SG, was for the first time detected in the urine, in addition to other metabolites MA, amphetamine (AP) and desmethylselegiline (DM-SG). A combination of a Sep-pak C18 cartridge for the solid-phase extraction, a semi-micro SCX column (1.5 mm I.D.x 150 mm) for HPLC separation and ESI-MS for detection provided a simple and sensitive procedure for the simultaneous determination of these analytes. Acetonitrile-10 mM ammonium formate buffer adjusted to pH 3.0 (70:30, v/v) at a flow-rate of 0.1 ml/min was found to be the most effective mobile phase. Linear calibration curves were obtained over the concentration range from 0.5 to 100 ng/ml for all the analytes by monitoring each protonated molecular ion in the selected ion monitoring (SIM) mode. The detection limits ranged from 0.1 to 0.5 ng/ml. Upon applying the scan mode, 10-20 ng/ml were the detection limits. Quantitative investigation utilizing this revealed that SGO was about three times more abundant (47 ng/ml, 79 ng/ml) than DM-SG in two SG users' urine samples tested here. This newly-detected, specific metabolite SGO was found to be an effective indicator for SG administration.

Chromatography, High Pressure Liquid↗

PubMed2001

Pigeons' timing of an arbitrary and a naturalistic auditory stimulus: tone versus cooing.

Previous animal research has traditionally used arbitrary stimuli to investigate timing in a temporal bisection procedure. The current study compared the timing of the duration of an arbitrary, auditory stimulus (a 500-Hz tone) to the timing of the duration of a naturalistic, auditory stimulus (a pigeon cooing). In the first phase of this study, temporal perception was assessed by comparing psychophysical functions for the duration of tone and cooing signals. In the first set of tests, the point of subjective equality (PSE) was significantly lower for the tone than for the cooing stimulus, indicating that tones were judged longer than equivalent durations of cooing. In the second set of tests, gaps were introduced in the tone signal to match those present in the cooing signal, and no significant difference in the PSE for the tone or the cooing signal was found. A repetition of the testing conducted with gaps removed from the tone signal, failed to replicate the difference in the PSEs for the tone and cooing signals originally obtained. In the second phase of the study, memory for the duration of tone and cooing was examined, and a choose-long bias was found for both signals. Based on these results, it appears that, for pigeons, there may be no significant differences in either temporal perception or temporal memory for arbitrary, auditory signals and more complex, naturalistic, auditory signals.

Journal Article↗

PubMed2001

Column-switching high-performance liquid chromatography-electrospray ionization mass spectrometry for identification of heroin metabolites in human urine.

In order to prove heroin (DAM) use, a simple, rapid and sensitive analytical method has been established by combining semi-microcolumn HPLC, a column switching technique and electrospray ionization mass spectrometry (ESI-MS). Urine samples were directly introduced to the system, and endogenous urinary constituents were removed by using on-line column switching solid-phase extraction with a strong cation-exchange (SCX) cartridge column (2.0 mm I.D. x 10 mm). Heroin and its metabolites enriched on the top of the column were then successfully analyzed with excellent separation by use of a SCX semi-microcolumn (1.5 mm I.D. x 150 mm), accompanied by ESI mass spectral detection. The proposed conditions are as follows: mobile phase, 10 mM ammonium acetate (pH 6.0)-acetonitrile (30:70, v/v) (for main separation) and 30 mM ammonium acetate (for trapping); flow-rates, 120 microl/min (for main separation) and 200 microl/min (for trapping); capillary voltage, +4.5 kV; cone voltage, 50 V. Linear calibration curves were obtained in the selected ion monitoring (SIM) mode using protonated molecular ions (m/z 370 for DAM, m/z 328 for MAM and m/z 286 for MOR) over the concentration ranges from 10 to 1000 ng/ml for morphine (MOR) and 1-100 ng/ml for DAM and 6-acetylmorphine (MAM). The detection limits were 0.1-3 ng/ml. Upon applying the scan mode, 2-30 ng/ml were the detection limits. The present HPLC-ESI-MS method was successfully applied to the determination of opiates in users' urine samples.

Chromatography, High Pressure Liquid↗

PubMed2001

Ocular dominance in anterior visual cortex in a child demonstrated by the use of fMRI.

Negative signal changes in the visual cortex have been observed during visual stimulation when performing functional magnetic resonance imaging (fMRI) in children. This report investigated whether the ocular dominance, which has been demonstrated in the contralateral anterior visual cortex in adults, could be observed in a child by the use of fMRI. A 5-year-old child was studied using fMRI at 1.5 T during alternating monocular visual stimulation under sedation with morphine and pentobarbital. The functional images were motion corrected, and statistical parametric maps were made by contrasting the left or right eye stimulation conditions vs the right or left eye stimulation conditions, respectively, at each voxel. Areas with negative signal changes were found on the left anterior visual cortex during monocular visual stimulation of the right eye and vice versa. There was no area with negative or positive signal change on the ipsilateral visual cortex to the stimulated eye and no area with positive signal change on the contralateral visual cortex. Contralateral ocular dominance of anterior visual cortex similar to that of adults was demonstrated in this child with a negative correlation with the visual stimulus. This finding suggests that peripheral visual fields are represented in the anterior visual cortex of 5-year-old children.

Child, Preschool↗

PubMed2001

Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells.

PROBLEM AND METHOD OF STUDY: We have shown that Tokishakuyaku-san (Toki) and Sairei-to (Sai) enhance T helper-1 (Th1) cytokine release from peripheral blood mononuclear cells (PBMCs): thereby, they could be a therapeutic means in the treatment of autoimmunity related recurrent abortion in which T helper-2 (Th2) polarization is exaggerated, the condition purported to benefit from these herbal medicines. However, an open question is whether these medicines might enhance Th1 cytokine release in decidual tissues and thereby stimulate the killer activity, thus, working counterproductively by accelerating maternal alloimmune reactions toward fetal tissues. To address this, we examined the effects of these medicines on the release of cytokines from decidual mononuclear cells (DMCs) in comparison with PBMCs on the assumption that they might act differently on these cell types. The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a nonclassical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Regarding Th1 cytokines. Toki marginally increased the release of tumor necrosis factor (TNF)-alpha, but not interferon (IFN)-gamma from DMCs while Sai did not affect the release of both. Both Toki and Sai were without effect in modulating the release of interleukin (IL)-4, a member of Th2 cytokines. Interestingly, the presence of HLA-G reduced the release of Th1 cytokines from DMCs regardless of the addition of Toki, Sai or none. These findings are in sharp contrast with PBMCs on which these medicines seem to act so as to enhance Th1 polarization and attenuate Th2 polarization. CONCLUSION: Differential effects of Toki and Sai on the release of Th1/Th2 cytokines between DMCs and PBMCs may afford the rationale of these medicines in the treatment of autoimmunity-related recurrent abortion.

Adult↗

PubMed2001

Effect of eicosapentaenoic acid (EPA) on tight junction permeability in intestinal monolayer cells.

UNLABELLED: The purpose of this study is to evaluate the effect of C18 and C20 long chain fatty acids on tight junction permeability in a model of intestinal epithelium. METHODS: Confluent Caco-2 cells on porous filters with double chamber system were used to measure fluorescein sulfonic acid (FS) permeability and transepithelial electrical resistance (TEER). Lactate dehydrogenase release and ultrastructure were evaluated. Effect of 200 microM eicosapentaenoic acid (EPA, C20:5 n-3), arachidonic acid (AA, C20: 4 n-6), alpha-linoleic acid (ALA, C18: 3 n-3), linoleic acid (LA, C18: 2 n-6), or oleic acid (OA, C18: 1 n-9) enrichment in the culture medium during 24 hours were compared. The effect of the cyclooxygenase inhibitor, indomethacin, lipoxygenase inhibitors, NDGA or AA861, and antioxidant, BHT, was evaluated as a mechanism to change tight junction permeability. RESULTS: Caco-2 cells formed polarized columnar epithelial cells with densely packed microvilli and well developed junctional complexes. Addition of EPA enhanced FS permeability to 3.0+/-1.6-fold and lowered TEER to 0.59+/-1.2-fold vs. control with concentration dependency without cell injury (P<0.01-0.05). OA, AA or LA did not change, but ALA enhanced tight junction permeability. Indomethacin and AA861 normalized the changes mediated by EPA. CONCLUSIONS: EPA affects tight junction permeability in intestinal monolayer cells specifically and concentration dependently via cyclooxygenase and lipoxygenase products.

Caco-2 Cells↗

PubMed2001

Soluble HLA-G influences the release of cytokines from allogeneic peripheral blood mononuclear cells in culture.

Exquisitely regulated cytokine balance during early pregnancy is thought to be necessary for promoting survival of the fetal allograft. Our previous studies have demonstrated that membrane-bound human leukocyte antigen (mHLA-G) expressed on trophoblasts is one of the key factors in regulating cytokine balance by shifting the Th1/Th2 balance toward Th2 polarization, a favourable milieu for the maintenance of pregnancy. Given that trophoblasts secrete soluble HLA-G (sHLA-G), we examined its biological roles in comparison with mHLA-G. We cultured peripheral blood mononuclear cells (PBMC) with either the HLA-A and -B-deficient B lymphoblast cell line (721.221 cells) or the same cell line transfected with mHLA-G (721.221-G1 cells), in the presence or absence of recombinant sHLA-G. Cytokine concentrations in the culture media were determined by enzyme-linked immunosorbent assay. In contrast to mHLA-G protein, sHLA-G stimulated the release of tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, whereas it reduced the release of interleukin (IL)-3, regardless of the presence of the presence of a stimulatory effect of the mHLA-G-expressing cells. Although mHLA-G reduced the release of IL-4, sHLA-G did not have any effect. Conversely, sHLA-G stimulated the release of IL-10 whereas mHLA-G was without effect. These results suggest that sHLA-G regulates the release of cytokines from PBMC chiefly by counterbalancing mHLA-G, and thereby may play a role in maintaining pregnancy.

Cell Line↗

PubMed2001

Visual activation in functional magnetic resonance imaging at very high field (4 Tesla).

OBJECTIVES: Functional magnetic resonance imaging (fMRI) at very high field strengths provides functional brain mapping with the enhanced signal to noise ratio and the larger blood oxygenation level-dependent (BOLD) effect. We report activated areas in the standard space detected by fMRI at 4 Tesla (T) during simple visual stimulation. MATERIALS AND METHODS: Twelve healthy young subjects were scanned using a 4 T scanner during binocular flashing visual stimulation. Functional images were realigned to the first scan and then spatially normalized. Individual and group data analyses were performed to identify areas of visual activation. RESULTS: Activation of the bilateral primary visual cortex (V1/V2) was observed along the entire calcarine fissure in all subjects. The activated area extended to the extrastriate cortex in all subjects. Activation of the bilateral lateral geniculate nucleus (LGN) was detected in all subjects. The group data showed activation of the bilateral primary visual cortex and the bilateral lateral geniculate nucleus. CONCLUSIONS: Robust activation of the vision-related areas was successfully obtained in all subjects using a 4 T magnetic resonance scanner. These results suggest that fMRI at very high field strengths may be effective in showing visual system physiology, and that it can be a promising method to assess visual function of human subjects.

Adult↗

PubMed2001

Functional magnetic resonance imaging of the visual system.

Functional magnetic resonance imaging (fMRI), which is a technique useful for non-invasive mapping of brain function, is well suited for studying the visual system. This review highlights current clinical applications and research studies involving patients with visual deficits. Relevant reports regarding the investigation of the brain's role in visual processing and some newer fMRI techniques are also reviewed. Functional magnetic resonance imaging has been used for presurgical mapping of visual cortex in patients with brain lesions and for studying patients with amblyopia, optic neuritis, and residual vision in homonymous hemianopia. Retinotopic borders, motion processing, and visual attention have been the topics of several fMRI studies. These reports suggest that fMRI can be useful in clinical and research studies in patients with visual deficits.

Amblyopia↗

PubMed2001

Human leukocyte antigen-G-expressing cells differently modulate the release of cytokines from mononuclear cells present in the decidua versus peripheral blood.

PROBLEM: To better understand the role of human leukocyte antigen (HLA)-G in regulating the T helper (Th)1/Th2 cytokine balance, one of key conditions in determining the fate of pregnancy, we asked whether the presence of HLA-G protein altered the release of cytokines from both decidual mononuclear cells and peripheral blood mononuclear cells (PBMCs). METHOD OF STUDY: The amounts of cytokines released from decidual mononuclear cells and PBMCs were compared in the presence or absence of HLA-G-expressing cells. RESULTS: When cocultured with HLA-G-expressing cells, the amounts of tumor necrosis factor-alpha and interferon-gamma released from decidual mononuclear cells and PBMCs were decreased, while the amounts of interleukin (IL)-4 from PBMCs was increased, with IL-4 release from decidual mononuclear cells being unchanged. CONCLUSIONS: Upon contact with HLA-G, decidual mononuclear cells, and PBMCs as well, modulate their ability to release cytokines in a way that may shift the Th1/Th2 balance towards relative Th2 dominance, suggesting a role for HLA-G in maintaining pregnancy.

Adult↗

PubMed2001

Polymorphism of human leukocyte antigen-E gene in the Japanese population with or without recurrent abortion.

PROBLEM: The aim of this study was to investigate the gene frequencies and shared alleles of human leukocyte antigen (HLA)-E gene in Japanese couples with or without recurrent abortion. METHOD OF STUDY: Polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis was carried out to detect polymorphism in exon 3 of the HLA-E gene in 30 Japanese couples with recurrent abortion and 38 normal Japanese couples with proven fertility. RESULTS: No point mutation was detected in exon 3 of HLA-E in both recurrent aborters and normal controls. HLA-EG and HLA-ER alleles were detected with frequencies of 66.7% and 33.3% in couples with recurrent abortion and 69.2% and 30.8 in normal couples, respectively. The gene frequency of HLA-EG was higher than that of HLA-ER, which is contrary to that found in Caucasian, African-American and Hispanic people but similar to Chinese people. The frequency of each allele was not significantly different between recurrent aborters and normal controls. The number of shared alleles between each couple with recurrent abortion is not significantly different from that with normal controls. CONCLUSION: Allele frequencies of HLA-E were suggested to be different in Asian people from those in other ethnic people. In light of no specific distribution pattern in recurrent aborters, HLA-E polymorphism does not seem to play a role in the pathogenesis of recurrent abortion.

Abortion, Habitual↗

PubMed2001

Cross-axis adaptation of pursuit initiation in humans.

PURPOSE: The initial acceleration of pursuit in the open-loop period is under adaptive control and undergoes motor learning. The current study was undertaken to examine the hypothesis that the direction of pursuit initiation can also be adaptively modified. METHODS: Four neurologically and ophthalmologically normal subjects participated in the experiment. A modified step-ramp paradigm was used to induce cross-axis adaptation, in which a ramp target changed its direction orthogonally just after the target crossed the center. Four direction changes were tested in separate experiments: left to up, left to down, down to left, and up to left. During a 30-minute adaptation session, the target moved in one of two randomly chosen directions (right to left or up to down) at one of two randomly chosen speeds (15.6 or 22.3 deg/sec), but the target changed orthogonally in only one direction. A linear regression fit to the initial 100-msec segment of the pursuit trace was used to determine the direction of pursuit initiation. RESULTS: In all cases, an adaptive change in pursuit initiation was gradually induced in the direction called for by the training paradigm. Adaptation was usually completed (90 degrees shift) within the 30-minute training session but declined quickly to an approximate 30 degrees -shift after training. The latency and vectorial amplitude of the initial acceleration remained unchanged. The adaptation was specific for the direction but not the velocity of the target. CONCLUSIONS: This study showed that the direction of pursuit initiation is under adaptive control, as has been shown for saccadic eye movements and the vestibulo-ocular reflex.

Adaptation, Ocular↗

PubMed2001

Adaptive changes in dynamic properties of human disparity-induced vergence.

PURPOSE: Vergence eye movements undergo adaptive recalibration in response to a training stimulus in which the initial disparity is changed just after vergence begins (the double-step paradigm). In the present study the changes in the dynamic properties of convergence, speed and acceleration, were examined by using this double-step paradigm, before and after adaptation. METHODS: Four normal subjects participated. Three-dimensional visual stimuli were provided by a head-mounted display with two liquid crystal diode (LCD) panels. To induce adaptation, a double step of disparity was used: an initial step from distances of 2 to 1 m was followed by a second step to distances of 0.7 m ("increasing paradigm") or 1.4 m ("decreasing paradigm") after a constant period of 0.2 seconds. The dynamic properties of vergence were compared before and after 30 minutes of training with these paradigms. RESULTS: Peak velocity of convergence became significantly greater (increasing paradigm) or smaller (decreasing paradigm) after 30 minutes' training. Changes in the dynamic properties of convergence were also obvious in phase-plane (velocity versus position) and main sequence (peak velocity versus amplitude) plots. Further analysis revealed that adaptive increases in vergence velocity were accomplished by an increase in the duration of the acceleration period, whereas adaptive decreases were induced by a decrease in the maximum value of acceleration. CONCLUSIONS: The pattern of change in the dynamic characteristics of vergence after adaptation was similar to that of saccades and the initiation of pursuit eye movements, suggesting common neural mechanisms for adaptive changes in the open-loop control of eye movements.

Adaptation, Ocular↗

PubMed2000

Contralateral monocular dominance in anterior visual cortex confirmed by functional magnetic resonance imaging.

PURPOSE: Although it is known that the damage to anterior striate cortex results in temporal peripheral visual field loss of the contralateral eye in patients with cerebral visual disturbance, the monocularity of anterior striate cortex has not been demonstrated in normal living humans. The aim of this study was to investigate whether this could be shown noninvasively using functional magnetic resonance imaging of the human visual cortex. METHODS: Eleven normal volunteers were studied with functional magnetic resonance imaging during alternating monocular visual stimulation using a 1.5 Tesla scanner. The data were motion corrected and spatially normalized to the standard brain. The monocular activation of the visual cortex was compared with the activation by the other eye. RESULTS: In the individual data analysis, contralateral eye dominance was always observed in the anterior striate cortex. In the group analysis from 11 subjects, the area with contralateral eye dominance was found in the most anterior part of primary visual cortex where the calcarine fissure merged with the parieto-occipital sulcus. CONCLUSIONS: This study shows that the contralateral eye dominance of anterior striate cortex can be detected noninvasively with functional magnetic resonance imaging during monocular visual stimulation. The finding confirms that the anterior striate cortex, where the monocular temporal crescent is represented, is primarily monocular, but the fact that greatest density of retinal ganglion cells and photoreceptors is in the nasal hemiretina must also be taken into account when interpreting these results.

Dominance, Cerebral↗

PubMed2000

Functional MRI in children with congenital structural abnormalities of the occipital cortex.

Functional MRI techniques were used to map the position of visual cortex in an awake and a sedated child with congenital anomalies of the posterior hemispheres. In one subject with cortical heterotopia, an activated cortex was found distinct from the structurally abnormal area detected on conventional MRI. In a sedated patient with holoprosencephaly, activated cortical areas in the posterior-medial portions of the hemispheres were identified. This study demonstrates the utility of functional MRI in such patients, both awake and sedated.

Adolescent↗

PubMed2000

Decrease of suppressor-inducer (CD4+ CD45RA) T lymphocytes and increase of serum immunoglobulin G due to perceived job stress in Japanese nuclear electric power plant workers.

To clarify the effects of perceived job stress on the immune system, a cross-sectional study was conducted in 116 male Japanese workers of a nuclear electric power plant (age, 20 to 39; mean, 31 years). Perceived job stress, i.e., psychological job demand, job control, worksite social support, and job strain, was assessed by means of the Japanese version of the Job Content Questionnaire. The job strain score was calculated as the ratio of the job demand score to the job control score. Blood samples were taken from all workers, and numbers of T and natural killer cell subpopulations, B lymphocytes, total lymphocytes and white blood cells, and serum concentrations of immunoglobulins (IgG, IgM, IgA, IgE and IgD) in their blood were measured. The workers were divided into higher and lower strain groups according to their job strain scores. The number of CD4+ CD45RA+ T lymphocytes in the higher strain group having the job strain score of 0.5 or more (41 workers) was significantly smaller than that in the lower strain group having the score of less than 0.5 (75 workers). In contrast, the serum IgG concentration in the former group was significantly higher than that in the latter group (analysis of covariance with age and smoking as covariates). Also, the numbers of total CD4+ T and total T (CD3+) lymphocytes and of white blood cells in the former group were significantly smaller than those in the latter group. After controlling for age and smoking by the partial correlation coefficient in all 116 workers, the number of CD57+ CD16+ natural killer cells was inversely correlated with job demand and with job strain; the number of CD8+ T lymphocytes was positively correlated with worksite social support; and serum IgG and IgM concentrations were positively correlated with job strain. It is suggested that higher job strain decreases the number of CD4+ CD45RA+ T lymphocytes in male Japanese workers but increases serum IgG concentrations.

Adult↗

PubMed2000

Immunotherapy prevents recurrent abortion without influencing natural killer receptor status.

PROBLEM: We assessed the expression of natural killer (NK) receptors in recurrent aborters before and after immunotherapy using their husbands' peripheral blood mononuclear cells (PBMCs). METHOD OF STUDY: Using stored PBMCs from recurrent aborters before and after the immunotherapy, the expression of NK receptors, CD158a, CD158b, CD159 and CD94, were analyzed using monoclonal antibodies for respective receptors. The diversity of killer activatory receptors (KARs) and killer inhibitory receptors (KIRs) was also examined using reverse transcriptase-polymerase chain reaction (RT-PCR)-single strand conformation polymorphism (SSCP) method. RESULTS: In recurrent aborters, no apparent changes in NK receptor expression and the balance between KARs and KIRs were found before and after the immunotherapy. CONCLUSION: The allo-human leukocyte antigen (HLA)-stimulation caused by the immunotherapy for recurrent aborters did not affect the expression of NK receptors and the ratio of KARs to KIRs regardless of the outcome of subsequent pregnancies, suggesting that recurrent aborters may benefit from the immunotherapy through mechanisms unrelated to alteration in NK receptor status.

Abortion, Habitual↗

PubMed2000

Theoretical basis for herbal medicines, Tokishakuyaku-san and Sairei-to, in the treatment of autoimmunity-related recurrent abortion by correcting T helper-1/T helper-2 balance.

PROBLEM AND METHOD OF STUDY: To get insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate T helper-1 (Th1) and T helper-2 (Th2) cytokine release from peripheral blood mononuclear cells (PBMCs). The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a non-classical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Toki and Sai increased the release of Th1 group cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma while preserving the inhibitory effect of HLA-G on the release of these cytokines. As for Th2 group cytokine release, Toki was without effect in modulating interleukin (IL)-4 release, regardless of the presence of HLA-G, whereas Sai nullified the effect of the presence of HLA-G to stimulate the release of IL-4 without affecting its release in the absence of HLA-G. CONCLUSION: Toki and Sai may have therapeutic potential, particularly in autoimmunity-related recurrent abortion where Th2 response is pathologically enhanced, but not in recurrent abortion involving alloimmune fetomaternal derangement, a condition of, rather, an enhanced Thl response.

Abortion, Habitual↗