Biomedical subjects

A Miki

Publications and source records attributed to A Miki.

At least 19 recordsLinked to original sources

PubMed2006

Gastrointestinal Candida colonisation promotes sensitisation against food antigens by affecting the mucosal barrier in mice.

BACKGROUNDS AND AIMS: Controversy still exists as to whether gastrointestinal colonisation by Candida albicans contributes to aggravation of atopic dermatitis. We hypothesised that Candida colonisation promotes food allergy, which is known to contribute to a pathogenic response in atopic dermatitis. We tested this using a recently established murine Candida colonisation model. METHODS: Candida colonisation in the gastrointestinal tract was established by intragastric inoculation with C albicans in mice fed a synthetic diet. To investigate sensitisation against food antigen, mice were intragastrically administered with ovalbumin every other day for nine weeks, and antiovalbumin antibody titres were measured weekly. To examine gastrointestinal permeation of food antigen, plasma concentrations of ovalbumin were measured following intragastric administration of ovalbumin. RESULTS: Ovalbumin specific IgG and IgE titres were higher in BALB/c mice with Candida colonisation than in normal mice. Gastrointestinal permeation of ovalbumin was enhanced by colonisation in BALB/c mice. Histological examination showed that colonisation promoted infiltration and degranulation of mast cells. Candida colonisation did not enhance ovalbumin permeation in mast cell deficient W/Wv mice but did in congenic littermate control +/+ mice. Reconstitution of mast cells in W/Wv mice by transplantation of bone marrow derived mast cells restored the ability to increase ovalbumin permeation in response to Candida colonisation. CONCLUSIONS: These results suggest that gastrointestinal Candida colonisation promotes sensitisation against food antigens, at least partly due to mast cell mediated hyperpermeability in the gastrointestinal mucosa of mice.

Animals↗

PubMed2006

Metabolism of the recently encountered designer drug, methylone, in humans and rats.

The urinary metabolites of methylone in humans and rats were investigated by analysing urine specimens from its abuser and after administrating to rats with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS), using authentic standards. The time-course excretion profiles of methylone and its three metabolites in rats were further investigated after a single intraperitoneal dosing of 5 mg kg-1 methylone hydrochloride. Two major metabolic pathways were revealed for both humans and rats as follows: (1) side-chain degradation by N-demethylation to the corresponding primary amine methylenedioxycathinone (MDC), partly conjugated; and (2) demethylenation followed by O-methylation of either a 3- or 4-OH group on the benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3-hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC), respectively, mostly conjugated. Of these metabolites, HMMC was the most abundant in humans and rats. The cumulative amount of urinary HMMC excreted within the first 48 h in rats was approximately 26% of the dose, and the amount of the parent methylone was not more than 3%. These results demonstrate that the analysis of HMMC will be indispensable for proof of the use of methylone in forensic urinalysis.

Adult↗

PubMed2006

Dosage adjustment of quinolone antibiotics and angiotensin-converting enzyme inhibitors in patients with renal dysfunction.

The aim of this study was to verify an approach for calculating pharmacokinetic parameters suitable for adjusting dosage regimens in patients with renal dysfunction. We carried out a retrospective analysis of the pharmacokinetic profiles of 12 new quinolone antibiotics and 11 angiotensin-converting enzyme inhibitors (ACEIs) in patients with normal and impaired renal function to obtain the renal excretion ratio (R(renal)) of each drug. We demonstrated that the pharmacokinetics of each drug in a patient with renal dysfunction can be adequately estimated using the R(renaI) value of each drug together with the creatinine clearance as an index of the individual's renal function. Using the R(renaI) value obtained, we could successfully simulate pharmacokinetic profiles of the drugs in publications other than that used to obtain the R(renal) values. On the other hand, age-related changes in the pharmacokinetics of new quinolone antibiotics are not always adequately predicted using the R(renal) value compared to using creatinine clearance alone as an index, and the reasons for this are not fully understood. These results demonstrate that dosage regimens of quinolone antibiotics and ACEIs in patients with renal dysfunction can be adequately optimized using the R(renal) value for each drug using the present approach.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Magnocellular and parvocellular visual pathways have different blood oxygen level-dependent signal time courses in human primary visual cortex.

PURPOSE: The magnocellular and parvocellular pathways (M and P pathways) are the major pathways of the visual system, with distinct histologic and physiologic properties that may also have different metabolic characteristics. We hypothesize that the differences of the 2 visual pathways would also manifest as differences in the signal time course of blood oxygen level-dependent functional MR imaging (BOLD fMRI). The differences in BOLD signal time course may provide insight into the metabolic requirements of the 2 pathways. METHODS: Eleven fMRI sessions on 6 subjects were performed using stimuli that preferentially activated the 2 pathways. Regions commonly activated by both the M and P stimuli in the primary visual cortex (V1) were determined, and the contrast elicited by the stimulus, time-to-peak (TTP), and the full width at half maximum (FWHM) of the BOLD signal time course were measured. RESULTS: The functional stimuli activated cortical regions described previously in the literature, such as V1, V4, and V5. Within V1, the TTP of the signal time course of the 2 stimuli were statistically different, with the P stimulus generating TTPs that were on average 12% faster than the M stimulus (P = .0037). CONCLUSION: We have demonstrated the ability to functionally differentiate the M and P stimuli in a commonly activated anatomic region. Because the BOLD response is dependent on the ratio of oxyhemoglobin and deoxyhemoglobin in the blood, the difference in the BOLD time course between the 2 stimuli suggests that the oxygen demand of the 2 pathways may be different.

Brain Mapping↗

PubMed2005

Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats.

The metabolism of 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a recently banned designer drug, in rats was studied by analysing its urinary metabolites. p-Hydroxy-TFMPP (p-OH-TFMPP) was isolated and identified as the main metabolite by using nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of TFMPP and p-OH-TFMPP in rats were investigated following a single intraperitoneal dosing of 5 mg kg(-1) TFMPP by using an optimized analytical procedure that combined solid-phase extraction and LC-ESI MS techniques. The cumulative amount of p-OH-TFMPP excreted within the first 48 h reached approximately 64% of the dose, of which 70% was the glucuronide conjugated form. The cumulative amount of parent TFMPP excreted was less than 0.7% of the dose. The results suggest that p-OH-TFMPP would be the most relevant metabolite to be detected for TFMPP exposure in the forensic and clinical analysis of human urine.

Animals↗

PubMed2004

Comparison of the collecting efficiency of microbiological air samplers.

It is important to evaluate the prevention of nosocomial infections caused by airborne micro-organisms in healthcare facilities. For that purpose, the use of an air sampler is required. A comparison of the collecting efficiency of air samplers has not been studied so far using a single culture medium. Use of the same culture medium is necessary because of the variation of the cultivation efficiency with different culture media. In this study a statistically significant difference in collecting efficiency among air samplers was observed in case of SCDA (soybean casein digest agar) culture medium, but not SCDALP (soybean casein digest agar lecithin polysorbate) culture medium. In addition, a statistically significant difference of the cultivation efficiency was observed between SCDA and SCDALP culture media (P<0.05). These results suggest that any air sampler can be used with SCDALP culture medium.

Air Microbiology↗

PubMed2003

Betaxolol-induced deterioration of asthma and a pharmacodynamic analysis based on beta-receptor occupancy.

OBJECTIVE: To report a case of deterioration of asthma associated with continuous use of oral betaxolol, a beta1-selective beta-blocking agent. We also analyzed the pharmacokinetics in this case by applying a receptor occupancy model. CASE SUMMARY: A 68-year-old woman taking 5 mg of betaxolol for hypertension occasionally experienced asthmatic coughing after upper respiratory tract infection. Two years after the start of betaxolol, her asthma gradually worsened. Although pharmacotherapy for asthma was introduced, betaxolol was continued. Finally, she was admitted to hospital with bronchospasm. When she was discharged after 2 months, betaxolol was discontinued and losartan potassium (25 mg/d) was initiated instead for her hypertension. Since then, she has been free from bronchospasm. METHOD: We calculated the mean receptor occupancy (phiSS) of the beta1- and beta2-receptors after the usual oral dose of betaxolol by using pharmacokinetic-pharmacodynamic parameters obtained from the literature. We estimated the decrease in the exercise pulse rate or the forced expiratory volume in 1 second (FEV1) by applying the phiSS values to the model previously reported by us. RESULTS: Betaxolol seems less likely than other beta1-blocking agents to cause pulmonary adverse effects. However, the estimated decrease in FEV1 after oral administration of betaxolol (5 mg) was close to that after oral bisoprolol (5 mg), which has been reported to induce asthma. CONCLUSIONS: Oral betaxolol may induce bronchospasm, although betaxolol is considered to be highly cardioselective and seems less likely than other beta1-selective blocking agents to cause pulmonary adverse effects. Betaxolol should be administered with caution to patients with asthma or chronic pulmonary disease.

Administration, Oral↗

PubMed2002

Urinary excretion of selegiline N-oxide, a new indicator for selegiline administration in man.

1. The metabolism of selegiline (SG) has been studied by investigating the time-course of urinary excretion of SG and its metabolites using high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS) in combination with solid-phase extraction. 2. The excretion profiles of SG and its four major metabolites, selegiline-N-oxide (SGO), N-desmethylselegiline (DM-SG), methamphetamine (MA) and amphetamine (AP), were investigated in six healthy volunteers after oral administrations of SG hydrochloride in a single dose of 2.5 or 7.5mg, and a repeat twice-daily dose of 5.0 mg day(-1) (for 3 days). 3. The cumulative amount of SGO excreted within approximately the first 8-12h was comparable with MA, and the amount in the first 72 h was 2.0-7.8 times larger (2.8-13.2% of the dose) than that of DM-SG. 4. These results demonstrate that SGO can be used in place of DM-SG, which is known to be a main specific metabolite of SG, as a new indicator for the discrimination of SG use compared with MA abuse.

Adrenergic Uptake Inhibitors↗

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↗