Biomedical subjects

N Horimoto

Publications and source records attributed to N Horimoto.

At least 19 recordsLinked to original sources

PubMed2001

Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure.

Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels are activated by various metabolic stresses, including hypoxia. The substantia nigra pars reticulata (SNr), the area with the highest expression of K(ATP) channels in the brain, plays a pivotal role in the control of seizures. Mutant mice lacking the Kir6.2 subunit of K(ATP) channels [knockout (KO) mice] were susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the postsynaptic K(ATP) channels, whereas in KO mice, the activity of these neurons was enhanced. K(ATP) channels exert a depressant effect on SNr neuronal activity during hypoxia and may be involved in the nigral protection mechanism against generalized seizures.

Adenosine Triphosphate↗

PubMed2001

Diurnal variation of eye movement and heart rate variability in the human fetus at term.

To elucidate diurnal variations in eye movement and fetal heart rate (FHR) variability in the term fetus, we observed these two parameters continuously for 24 h, using real-time ultrasound and Doppler cardiotocograph, respectively. Studied were five uncomplicated fetuses at term. The time series data of the presence and absence of eye movement and mean FHR value for each 1 min were analyzed using the maximum entropy method (MEM) and subsequent nonlinear least squares fitting. According to the power value of eye movement, all five cases were classified into two groups: three cases in the large power group and two cases in the small power group. The acrophases of eye movement and FHR variability in the large power group were close, thereby implying the existence of a diurnal rhythm in both these parameters and also that they are synchronized. In the small power group, the acrophases were separated. The synchronization of eye movement and FHR variability in the large power group suggests that these phenomena are governed by a common central mechanism related to diurnal rhythm generation.

Adult↗

PubMed2001

Diurnal changes in the power spectral characteristics of eye movements and heart rate variability in the human fetus at term.

It is well known that 1/f characteristics in power spectral patterns exist in various biological factors including heart rate variability. In the present study, we tried to elucidate the diurnal variation in spectral properties of eye movement and heart rate variability in the human fetus at term, via continuous 24-h observation of both these parameters. Studied were five uncomplicated fetuses at term. We observed eye movement and fetal heart rate (FHR) with real-time ultrasound and Doppler cardiotocograph, respectively, and analyzed the diurnal change in spectral properties, using the maximum entropy method. In four of five cases, the slope values of power spectra for both eye movement frequency and FHR, ranging approximately between 0.5 and 1.8, indicated diurnal variation, where the slopes tended to have high values during the day and low values at night. These findings suggest that, in the human fetus at term, eye movement and FHR are under the control of a common central mechanism, and this center changes its complexity as seen through diurnal rhythm.

Adult↗

PubMed2000

Measurement of glucose uptake and intracellular calcium concentration in single, living pancreatic beta-cells.

There has been no method previously to measure both glucose transport and its effect on the various intracellular functions in single, living mammalian cells. A fluorescent derivative of d-glucose, 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG), that we have developed has made such measurements possible. COS-1 cells that overexpress the human glucose transporter GLUT2 show significantly greater 2-NBDG uptake than mock transfected cells. Using GLUT2-abundant mouse insulin-secreting clonal MIN6 cells, we found that 2-NBDG was incorporated into the cells in a time- and concentration-dependent manner. The 2-NBDG uptake was inhibited by high concentrations of d-glucose in a dose-dependent manner and also was almost completely inhibited by 10 micrometer cytochalasin B. We then measured both glucose uptake and the intracellular calcium concentration ([Ca(2+)](i)) in single, living pancreatic islet cells. 2-NBDG and fura-2 were used as the tracer of glucose and indicator of intracellular calcium, respectively. All of the cells that showed an increase in [Ca(2+)](i) in response to a high concentration of glucose (16.8 mm) rapidly incorporated significant 2-NBDG. Immunocytochemical examination confirmed these cells to be insulin-positive beta-cells. All of the cells that showed no significant, rapid 2-NBDG uptake lacked such glucose responsiveness of [Ca(2+)](i), indicating that these cells were non-beta-cells such as glucagon-positive alpha-cells. These results show the uptake of glucose causing a concomitant increase of [Ca(2+)](i) in beta-cells. Because 2-NBDG is incorporated into mammalian cells through glucose transporters, it should be useful for the measurement of glucose uptake together with concomitant intracellular activities in many types of single, living mammalian cells.

Animals↗

PubMed1997

Arachidonic acid activation of potassium channels in rat visual cortex neurons.

We investigated the effects of arachidonic acid on K+ channels in freshly dissociated neurons of 10- to 20-day-old rat visual cortex, using a perforated and conventional whole-cell patch-clamp and inside-out excised patch configurations. Arachidonic acid at 5-30 microM induced an outward current in 88.1% of the neurons in whole-cell mode, and evoked channel opening with a conductance of 170-238 pS in 90.5% of neurons under inside-out patch recording. Arachidonic acid-activated K+ channels were partially blocked by extracellular administration of 1 mM tetraethylammonium and 100 nM charybdotoxin. However, Ba2+ completely blocked the channel in all cases. None of the other K+ channel blockers, including 4-aminopyridine, quinidine, apamin and glibenclamide, inhibited the arachidonic acid-activated channels. Intracellular perfusion with Ca2+-free and 5 mM BAPTA in Ca2+-free extracellular perfusate containing 2 mM EGTA in conventional whole-cell recording did not inhibit the K+ channel, implying that the channel is not Ca2+ dependent. Neither guanosine 5'-O-(2-thiodiphosphate) nor staurosporine applied in inside-out mode affected the arachidonic acid-activated channels, indicating that G-protein and protein kinase C are not involved in this phenomenon. In addition, neither indomethacin nor nordihydroguaiaretic acid blocked the channel currents, demonstrating that it is arachidonic acid itself but not its metabolites that induced the effect. Among the fatty acids tested, only cis-unsaturated fatty acids, having more than two double bonds, such as arachidonic acid, docosahexaenoic acid and linolenic acid, activated the K+ channels. These findings suggest that there exists a novel type of K+ channel activated by arachidonic acid which may play a critical role in modulating neuronal excitability in cortical neurons.

4-Aminopyridine↗

PubMed1996

Developmental changes in arachidonic acid potentiation of NMDA currents in cortical neurones.

Developmental changes in the effects of arachidonic acid (AA) on N-methyl-D-aspartate (NMDA) receptor-mediated currents were investigated in acutely dissociated rat cortical neurones using a whole-cell patch-clamp method. AA potentiated peak NMDA currents (INMDA) in a concentration-dependent manner. Potentiation by AA was greater at 2-4 postnatal days (P2-4) than at P7-8 and P15-18. Indomethacin reduced the potentiating effect of AA only at P2-4, while caffeic acid and baicalein showed no apparent effect, indicating that metabolites of the cyclooxygenase pathway contribute to INMDA potentiation at P2-4. Staurosporine diminished the potentiation of INMDA at P2-4, suggesting that protein kinase C might participate in the effect of AA. These findings suggest that the greater potentiation of INMDA by AA at P2-4 has a different underlying mechanism from effects seen at P7-8 or older.

Animals↗

PubMed1996

Alpha 1 adrenoceptor activation potentiates taurine response mediated by protein kinase C in substantia nigra neurons.

1. The potentiation of glycine receptor-mediated taurine response (Itau) by alpha 1 adrenoceptor activation was investigated in neurons freshly dissociated from the rat substantia nigra (SN) using a nystatin perforated-patch recording. 2. Norepinephrine (NE) at a concentration of 10(-4) M in the presence of 10(-5) M yohimbine and 10(-5) M propranolol potentiated the peak amplitude of Itau (10(-3) M) at a holding potential of -40 mV under voltage clamp conditions. NE could be substituted by phenylephrine at this potentiation. 3. This potentiation of the taurine response persisted in the treatment with pertussis toxin (500 ng/ml) for 18 h. The intracellular application of GDP-beta S (100 microM) with a conventional whole cell patch recording mode abolished the effect of alpha 1 adrenoceptor activation on the Itau. 4. Staurosporine (10(-7) M) blocked the enhancement of Itau by 10(-4) M NE with 10(-5) M yohimbine and 10(-5) M propranolol. In additional phorbol-12-myristate 13-acetate (10(-5) M) potentiated Itau. 5. The intracellular application of 0.275 U/ml protein kinase C (PKC) with a conventional whole cell configuration gradually increased the peak amplitude of Itau. On the other hand, intracellular perfusion either without PKC or with PKC plus 4 microM PKC (19-36), a PKC inhibitor, did not potentiate Itau. 6. A single channel recording in a cell attached configuration revealed that NE (10(-4) M) with 10(-5) M yohimbine and 10(-5) M propranolol increased the total open time of the taurine-activated channel. This increase of the channel opening was antagonized by staurosporine (10(-7) M). 7. Neither tapsigargin (10(-6) M), LiCl (10(-4) M), trifluoperazine (10(-5) M) nor (S)-5-isoquinolinesulfonic acid, 4-[2-[(5-isoquinolinylsulfonyl) methylamino]-3-oxo-(4-phenyl-1-piperazinyl)-propyl]phenyl ester (10(-4) M) applied in the perfusate were found to affect the potentiation of Itau by alpha 1 adrenoceptor. The intracellular application of inositol triphosphates (10(-4) M) in a conventional whole cell recording also had no effect on Itau. 8. These findings thus indicate that alpha 1 adrenoceptor coupled with pertussis-insensitive G protein increases the intracellular PKC activity, thus leading to an increase in the channel opening activated by taurine and an enhancement of the peak amplitude of Itau in the SN neurons.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1995

Developmental change of the potentiation of NMDA response by spermine.

Developmental change in the potentiation of N-methyl-D-aspartate (NMDA) responses by spermine was investigated on the ventromedial hypothalamic neurones acutely dissociated from the rats aged between 5 and 21 days, using a nystatin perforated patch clamp recording in a whole cell mode. Spermine potentiated the NMDA response in a concentration dependent manner between 10(-5) M and 10(-5) M at all ages examined. This potentiation decreased significantly with age. On the other hand, spermine did not affect the kainate and AMPA responses at any age. This developmental change of the modulation of NMDA responses might influence to or be influenced by the behavioural and neuronal changes related to the VMH in the early postnatal life.

Aging↗

PubMed1995

Penile tumescence in the human fetus at term--a preliminary report.

The aim of this study is to reveal whether the penis per se actually becomes tumescent and flaccid, in time sequence, in the human fetus at term. We observed the fetal penis with real-time ultrasonography in 50 male human fetuses at 36-39 weeks' gestation and measured the penile length once at a given time per 1-min epoch for each case during the 60-min window of examination. Thirty-eight were excluded due to a lack of continuous ultrasound visualization of the penis. Penile length changes were statistically analyzed for the remaining 12 fetuses using the 'least median of squares regression'. Penile length was seen to be significantly stratified into two groups: 22.5% at tumescence (group median = 20.8 mm) and 77.5% at flaccidity (group median = 16.0 mm). Penile tumescence was found to occur at the following frequency during the given observation period: once in 41.7%, twice in 50.0% and three times in 8.3% with durations ranging from 5 to 17 min. These findings indicate penile tumescence exists in the term fetus. The frequency and duration of penile tumescence are in good correlation with neonates.

Fetus↗

PubMed1995

Breech presentation: is there a difference in eye movement patterns compared with cephalic presentation in the human fetus at term?

OBJECTIVE: Our purpose was to characterize eye movement patterns in the human fetus at term persisting in breech presentation. STUDY DESIGN: Studied were 11 fetuses in breech presentation and 12 in cephalic presentation at 36 to 41 weeks' gestation, of which the presentation remained unchanged from 32 weeks' gestation until delivery. With real-time ultrasonography we analyzed three measurements by means of the Mann-Whitney rank-sum test: (1) duration of eye-movement and no-eye-movement periods, (2) frequency of eye movements, and (3) proportion of horizontal, vertical, and oblique eye movements. RESULTS: There were significant differences in the eye movement directions between breech and cephalic fetuses: horizontal (median 70.3% vs 80.2%), vertical (17.4% vs 11.0%), and oblique (13.1% vs 9.1%), respectively. No differences were noted in the duration of eye-movement and no-eye-movement periods or in the frequency of eye movements. CONCLUSION: Eye movement pattern, in direction, of term fetuses persisting in breech presentation run on a different in-utero developmental course of neural control from those in cephalic fetuses.

Breech Presentation↗

PubMed1995

Heterogeneous development of voltage dependency of NMDA receptor-mediated response in central nervous system.

Developmental changes of voltage dependency of NMDA response were investigated on nucleus solitarii (NTS) ventromedial hypothalamic (VMH) and visual cortical neurons acutely dissociated from rats aged between 19 days in gestation (E19) and 21 days after birth (P21) using a whole cell patch clamp recording. Sensitivity of NMDA response to extracellular Mg2+ developed by P3 in the NTS, by P6 in the VMH and by P6 in the VMH and by P12 in the VMH and by P12 in the cortex, Protein kinase C modulators could not modulate the voltage dependency of NMDA response in immature neurons. These finding suggest that a regional heterogeneity of developmental change of the sensitivity of NMDA response to extracellular Mg2+ exists. This regional difference in development of NMDA response might be related to the order of vital necessities after birth.

Animals↗

PubMed1994

Fetal heart rate variation described using a probability distribution matrix.

We devised a new method using a probability distribution matrix to simultaneously describe variation in the characteristics of fetal heart rate (FHR) and beat-to-beat difference (DFHR) between the present and the immediately following FHR. The FHRs were plotted in columns, DFHRs in rows and probabilities in the corresponding elements of the matrix. The age-related changes of FHR data obtained from 743 fetuses at 23-40 weeks gestation were analysed using a pulsed Doppler cardiotocograph with an autocorrelation system. While keeping an almost symmetrical spread around 0 beats/min of DFHR, three particular probability distribution patterns of FHR versus DFHR emerged with advance in gestation: (i) oval with a monomodal peak from 23/24 to 29/30 weeks, (ii) ellipsoid with a monomodal peak and plateau from 31/32 to 33/34 weeks and (iii) elongated ellipsoid with bimodal peaks from 35/36 weeks of gestation onwards. The probability distribution matrix presented enables one to condense any amount of FHR data into one uniform description. This allows analysis of data, en bloc, achieving a quantitative inter-group comparison, on an equivalent scale.

Age Factors↗

PubMed1993

Fetal eye movements.

Since 1981, when eye movements of the human fetus were first reported, the study of fetal eye movements has increased, mainly focusing on the ontogenesis of eye movements and as one parameter of behavioral states. Using real-time ultrasound, fetal eye movements can be clearly observed from 14 weeks of gestational age. Fetal eye movements may be described in terms of their pattern, frequency and incidence of periods containing eye movements and no eye movements. Furthermore, the relationship of eye movements to other behaviors may be used to give information on the integration of central nervous system function. A picture of normal fetal eye movements can be constructed and used to detect abnormalities in eye movements which can indicate underlying abnormalities of the central nervous system. This paper concludes that, although in its early stages, the study of fetal eye movements holds promise for a greater understanding of brain development and the assessment of the condition of the fetus.

Journal Article↗

PubMed1993

Can brain impairment be detected by in utero behavioural patterns?

Fetal behavioural patterns were examined to test whether they could be used to localise sites of brain damage antenatally. Decreased fetal movement, persistent nonreactive fetal heart rate (FHR) pattern, and/or central nervous system malformation were used as indicators of possible neurological impairment. Ten fetuses tested in this way underwent further ultrasound examination observing movement of the extremities, chest wall (breathing), and eye and mouth, and active/quiet FHR patterns. Eight of these 10 fetuses were found on postnatal examination to have a brain impairment. The fetuses having potential in utero brain impairment were divided into four groups: those with (1) lesion sites at, or caudal to, the pons-medulla that were specifically identified by fetal behaviour, (2) diffuse lesions in the brain which, although resulting in abnormal behaviour, could not be localised by this behaviour, (3) lesions localised in the cerebral hemisphere(s) but with no abnormal behaviour and (4) temporally abnormal behaviour in utero, finally changing over to a normal pattern with no neonatal neurological abnormality. A screening system for the antenatal assessment of brain impairment is thus proposed.

Brain Damage, Chronic↗

PubMed1993

Abnormal behavioral patterns in the human fetus at term: correlation with lesion sites in the central nervous system after birth.

We describe three fetuses at term that demonstrated abnormal behavioral patterns in utero when observed using real-time ultrasound. The abnormal patterns turned out to have neurologic correlations after birth. In case 1, despite a normal breathing pattern, no movement in any of the four extremities was observed, thus suggesting the existence of a spinal cord lesion at the rostral end, located at C4 or C5. In case 2 a lack of breathing movement was noted repeatedly, together with the abnormal finding that alternation of periods of rapid eye movement (REM) sleep with those of non-rapid eye movement (NREM) sleep was not present. These findings implied a lesion involving the pons and/or medulla oblongata. In case 3 movement of the four extremities, breathing movement, and alternating periods of REM sleep and NREM sleep were found to be within the normal range. The concurrence of regular mouthing and the NREM sleep period was not observed, however, suggesting impairment in the brain function responsible for NREM sleep located from the pons through the thalamocortical connection to the cerebral hemisphere.

Adult↗

PubMed1992

The temporal relationship between the onset of rapid eye movement period and the first micturition thereafter in the human fetus with advance in gestation.

The objective of this study was to investigate whether micturition occurs, temporally related to the onset of the rapid eye movement (REM) period, in the human fetus. The study was made on 139 fetuses at 33-36 weeks and 153 at 37-41 weeks gestation. The discrepancies between the expected (F(exp)) and observed (F(obs)) frequencies of time lag between the onset of the REM period and the first micturition thereafter were assessed using the goodness-of-fit test. At 33-36 weeks gestation, there was no statistical difference between F(obs) and F(exp) (P greater than 0.05). At 37 weeks onwards, however, significant differences were noted between F(obs) and F(exp) (P less than 0.005). Seventy-two percent of all micturitions occurred within eight minutes after the onset of the REM period. This indicates that there is a temporal relationship between the onset of the REM period and the first micturition thereafter, at term, during 37-41 weeks of gestation.

Embryonic and Fetal Development↗

PubMed1992

Changes in pupillary diameter in relation to eye-movement and no-eye-movement periods in the human fetus at term.

OBJECTIVE: The aim of our study was to reveal whether pupils dilate and constrict in a time sequence in the human fetus and to assess the relationship between changes in pupillary diameter and eye-movement-no-eye-movement periods. STUDY DESIGN: We simultaneously observed pupil and eye movement with real-time ultrasonography in 30 human fetuses at 36 to 41 weeks' gestation. Eighteen were excluded because of data loss. Statistical analysis of pupillary diameter changes were made on the remaining 12 fetuses with the least median of squares regression. RESULTS: Pupillary diameters were found to be differentiated with statistical significance into two groups: 9.7% for the dilated pupil (median 3.0 mm) and 90.3% for the constricted pupil (1.7 mm). The percentage of dilated pupils during the eye-movement period (14.3%) was significantly greater than that during the no-eye-movement period (2.3%; Wilcoxon rank sum test, p < 0.0001). CONCLUSION: These findings indicate a close relation between pupillary dilatation and eye-movement periods in the human term fetus.

Eye Movements↗

PubMed1992

[The in utero determination of lesion site affecting the central nervous system assessed by abnormal behavioral patterns in the human fetus].

In order to reveal whether or not brain impairment occurs in the human fetus during the intrauterine period, we described three term fetuses, having successful prenatal diagnosis of localized brain lesion, through the real-time ultrasound observation of in utero behavioral patterns. Movement of extremities, breathing movement, alternation of REM (rapid eye movement) and NREM (non-rapid eye movement) periods, and the concurrence of regular mouthing movement with the NREM period were used as parameters. Despite normal breathing movement patterns, in case 1, there were no movements observed in any of the four extremities, thereby suggesting impairment of the spinal cord at and below C5. This diagnosis was compatible with the neonatal MRI findings which showed a well circumscribed hyperintensity located at C5-6. In case 2, the repeated lack of breathing movement was noted, combined with the absence of alternation of the REM/NREM period, implying a lesion involved the pons and/or medulla oblongata. Our diagnosis was in good accordance with the actual neonatal CT findings, which showed a calcified lesion spreading from the pons to medulla oblongata. As for case 3, although movement of extremities, breathing movement and REM/NREM period alternation were all found to be within the normal range, there was no concurrence between regular mouthing and the NREM period. This suggested impairment of brain function responsible for NREM sleep, located from the pons through the thalamocortical connection to the cerebral hemisphere. Neonatal CT were found to be in agreement, by indicating a lesion, diffusely involving the cerebral white matter.

Adult↗