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Biomedical subjects

Koji Inui

Publications and source records attributed to Koji Inui.

At least 19 recordsLinked to original sources
PubMed2004

In vivo studies of phenylalanine hydroxylase by phenylalanine breath test: diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.

Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg . kg(-1) . d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.

Adolescent↗
PubMed2004

Effects of citrin deficiency in the perinatal period: feasibility of newborn mass screening for citrin deficiency.

Deficiency of citrin due to mutations of the SLC25A13 gene causes adult-onset type II citrullinemia (CTLN2) and one type of neonatal intrahepatic cholestasis (NICCD). About half of the NICCD patients are detected based on high galactose, phenylalanine, and/or methionine concentrations on newborn mass screening (NMS). To clarify the perinatal and neonatal effects and the inconsistent results on NMS, we examined aminograms, the levels of bile acids and galactose in dried blood spots for NMS from 20 patients with NICCD. Birth weight was low for gestational age (-1.4 +/- 0.7 SD). Affected fetuses may have suffered intrauterine citrin deficiency. The first abnormality detected after birth was citrullinemia, and 19 of 20 patients had citrulline levels higher than +2 SD of controls. Tyrosine, phenylalanine, methionine, galactose, and bile acids were less affected than citrulline on d 5 after birth. Galactose and bile acids levels were increased at 1 mo in comparison with d 5 after birth due to impairment of the cytosolic NADH reducing-equivalent supply into mitochondria of hepatocytes. Patients with negative findings on NMS had low levels of total 20 amino acids. Citrulline/serine, citrulline /leucine plus isoleucine, and citrulline/total amino acids ratios, controlled for the confounding effect of low amount of total amino acids, were higher in all patients than +2 SD, +2 SD, and +3 SD of controls, respectively. NMS for citrin deficiency (frequency of homozygote with SLC25A13 mutation: 1/10,000-1/38,000 in East Asia) will be useful for clarification of the clinical course, treatment, and prevention of this disease.

Amino Acids↗
PubMed2004

Temporal dynamics of neural adaptation effect in the human visual ventral stream.

When the same visual stimulus is repeatedly presented with a brief interval, the brain responses to that stimulus are attenuated relative to those at first presentation [neural adaptation (NA)]. Although this effect has been widely observed in various regions of human brain, its temporal dynamics as a neuronal population has been mostly unclear. In the present study, we used a magnetoencephalography (MEG) and conducted a macrolevel investigation of the temporal profiles of the NA occurring in the human visual ventral stream. The combination of MEG with our previous random dot blinking method isolated the neural responses in the higher visual cortex relating to shape perception. We dissociated three dimensions of the NA: activation strength, peak latency, and temporal duration of neural response. The results revealed that visual responses to the repeated compared with novel stimulus showed a significant reduction in both activation strength and peak latency but not in the duration of neural processing. Furthermore, this acceleration of peak latency showed a significant correlation with reaction time of the subjects, whereas no correlation was found between the reaction time and the temporal duration of neural responses. These results indicate that (1) the NA involves the brain response changes in the temporal domain as well as the response attenuation reported previously, and (2) this temporal change is primarily observed as a rapid rising of "what" responses, rather than a temporal shortening of neural response curves within the visual ventral stream as considered previously.

Adult↗
PubMed2004

Analysis of recombinant human saposin A expressed by Pichia pastoris.

Saposins (SAPs) are small glycoproteins required for activation of sphingolipid hydrolysis by lysosomal enzymes. Four SAPs, SAP-A, -B, -C, and -D, are proteolytically cleaved from a single gene product termed prosaposin. The mature coding sequence of human SAP-A tagged with 6-histidine was expressed in Pichia pastoris and the recombinant protein was purified from the culture supernatant by simple purification steps with an immobilized metal ion affinity column, a Concanavalin A column, and reversed-phase HPLC. Secreted SAP-A contained both glycosylated and nonglycosylated forms. Both forms of SAP-A activated galactocerebroside and 4-methylumbelliferyl beta-d-glucoside hydrolysis by galactocerebrosidase and glucocerebrosidase. SAP-A expressed in P. pastoris should be useful for further structural and functional analysis of this protein.

Amino Acid Sequence↗
PubMed2004

Serial processing in the human somatosensory system.

Although numerous anatomical and electrophysiological findings in animal studies have supported a hierarchical scheme of somatosensory processing, precise activation timings of each cortical area are not known. Therefore we examined the temporal relationship of activities among multiple cortical areas using magnetoencephalography in humans. We found activations in Brodmann's areas 3b, 4, 1, 5 and the secondary somatosensory cortex region in the right hemisphere following transcutaneous electrical stimulation of the dorsum of the left hand. The mean onset latencies of each cortical activity were 14.4, 14.5, 18.0, 22.4 and 21.7 ms, respectively. The differences of onset latencies among these activations indicated the serial mode of processing both through the postcentral gyrus and through the primary and secondary somatosensory cortices.

Adult↗
PubMed2004

Effects of a go/nogo task on event-related potentials following somatosensory stimulation.

OBJECTIVE: We investigated the effects of a go/nogo task on event-related potentials (ERPs) evoked by somatosensory stimuli. METHODS: ERPs following electrical stimulation of the second (go stimulus) or fifth (nogo stimulus) left-handed digit were recorded from 9 subjects. The recordings were conducted in 3 conditions: Control, Count and Movement. The subjects were instructed to count the go stimuli silently in Count, and respond to the go stimuli by grasping right hands in Movement. Go and nogo stimuli were presented at an even probability. RESULTS: N140 was recorded in all conditions and P300 in Count and Movement. The mean amplitudes of the nogo stimuli in the interval 140-200 msec and nogo-N140 amplitude were significantly more negative than those of the go stimuli in Count or Movement. Nogo-P300 was larger in amplitude than go-P300 in Movement but not Count. The effect of P300 was applied to Fz and Cz, but not at Pz. CONCLUSIONS: In the present study, effects of a somatosensory go/nogo task on ERPs were investigated, and our findings were very similar to those of previous studies using visual and auditory go/nogo tasks. Therefore, we suggest that cortical activities relating to go/nogo tasks are not dependent on sensory modalities. SIGNIFICANCE: The present study showed for the first time the go/nogo effects on somatosensory-evoked ERPs. These effects were similar to those in visual and auditory ERP studies.

Acoustic Stimulation↗
PubMed2004

Effects of distraction on magnetoencephalographic responses ascending through C-fibers in humans.

OBJECTIVE: Using magnetoencephalography (MEG), we evaluated the cerebral regions relating to second pain perception ascending through C-fibers and investigated the effect of distraction on each region. METHODS: Thirteen normal subjects participated in this study. CO2 laser pulses were delivered to the dorsum of the left hand to selectively activate C-fibers. The MEG responses were analyzed using a multi-dipole model. RESULTS: (1) primary somatosensory cortex (SI), and (2) secondary somatosensory cortex (SII)--insula were the main generators for the primary component, 1M, whose mean peak latency was 744 ms. In addition to (1) and (2), (3) cingulate cortex and (4) medial temporal area (MT) were also activated for the subsequent component, 2M, whose mean peak latency was 947 ms. During a mental calculation task (Distraction), all 6 sources were significantly reduced in amplitude, but the SII-insula (P < 0.01) and cingulate cortex (P < 0.001) were more sensitive than the SI (P < 0.05) and MT (P < 0.05). CONCLUSIONS: We confirmed that SI in the contralateral hemisphere and SII-insula, cingulate cortex and MT in bilateral hemispheres play a major role in second pain perception, and all sites were much affected by a change of attention, indicating that these regions are related to the cognitive aspect of second pain perception. SIGNIFICANCE: The SI, SII, cingulate and MT were activated during the C-fiber-related MEG response, and responses in these regions were significantly diminished during mental distraction.

Adult↗
PubMed2004

Cognitive processes in two-point discrimination: an ERP study.

OBJECTIVE: To elucidate the temporal features of the cognitive process in two-point discrimination (TPD). METHODS: We measured somatosensory event-related potentials (ERPs) in 9 subjects during the TPD task, in which we provided a pair of electrical pulses simultaneously, altering the distance between the electrodes. We analyzed the TPD-related ERPs and investigated the relationship between the potentials and the subjects' judgments. RESULTS: During the TPD task, a negative potential approximately 140 ms after the stimulation (N140) was enhanced as compared to a stimulus counting task. Two late positive components, LPC-1 and LPC-2, whose peak latencies were 300 and 500 ms, respectively, were identified only in the TPD task. The LPC-1 was recorded dominantly in the fronto-central area, while the LPC-2 was detected dominantly in the centro-parietal area. The amplitude of the LPC-2 was significantly modulated by the degree of consistency in the subjects' judgment. On the other hand, these ERP components did not show significant difference between the alternate judgments, i.e. 'one-point' or 'two-point' judgment. CONCLUSIONS: Our results suggest that the N140 is related to the attention toward the stimulation. The LPC-1 and LPC-2 are likely to correspond to the processes represented by P3a and P3b, based on their temporal and spatial behavior.

Adult↗
PubMed2004

Face representation in the human primary somatosensory cortex.

To investigate the representation of facial skin areas in the primary somatosensory cortex (SI), we recorded magnetic fields evoked by air pressure-induced tactile stimulation applied to six points on the face, lower lip and thumb. The thumb area in the SI was located more medial and superior to the lip area, which was consistent with Penfield's homunculus. However, the representations of all skin-covered areas including forehead, cheek, nose and chin in the SI were located between the thumb and lower lip area. There was no significant difference in location among the six facial points. Our results imply that lips occupy a large area of the face representation in the SI, whereas only a small area located between the thumb and lip areas is devoted to skin-covered surfaces. This is the first study showing that the facial skin areas in the human SI are located between the thumb and lower lip areas and close together.

Adult↗
PubMed2004

Movements modulate cortical activities evoked by noxious stimulation.

To evaluate the effects of movement on cortical activities evoked by noxious stimulation, we recorded magnetoencephalography following noxious YAG laser stimulation applied to the dorsum of the left hand in normal volunteers. Results of the present study can be summarized as follows: (1) active movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of both primary and secondary somatosensory cortices (SI and SII) in the hemisphere contralateral to the stimulated hand (cSI and cSII). Activity in the hemisphere ipsilateral to the side of stimulation (iSII) was not affected. (2) Active movement of the hand contralateral to the side of noxious stimulation resulted in significant attenuation of cSII. Activity in cSI and iSII was not affected. (3) Passive movement of the hand ipsilateral to the side of noxious stimulation resulted in significant attenuation of cSI. Activity in cSII and iSII was not affected. (4) Visual analogue scale (VAS) changes showed a similar pattern to the amplitude changes of cSII. These results suggest that activities in three regions are modulated by movements differently. Inhibition in cSI was considered to be mainly due to an interaction in SI by the signals ascending from the stimulated and movement hand. Inhibition in cSII was considered to be mainly due to particular brain activities relating to motor execution and/or movement execution associated with a specific attention effect. In addition, since VAS changes showed a similar relationship with the amplitude changes of cSII, cSII may play a role in pain perception.

Adult↗
PubMed2003

Microneurographic study of C fiber discharges induced by CO2 laser stimulation in humans.

We investigated C-fiber discharges and cerebral potentials evoked by weak CO(2) laser beams applied to a tiny skin area in five healthy subjects. Microneurography was performed from the peroneal nerve in the right popliteal area. Cerebral potentials were recorded from the Cz electrode referred to linked earlobes. The mean conduction velocity of five stable single units was 1.1+/-0.3 m/s. The mean latency of the positive peak of cerebral potentials was 1327.4+/-46.2 ms. These findings indicated that this new stimulation method selectively activated C-fiber nociceptors of the skin.

Adult↗
PubMed2003

Central mechanisms for two-point discrimination in humans.

We studied the cognitive mechanisms for two-point discrimination (TPD) in 11 normal subjects, using electrical pulses. We used six ball-shaped electrodes placed in line on the dorsal surface of the left hand, and two-point was stimulated by two electrodes randomly selected. We measured the reaction time for TPD and calculated the percentage of correct responses for each two-point stimulation. The subjects' response was significantly affected by the preceding stimuli as well as the distance of the stimuli: for a two-point stimulus condition, subjects tended to feel the stimuli as two-point when the distance between the stimuli was longer than that of preceding stimuli, whereas they felt the stimuli as one-point when the distance was shorter than that of the preceding stimuli. The present results indicate that the TPD process involved evaluation of the distance between the stimuli relatively to that of the preceding stimuli, as well as evaluation of absolute distance between the stimuli.

Adult↗
PubMed2003

Effects of sleep on pain-related somatosensory evoked potentials in humans.

We investigated effects of sleep on pain-related somatosensory evoked potentials (SEP) following painful electrical stimulation of the left index finger. The biggest advantage of this method is that signals ascending through both A-beta fibers relating to touch and A-delta fibers relating to pain can be recorded simultaneously. While the subject was awake, non-painful stimulation evoked early- and middle latency components, N20, P30 and N60, at the C4 electrode, and painful stimulation evoked not only early- and middle latency components at the C4 but also later pain-specific components, N130 and P240, at the Cz electrode. During sleep, N20 and P30 did not show a significant change in amplitude, N60 showed a slight but significant amplitude reduction, and N130 and P240 significantly decreased in amplitude or disappeared, as compared with those while awake. Therefore, we speculate on the mechanisms generating each component as follows; (1) N20 and P30 are the primary components generated in SI ascending through A-beta fibers. (2) N60 is the secondary component generated in SI involving cognitive function to some degree. (3) N130-P240 are the pain-specific components ascending through A-delta fibers, and closely related to cognitive function, because they were much affected by consciousness, different from the components ascending through A-beta fibers.

Adult↗
PubMed2003

Cerebral responses following stimulation of unmyelinated C-fibers in humans: electro- and magneto-encephalographic study.

There are two kinds of pain, a sharp pain ascending through Adelta fibers (first pain) and a second burning pain ascending though C fibers (second pain). By using a novel method, the application of a low intensity CO(2) laser beam to a tiny area of skin using a very thin aluminum plate with numerous tiny holes as a spatial filter, we succeeded in selectively stimulating unmyelinated C fibers of the skin in humans, and could record consistent and clear brain responses using electroencephalography (EEG) and magnetoencephalography (MEG). The conduction velocity (CV) of the C fibers of the peripheral nerve and spinal cord, probably spinothalamic tract (STT), is approximately 1-4 m/s, which is significantly slower than that of Adelta (approximately 10-15 m/s) and Abeta fibers (approximately 50-70 m/s). This method should be very useful for clinical application. Following C fiber stimulation, primary and secondary somatosensory cortices (SI and SII) are simultaneously activated in the cerebral hemisphere contralateral to the stimulation, and then, SII in the hemisphere ipsilateral to the stimulation is activated. These early responses are easily detected by MEG. Then, probably limbic systems such as insula and cingulate cortex are activated, and those activities reflected in EEG components. Investigations of the cortical processing in pain perception including both first and second pain should provide a better understanding of pain perception and, therefore, contribute to pain relief in clinical medicine.

Animals↗
PubMed2003

Effects of sleep on pain-related somatosensory evoked magnetic fields in humans.

We investigated the effects of sleep on pain-related somatosensory evoked magnetic fields (SEFs) following painful electrical stimulation to identify the mechanisms generating them in both fast A-beta fibers relating to touch and slow A-delta fibers relating to pain. While the subjects were awake, non-painful and painful electrical stimulations were applied, and while asleep, painful stimulation was applied to the left index finger. During awake, five components (1M-5M) were identified following both non-painful and painful stimulation, but the 4M and 5M at around 70-100 ms and 140-180 ms, respectively, were significantly enhanced following painful stimulation. During sleep, 1M and 2M generated in the primary somatosensory cortex (SI) did not show a significant change, 3M in SI showed a slight but significant amplitude reduction, and 4M and 5M generated in both SI and the secondary somatosensory cortex (SII) were significantly decreased in amplitude or disappeared. The 4M and 5M are complicated components generated in SI and SII ascending through both A-beta fibers and A-delta fibers. They are specifically enhanced by painful stimulation due to an increase of signals ascending through A-delta fibers, and are markedly decreased during sleep, because they much involve cognitive function.

Adult↗
PubMed2003

Sensory perception during sleep in humans: a magnetoencephalograhic study.

We reported the changes of brain responses during sleep following auditory, visual, somatosensory and painful somatosensory stimulation by using magnetoencephalography (MEG). Surprisingly, very large changes were found under all conditions, although the changes in each were not the same. However, there are some common findings. Short-latency components, reflecting the primary cortical activities generated in the primary sensory cortex for each stimulus kind, show no significant change, or are slightly prolonged in latency and decreased in amplitude. These findings indicate that the neuronal activities in the primary sensory cortex are not affected or are only slightly inhibited during sleep. By contrast, middle- and long-latency components, probably reflecting secondary activities, are much affected during sleep. Since the dipole location is changed (auditory stimulation), unchanged (somatosensory stimulation) or vague (visual stimulation) between the state of being awake and asleep, different regions responsible for such changes of activity may be one explanation, although the activated regions are very close to each other. The enhancement of activities probably indicates two possibilities, an increase in the activity of excitatory systems during sleep, or a decrease in the activity of some inhibitory systems, which are active in the awake state. We have no evidence to support either, but we prefer the latter, since it is difficult to consider why neuronal activities would be increased during sleep.

Adult↗
PubMed2003

Mechanisms of differences in gating effects on short-and long-latency somatosensory evoked potentials relating to movement.

We investigated the mechanisms underlying the differences in gating effects on short- and long-latency somatosensory evoked potentials (SEPs) relating to movement. SEPs were recorded in normal subjects for 6 different tasks in Experiment 1: Control, Movement, Distraction, Attention, Movement during Distraction and Movement during Attention, and for 4 different tasks in Experiment 2: Control, Passive Movement, Contralateral Movement and Movement Imagery. The amplitudes of short-latency SEPs were significantly reduced by active and passive movement of the stimulated hand, but long-latency SEPs (N140-P200) were significantly enhanced by active movement of the stimulated hand. Attention, Distraction, Contralateral Movement and Movement Imagery did not affect the amplitudes of SEPs. The degree of enhancement of long-latency SEPs by active Movement was greater than that by active movement with Attention or Distraction. Gating effects on long-latency SEPs were different from those on short-latency SEPs. Since this effect was not related to Attention/Distraction, Passive Movement, Movement Imagery or Movement of another site, it is probably due to specific centrifugal effects, which are different from more direct gating effects on short-latency components. This study showed the difference in gating effects on somatosensory perception depending on time periods following stimulation, which may indicate an interaction between motor and somatosensory cortex.

Adult↗