High-frequency oscillatory activities during selective attention in humans.
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Adult↗
Biomedical subjects
Isao Hashimoto
Publications and source records attributed to Isao Hashimoto.
Interferon-gamma down-regulates expression of the 230-kDa bullous pemphigoid antigen gene (BPAG1) in epidermal keratinocytes via novel chimeric sequences of ISRE and GAS.
The 230-kDa bullous pemphigoid antigen (BPAG1) is an integral component of hemidesmosomes. We have previously reported that interferon-gamma (IFNgamma) inhibits the transcription of the BPAG1 gene (1). Here we investigated the target sequences of IFNgamma-signal transduction pathway in the BPAG1 promoter in epidermal keratinocytes. Transient transfections with 5'-deletion constructs of BPAG1 promoter-luciferase reporter gene plasmids in cultured normal human epidermal keratinocytes (NHEK) allowed us to narrow the DNA region containing IFNgamma inhibitory element (IGIE) to between -1 and -89, upstream from the transcription initiation site (+1). Homology search in this region identified a chimeric sequence, consisting of IFN-stimulated responsive element (ISRE) with a partial 7-bp sequence of IFNgamma activation site (GAS), as identified in the guanylate-binding protein (GBP) gene, inserted at its center. Functional analysis of IGIE, inserted in front of the heterologous thymidine kinase promoter, indicated that IGIE acts as a down-regulatory element of the promoter through IFNgamma-dependent signal pathway. Transient transfection studies with BPAG1 promoter-reporter gene constructs containing mutated IGIE (with TT to GG transversions in the region of 5'ISRE, GAS, and 3'ISRE) demonstrated that disruption of the ISRE sequences, but not GAS, markedly suppressed the BPAG1 basal promoter activity and resulted in attenuated IFNgamma response in keratinocytes. Our findings provide novel insight into the mechanism of IFNgamma regulation in keratinocyte differentiation and proliferation.
Base Sequence↗
Attention induces reciprocal activity in the human somatosensory cortex enhancing relevant- and suppressing irrelevant inputs from fingers.
OBJECTIVE: We studied whether attention regulates information processing in the human primary somatosensory cortex (SI) by selective enhancement of relevant- and suppression of irrelevant information. METHODS: Under successive and simultaneous electric stimuli to both the right index and middle fingers, tactile stimuli were randomly (20%) presented on one of the two fingers in separate two runs exchanging the finger. Subjects were requested to discriminate the tactile stimuli in an attention task to induce attention to one finger and to ignore the stimuli in a control task to avoid such an attention focus. Somatosensory evoked magnetic fields were measured only for the two-finger electric stimulation and an early component (M50) was analyzed. RESULTS: In spite of the two-finger simultaneous stimulation, attention to either the index or middle finger lowered or heightened the M50-sourse location, respectively. The attention task did not increase the M50 amplitude. CONCLUSIONS: Attention to a finger enhanced selectively the representation of the finger in the SI cortex. However, this SI activity did not increase the M50 amplitude, suggesting that the attention suppressed another finger region receiving the unattended inputs. SIGNIFICANCE: Attention regulates the SI activity by selectively enhancing the task-relevant information and by filtering out other noise inputs.
Adult↗
Keratinocyte-specific modulation of type VII collagen gene expression by pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1beta).
Previous studies have shown that pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta up-regulate type VII collagen gene (COL7A1) expression in cultured dermal fibroblasts. The present study was designed to investigate the effects of TNF-alpha and IL-1beta on COL7A1 expression in epidermal keratinocytes. We demonstrated that both TNF-alpha and IL-1beta reduced COL7A1 expression in epidermal keratinocytes in an additive manner, whereas they increased COL7A1 expression in dermal fibroblasts. Thus, regulation of COL7A1 by pro-inflammatory cytokines is cell type specific. In particular, the inhibitory effects of TNF-alpha and IL-1beta occurred, at least in part, at the transcriptional level. Finally, we demonstrated that TNF-alpha and IL-1beta enhanced the TGF-beta-mediated up-regulation of COL7A1 expression in HaCaT keratinocytes, suggesting that the combination of TGF-beta and TNF-alpha or IL-1beta induces a signaling pathway that is completely different from that induced by either pro-inflammatory cytokine alone.
Blotting, Western↗
Neural mechanisms of the ultrafast activities.
A brief review of previous studies is presented on ultra-fast activities > 300 Hz (high frequency oscillations, HFOs) overlying the cortical response in the somatosensory evoked potential (SEP) or magnetic field (SEF). The characteristics of somatosensory HFOs are described in terms of reproducibility and origin (area 3b and 1) of the HFOs, changes during a wake-sleep cycle, effects of higher stimulus rate or tactile interference, etc. Also, several hypotheses on the neural mechanisms of the HFOs are introduced; the early HFO burst is probably generated from action potentials of thalamocortical fibers at the time when they arrive at the area 3b (and 1), since this component is resistant to higher stimulus rate > 10Hz or general anesthesia: by contrast, the late HFO burst is sensitive to higher stimulus rate, reflecting activities of a postsynaptic neural network in the somatosensory cortices, area 3b and 1. As to possible mechanisms of the late HFO burst genesis, an interneuron hypothesis, a fast inhibitory postsynaptic potential (IPSP) hypothesis of the pyramidal cell and a chattering cell hypothesis will be discussed on the basis of physiological and pathological features of the somatosensory HFOs.
Action Potentials↗
Serial N20m dipoles in somatosensory evoked magnetic fields move along the distal-proximal representation of the digit area 3b of the human cortex.
We studied the relationship between the distal-proximal representation of the digit in area 3b and moving dipoles of the primary magnetic response (N20m). By the use of ring electrodes, a distal or proximal portion of the middle finger was stimulated to elicit N20m. The dipole locations were sequentially analyzed around the N20m peak. The dipole locations did not differ between distal and proximal stimulation before the N20m peak. After 0.4 ms post-N20m peak, however, the dipoles following proximal stimulation substantially and progressively shifted laterally to those following distal stimulation. The result suggests that the N20m dipole moves from the distal representation toward the proximal representation of the digits in area 3b.
Adult↗
Disinhibition of the somatosensory cortex in cervical dystonia-decreased amplitudes of high-frequency oscillations.
OBJECTIVE: To determine whether patients with cervical dystonia have electrophysiological signs of disinhibition in the somatosensory cortex by recording high-frequency oscillations (HFOs) in somatosensory evoked potentials (SEPs). METHODS: HFOs were recorded in 13 patients and 10 age-matched control subjects, and the data were analyzed statistically by paired comparison and by Pearson's correlation. RESULTS: In patients with cervical dystonia, the early part of HFOs showed a significant decrease in amplitude, and the amplitude ratios of both early and late parts of HFOs/N20 potential were also significantly decreased. The amplitudes of HFOs and N20 potential were linearly correlated in the control subjects but not in dystonia patients. CONCLUSIONS: Patients with cervical dystonia may suffer from a disturbance of inhibition in the sensory cortex. This disturbance is reflected by decreased HFO amplitude, representing decreased activities of inhibitory interneurons in area 3b.
Adult↗
Rapid change of tonotopic maps in the human auditory cortex during pitch discrimination.
OBJECTIVE: To study early cognitive processes and hemispheric differences in the primary auditory cortex during selective attention. METHODS: We measured auditory evoked magnetic fields (AEFs) to 400 and 4000 Hz tone pips that were randomly presented at the right or left ear. Subjects paid attention to target stimuli during pitch (high or low) or laterality (left or right) discrimination tasks. In the control session, 400 or 4000 Hz tone alone was presented at the left or right ear. We calculated the location and strength of N100m dipole for 400 and 4000 Hz tones, based on the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: N100m amplitude increased in both hemispheres in pitch or laterality discriminating conditions. N100m latency also shortened during selective attention. The N100m dipole distance between 400 and 4000 Hz tones was enlarged, especially in the right auditory cortex during pitch discrimination task, but was unchanged during the laterality discrimination task. CONCLUSIONS: We conclude that these dynamic changes in the N100m dipole reflect short-term plastic changes in the primary auditory cortex, supporting early selection models. SIGNIFICANCE: This work is the first to disclose short-term plastic changes during pitch discrimination in the human auditory cortex based on the analysis of magnetoencephalography.
Acoustic Stimulation↗
Functional connectivity between forearm and digits representations in human somatosensory area 3b.
OBJECTIVE: We compared the effects of tactile interference to the forearm on magnetic responses evoked by electric stimulation of the little finger (D5) and the thumb (D1). METHODS: Electric stimulation was delivered to D5 or D1 individually. In each stimulus session, magnetic recordings were conducted with or without concurrent tactile interference to the radial side of the anterior forearm. RESULTS: With forearm interference, the amplitude of the primary response (N20m) following D5 stimulation was reduced to 90.7% of the control value without interference, while that following D1 stimulation was not affected (100.7%). CONCLUSIONS: In human somatosensory area 3b, the representation of the forearm is immediately adjacent to that of the D5, and distant from that of the D1. Thus, the result suggests that the tactile interference effect on N20m depends on the cortical distance between electrically and mechanically activated 3b areas. SIGNIFICANCE: Intrinsic synaptic connections between the 3b hand representation and its surroundings have been hypothesized as a neural basis for plastic changes of the human brain, such as a phantom hand phenomenon. The present finding implies that these connections may play some physiological roles even in normal adult humans.
Adult↗
Is there training-dependent reorganization of digit representations in area 3b of string players?
OBJECTIVE: The digit representations in area 3b were studied to examine whether there is training-dependent reorganization in string players. METHODS: Somatosensory evoked magnetic fields were recorded following electrical stimulation of digits 1 (D1), 2 (D2) and 5 (D5) of both hands in 8 string players and of the left hand in 12 control subjects. The N20m and P30m responses, and high-frequency oscillations (HFOs) were separated by 3-300 Hz and 300-900 Hz bandpass filtering. RESULTS: The dipole locations on the coronal plane and strengths of D1, D2 and D5, and D1-D5 cortical distance estimated at the peak of N20m or P30m did not differ between left and right hand in string players or between left hand in string players and controls. On the other hand, the dipole locations of D2 estimated from N20m and P30m and of D1 from N20m were significantly anterior, the D2-D5 distance from P30m longer, and the number of HFO peaks larger for D5 in string players than controls. CONCLUSIONS/SIGNIFICANCE: With strong mutual competition among the fingering digits, the scale of reorganization should be much smaller as compared with the competition-free denervation-induced reorganizations. Taken together, the training-dependent reorganization of somatosensory cortex in string players is manifest not only in the enlarged cortical representation but also in the enhanced HFOs presumably representing activity of the fast-spiking interneurons.
Adolescent↗
Japanese guidelines for diagnosis and treatment of junctional and dystrophic epidermolysis bullosa.
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Epidermolysis Bullosa Dystrophica↗
History of the establishment and revision of diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan.
We summarize the process of establishing and revising the diagnostic criteria, severity index and therapeutic guidelines for pemphigus in Japan (including the results of a nationwide survey regarding these guidelines). We also summarize the content and present an evaluation of the utility of these guidelines. Due to the publication of these documents throughout the Japanese medical community, it appears that patients with pemphigus have recently begun to receive appropriate treatment, dramatically improving their quality of life and prognosis. Continuous examination of these criteria by means of follow-up studies of patients treated according to the guidelines is necessary to determine the long-term efficacy of treatment. To this end, it is hoped that these guidelines will be more extensively disseminated among the medical community.
History, 20th Century↗
Genetic abnormalities and clinical classification of epidermolysis bullosa.
Genetic abnormalities for different subtypes of epidermolysis bullosa (EB) have been described. In dominant simplex type EB, mutations of the K5 or K14 gene lead to disruption of basal cells and the formation of bullae. The recessive simplex types include EB with muscular dystrophy due to abnormal plectin, EB without muscular dystrophy in patients homozygous for K14 gene abnormalities, and skin fragility syndrome, with formation of acantholytic vesicles within the epidermis due to PKP1 gene mutations. In junctional EB, mutations of the laminin 5, type XVII collagen, and alpha 6 beta 4 integrin genes have been reported. Dystrophic type EB is associated with various abnormalities of the type VII collagen gene. A new classification of EB based on these genetic abnormalities has been proposed. However, some concern has been voiced regarding the clinical utility of a classification based solely on genetic abnormalities. Although the reasons are unclear, identical genetic abnormalities have been known to be associated with different clinical features. A classification including a component based on clinical features would therefore be preferable. This article describes recently discovered genetic abnormalities and offers a new classification scheme for EB.
Epidermolysis Bullosa↗
A novel Sp1-family-related cis-acting element for transcription of type VII collagen gene (COL7A1).
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Collagen Type VII↗
Equivalent current dipole estimated from SSR potential distribution over the human hand. Sympathetic skin response.
OBJECTIVE: We aimed to determine whether or not the potential distribution of the sympathetic skin response (SSR) on the palm and dorsum of the hand can be described by an equivalent current dipole (ECD) as an SSR source model. METHODS: The SSR of 22 normal subjects were simultaneously obtained from two electrodes placed on the palm and the dorsum of hand, with an indifferent electrode on the thumbnail. We then measured the SSR potential distribution in 10 of the 20 subjects who had responded to stimulation with a clear dorsal SSR. To do this, 18 electrodes were attached to the palm and dorsum of the hand. SSR-evoking stimulation (sound, voice and rapid inspiration) were randomly delivered to the subject at time intervals of more than 1min to minimize the habituation effect. We estimated the ECD from the measured potential distribution. RESULTS AND CONCLUSIONS: The SSR-evoked by stimulation was negative in potential at the palmar sites of all 22 subjects, and was positive in potential at the dorsal sites of the hand in 20 of the 22 subjects. The SSR potential distribution, which was measured in 10 subjects, reached its maximum negative and positive potential near the base of the middle finger on the palm, and near the corresponding site on the dorsum of the hand, respectively. The SSR potential measured on the dorsum of the hand, however, was about 1/3 in amplitude of those on the palmar sites. These results suggest that the SSR source is located on the palm (probably the sweat glands) as confirmed by the estimated ECD (a negative pole on the palm and a positive pole on the dorsum of the hand). We speculate that the SSR may result from the potential difference caused by the Na(+) concentration gradient in the sweat, which results from intracanal reabsorption of Na(+). SIGNIFICANCE: The ECD resulting from the Na(+) concentration gradient within the canal of sweat glands is thought to be the source of the SSR from the negative pole on the palm to the positive pole on the dorsum.
Adolescent↗
Dynamic movement of N100m dipoles in evoked magnetic field reflects sequential activation of isofrequency bands in human auditory cortex.
OBJECTIVE: To investigate spatiotemporal features of the isofrequency bands for 400 and 4000 Hz tones in human auditory cortex and on the hemispheric differences in the arrangement of isofrequency bands. METHODS: We recorded auditory evoked magnetic fields (AEFs) to 400 or 4000 Hz tone pips presented at right or left ear from 31 normal subjects. The dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: In the right hemisphere, the current sources for 400 and 4000 Hz moved toward the anterolateral direction before the N100m peak, showing parallel arrangement of the isofrequency bands (4000 Hz in medial location). In the left hemisphere, the movement direction of 400 Hz dipoles was anterolateral, while that of 4000 Hz dipoles was lateral. CONCLUSIONS: This difference in the organization of isofrequency bands between right and left auditory cortices reflects distinct functional roles in auditory information processing such as pitch vs. language discrimination. SIGNIFICANCE: This work is the first to disclose isofrequency bands in human auditory cortex based on the analysis of magnetoencephalography.
Acoustic Stimulation↗
Muscle afferent inputs from the hand activate human cerebellum sequentially through parallel and climbing fiber systems.
OBJECTIVE: Spatio-temporal response characteristics of the human cerebellum to median nerve stimulation (MNS) were studied with the use of a whole-head magnetoencephalographic (MEG) system covering the cerebellum and upper cervical spine. METHODS: Neuromagnetic responses from the cerebellum were recorded following electric stimulation of the right median nerve in 12 subjects. In 6 out of 12 subjects, the responses to the left median nerve and to the right index or middle finger stimulation were also recorded. RESULTS: The medial part of the cerebellum (spinocerebellum) was activated by MNS. In contrast, there were no responses from the cerebellum to the finger stimulation, suggesting that muscle afferent inputs are the source of cerebellar activation for MNS. The cerebellar responses consisted of 3 or 4 components of alternating polarity within 90 ms post-stimulus: the current direction for the first component was from the depth to the surface of the anterior lobe. CONCLUSIONS: From the timing and current direction, we speculate that the 4 components reflect, respectively, (1) excitatory postsynaptic potentials (EPSPs) of granule cells, (2) Purkinje cell EPSPs at the distal dendrites driven by parallel fibers, (3) Purkinje cell EPSPs at the soma and the proximal dendrites mediated by climbing fibers and (4) second Purkinje cell EPSPs at the distal dendrites driven by parallel fibers. SIGNIFICANCE: We first visualized serial activation of the human spinocerebellum following MNS noninvasively with MEG.
Adult↗
Tactile interference to the face affects magnetic responses elicited by electric thumb stimulation.
OBJECTIVE: We examined the effect of tactile interference to the face on somatosensory evoked magnetic fields (SEFs) following electric thumb stimulation. METHODS: SEFs were elicited by electric stimulation of the right thumb in a control and two interference conditions. In the interference conditions, continuous tactile stimuli were delivered to the skin surface over the right upper face or the right thumb. RESULTS: The face interference significantly attenuated N20m and enhanced P30m. The amplitudes of N20m in the face and thumb interference conditions were 90.3 and 70.3% of the value in the control condition, respectively, while those of P30m were 120.2 and 74.4%. CONCLUSIONS: In human somatosensory area 3b, the representation of the thumb is immediately adjacent to that of the face although the thumb and face are physically distant. We suggest, therefore, that the effect of tactile interference on N20m depends on a cortical distance between electrically and mechanically activated 3b areas, rather than a physical distance between the body parts to which these two stimuli were administered. Although it is unclear why the face interference specifically enhanced the P30m, it is suggested that the generating mechanism of the interference effect on P30m may be different from that on N20m. SIGNIFICANCE: The tactile interference effect on N20m does not depend on the physical distance between electrically and mechanically activated skin areas, but on the distance of the 3b cortex receiving these two inputs.
Adolescent↗