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Biomedical subjects

Isao Hashimoto

Publications and source records attributed to Isao Hashimoto.

27 records · Page 2Linked to original sources
PubMed2003

Keratinocyte responsive element 3: analysis of a keratinocyte-specific regulatory sequence in the 230-kDa bullous pemphigoid antigen gene promoter.

The 230-kDa bullous pemphigoid antigen gene is expressed primarily, if not exclusively, in basal keratinocytes of the epidermis. Keratinocyte responsive element 3, a cis-element at position -216 to -197 of the human 230-kDa bullous pemphigoid antigen gene promoter, confers tissue-specific expression to this gene (Tamai et al: J Biol Chem 270:7609-7614, 1995). In this study, we investigated the functional characteristics of keratinocyte responsive element 3 on the 230-kDa bullous pemphigoid antigen gene core promoter by transient transfections of cultured normal human keratinocytes and normal human fibroblasts, as well as of lung carcinoma (A549), osteosarcoma (OST), and gastric adenocarcinoma (GT3TKB) cell lines. A 230-kDa bullous pemphigoid antigen gene core promoter/luciferase reporter gene plasmid construct, pBPL, was modified to develop a series of constructs (pKBPL-p4KBPL), which have insertions of one, two, three, or four tandem repeats of keratinocyte responsive element 3, and these plasmids were used in transient transfections of the cultured cells. The promoter activities of pKBPL-p4KBPL constructs, relative to pBPL, in normal human keratinocytes were 7.6-, 15.5-, 4.6-, and 2.7-fold higher, respectively, whereas no upregulatory effect by keratinocyte responsive element 3 insertion was observed in other cell lines tested. prKBPL, a plasmid constructed with keratinocyte responsive element 3 in reverse orientation, showed essentially no activity in normal human keratinocytes. Insertion of a random 20 bp sequence between keratinocyte responsive element 3 and the 230-kDa bullous pemphigoid antigen gene core promoter resulted in about 40% reduction of luciferase activity in normal human keratinocytes. These data suggest that keratinocyte responsive element 3 functions as a position-, copy number-, and orientation-dependent cis-element contributing to tissue-specific regulation of the 230-kDa bullous pemphigoid antigen gene.

Autoantigens↗
PubMed2002

Selective attention regulates spatial and intensity information processing in the human primary somatosensory cortex.

Attention-related cognitive processes in the primary somatosensory cortex (SI) were studied by measuring somatosensory evoked magnetic fields (SEFs). Twenty-one normal adult human subjects participated in this study for investigating effects of attention and stimulus intensity on cortical finger representation in the SI cortex. Electric stimuli at low and high intensity were delivered to the index or middle finger in finger discrimination and non-discrimination task. For the low intensity stimulation at 1.25 times sensory threshold, an early component (M50) showed clear segregation of the sources for the two fingers and an increase of the amplitude specific to the finger discrimination task. Such an attentional effect on the SI cortex was masked by the high intensity stimulation (2.5 times sensory threshold); the M50 source separation by the fingers was induced irrespective of the discrimination or non-discrimination task. The results suggest that a conscious regulation of stimulus intensity coding in the SI cortex underlies the attention-dependent enhancement of spatial finger information processing.

Adult↗
PubMed2002

Effects of movement on somatosensory N20m fields and high-frequency oscillations.

Somatosensory evoked fields were recorded to determine the effects of movement and attention on high-frequency oscillations during active finger movements of the ipsilateral and contralateral sides in response to electrical stimulation of the median nerve. A whole-scalp neuromagnetometer was used to record somatosensory evoked fields from eight subjects following electric median nerve stimulation at the wrist. The following three sessions were performed: (1). rest, (2). movement of fingers on the ipsilateral in response to stimulation and (3). movement of fingers on the contralateral in response to stimulation. The somatosensory evoked fields with a wide-bandpass (0.1-1000 Hz) were recorded. High-frequency oscillations and N20m were separated by subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. The maximum amplitude of high-frequency oscillations decreased during finger movements accompanying a decrease in somatosensory N20m dipole strength. Activation of the motor cortex appeared to suppress both the amplitude of high-frequency oscillations and the N20m dipole strength.

Adult↗
PubMed2002

Dynamic anterolateral movement of N100m dipoles in evoked magnetic field reflects activation of isofrequency bands through horizontal fibers in human auditory cortex.

To analyze the temporal changes in localization of an equivalent current dipole (ECD) for the auditory N100m, we recorded auditory evoked magnetic fields (AEFs) to 400 Hz tone pips presented at the right or left ear. Using a single ECD model, the dipole location for the N100m sources was successively calculated from the AEFs obtained from the hemisphere contralateral to the stimulated ear. We found that the location of the N100m current sources moved dynamically in medio-lateral and postero-anterior directions before the N100m peak. This direction was parallel to the surface of the supratemporal cortex. We propose that the dynamic movement of the N100m dipole reflects spread of intracortical activation through horizontal fibers of pyramidal neurons in the auditory cortex, forming the isofrequency bands in humans.

Acoustic Stimulation↗
PubMed2002

Contribution of primary somatosensory area 3b to somatic cognition: a neuromagnetic study.

Interference effects on somatic cognition were compared with those on primary magnetic N20m responses. During tactile interference to various sets of digits, sensory thresholds for electric middle finger stimulation were measured, and then N20m was elicited with the intensity 4 mA above the sensory threshold measured without interference. After the recording, subjective magnitudes for the test stimuli were reported. Modifications of N20m and above psychophysical measures were dependent on the distance between electrically and mechanically activated areas. The differential N20m attenuation is considered to be generated within the neural circuitry in area 3b consisting of mechanically and electrically activated pyramidal neurons. The result indicates that such circuitry plays a fundamental role in magnitude estimation of somatic stimuli.

Adult↗
PubMed2002

Neural mechanisms for generation of tactile interference effects on somatosensory evoked magnetic fields in humans.

OBJECTIVES: We examined modification of somatosensory evoked fields following electric middle finger stimulation with interference to the same and surrounding digits in 13 subjects. METHODS: During electric middle finger stimulation, concurrent tactile stimulation was applied to the middle finger, to the index and ring fingers, and to the thumb and the little finger, individually. RESULTS: The amplitudes of the N20m and the P30m were significantly reduced by the interference to the middle finger, and to the index and ring fingers. The former interference induced more prominent attenuation than the latter. The amplitudes of the P60m did not show significant changes by any kind of the interference. CONCLUSIONS: The N20m and the P30m were attenuated according to the cortical distance between electrically and mechanically activated 3b areas. Pyramidal neurons are interconnected by intrinsic horizontal collaterals, even if their representations are segregated. The activation of the intrinsic collaterals induces direct excitation and indirect inhibition (via inhibitory interneurons) to the target pyramidal neurons. The result indicates that the activation of the intrinsic collaterals inhibits, on balance, the postsynaptic pyramidal targets, thereby generating the attenuation of the N20m and P30m.

Adult↗
PubMed2002

Movement interference attenuates somatosensory high-frequency oscillations: contribution of local axon collaterals of 3b pyramidal neurons.

OBJECTIVES: We examined the effects of movement interference on high-frequency oscillations (HFOs) and N20m in 10 healthy subjects. METHODS: For the movement interference condition, somatosensory evoked magnetic fields (SEFs) following electric median nerve stimulation were recorded during voluntary movement of the digits. For the control condition, the SEFs were recorded without interference. The N20m and HFOs were separated by 3-300Hz and 300-900Hz bandpass filtering. Then, the peak-to-peak amplitudes were measured. RESULTS: Both interference/control amplitude ratios for the N20m and HFOs were smaller than 100%. In contrast, the HFO/N20m amplitude index, which was calculated by dividing the interference/control amplitude ratio for the HFOs with that for the N20m, was significantly greater in the movement interference condition than in the control condition. CONCLUSIONS: Although the overall amplitude of the HFOs was decreased by movement, enhancement of the HFOs by the movement was revealed by the HFO/N20m amplitude index. Thus, we suggest that the HFOs represent activity of the inhibitory interneurons excited by both thalamocortical afferent impulses and excitatory synaptic inputs from pyramidal neurons in area 3b through their local axon collaterals, thereby reflecting both feed-forward and feedback inhibitory effects onto the post-synaptic pyramidal neurons.

Adult↗
PubMed2002

Keratinocyte gene therapy: cytokine gene expression in local keratinocytes and in circulation by introducing cytokine genes into skin.

Using the plasmid DNA injection method, we introduced cytokine genes into skin to determine whether systemic expression of cytokine genes is possible. Eight human cytokine [interleukin-4 (IL-4), IL-6, IL-10, transforming growth factor beta1 (TGF-beta1), monocyte chemotactic and activating factor (MCAF), granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma)] gene expression vectors were constructed and injected into rat skin. Transgenic cytokines in local keratinocytes and in the sera were assayed with ELISA. Our results showed that transgenic cytokines were markedly increased in keratinocytes at the injection site. The serum concentrations of IL-4, 6, 10 and TauGF-beta1 reached levels high enough to have systemic biologic effects. However, other cytokines used in this study could not be detected in the sera. Moreover, the serum transgenic IL-10 level after subcutaneous injection was significantly higher than after intramuscular injection. We suggest that keratinocytes can be used as a bioreactor to achieve systemic expression of cytokine genes by DNA injection, but the transgenic protein level in circulation depends on different kinds of cytokine. This level also depends on different target cells used for gene transfer.

Animals↗