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S Miyauchi

Publications and source records attributed to S Miyauchi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Attention-regulated activity in human primary visual cortex.

Effects of attention to a local contour of a moving object on the activation of human primary visual cortex (area V1) were examined. Local cerebral oxygenation changes (an index of neuronal activity) in human area V1 were measured with functional magnetic resonance imaging (fMRI) in conditions including the following two: 1) when attention was selectively directed toward one side of a moving wedge (the attention condition) and 2) when the wedges were viewed passively (the passive condition). Activation in area V1 was found to be higher in the attention condition than in the passive condition. To our knowledge, this is the first finding that attention to motion activates as early as area V1. We suggest that attentional activation of area V1 is task dependent.

Attention↗
PubMed1998

Visualization of the information flow through human oculomotor cortical regions by transcranial magnetic stimulation.

We investigated the topography of human cortical activation during an antisaccade task by focal transcranial magnetic stimulation (TMS). We used a figure-eight shaped coil, with the stimulus intensity set just above the threshold for activation of the hand motor areas but weak enough not to elicit blinks. TMS was delivered at various time intervals (80, 100, and 120 ms) after target presentation over various sites on the scalp while the subjects performed the antisaccade task. It was possible to elicit a mild but significant delay in saccade onset over 1) the frontal regions (a region 2-4 cm anterior and 2-4 cm lateral to hand motor area) and 2) posterior parietal regions (6-8 cm posterior and 0-4 cm lateral to hand motor area) regardless of which hemisphere was stimulated. The frontal regions were assumed to correspond to a cortical region including the frontal eye fields (FEFs), whereas the parietal regions were assumed to represent a wide region that includes the posterior parietal cortices (PPCs). The regions inducing the delay shifted from the posterior parietal regions at an earlier interval (80 ms) to the frontal regions at a later interval (100 ms), which suggested an information flow from posterior to anterior cortical regions during the presaccadic period. At 120 ms, the effect of TMS over the frontal regions still persisted but was greatly diminished. Erroneous prosaccades to the presented target were elicited over a wide cortical region including the frontal and posterior parietal regions, which again showed a forward shift with time. However, the distribution of effective regions exhibited a clear contralateral predominance in terms of saccade direction. Our technique provides a useful method not only for detecting the topography of cortical regions active during saccadic eye movement, but also for constructing a physiological map to visualize the temporal evolution of functional activities in the relevant cortical regions.

Adult↗
PubMed1998

Effects of dermatan sulfate, a heparin cofactor II mediated thrombin inhibitor, on the endotoxin-induced disseminated intravascular coagulation model in the rat: comparison with low-molecular weight heparin, nafamostat mesilate and argathroban.

Effects of dermatan sulfate (DS) on the endotoxin-induced disseminated intravascular coagulation (DIC) rat model were compared with those of low-molecular weight heparin (LMWH), nafamostat mesilate (NM) and argathroban (AR). At doses of 5, 10 or 20 mg/kg/4 hr, DS significantly ameliorated the decrease of fibrinogen (Fbg), the increase of fibrin-fibrinogen degradation products (FDP) and except at the highest dose (20 mg/kg/4 hr), the prolongation of thrombin clotting time (TCT). It also decreased the glomerular fibrin deposits (%GFD) at doses of 10 or 20 mg/kg/4 hr. LMWH suppressed the decrease of Fbg and the increase of FDP at doses of 1.4 or 2.8 mg/kg/4 hr. Only the highest dose of LMWH suppressed the decrease of the platelet count (PL), the prolongation of prothrombin time, and improved the %GFD. AR suppressed the decrease of PL and improved the %GFD. At the dose required to improve the %GFD, DS (5, 10 mg/kg/4 hr) significantly suppressed the prolongation of TCT, which is related to the bleeding frequency, while LMWH and AR further increased the prolongation of the TCT. These results suggest that DS has potential as a therapeutic drug with a lower hemorrhagic risk as compared with LMWH and AR in the treatment of DIC.

Animals↗
PubMed1998

Production of superoxide and nitric oxide by alveolar macrophages in the bleomycin-induced interstitial pneumonia mice model.

To elucidate the potential role of superoxide (O2-) and nitric oxide (NO) in the pathogenesis of interstitial pneumonia, the quantity of O2- and NO produced by the alveolar macrophages (AM) were determined in the bleomycin (BLM)-induced interstitial pneumonia mouse model. The production of O2- and NO increased on days 7, 14 and 21 after BLM injection. Strong expression of peroxynitrite (ONOO-) was seen in AM by using immunostaining for nitrotyrosine. The hydroxyproline contents increased on day 21 after BLM injection. O2- and NO are thought to play an important role in the pathology of fibrosis.

Animals↗
PubMed1998

Molecular weight-dependent effects of hyaluronate on the arthritic synovium.

Intra-articular injection of hyaluronate (HA) is widely used in the treatment of arthropathies. However, the mechanism of the effects of HA preparations on the arthritic synovium and the relationship between their effects and molecular weights (MW) remains unknown. The objectives of this study were to compare the effects of two hyaluronate preparations, HA84 (MW: 84 X 10(4)) and HA230 (MW: 230 X 10(4)), on the synovium of an arthritis model and to examine the mechanism of the effects of HA. The HA preparations were intra-articularly injected in a model of canine arthritis induced by anterior cruciate ligament transection for a total trial of 5 weeks. To define the accessibility of HA preparations to the synovial lining layers, fluorescein-labeled HA84 or HA230 was injected at the last administration. Pathological changes analyzed included increases in volumes and prostaglandin E2 concentrations in synovial fluids, thickening of the synovial lining layers, vacuolar alterations in the lining cells, and stainability of HA in the synovium. Expression levels of Heat shock protein 72 (Hsp72) were immunohistochemically detected in the tissues to investigate the ability of the cells to survive the degeneration. The pathological changes described above were more significantly suppressed in the HA84-treated than in the HA230-treated groups. In most cases of the HA84-treated group (five cases out of six), fluorescein particles were intensely distributed in the synovial lining layers, but only two cases in the HA230-treated group showed a weak distribution of fluorescein particles in the layers, indicating a certain difference in the accessibility of HA preparations to the lining cells between the two HA molecules. Moreover, the immunoreactivity for Hsp72 in the lining cells as more intense in the HA84-treated than in the HA230-treated groups. The difference in the accessibility of HA molecules corresponded well with that in the inducibility of Hsp72 in the lining cells. These results suggest that the up-regulation of Hsp72 may offer a new concept concerning mechanism of the effects of HA preparations on the arthritic synovium.

Animals↗
PubMed1997

Adenosine 5'-triphosphate binding to bovine serum albumin.

Binding of ATP to bovine serum albumin was shown by ultrafiltration and NMR. The binding was pH dependent. Scatchard analysis revealed that at pH 5.4, 6.4 and 7.4, dissociation constant Kd was 13, 40 and 120 microM, respectively, and no binding was observed at pH 8.4. The binding stoichiometry was 1:1 for all pH. Dimer of BSA did not bind ATP. From chemical shifts of 31P-NMR, Kd was estimated to be 15 microM at pH 5.4, which is very close to that determined by ultrafiltration. While adenosine did not interfere with the binding. GTP, dCTP, ADP, UTP, AMP, phosphate and pyrophosphate were competitive inhibitors and their inhibition constants Ki were 25, 32, 36, 50, 130, 1000 and 186 microM, respectively. Fatty acids such as lauric acid and palmitic acid did not interfere with the binding. Warfarin was a non-competitive inhibitor. Cl- competitively inhibited the binding, and the inhibition constant was 20 mM. The dissociation constants of the Cl- binding were reported to be 0.42 mM for the first binding site, 10-5 mM for the second and 303-143 mM for the third [G. Scatchard, W.T. Yap, J. Am. Chem. Soc., 86 (1964) 3434; G. Scatchard et al., J. Am. Chem. Soc. 79 (1957) 12]. This suggests that the ATP binding site may be the second Cl- binding site.

Adenosine Triphosphate↗
PubMed1997

Visual motion sensation yielded by non-visually driven attention.

When a visual stimulus (the "cue") is presented and followed by a line, the line is perceived to grow rapidly from the cued side even when it is presented physically simultaneously (the "line-motion effect"). We now report that the same line motion can be observed when the cue is presented in a non-visual modality, such as auditory or somatosensory. A beep sound was presented either from the left or the right speaker as an auditory cue, or an electric pulse was applied to a finger put on the left or the right side of a CRT display as a somatosensory cue. A line probe was then presented between the two possible cue positions. Both the auditory and the somatosensory cues led to line motion, thus the line motion could not be interpreted as a variation of within-modality effects, such as visual apparent motion. When the cue lead time was manipulated, the obtained time courses of the effects were similar across the three cue modalities (Experiment 1). The minor differences could be explained simply in terms of latency of detection, according to results of another experiment (Experiment 2). Finally, the line-motion task was compared with a task of temporal order judgment, where two targets were presented simultaneously at the cued and the uncued sides, and the subject was asked to judge which of the targets had appeared first. As a result, similar dependencies on cue lead time were obtained between the two tasks within subjects (Experiment 3). Thus, the non-visual cue seems to facilitate "prior entry" of a visual stimulus nearby in the spatial representation, much the same way as a visual cue does. These effects should be attributed to modality non-specific spatial attention, i.e., a "gradient" of information processing efficiency across various locations.

Acoustic Stimulation↗
PubMed1997

Drug extrusion in Corynebacterium glutamicum.

We selected a mutant of Corynebacterium glutamicum, EBR, which can grow in a medium containing cytotoxic ethidium bromide (EtBr) at a high concentration of 100 microM. The resistance to EtBr in the mutant was reversed by 2 microM reserpine, a potent inhibitor of mammalian p-glycoprotein and bacterial multidrug resistance (MDR) transporter, whereas reserpine alone had a minimal effect on cell growth. The mutant showed a much higher efflux rate of EtBr than wild-type cells, and the efflux was completely inhibited by 2 microM reserpine. In addition to reserpine, structurally unrelated chemicals such as quinidine, trifluorperazine, tetraphenylarsonium chloride, chlorpromazine and quinine inhibit the EtBr efflux, revealing that the putative efflux system(s) can recognize a variety of chemicals. The efflux activity was correlated with the membrane potential but not the intracellular ATP contents. We, therefore, concluded that the EtBr resistance may be involved by proton-motive-force driven multidrug efflux system(s).

Adenosine Triphosphate↗
PubMed1997

Culture in the presence of sugars increases activity of multi-drug efflux transporter on Haloferax volcanii.

We found that when a growth medium contained glucose, wild-type cells of Haloferax volcanii were able to grow even in the presence of doxorubicin (DOX), an anti-cancer reagent, whereas they usually cannot grow in its presence. The reason was that cells grown in the presence of glucose (glucose-grown cells) showed high multi-drug efflux activity even though the growth medium contained no DOX or substrates of the transporter. This transporter was ATP-driven and the elevation of efflux activity was not due to an increase in intracellular ATP contents. The activity was increased not only by glucose but also by sugars that could be metabolized.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Merkel cell carcinoma and multiple Bowen's disease: incidental association or possible relationship to inorganic arsenic exposure?

An 81-year-old Japanese male was referred to our clinic in 1991 with multiple Bowen's disease. The associated hyperpigmentation of the trunk and extremities and palmoplantar keratotic nodules indicated that he had suffered from chronic arsenic poisoning. Interestingly, he was a native of Namikata in Ehime, Japan, where many residents have suffered from multiple Bowen's disease with internal malignancy. Arsenic exposure was strongly suspected. Two years later, Merkel cell carcinoma developed on the dorsum of his right hand, where Bowen's disease lesions were absent. Metastasis of this Merkel cell carcinoma led to his eventual death one year later. To our knowledge, this is the first report of Merkel cell carcinoma associated with multiple Bowen's disease. Chronic arsenic poisoning may be responsible for the association of these two rare skin neoplasms.

Aged↗
PubMed1997

Effect of lecithinized-superoxide dismutase on the rat colitis model induced by dextran sulfate sodium.

Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in blood and higher cell affinity than unmodified SOD. The effects of PC-SOD were evaluated using the rat ulcerative colitis model induced by 3% dextran sulfate sodium. Intravenous injection of rats with 0.5 or 1 mg/kg of PC-SOD suppressed the progression of bloody stools, the formation of erosion, and the infiltration of the colon with inflammatory cells. Furthermore, it also reduced the increase of leukocytes in blood. Thus, PC-SOD may have therapeutic potential in the treatment of ulcerative colitis.

Animals↗
PubMed1997

Effect of lecithinized-superoxide dismutase on the interstitial pneumonia model induced by bleomycin in mice.

Superoxide anion (O2-) acts as an exacerbation factor in interstitial pneumonia. Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in plasma and higher affinity to cell membranes than unmodified SOD. The effect of PC-SOD was evaluated using the bleomycin-induced interstitial pneumonia mouse model. Treatment with PC-SOD at 10 mg/kg significantly reduced the hydroxyproline content and fibrosis score. Namely, PC-SOD suppressed the progression of pulmonary fibrosis on the bleomycin-induced interstitial pneumonia mouse model. PC-SOD may be a potential drug for interstitial pneumonia therapy.

Animals↗
PubMed1997

Massive cutaneous mucinosis associated with systemic lupus erythematosus.

We describe a 23-year-old Japanese man with systemic lupus erythematosus (SLE) who developed massive cutaneous mucinosis. He was diagnosed with SLE when he was 11 years old. Prednisolone therapy (30 mg/day) was initiated and reduced to 10 mg/day 3 months later; the SLE had been well-controlled with this dose of prednisolone for 12 years. However, infiltrated erythematous plaques developed on the middle-lateral area of his back at 17 years old and progressed to erythematous and elastic soft tumorous masses over 20 cm in diameter at 23 years old. Biopsies of the lesions on the nape revealed massive mucin deposition. Topical injection with hyaluronidase decreased the lesion. This cutaneous mucinosis can be distinguished clinically and histopathologically from papular and nodular mucinosis associated with SLE. The present case might be an unusual clinical variant of cutaneous mucinosis associated with SLE.

Adult↗
PubMed1996

Chemonucleolytic effects of chondroitinase ABC on normal rabbit intervertebral discs. Course of action up to 10 days postinjection and minimum effective dose.

STUDY DESIGN: This study demonstrated the chemonucleolytic effects of chondroitinase ABC and its histologic and biochemical background. OBJECTIVES: To determine the course of chondroitinase ABC action on normal rabbit discs, and to find its minimum effective dosage. SUMMARY OF BACKGROUND DATA: No previous study has assessed the chemonucleolytic action of chondroitinase ABC in a time- and dose-dependent manner. This study also investigated the biochemical causes of radiologic and histologic changes in the discs. METHODS: Rabbits were injected with 4 U of pharmaceutical-grade chondroitinase ABC intradiscally. They were radiologically and histologically observed, and biochemical analyses of the discs were conducted on days 1, 3, 5, 7, and 10 postinjection in the time course study. Different doses of chondroitinase ABC were injected, and radiologic observations and water content of the discs were measured in the dose-finding study. RESULTS: The time course study revealed that the chondroitin sulfate content of discs significantly decreased from day 1 postinjection until the end of the experimental period. The weight and water content of the nucleus pulposus decreased on day 3, and disc space narrowing was observed from the day after injection. The dose-finding study showed that a dose of 0.0002 U/disc still induced disc space narrowing and a decrease in water content. CONCLUSIONS: Chondroitinase ABC is estimated to have a chemonucleolytic effect at least by day 3 postinjection at a dose level of 0.0002 U/disc or higher in rabbits.

Animals↗
PubMed1996

Rhodamine 123 efflux transporter in Haloferax volcanii is induced when cultured under 'metabolic stress' by amino acids: the efflux system resembles that in a doxorubicin-resistant mutant.

In this paper, we report that an archaebacterium, Haloferax volcanii, cultured in medium containing a large excess of amino acids showed very low levels of rhodamine 123 (RH123), which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. This low level involved the active efflux of RH123 from the cells. The level of intracellular RH123 was increased and the efflux inhibited by the Ca2+-channel antagonist verapamil and also by various anti-cancer drugs. The efflux transporter was suggested to be ATP-driven. We have previously selected a mutant of H. volcanii with resistance to doxorubicin, by repeatedly culturing cells in 1.5 microM doxorubicin [Miyauchi, Komatsubara and Kamo (1992) Biochim. Biophys. Acta 1110, 144-150]. The acquisition of resistance to doxorubicin involves the active expulsion of lipophilic drugs such as RH123 and doxorubicin. It is notable that the drug spectrum and ATP-dependency of the amino acid-induced efflux transporter resemble those of the efflux transporter induced by doxorubicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Orienting a spatial attention--its reflexive, compensatory, and voluntary mechanisms.

Attention is a mechanism to select sensory information. It is a modulatory process which normally cannot be observed as overt responses. We have studied spatial attention using a new visual illusion of motion--line-motion effect: a line, which was presented physically at once, was perceived to be drawn from one side when attention was captured to that side of the line by a preceding visual cue stimulus. This effect was due to acceleration of visual information processing at the locus of attention. The motion illusion was produced by both stimulus-induced (bottom-up) and voluntary (top-down) attention, which suggested that the two kinds of attention act on relatively early stages of visual processing. The objective of this study was to examine how various modes of spatial attention might be represented and reorganized in the brain. Using the induction of illusory line motion as a measure we found that: (1) once attention is captured by a moving object, it follows the object as it moves; and (2) attention moves with a saccade in the retinal coordinates such that its focus remains fixed in space. We then asked whether attention acts across different sensory modalities. We found that both auditory and somatosensory cues induced focal visual attention in space where the cue was presented. Based on these findings we propose a model which would allow (1) matching of visual spatial information obtained across saccades, and (2) matching of spatial information obtained in different sensory modalities.

Adaptation, Physiological↗
PubMed1996

Combined effect of clinically relevant doses of emitefur, a new 5-fluorouracil derivative, and radiation in murine tumours.

We investigated the combined effect of radiation and clinically relevant doses of emitefur (BOF-A2), a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation, in two types of murine tumours. In preliminary pharmacokinetic studies, the area under the curve for 5-FU in plasma, after administration of 12.5 mg kg-1 and 25 mg kg-1 emitefur in mice, appeared to be similar to that obtained on the first day and that on the seventh day, respectively, after starting administration of 400-600 mg day-1 in humans. These doses (12.5 and 25 mg kg-1) of emitefur were evaluated either alone or in combination with single (15 Gy), five-fraction (4 Gy each) or ten-fraction (2.8 Gy each) irradiation using a tumour growth delay assay for SCCVII tumours and in combination with four-fraction (5 Gy each) irradiation using an in vivo-in vitro assay for EMT6 tumours. The anti-tumour and radiation-enhancing effects of 12.5 mg kg-1 emitefur were not significant in any except the ten-fraction experiment. On the other hand, multiple doses of 25 mg kg-1 emitefur given either alone or in combination with radiation produced marked effects. The mean tumour growth delay time (the time to double in volume for treated tumours minus that for untreated tumours) was 8.1 days for five administrations of 25 mg kg-1 emitefur. 10.4 days for five fractions of 4 Gy and 22.1 days for five treatments with the combination of the two. Thus, the increase in growth delay afforded by this combination was at least additive. The effect of four fractions of 5 Gy with 25 mg kg-1 emitefur in EMT6 tumours was lower than that of four fractions of 7.5 Gy, but the effect of five fractions of 4 Gy with this dose of emitefur in SCCVII tumours was similar to the effect of five fractions of 6 Gy, and the effect of ten fractions of 2.8 Gy with 25 mg kg-1 emitefur was much higher than that of ten fractions of 4.2 Gy. In conclusion, emitefur given either alone or in combination with radiation appears to have a significant anti-tumour effect even at clinically relevant dose levels, although a threshold dose exists between 12.5 and 25 mg kg-1. Further clinical studies of this compound are warranted.

Animals↗