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Biomedical subjects

S Yazawa

Publications and source records attributed to S Yazawa.

At least 37 records · Page 2Linked to original sources

Different activation of presupplementary motor area, supplementary motor area proper, and primary sensorimotor area, depending on the movement repetition rate in humans.

In order to clarify the functional role of the supplementary motor area (SMA) and its rostral part (pre-SMA) in relation to the rate of repetitive finger movements, we recorded movement-related cortical potentials (MRCPs) directly from the surface of the mesial frontal lobe by using subdural electrode grids implanted in four patients with intractable partial epilepsy. Two subregions in the SMA were identified based on the anatomical location and the different response to cortical stimulation. In three of the four subjects, we also recorded MRCPs from the surface of the lateral convexity covering the primary sensorimotor areas (SI-MI), which were defined by cortical stimulation and SEP recording. The subjects extended the middle finger or opposed the thumb against other fingers of the same hand at a self-paced rate of 0.2 Hz (slow) and 2 Hz (rapid), each in separate sessions. As a result, pre-and postmovement potentials were clearly seen at the SI-MI in both slow- and rapid-rate movements. By contrast, in the SMA, especially in the pre-SMA, premovement potentials were not seen and postmovement potentials were seldom seen in the rapid rate movement. In the slow-rate condition, pre- and postmovement potentials were clearly seen in both the pre-SMA and the SMA proper. In conclusion, the SMA, especially the pre-SMA, is less activated electrophysiologically in the rapid-rate movements, while the SI-MI remains active regardless of the movement rate.

Adolescent↗

Human presupplementary motor area is active before voluntary movement: subdural recording of Bereitschaftspotential from medial frontal cortex.

Bereitschaftspotential (BP) was recorded directly from the right supplementary motor area proper (SMA-proper) and its rostral part by chronically implanted subdural electrodes in three patients with intractable focal motor seizure. Cortical electrical stimulation of the SMA-proper revealed the somatotopy as previously reported, and the supplementary negative motor area (SNMA) was identified just anterior to the SMA-proper in two of three cases. In patient 1, eight kinds of simple movements, i.e., left and right middle finger extension, left arm abduction, left and right foot dorsiflexion, left knee extension, tongue protrusion and saccadic eye movement, were studied to record BP. In patient 2, three kinds of movements, i.e., left and right middle finger extension and left foot dorsiflexion, were adopted as movement tasks. In patient 3, four kinds of movements, i.e., left and right middle finger extension and left and right foot dorsiflexion, were adopted. In the SMA-proper, somatotopically distributed BP preceding movements were observed in all three patients. In the SNMA and its rostrally adjacent areas, "SNMA-plus" BPs were generated invariably regardless of the sites of movement. There was no significant difference in the onset time of BPs between the SMA-proper and the SNMA-plus. The present findings suggest that the SNMA-plus is more consistently involved in the preparation for various simple movements than the SMA-proper. This functionally independent region (SNMA-plus) just rostral to the SMA-proper most likely corresponds to a part of the presupplementary motor area which was originally defined in nonhuman primates. Since a part of this area elicited the inhibition of various movements by cortical stimulation, and since it generated BPs regardless of the sites of movement, it may play a higher role in the movement preparatory process than the SMA-proper.

Adult↗

Tumor cells as the origin of elevated serum alpha1,3fucosyltransferase in association with malignancy.

We have previously reported that the elevated activities of serum alpha 1,3fucosyltransferase reverted to normal levels after curative removal of the tumors. To determine the origin of elevated serum alpha 1,3fucosyltransferase, blood samples were obtained from both the drainage vein and the artery in patients with different stages of colorectal cancer at surgery. The enzyme levels in all samples from the drainage vein were found to be higher than the levels in the artery that fed the tumor. Hence, the origin of elevated alpha1,3fucosyltransferase in serum was thought to be the tumor rather than the liver that is the normal source of serum alpha1,3fucosyltransferase. When serum samples not only from colorectal cancer patients but also from patients with gastric, liver, lung, pancreas, bladder and esophagus cancer were treated with anti-FUTVI antibody, the measured activities of alpha1,3fucosyltransferase were markedly reduced. Further, secretion of alpha1,3fucosyltransferase from human colorectal carcinoma cells was also detected in the culture medium by Western immuno-blot analysis with anti-FUTVI antibody.

Aged↗

A new method for assaying adhesion of cancer cells to the greater omentum and its application for evaluating anti-adhesion activities of chemically synthesized oligosaccharides.

A new ex vivo method for assaying adhesion of cancer cells to the greater omentum has been developed using mouse greater omentum and [3H]labelled human gastric and mouse colorectal cancer cells. Since the adhesion rates were found to increase up to 18 h and labelled cells seemed to be stable during the period, the present method could be useful for investigating adhesion of cancer cells to the greater omentum, which must occur at the first step of the peritoneal dissemination. The adhesion of cancer cells to the greater omentum was inhibited by a series of chemically synthesized oligosaccharides and Gal beta1,3[3OMeGal beta1,4GlcNAc beta1,6]alphaBn was found to be the best inhibitor. The anti-tumor effect of this novel tetrasaccharide in vivo was shown in preliminary experiments using Balb/c mice and colon26 cells.

Animals↗

Movement-related change of electrocorticographic activity in human supplementary motor area proper.

We investigated movement-related change in the cortical EEG signal by simultaneous recording from the primary sensorimotor area (S1-M1) and the supplementary motor area proper (SMA proper) in four patients with intractable partial epilepsy. By the use of temporal spectral evolution (TSE) analysis, the change in background cortical activity in relation to self-paced finger/wrist extension was compared among the SMA proper, S1 and M1. All three areas showed a decrease in the amount of activity for the frequency range between 10 and 40 Hz before the onset of movement [event-related desynchronization (ERD)]. The SMA proper showed earlier onset of ERD for 18-22 Hz activity (-3.4 +/- 0.5 s, mean +/- standard deviation) than M1 (-1.7 +/- 0.7 s) and S1 (-1.4 +/- 0.5 s). The degree of ERD in S1 was greatest for 10-14 Hz and that in M1 for 18-22 Hz, whereas in the SMA proper ERD was observed throughout the frequency bands from 10 to 40 Hz. Neither the degree nor the onset time of ERD in the SMA proper was lateralized to either the ipsilateral or the contralateral side with respect to the movement. A transient increase in activity after movement [event-related synchronization (ERS)] was observed in all three areas. In the SMA proper, two out of four subjects showed ERS for frequency bands below 40 Hz with both ipsilateral and contralateral movements. By contrast, in S1 and M1, ERS was recorded for frequency bands between 20 and 90 Hz, and was predominantly associated with the contralateral movement. The present study suggests that the background cortical activity in the SMA proper has a specific temporal pattern with respect to self-paced movement, and that the SMA proper is involved in motor preparation earlier than S1-M1 in a bilaterally organized manner.

Adult↗

Experimental reinfection with homologous porcine reproductive and respiratory syndrome virus in SPF pigs.

The present examination was conducted to determine if the pigs infected with one strain of porcine reproductive and respiratory syndrome virus (PRRSV) would be protected against a subsequent homologous virus challenge. Sixteen 4-week-old SPF pigs were assigned to 2 experimental groups A and B. The pigs in group A were inoculated with 10(6.5) TCID50 of PRRSV by intranasal route. On 77 days post-inoculation (PI), pigs in groups A and B were similarly inoculated with same virus. After the secondary inoculation, the pigs in group A didn't show any clinical sign including pyrexia and reduction of white blood cell (WBC) number. Viremia was detected only on 3 days PI with low virus titer and any virus was not recovered from serum and tissues at the time of necropsy on 14 or 28 days PI. In contrast, pigs in group B showed pyrexia for 14 days and reduction of WBC number on 3 days PI. Viremia was detected between 3 and 28 days PI, and virus was isolated from several tissues of all pigs. These results indicate that previous exposure to PRRSV can prevent development of clinical signs and reduce virus proliferation in pigs after subsequent infection with the homologous PRRSV.

Animals↗

Superficial temporal artery dilatation in a patient with infectious temporal headache clinically mimicking temporal arteritis.

A 57-year-old woman noticed a pulsatile shooting headache in her right temporal region 3 days after extraction of a tooth from the right mandible. The following day, a localized headache over the right superficial temporal artery (STA), low grade fever, and jaw claudication appeared and progressed subacutely. Seven days after the onset, magnetic resonance imaging and angiography (MRI/MRA) disclosed inflammatory swelling of the right temporal muscle and dilatation of the right STA. All the symptoms disappeared following antibiotic treatment, and neuroimaging findings were improved. In conclusion, MRA is thought to be useful to non-invasively identify reversible inflammatory dilatation of extracranial vessels.

Bacterial Infections↗

Elevated serum haptoglobin in pigs infected with porcine reproductive and respiratory syndrome virus.

We examined the two acute phase proteins, alpha (alpha)-1 acid glycoprotein (AGP) and haptoglobin (HP), in serum of pigs following experimental porcine reproductive and respiratory syndrome (PRRS) virus infection. Increased levels of serum HP, but not AGP, were observed from 7 to 21 days post-inoculation in the infected pigs. Furthermore, serum IL-6 increased in the infected pigs, but TNF-alpha did not. The increase of serum IL-6 in pigs following PRRS virus infection may induce production of HP. Also, in the field investigation, serum HP in pigs was dramatically increased after exposure to the PRRS virus.

Acute-Phase Proteins↗

Somesthetic function of supplementary motor area during voluntary movements.

To clarify the somesthetic functions of the supplementary motor area (SMA), we recorded the cortical potentials following the median nerve electric stimulation directly from the SMA and investigated the modulation caused by voluntary movements in two patients with intractable SMA seizures. The evoked potentials over the SMA consisted of positive (61.5ms) and negative (100.0 ms) peaks, which were enlarged by voluntary movements of the stimulated hand. The present finding is in strong contrast with the attenuation (gating) of the response at the primary sensorimotor area (SM1) and suggests that the voluntary movements differently modulate the somatosensory functions of SMA and SM1.

Adult↗

Affinity of 5-thio-L-fucose-containing Lewis X (LeX) trisaccharide analogs to anti-LeX monoclonal antibody.

5-Thiofucose-containing LeX trisaccharide analogs Gal beta(1,4)[5SFuc alpha(1,3)]GlcNAc-OMe (2) and Gal beta(1,4)[5SFuc beta(1,3)]GlcNAc-OMe (4) were synthesized via 5-thiofucosylation of methyl 2-azido-lactoside derivative 6 by the trichloroacetimidate method. Inhibitory activity of these analogs for the binding of LeX to anti-Lex antibody was evaluated by enzyme immunoassay, indicating that anti-LeX strictly recognizes alpha-configuration of the fucose moiety and its binding pocket includes no advantageous region, such as hydrophobic area, for recognizing the ring sulfur atom of 5-thiofucosyl LeX analog 2.

Antibodies, Monoclonal↗

Movement-related cortical potentials associated with voluntary relaxation of foot muscles.

OBJECTIVE: In our previous study of movement-related cortical potential (MRCP) in association with the voluntary relaxation of the hand muscle, Bereitschaftspotential (BP) was maximal at the vertex and symmetrically distributed, and Negative Slope (NS') was maximal over the contralateral central region. In order to clarify the generator sources of MRCP with voluntary muscle relaxation, we recorded MRCP in association with voluntary relaxation of the foot. METHODS: MRCP in association with plantar flexion of the foot caused by voluntary relaxation of the tibialis anterior muscle was recorded in 10 normal subjects. RESULTS: The BP started at about 1.7 s before the onset of the muscle relaxation, followed by NS' starting at about 650 ms before it. Both were maximal at the vertex and symmetrically distributed. There was no additional EEG activity in the lateral frontal areas, which are presumably located over the primary negative motor areas (PNMA). CONCLUSIONS: It is concluded that the voluntary muscle relaxation, similarly to the voluntary muscle contraction, involves the cortical preparatory activity at least in the primary motor area (M1) and probably the supplementary motor areas (SMAs). There is no evidence to suggest that the PNMA is also active prior to the voluntary muscle relaxation.

Adult↗

Brain structures related to active and passive finger movements in man.

A PET study was performed in six normal volunteers to elucidate the functional localization of the sensory afferent component during finger movement. Brain activation during the passive movement driven by a servo-motor was compared with that during an auditory-cued active movement which was controlled kinematically in the same way as the passive one. A newly developed device was used for selectively activating proprioception with a minimal contribution from tactile senses. Active movement was associated with activation of multiple areas, including the contralateral primary sensorimotor cortex, premotor cortex, supplementary motor area (SMA), bilateral secondary somatosensory areas and basal ganglia and ipsilateral cerebellum. In contrast, only the contralateral primary and secondary somatosensory areas were activated by the passive movement. It is likely that the contribution of proprioceptive input to the activation of the premotor cortex, SMA, cerebellum and basal ganglia, if any, is small. However, the present results do not rule out the possibility that the cutaneous afferent input or the combination of cutaneous and proprioceptive input participates in the activation of those areas during the active movement.

Acoustic Stimulation↗

Focal ictal direct current shifts in human epilepsy as studied by subdural and scalp recording.

In order to clarify further the characteristics of ictal direct current (DC) shifts in human epilepsy, we investigated them by subdural and scalp recording in six and three patients, respectively, both having mainly neocortical lobe epilepsy (five with frontal lobe epilepsy, two with parietal lobe epilepsy and two with temporal lobe epilepsy). By using subdural electrodes made of platinum, ictal DC shifts were observed in 85% of all the recorded seizures (89 seizures) among the six patients, and they were localized to just one or two electrodes at which the conventional initial ictal EEG change was also observed. They were closely accompanied by the electrodecremental pattern in all patients except for one in whom 1 Hz rhythmic activity was superimposed on clear negative slow shifts. Seizure control after resection of the cortex, including the area showing DC shifts, was favourable irrespective of histological diagnosis. Scalp-recorded ictal slow shifts were observed in 23% of all the recorded seizures (60 seizures) among the three patients. They were, like the subdurally recorded ones, mainly surface-negative in polarity, closely related to the electrodecremental pattern and consistent in their location. It seems that scalp-recorded DC shifts were detected particularly when seizures were clinically intense, while no slow shifts were observed in small seizures. It is concluded that at least subdurally recorded ictal slow shifts are clinically useful before epilepsy surgery to delineate more specifically an epileptogenic area as well as to further confirm the conventional initial ictal EEG change, and that scalp-recorded ictal slow shifts also have high specificity although their low sensitivity is to be taken into account.

Adolescent↗

Cognitive motor control in human pre-supplementary motor area studied by subdural recording of discrimination/selection-related potentials.

To clarify the functional role of human pre-supplementary motor area (pre-SMA) in 'cognitive' motor control as compared with other non-primary motor cortices (SMA-proper and lateral premotor areas) and prefrontal area, we recorded epicortical field potentials by using subdural electrodes in five epileptic patients during presurgical evaluation, whose pre-SMA, SMA-proper, prefrontal and lateral premotor areas were defined by electric cortical stimulation and recent anatomical orientations according to the bicommissural plane and callosal grid system. An S1-Go/NoGo choice and delayed reaction task (S1-choice paradigm) and a warned choice Go/NoGo reaction task (S2-choice paradigm) with inter-stimulus intervals of 2 s were employed. The results showed (i) transient potentials with onset and peak latencies of about 200 and 600 ms, respectively, after S1 in the S1-choice paradigm mainly at pre-SMA and to a lesser degree at the prefrontal and lateral premotor areas, but not in the S2-choice paradigm. At SMA-proper, a similar but much smaller potential was seen after S1 in both S1- and S2-choice paradigms and (ii) slow sustained potentials between S1 and S2 in both S1- and S2-choice paradigms in all of the non-primary motor areas investigated (pre-SMA, SMA-proper and lateral premotor areas) and prefrontal area. It is concluded that pre-SMA plays a more important role in cognitive motor control which involves sensory discrimination and decision making or motor selection for the action after stimuli, whereas SMA-proper is one of the main generators of Bereitschaftspotential preceding self-paced, voluntary movements. In the more general anticipation of and attention to the forthcoming stimuli, non-primary motor cortices including pre-SMA, SMA-proper and lateral premotor area, and the prefrontal area are commonly involved.

Adult↗

Abnormal cortical processing of voluntary muscle relaxation in patients with focal hand dystonia studied by movement-related potentials.

In order to clarify the abnormality in cortical motor preparation for voluntary muscle relaxation of the hand in patients with focal hand dystonia, Bereitschaftspotentials (BPs) preceding voluntary muscle contraction and relaxation were recorded in eight patients (three with simple writer's cramp and five with dystonic writer's cramp), and were compared with those from 10 normal subjects. Voluntary muscle relaxation: after keeping the right wrist in an extended position for > 5 s, the subject let the hand drop by voluntarily terminating muscle contraction of the wrist extensor without any associated muscle contraction. Voluntary muscle contraction: the right wrist was flexed by voluntarily contracting the wrist flexor muscle. Scalp EEGs were recorded from 11 electrodes placed over the frontal, central and parietal areas. In the control group, the BP measured at the movement onset was maximal at the left central area (C1), and distributed predominantly over the left hemisphere equally in both the contraction and relaxation tasks. In the focal hand dystonia group, BP was maximal at C1 in the contraction task, whereas, in the relaxation task, it was maximal at the midline central area (Cz) and symmetrically distributed. At the left central area, the BP amplitude in the focal hand dystonia group was diminished significantly in the relaxation task compared with the contraction task (P < 0.05). The present results demonstrate for the first time that the cortical preparatory process for voluntary muscle relaxation, or motor inhibition, is abnormal in focal hand dystonia.

Adult↗

Molecular behavior of mutant Lewis enzymes in vivo.

The expression of type-1 Lewis antigens on erythrocytes and in digestive organs is determined by a Lewis type alpha(1,3/1, 4)-fucosyltransferase (Lewis enzyme) encoded by the Fuc-TIII gene ( FUT3 gene; Lewis gene). We have classified the Lewis alleles in the Japanese population into four types, the wild-type allele ( Le ) and three mutated alleles, i.e., le1, which has missense mutations T59G and G508A, le2, which has T59G and T1067A, and le3, which has only T59G. Here we carried out an extensive study on the biological properties of the three mutant Lewis enzymes, the le1, le2, and le3 enzymes, using native tissues and obtained the following results. (1) In in vivo and in vitro experiments, the le1 and le2 enzymes were found to be susceptible to protease digestion probably because the one missense mutation in the catalytic domains, i.e., Gly170 to Ser in the le1 enzyme and Ile356 to Lys in the le2 enzyme, makes the three-dimensional structures of the enzymesunstable, while the le3 and wild-type Lewis enzymes wereresistant to protease digestion. (2) The le1 and le2 enzymes cannot synthesize type 1 Lewis antigens on either glycolipids or mucins. The le3 enzyme cannot synthesize Lewis-active glycolipids, which result in the Lewis antigen-negative phenotype of erythrocytes, while it can synthesize Lewis antigens on mucins in normal and cancerous colon tissues. The missense mutation, Leu20 to Arg, in the transmembrane domain reduces retention of the le3 enzyme in the Golgi membrane resulting in an apparent reduction of enzyme activity as revealed by the lack of Lewis antigen synthesis. (3) The Lewis gene dosage actually has effects in vivo on the amount of the Lewis enzyme, its activity, and finally the amounts of Lewis carbohydrate antigens. This is the first article that clearly demonstrates the gene dosage effects on the amount of the glycosyltransferase protein, its activity, and the amounts of carbohydrate products in vivo.

Alleles↗

Plasma alpha1,3-fucosyltransferase deficiency in schizophrenia.

Levels of plasma alpha1,3-fucosyltransferase (alpha1,3FT) were assayed in 44 patients with schizophrenia and in 50 healthy controls. Significantly reduced enzyme activities were observed in patients (p < 0.05) and 4 unrelated patients were found, for the first time in Japan, to be deficient in the enzyme activity. Two point mutations in the coding region of the FUT6 gene encoding plasma alpha1,3FT that were responsible for the inactivation of the enzyme activity were detected in those patients. Genotyping of the Le gene (FUT3) in these patients demonstrated that 2 of them were also FUT3 deficient and were grouped as Lewis- individuals whereas the rest were Lewis+.

Case-Control Studies↗