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Biomedical subjects

Y Terao

Publications and source records attributed to Y Terao.

At least 73 records · Page 4Linked to original sources

Nucleotide sequence and molecular characterization of a gene encoding GTP-binding protein from Streptococcus gordonii.

A 1286-bp fragment of chromosomal DNA from Streptococcus gordonii strain Challis was cloned and sequenced. The gene sgg consisted of 897-bp nucleotides encoding a 299-amino acid polypeptide (33,200 Da). The deduced amino acid sequence exhibited significant similarity to Era, G protein of Escherichia coli. The nucleotide binding assay demonstrated that recombinant Sgg bound [32P]GTP but not [32P]ATP, [32P]CTP, or [32P]UTP. These findings indicate that Sgg is a member of the G protein superfamily in the genus Streptococcus.

Amino Acid Sequence↗

Preferential activation of different I waves by transcranial magnetic stimulation with a figure-of-eight-shaped coil.

Transcranial magnetic stimulation (TMS) over the human primary motor cortex (MI) evokes motor responses in the contralateral limb muscles. The latencies and amplitudes of those responses depend on the direction of induced current in the brain by the stimuli (Mills et al. 1992, Werhahn et al. 1994). This observation suggests that different neural elements might be activated by the differently directed induced currents. Using a figure-of-eight-shaped coil, which induces current with a certain direction, we analyzed the effect of direction of stimulating current on the latencies of responses to TMS in normal subjects. The latencies were measured from surface electromyographic responses of the first dorsal interosseous muscles and the peaks in the peristimulus time histograms (PSTHs) of single motor units from the same muscles. The coil was placed over the MI, with eight different directions each separated by 45 degrees. Stimulus intensity was adjusted just above the motor threshold while subjects made a weak tonic voluntary contraction, so that we can analyse the most readily elicited descending volley in the pyramidal tracts. In most subjects, TMS with medially and anteriorly directed current in the brain produced responses or a peak that occurred some 1.5 ms later than those to anodal electrical stimulation. In contrast, TMS with laterally and posteriorly directed current produced responses or a peak that occurred about 4.5 ms later. There was a single peak in most of PSTHs under the above stimulation condition, whereas there were occasionally two peaks under the transitional current directions between the above two groups. These results suggest that TMS with medially and anteriorly directed current in the brain readily elicits I1 waves, whereas that with laterally and posteriorly directed current preferentially elicits I3 waves. Functional magnetic resonance imaging studies indicated that this direction was related to the course of the central sulcus. TMS with induced current flowing forward relative to the central sulcus preferentially elicited I1 waves and that flowing backward elicited I3 waves. Our finding of the dependence of preferentially activated I waves on the current direction in the brain suggests that different sets of cortical neurons are responsible for different I waves, and are contrarily oriented. The present method using a figure-of-eight-shaped coil must enable us to study physiological characteristics of each I wave separately and, possibly, analyse different neural elements in MI, since it activates a certain I wave selectively without D waves or other I waves.

Adult↗

Shortening of simple reaction time by peripheral electrical and submotor-threshold magnetic cortical stimulation.

Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can shorten the simple reaction time in contralateral arm muscles if the cortical shock is given at about the same time as the reaction stimulus. The present experiments were designed to investigate whether this phenomenon is due to a specific facilitatory effect on cortical circuitry. The simple visual reaction time was shortened by 20-50 ms when subthreshold TMS was given over the contralateral motor cortex. Reaction time was reduced to the same level whether the magnetic stimulus was given over the bilateral motor cortices or over other points on the scalp (Cz, Pz). Indeed, similar effects could be seen with conventional electrical stimulation over the neck, or even when the coil was discharged (giving a click sound) near the head. We conclude that much of the effect of TMS on simple reaction time is due to intersensory facilitation, although part of it may be ascribed to a specific effect on the excitability of motor cortex.

Electric Stimulation↗

Motor cortical reflex myoclonus: a case study with MEG.

Cortical reflex myoclonus usually depends for its generation on the hyperexcitability of sensory cortex, which manifests itself as an enhanced somatosensory evoked potential (SEP). A 25-year-old female, presenting with involuntary jerky dorsiflexion of the left foot, was found to have cortical reflex myoclonus which was aggravated during intended movements. The jerks were also elicited by electrical stimulation of the posterior tibial nerve, although the SEP evoked by the same stimulus was normal in latency and amplitude. Both the spontaneous spikes and the premyoclonus spike demonstrated by jerk-locked back averaging were localized to the superior frontal gyrus, just anterior to the paracentral sulcus. Paired-pulse magnetic stimulation disclosed lack of inhibition in the right hemisphere leg motor area, whereas the excitability of sensory cortex as studied by paired SEP testing was normal. This suggests that the myoclonus was caused mainly by enhanced excitability of the motor cortex and that this alone was enough for the production of long loop reflexes. We propose to designate this type of cortical myoclonus as motor cortical reflex myoclonus. It is generated in the motor cortex, but is at the same time stimulus-sensitive.

Adult↗

Magnetic stimulation over the cerebellum in patients with ataxia.

We studied 20 patients with ataxia caused by various disorders using magnetic stimulation over the cerebellum. Results were compared with normal values found for 12 normal volunteers. In normal subjects, a magnetic stimulus over the cerebellum reduced the size of responses evoked by magnetic cortical stimulation when it preceded cortical stimulus by 5, 6 and 7 ms. The grand average of the ratios of the areas of conditioned responses at intervals of 5, 6 and 7 ms to those of control responses was designated the average area ratio (5-7 ms). Suppression of motor cortical excitability was reduced or absent in patients with a lesion in the cerebellum or cerebellothalamocortical pathway, but was normal in patients with a lesion in the afferent pathway to the cerebellum. Normal suppression was observed in Fisher's syndrome. The average area ratio (5-7 ms) correlated well with the severity of ataxia in patients with degenerative late-onset ataxia. These results are consistent with those for electrical stimulation of the cerebellum reported previously. We conclude that magnetic stimulation over the cerebellum produces the same effect as electrical stimulation even in ataxic patients. This less painful method can be used clinically to clarify the pathomechanisms for ataxia. Two other clinical uses of this technique were that it revealed clinically undetectable cerebellar dysfunction in patients whose extrapyramidal signs masked cerebellar signs, and that the slow progression of ataxia could be followed quantitatively in patients with degenerative late-onset ataxia.

Adult↗

Magnetic stimulation of the descending and ascending tracts at the foramen magnum level.

To test the possibility that stimulation over the foramen magnum activates ascending tracts as well as descending tracts, we studied 4 patients with myoclonic epilepsy all of whom had enhanced cortical long loop reflexes (LLRs) and 10 normal subjects, using our previously reported method (Ugawa et al., Ann. Neurol., 1994, 36: 618-624). For latency comparisons, peripheral nerve stimulation at the elbow and spinal motor root were also performed. In all patients, magnetic stimulation at the foramen magnum consistently elicited long loop reflexes as well as direct responses caused by stimulation of the descending tracts. In contrast, no LLRs were ever seen in any normal subjects. The latencies of both types of response were the same whether stimulation used upward or downward current in the brain, although the former was always more effective. This indicates that stimulation at the level of the foramen magnum activates ascending tracts as well as descending tracts at a fixed position. The threshold for LLRs was lower than that for activation of the descending tracts. This threshold difference is compatible with the hypothesis that large diameter fibers from muscle afferent conduct the central afferent volley for LLRs (Marsden et al., Brain, 1977, 100: 185-200).

Afferent Pathways↗

Isolation and chemical-structural determination of a novel aromatic amine mutagen in water from the Nishitakase River in Kyoto.

Water samples from the Nishitakase River in Kyoto, Japan, especially taken at sites below sewage plants, show significantly high mutagenicity in the Ames test. In the present study, mutagens in the river water were adsorbed to 24 g of blue rayon, extracted, and separated by HPLC on ODS columns. Five mutagenic compounds (I-V) were isolated, and they accounted for 21%, 17%, 11%, 12%, and 6%, respectively, of the total mutagenicity of the blue rayon-adsorbed materials. With compound I obtained from adsorbate to 24 g of blue rayon as a marker, a large quantity (1.1 mg) of mutagenic compound I was isolated by Sephadex LH-20 column chromatography and HPLC on ODS columns from material adsorbed to 27 kg of blue cotton. X-ray crystal analysis was carried out with the debrominated derivative of compound I. Based on this X-ray crystallography data and the UV, mass, and 1H-NMR spectra of both the derivative and compound I, the structure of compound I was determined to be 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)amino]-5-methoxyphenyl]-5-amino - 7-bromo-4-chloro-2H-benzotriazole (PBTA-1). PBTA-1 is a newly identified potent mutagen, inducing 1,200,000 revertants of Salmonella typhimurium YG1024 per microgram in the presence of S9 mix.

Amines↗

Double product response is accelerated above the blood lactate threshold.

Catecholamine concentrations are known to increase sharply in the blood at work rates above the blood lactate threshold (LT); thus, we hypothesized that the double product (DP, heart rate-systolic blood pressure product) may also abruptly increase at work rates above the LT. Ninety healthy students performed a stepwise incremental test on a cycle ergometer. The slopes of the two regression lines below and above the LT for the heart rate (HR), the indirectly measured systolic blood pressure (SBP), and the DP, respectively, were compared using VO2 as an independent variable. For all three parameters the slope of the regression line above the LT was significantly higher than that below the LT. Although either the same or a lower slope was found in the HR (N = 23) or SBP (N = 22) responses in some subjects above the LT as compared with that below the LT, a steeper DP slope above the LT was evident in all 90 subjects. The same results were also obtained during 4-min constant work rate exercise sessions at a variety of submaximal intensities performed in a random order in seven subjects. In addition, we established the DP break point (DPBP) determining protocol with a fairly good test-retest reliability (r = 0.951) and a correlation coefficient between the DPBP and the LT (r = 0.900). These results suggest that the DP increases more steeply above the LT, and, as a result, the DPBP is considered to be a valid and useful parameter as a marker of the LT.

Adult↗

Phospholipase A2 is activated in the kidney, but not in the liver during ischemia-reperfusion.

Phospholipase A2 (PLA2) has been demonstrated to play an important role in the reperfusion injury of the kidney, gut, brain, heart and pancreas. This study was carried out to clarify whether PLA2 was involved in the ischemia-reperfusion injury of the liver. Rats were anesthetized and underwent laparotomy. They were allocated into one of 4 groups, i.e., the groups of renal ischemia (group RI), renal control (group RC), hepatic ischemia (group HI), and hepatic control (group HC). In group RI, the left renal pedicle was occluded for 1 hr, and the left kidney was removed after 1-hr reperfusion. In group HI, the portal and the hepatic artery supplying the left and middle lobes were clamped for 1 hr, followed by reperfusion. After predetermined periods of reperfusion up to 24 hr, the ischemic lobes were removed, homogenized and centrifuged. PLA2 activities in the mitochondrial fraction and the cytosolic fraction were measured with 14C-phosphatidylcholine (PC) and 14C-phosphatidylethanolamine (PE) as exogenous substrates. PLA2 activities of the both fractions in the kidney were significantly enhanced after 1-hr ischemia followed by 1-hr reperfusion. However, there was no enhancement of PLA2 activity of the either fraction in the group HI compared with the group HC. The results indicate that PLA2 is activated in the kidney but not in the liver during ischemia-reperfusion.

Alanine Transaminase↗

Ipsilateral cortico-cortical inhibition of the motor cortex in various neurological disorders.

We used a paired-pulse magnetic stimulation technique to study ipsilateral cortico-cortical inhibition of the motor cortex in 48 patients with various neurological disorders and in 20 normal volunteers. In the normal subjects, the first subthreshold conditioning stimulus suppressed responses to the second suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-5 ms (inhibition at short intervals), and facilitated them at ISIs of 8-15 ms (facilitation at long intervals). Patients with motor neuron disease, except those in whom brain stimulation produced control responses that were generated by direct activation of corticospinal neurons (D-waves), had normal inhibition at short intervals. Facilitation at long intervals was not elicited in some patients with amyotrophic lateral sclerosis. Less inhibition at short intervals and normal facilitation at long intervals was found for all the patients with progressive myoclonic epilepsy, a condition in which the excitability of cortical inhibitory interneurons is thought to be affected. Inhibition at short intervals was disturbed, but facilitation at long intervals was intact in the patients with movement disorders (Parkinson's disease, corticobasal degeneration, and Wilson's disease). In these patients, positron emission tomography (PET) studies showed decreased regional cerebral blood flow (rCBF) in the basal ganglia in the relaxed state. However, normal suppression was elicited in the patients with Parkinson's disease with normal rCBF. In four patients with chorea, the time-course of inhibition and facilitation was normal, even though PET studies showed decreased rCBF in the basal ganglia in two of them. Normal inhibition could not be elicited in patients who had a small lesion in the basal ganglia or in the pathway from basal ganglia to the primary motor cortex; the putamen, globus pallidus, and supplementary motor cortex. In contrast, patients who had a lesion in a sensory system (sensory cortex or sensory thalamus) or in the pontine nucleus had normal suppression. We conclude that the results of ipsilateral cortico-cortical inhibition with paired magnetic stimulation reflect the excitability of inhibitory interneurons in the motor cortex and that outputs from the basal ganglia markedly affect this inhibition, but outputs from somato-sensory systems or cerebellum do not. Moreover, dysfunction of the corticospinal tract or spinal motoneurons does not affect results obtained by the paired magnetic stimulation technique when the control responses are generated by I-waves (i.e. descending volleys are produced by transsynaptic activation of the corticospinal tract neurons.

Adult↗

Long-term cryopreserved allogeneic nervous and vascular tissue transfers in monkeys.

Four adult Japanese monkeys were used. Donor tissues were harvested from the radial artery, saphenous vein and median nerve, 10 cm in length, and cryopreserved at -196 degrees C in a stepwise manner for long-term preservation for more than 6 months. After rapid thawing of the tissue, the allogeneic tissue transfer was performed of the radial artery to the radial artery, the saphenous vein to the ulnar artery and the median nerve to the median nerve between male and female monkeys. After one year follow-up, angiography was performed and the transferred tissue was harvested for scanning electron microscopic examination and histological examination. As a result, the allogeneic artery in the radial artery was completely patent with no stenosis, whereas there was obstruction of the allogeneic vein in the ulnar artery. Good axonal recovery of the median nerve was observed on histological examination. The cellular structure of neurovascular tissue can be maintained even after long-term cryopreservation. The antigenicity of tissue may be reduced significantly by being frozen, and cryopreserved allogeneic artery can be transferred successfully without the use of immunosuppressive agents. In this report, clinical aspects and the great potential of allogeneic neurovascular tissue transfer, especially in combination with arterial transfer, using cryopreservation are discussed.

Animals↗

Magnetoencephalographic analysis of cortical myoclonic jerks.

We studied the pre-myoclonus spike using magnetoencephalography in patients with cortical myoclonus (6 with cortical reflex myoclonus and one with epilepsia partialis continua). The spike was estimated as a single current dipole on the pre-central gyrus in one patient with epilepsia partialis continua. In contrast, it was estimated as a single dipole on the post-central gyrus in 5 of 6 patients with cortical reflex myoclonus, and as two dipoles on the pre- and post-central gyrus in the remaining patient. We conclude that there are 3 physiological types of cortical myoclonus: (1) abnormal discharges in the motor cortex produce the myoclonus; (2) the source of the myoclonus is mainly the sensory cortex; (3) both the motor and sensory cortices play important roles in the production of myoclonus.

Epilepsies, Myoclonic↗

Clinical utility of magnetic corticospinal tract stimulation at the foramen magnum level.

We applied magnetic stimulation of the corticospinal tract at the foramen magnum level to 19 patients with various neurological disorders. Results were consistent with our previous speculation that activation occurs at the foramen magnum level. This method was clinically useful for the following conditions. (1) Detection of subclinical lesion: one patient who had transient ischemic attack that caused no clinical symptoms at examination was shown to have dysfunction of the corticospinal tract. (2) Multiple lesions: our method disclosed at least one lesion above and below the foramen magnum in two patients with multiple sclerosis. (3) Unmasking of dysfunction of the corticospinal tract masked by peripheral neuropathy: magnetic stimulation showed conduction delay in the corticospinal tract in two patients in whom no pyramidal signs were evident because of muscular atrophy due to neuropathy. One patient had multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy, the other had degenerative ataxia and neuropathy. (4) Association of disorders: conduction delay rostral to the foramen magnum, which should not occur in patients with only cervical myelopathy, was shown in a patient with cervical myeloradiculopathy and amyotrophic lateral sclerosis. We conclude that this magnetic stimulation method which is less painful than electrical stimulation has extensive clinical usefulness.

Adult↗

Cortical dysgenesis in a patient with Turner mosaicism.

In a patient with Turner mosaicism who had mental retardation, epilepsy and cerebellar ataxia, MRI showed cerebellar atrophy and a bizarre cortical dysgenesis of the cerebrum, which was considered to comprise a mixture of relatively normal gyri and structures resembling pachygyria and lissencephaly. The karyotype of the patient was 45,X/47,XXX, but the brain dysgenesis could not be explained solely on the basis of this mosaicism, which is rarely associated with a gross abnormality in brain pathology. Abnormality of the X chromosome seems to have some potential for inducing cortical dysgenesis, and this case may be partially attributable to an abnormal locus on the X chromosome.

Adult↗

[Involuntary movements observed in a patient with Russian spring summer encephalitis].

A 38-year-old woman had an episode of headache, fever and convulsion in October, 1993. She became alert in two weeks, though weakness and atrophy remained in the upper limb muscles. She was diagnosed as Russian spring summer encephalitis (RSSE) based on several serological studies. Three kinds of involuntary movements were noted after recovery. These were spontaneous muscle jerks in the left arm, action tremor in the right arm and pathological associated-movement in the right leg. The movements were studied physiologically by electroencephalogram (EEG)-electromyogram (EMG) polygraphic recordings, jerk-locked averaging (JLA), magnetencephalography (MEG), and sensory evoked potentials (SEPs). The jerky movements in her left arm were observed at rest and aggravated by emotional stress. EEG-EMG polygraph showed that the jerks were sometimes associated with small spikes thus were considered to be due to epilepsia partialis continua (EPC). JLA analysis revealed a pre-myoclonus spike on the right hemisphere which preceded the onset of the jerk in the left first dorsal interosseous muscle by 25.2ms, which was equal to the magnetic cortical latency of that muscle. Jerk-locked magnetic field, obtained by averaging neuromagnetic activities with respect to the onset of myoclonus, showed that the spike preceding the jerk, originated from the right motor cortex. The spontaneous spikes were localized mainly on the right motor cortex. Sensory evoked potentials (SEPs) were normal in both size and latency. No hyperexcitability of the sensory cortex was demonstrated even by using paired stimulation SEPs. Based on these results, we conclude that the jerky movements in this patient were produced by abnormal spontaneous discharges in the motor cortex. The action tremor had a frequency of 4-5 Hz and its clinical features were compatible with cerebellar tremor. This is thought to result from a lesion in the left thalamus, affecting the cerebellothalamic pathways. Her right leg unintentionally moved whenever she began to move the hands. This was considered to be a pathological associated-movement due to dysfunction of the pyramidal tracts.

Adult↗

Magnetic stimulation over the cerebellum in humans.

Magnetic stimulation performed with a double-cone coil placed over appropriate positions on the back of the head reduced the size of electromyographic responses evoked by magnetic cortical stimulation in the first dorsal interosseous muscle when it preceded the cortical stimulus by 5, 6, and 7 msec. No suppression of responses to electrical cortical stimulation occurred. Greater suppression was evoked by stronger cerebellar stimuli; lesser suppression was elicited by stronger cortical stimuli. These physiological findings correspond to those obtained with electrical cerebellar stimulation. The most effective position for magnetic stimulation over the back of the head was slightly rostral to the foramen magnum level on the ipsilateral side of the muscle studied. This indicates that the conditioning stimulus activates certain structures at the back of the head on the ipsilateral side of the muscle, consistent with the cerebellum, because the part of the cerebellum regulating limb muscles is positioned about there on the ipsilateral side. In 2 patients with only cerebellar dysfunction, this suppression effect was not elicited, which also supports that the suppression is caused by activity in cerebellar structures. We conclude that magnetic stimulation over the cerebellum with a double-cone coil elicits the same suppressive effect on the motor cortex as electrical stimulation, but with less discomfort; moreover, we believe that this effect is produced by activation of certain cerebellar structures.

Adult↗

Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl.

Although thiobarbiturates potentiate, and fentanyl attenuates peripheral vasoconstriction, the intracellular mechanism involved in this phenomenon is not clear. Because smooth muscle contraction induced by alpha 1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrine-induced PI response in rat aortic slices. Rat aortic slices were incubated in Krebs-Henseleit solution containing 5 mM LiCl, [3H]myo-inositol, and varying concentrations of thiamylal or fentanyl. The Pl response was stimulated by 0.9 microM (ED50) norepinephrine (NE). The [3H]inositol monophosphate (IP1) was separated from [3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. The basal IP1 accumulation was not affected by thiamylal and fentanyl. Norepinephrine-induced IP1 accumulation was potentiated by thiamylal at concentrations of 10 microM and 100 microM. Norepinephrine-induced IP1 accumulation was attenuated by 1 microM and 10 microM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attenuates NE-induced PI response, which would attenuate the vasoconstriction.

Anesthetics, Intravenous↗