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Biomedical subjects

M Kunimoto

Publications and source records attributed to M Kunimoto.

At least 91 records · Page 5Linked to original sources

Effects of unilateral lesion of the nucleus basalis of Meynert on brain glucose utilization in callosotomized baboons: a PET study.

Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in baboons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides despite persistent deficit in cortical ChAT activity. To investigate the role of the corpus callosum (CC) in this bilateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion greater than 3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by positron emission tomography; ChAT activity was measured and histological sections obtained after death. In these animals, the NbM lesion also induced significant metabolic depression over the ipsilateral cortex, proportional to the reduction in ChAT activity. Corpus callosotomy did not prevent the contralateral metabolic effects, suggesting that the latter do not normally operate through the CC. However, there was no significant recovery of glucose utilization, suggesting that, following unilateral NbM lesion, the CC normally mediates, at least in part, the recovery of cortical glucose utilization.

Animals↗

Effects of anterior corpus callosum section on cortical glucose utilization in baboons. A sequential positron emission tomography study.

Cortical glucose utilization was measured under light anaesthesia using positron emission tomography and 18F-fluorodeoxyglucose before and serially after stereotaxic anterior corpus callosum section in 3 adult baboons (Papio papio); in 1 animal needles were introduced but callosotomy was not performed ('sham' operation). Lesion efficacy was verified by x-ray computerized tomography and by postmortem examination which indicated effective anterior two-thirds callosal section in all 3 baboons, as well as a small contusional area in the medial frontal cortex. A two-way layout analysis of variance performed on the regional cerebral metabolic rate of glucose (CMRGlc) data obtained in the frontotemporal, temporal and occipital areas revealed significant effects for both the time and the region factors (P less than 0.00001 for each); the time effects indicated a significant initial metabolic depression (P less than 0.01) at day 11 and 18, and a subsequent recovery (P less than 0.01 to 0.05) at day 98. Average CMRGlc changes from preoperative values at successive studies were -23%, -27%, -17%, -8% and +2%, and -17%, -21%, -10%, -5% and +6% in the 'surgically approached' and the contralateral frontotemporal area, respectively. The frontotemporal/occipital CMRGlc ratio was significantly depressed at days 11, 18 and 32 (P less than 0.01, 0.01 and 0.05, respectively), indicating a transient postoperative alteration in the cortical metabolic pattern. In the 'sham' animal, surgery induced negligible metabolic effects. Our results indicate that effective anterior corpus callosum section induces a transient bilateral depression of cortical metabolism, which predominates in the anterior parts of the brain, while metabolic recovery suggests efficient neuronal adaptation. These functional effects in the cortex may underlie the transient behavioural changes that follow anterior callosotomy in man.

Animals↗

GABA withdrawal syndrome: a model of the epilepsia partialis continua.

After the chronic infusion of GABA into the cortex of baboon Papio Papio, a sudden stop of the infusion provoked cortical epileptic discharges around the infused area. And the baboon exhibited partial epilepsy for about 3 days. The result suggested that GABA withdrawal syndrome should be a good model not only to understand the mechanism of epilepsia partialis continua but also partial epilepsy with a circumscribed cortical focus.

Animals↗

[A case of chronic inflammatory demyelinating polyradiculoneuropathy with orthostatic hypotension].

A 27-year-old man was admitted to our hospital for his legs' numbness of subacute onset and discomfort while standing. No specific previous history was found and his family history was non-contributory. On admission, his general status was unremarkable except for arterial hypertension and mild tachycardia. Moderate impairment of superficial sensations and dysesthesia were noted in the distal extremities, tongue, oral cavity, and lips. Deep sensation was moderately impaired in the lower legs. Romberg sign was positive. He had mild weakness in the proximal muscles of the lower extremities. Hyporeflexia was noted in all extremities, but Achilles reflexes were absent. Pathologic reflexes were not noted. He fainted after two minute standing. On laboratory examination, serum IgM, C3, and C4 were mildly elevated. CSF protein level was prominently high without CSF pleocytosis. MCV was mildly decreased, and F wave conduction velocity was prominently decreased in the posterior tibial nerve, SCV was also mildly decreased in the right sural nerve. Needle electromyography showed mild neuropathic changes. Left sural nerve biopsy showed no abnormal finding in the myelinated and unmyelinated fibers. A 60 degree head-up tilting test caused a hypotensive attack, and Valsalva ratio was decreased. However, hand grip test and cold pressor test were normal. The response to noradrenaline infusion test and CVR-R were also normal. Muscle sympathetic activity (MSA) was recorded from the tibial nerve using a tungsten microelectrode (Iwase, et al.). His basic activity was higher and responsiveness was lower than age-matched normal controls. The regression line existed above the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Changes in plasma norepinephrine levels to stepwise tilting--comparisons between the young and aged].

Plasma norepinephrine level was measured in the 9 young (22-26 years old) and the 8 aged (66-81 years old) normal volunteers in stepwise tilting. After 30 minutes rest in recumbent position, the table was tilted in stepwise manner (15 degrees, 30 degrees, 45 degrees, 80 degrees) each for 5 minutes and blood samples were taken at the end of the each angle. The changes of the level was compared between the two groups and with the data resulted from the examination of muscle sympathetic activities by microneurography. The norepinephrine level increased with the stepwise tilting and the positive linear correlation was observed between the levels and the sine values of tilting angles. The absolute levels in the aged were significantly higher than those in the young in 0 degrees, 15 degrees, and 30 degrees. The increasing rates of plasma norepinephrine (percentages of increase against the level in 0 degrees position) in the aged were significantly lower than those in the young in 45 degrees and 80 degrees. These partly resembled the character observed in the two groups in muscle sympathetic activity. However, the gradients of the mean regression lines of the two groups in plasma norepinephrine level were not significantly different, although they were clearly different in muscle sympathetic activity. This means that the difference between the young and the aged was more clearly shown in muscle sympathetic activity than in plasma norepinephrine level.

Adult↗

Anticonvulsant activity of the diaryltriazine, LY81067: studies using electroencephalographic recording and positron emission tomography.

It is reported that LY81067, a new diaryltriazine, possesses anticonvulsant properties against grand mal status epilepticus induced by intravenous administration of picrotoxin binding site ligands (Ro 5-4864 and pentylenetetrazole) in the baboon. Intravenous administration of LY81067 during the seizures blocked grand mal type electroencephalographic (EEG) paroxysmal discharges and led to a long electrical silence, progressively replaced by spike-and-wave discharges of low frequency (2 c/sec). A transient blocking effect was also observed when LY81067 was injected during grand mal status epilepticus induced by the benzodiazepine inverse agonist methyl beta-carboline-3-carboxylate; however, the long electrical silence observed after administration of LY81067 was rapidly followed by grand mal type paroxysmal discharges in the EEG, which could be stopped by a subsequent injection of Ro 15-1788. However, LY81067 also displayed intrinsic epileptogenic properties. Administration of this drug alone led to the appearance of rhythmic EEG (2-3 c/sec) associated with myoclonia. Concomitantly with the EEG studies, interactions of all these drugs with benzodiazepine receptors were observed in vivo using [11C]Ro 15-1788 as radioligand and positron emission tomography (PET) as a non-invasive technique to measure the binding of the [11C]benzodiazepine antagonist in brain, in vivo. The [11C]Ro 15-1788 bound in the brain could not be displaced by the administration of LY81067 but rather, the [11C]antagonist binding in the brain was somewhat enhanced. Administration of pentylenetetrazole or Ro 5-4864 decreased the rate of wash-out of the radioligand. This fast effect of these two convulsant drugs was partially inhibited by the subsequent administration of LY81067. The concomitant blocking of the grand mal status epilepticus was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of the cytoskeleton fractions of rat red blood cells prepared with non-ionic detergents.

The characteristics of cytoskeleton fractions prepared from rat red cell ghosts with four non-ionic detergents were studied. One percent (w/v) solutions of Triton X-100, Emulgen 911, MEGA-9 (nonanoyl-N-methylglucamide), and octylglucoside solubilized 78, 68, 80, and 92% of the ghost phospholipid, while they solubilized 82, 78, 72, and 62% of the ghost band 3, a transmembrane protein, respectively. There was no correlation between the solubilization percentages of phospholipid and band 3. Phospholipids retained in cytoskeleton fractions were shown to exist as blebs on the surface by electron microscopic observation. The cytoskeleton fraction prepared with octylglucoside retained about two-fold more band 3 than that with Triton X-100 (Triton shells). However, cytoskeleton fractions prepared from p-chloromercuribenzoate-treated ghosts with the two detergents retained almost equal amounts of band 3, less than 5% of that in the ghosts. Under this condition, most of band 2.1, a protein linking band 3 to the spectrin-actin network, was released from the cytoskeleton fractions. The band 3 solubilized with octylglucoside sedimented faster in a linear sucrose gradient and had a larger Stokes' radius than that with Triton X-100, which is known to exist as dimer. These results strongly suggest that octylglucoside does not disturb the association of tetrameric band 3 with the spectrin-actin network, while Triton X-100 dissociates tetrameric band 3 to the dimer, resulting in the difference in the amount of band 3 retained in cytoskeleton fractions. In conclusion, octylglucoside can produce a more native cytoskeleton fraction of red cell membranes than Triton shells.

Animals↗

Electron microscopic study of the colloid-like substance in solar elastosis.

We have made electron microscopic studies on the elastotic material of solar elastosis which developed in cutis rhomboidalis nuchae taken from 10 males, 50-83 years of age. It was revealed that this material of the cutis rhomboidalis nuchae contained a colloid-like substance consisting of both a fine granular and an amorphous component. The colloid-like substance closely resembled that which is seen in the adult-type colloid milium, and could not be distinguished from it under light microscopy. In view of the morphological similarity at the ultrastructural level between the elastotic material and the colloid-like substance, it was proposed that normal elastic fibers can change into elastotic material and then further degenerate into the colloid-like substance, eventually becoming the typical colloid substance seen in colloid milium.

Aged↗

[Clinical evaluation of local administration of RIL-2 in head and neck cancer].

Recombinant Interleukin-2 (rIL-2) was administered locally to 20 patients with head and neck cancer. 800 thousand units of TGP-3 were injected around the tumor mass every day for about 4 weeks. Complete response (CR) was obtained in two cases with lip cancer and one with lingual cancer showed partial response (PR), and minor response (MR) in oral floor cancer. No recurrence of tumors was observed in the two cases of lip cancer. Chemotherapy was performed with rIL-2 in cases responding only insufficiently to rIL-2. It was interesting that arterial infusion of anticancer drugs subsequent to local administration of rIL-2 resulted in a dramatic decrease in tumor size in a short time. It is suggested that local administration of rIL-2 may play an important role in multimodal treatment for head and neck cancer.

Adult↗

[Acute effect of penicillin G on feline models of focal epilepsy].

Penicillin is well known as a potent convulsive agent. A cortical topical, intracerebral or systemic administration of penicillin produces abnormal and paroxysmal activity which may lead to seizure, and has been used in the investigation of the mechanisms of epilepsy. This is a report on the studies of an acute effect of potassium penicillin G on two models of experimental focal epilepsy: a) amygdaloid kindling model, and b) kainic acid-induced limbic seizure model. Twelve adult cats for amygdaloid kindling model (kindling group), six for KA-induced limbic seizure model (KA group) and four for a control group were prepared for this study. In kindling group, after completion of kindling procedure, 40-60 X 10(4) unit/kg of potassium penicillin G (PC), dissolved in sterilized normal saline, was injected intraperitoneally during an interictal period. In KA group, 1 micrograms of KA was injected into the left amygdala. Limbic seizures occurred frequently during the initial 5 hours but subsided completely within 3 days. After a latent period, spontaneous secondarily generalized convulsion occurred from 30 to 60 days after KA injection. The cats were completely normal in their behavior during the interictal period. During the interictal stage after the first generalized convulsion has been observed, 15-20 X 10(4) unit/kg of PC was injected intraperitoneally. In the control group, 40-60 X 10(4) unit/kg was injected intraperitoneally. Electroclinical observations were continued until 5 hours after PC injection in three groups. In the control group, no cats developed generalized convulsion. In the kindling group, 4 of 12 cats developed focal amygdaloid seizures with secondary generalization by nearly the identical doses required in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

[Evaluation of the skin sympathetic function by the decrease of skin temperature at the finger tip immersed into cold water].

The change of the skin temperature at the finger tip immersed into cold water was measured in normal volunteers and in patients with disturbances of various portions of sympathetic nervous system with copper-constant thermocouple. The skin temperature of the normal subjects decreased soon after the immersion, partly due to cooling by the cold water, and partly due to the decrease of the skin blood flow. The skin sympathetic activity recorded from three normal subjects using the technique of microneurography presented an increase during the decreasing phase of the skin temperature. The skin temperature of the patients who received stellate ganglion block did not fall and maintained higher level compared to that of normal subjects. These data indicated that the decreasing phase of the skin temperature of the immersed finger is related to the increase of skin sympathetic activity. Cases of vascular neuropathy (lesion in post-ganglionic fiber), Shy-Drager syndrome and pure autonomic failure (lesion in pre-ganglionic fiber), cervical spondylosis and cervical disc herniation (lesion in descending tract of sympathetic system in spinal cord), and bleeding in pons tegmentum (lesion in descending tract in brain stem) were examined and all of them presented poor decrease of the skin temperature during the immersion. The skin temperature decreased, but incompletely in the patients, who had suffered from thalamic infarct and post-central gyrus infarct, and did not feel any sense on the immersion. These results indicate that the decreasing phase of the skin temperature of the finger immersed into cold water depends more upon the efferent than upon the afferent system, and this test is useful for evaluation of the skin sympathetic function.

Adult↗

[Asymmetrical patchy muscle involvement in manifesting carriers of Duchenne muscular dystrophy--computed tomographical and histological study].

Two cases of manifesting carriers of Duchenne muscular dystrophy (DMD) were described. Case 1. The 41 year-old woman presented gait disturbance at the age of 40. She had two sons. The first son died of pneumonia soon after birth. The second son developed DMD and died of heart failure when he was 17 years old. Neurological examination revealed mild muscle weakness in neck flexors, gluteus maximus (left side dominance) and hamstrings (right side dominance) as well as bilateral calf pseudohypertrophy. Electromyography showed myopathic changes and serum creatine kinase (CK) was elevated (1941IU/l). The karyotype was 46XX. Computed tomography (CT) of skeletal muscles showed that the following muscles were partly replaced by fatty tissue: bilateral paravertebral muscles, left gluteus maximus, left quadriceps femoris, right adductor magnus, long head of right biceps femoris, bilateral peroneus longus and medial head of left gastrocnemius. Histological examination of left quadriceps femoris revealed only minimal change of focal endomysial proliferation and fiber size variation, demonstrating no necrotic fiber or no abnormalities in fiber type. Case 2. The 42 year-old woman was admitted to the hospital complaining of dyspnea and palpitation. The disease was initially diagnosed as myocardial infarction based on cardiomegaly, ECG abnormality (Q in aVL, V5,6., ST depression and negative T in V5,6, ST elevation in I, aVL) and elevated serum CK. However, the diagnosis was rejected due to the lack of subsequent changes in ECG and the continued elevation of serum CK even after her complaints had disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Limbic seizure and ibotenic acid-induced lesions of substantia innominata in cats].

The substantia innominata (SI) contains a lot of cholinergic neurons and mainly project their fibers to the cerebral cortex and to the amygdala. Degenerative lesions were made in the bilateral SI and influences of these lesions upon kainic acid-induced limbic seizure were studied. Eleven adult cats were stereotaxically implanted and 2.5 micrograms of ibotenic acid (IBO) was injected into the bilateral SI in 6 cats (IBO group) and 1 microliter of phosphate buffer (PB) in 5 cats (PB group). All animals were given freedom at least 8 days to recover from the operation. Kainic acid microinjection was made into the left amygdala and electroclinical observation was done. In PB group, the limbic status was elicited and these seizures persisted for about 3 days after the KA injection. Seizures were subsided but interictal discharges were observed at the injected site of the amygdala. Then, limbic seizures reappeared within 10 days and a slowly progressive development of limbic seizure was observed. These seizures developed further. Occasionally, these limbic seizures successively developed and secondarily generalized seizures occurred once or twice a week. Otherwise, their clinical behaviors were normal during the interictal periods. In IBO group, the limbic status were elicited and lasted for about 3 days after the KA injection. Although interictal discharges reappeared at the injected site of the amygdala, successive development of the limbic seizure was not observed. The secondarily generalized seizure never occurred in the IBO group. Histopathological studies revealed circumscribed degenerative changes in the bilateral SI. The KA microinjection into the amygdala resulted stereotyped amygdaloid degenerative lesions in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

The GABA-withdrawal syndrome: a new model of focal epileptogenesis.

A novel model of focal, cortical epilepsy is described. Chronic (6 h to 14 days), localized application of gamma-aminobutyric acid (GABA) into the somatomotor cortex of rats induces, upon withdrawal, the appearance of epileptogenic activity with maximal electrographic expression circumscribed to the infused site. This GABA-withdrawal syndrome (tested for a 100 micrograms/microliter/h dose) lasted from 24 to 168 h (mean values). A significant correlation was found between infusion time and duration of the excitability rebound, with the longer duration corresponding to the shorter infusion time. A distant lesion effect was observed in the thalamic area of cortical projection. The potential use of this neurotransmitter-induced phenomenon in the study of brain plasticity in general, and of epilepsy in particular, is discussed.

Animals↗

Relationship between sleep-wakefulness cycle and regional cerebral blood flow in kainic acid-induced epileptic focus in hippocampus.

Concurrent monitorings of polygraph and continuous measurements of rCBF of the epileptic focus were made in the nonanesthetized chronic cats. The influences of the sleep-wakefulness cycle on IIDs and rCBF of the epileptic focus of the hippocampus were analyzed. 1) IIDs increased remarkably during LSW and DSW but not as much as during DSW-P. 2) The rCBF decreased gradually during LSW and DSW. But the rCBF during DSW-P increased slightly as compared to that of DSW. 3) The frequencies of IIDs increased in association with hypoperfusion of the epileptic focus. 4) The spiking rate of the hippocampal focus decreased with the appearance of PGO during the deep slow wave sleep stages.

Animals↗

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome.

We observed changes in postganglionic efferent discharges of muscle sympathetic nerve (muscle sympathetic activity, MSA) microneurographically before and after the oral administration of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine, in a patient with Shy-Drager syndrome and irregular fluctuations of blood pressure. Before drug administration, MSA was only rarely observed with the patient in the supine position. There was a slight increase in MSA during head-up tilting to 40 degrees, and orthostatic hypotension (OH) occurred just after the body was tilted head upward to 40 degrees. MSA became prominent 30 minutes after the oral administration of 200 mg of L-threo-DOPS while the patient was in a 40 degree head-up position, and the OH was improved. The MSA discharge rate decreased and OH reappeared 3 hours after oral administration, when the plasma concentration of norepinephrine was at its highest level. We suggest that the OH improved mainly because of the increase in MSA due to L-threo-DOPS, and that the drug may activate sympathetic outflow at a site proximal to the sympathetic ganglion.

Autonomic Nervous System Diseases↗

[Acute effect of flunarizine on amygdaloid kindling in cats].

Flunarizine (Flu), a difluoro derivative of cinnarizine, is well known as a calcium channel blocker. Recently, many authors have reported an antiepileptic effect of this drug in experimental models of epilepsy and in the clinical use. In the present study, acute effect of Flu was examined in the amygdaloid kindled cats, and add-on effects of Flu with valproic acid (VA) was also studied. Twenty three cats were used in this study. Amygdaloid kindling was established as previously reported. A strength of stimulations for kindling was at 300 microA. Same strength was used after completion of kindling. In this "high intensity" kindling, daily stimulation invariably induced initial amygdalo-hippocampal seizures followed by secondarily generalized seizures after completion of kindling. In addition, one amygdaloid stimulation was given daily for 5 days after completion of kindling in order to make it certain to induce secondarily generalized seizures. Drugs were injected on the 6th day intraperitoneally one or two hours before the stimulation daily given for 5 days after completion of kindling (GS 6) or after 4 days clearance period of previous administration of the drug. Pretreatment with Flu (high doses: 30 or 50 mg/kg, i.p.) abolished the secondary generalization after the GS 6. With this high doses of Flu animals died of side effect within 3 days after intraperitoneal administration. With lower doses of Flu less than 3 mg/kg, i.p. of Flu no side effect was encountered but antiepileptic effect was not obtained as well. Then add-on trials of Flu were performed with valproic acid (VA). The most effective combination was 100 mg/kg, i.p. of VA with 3 mg/kg, i.p. of Flu. With this combination, secondary generalization was suppressed at a ratio of 54.5% The results confirmed antiepileptic effect of Flu and add-on effect of Flu to VA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗