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Biomedical subjects

J Kohyama

Publications and source records attributed to J Kohyama.

At least 19 recordsLinked to original sources

Medullary reticulospinal tract mediating the generalized motor inhibition in cats: parallel inhibitory mechanisms acting on motoneurons and on interneuronal transmission in reflex pathways.

The present study was designed to elucidate the spinal interneuronal mechanisms of motor inhibition evoked by stimulating the medullary reticular formation. Two questions were addressed. First, whether there is a parallel motor inhibition to motoneurons and to interneurons in reflex pathways. Second, whether the inhibition is mediated by interneurons interposed in known reflex pathways. We recorded the intracellular activity of hindlimb motoneurons in decerebrate cats and examined the effects of medullary stimulation on these neurons and on interneuronal transmission in reflex pathways to them. Stimuli (three pulses at 10-60microA and 1-10ms intervals) delivered to the nucleus reticularis gigantocellularis evoked inhibitory postsynaptic potentials in alpha-motoneurons (n=147) and gamma-motoneurons (n=5) with both early and late latencies. The early inhibitory postsynaptic potentials were observed in 66.4% of the motoneurons and had a latency of 4.0-5.5ms with a segmental delay of more than 1.4ms. The late inhibitory postsynaptic potentials were observed in 98.0% of the motoneurons and had a latency of 30-35ms, with a peak latency of 50-60ms. Both types of inhibitory postsynaptic potentials were evoked through fibers descending in the ventrolateral quadrant. The inhibitory postsynaptic potentials were not influenced by recurrent inhibitory pathways, but both types were greatly attenuated by volleys in flexor reflex afferents. Conditioning medullary stimulation, which was subthreshold to evoke inhibitory postsynaptic potentials in the motoneurons, neither evoked primary afferent depolarization of dorsal roots nor reduced the input resistance of the motoneurons. However, the conditioning stimulation often facilitated non-reciprocal group I inhibitory pathways (Ib inhibitory pathways) to the motoneurons in early (<20ms) and late (30-80ms) periods. In contrast, it attenuated test postsynaptic potentials evoked through reciprocal Ia inhibitory pathways, and excitatory and inhibitory pathways from flexor reflex afferent and recurrent inhibitory pathways. The inhibitory effects were observed in both early and late periods. The present results provide new information about a parallel inhibitory process from the medullary reticular formation that produces a generalized motor inhibition by acting on alpha- and gamma-motoneurons, and on interneurons in reflex pathways. Interneurons receiving inhibition from flexor reflex afferents and a group of Ib interneurons may mediate the inhibitory effects upon motoneurons.

Animals↗

Polysomnographical assessment of the pathophysiology of West syndrome.

In this brief review, the sleep studies on patients with West syndrome (WS) were summarized. In addition to the previously reported common finding for sleep in WS--reduction of the amount of rapid-eye-movement (REM) sleep--weakness of phasic suppression of chin muscle activity in WS patients has recently been found. The degree of this weakness is quantified by the phasic inhibition index (PII), which has been found to reflect a patient's prognosis as to convulsions. PII is proposed to be a useful parameter for assessing the prognosis of WS. Since the pontine tegmentum is involved in the production of the REM-related phasic loss of muscle activity in REM sleep, WS patients are hypothesized to have a functional instability of the pontine tegmentum. After adrenocorticotropin (ACTH) treatment, PII decreased significantly in all WS patients examined. Taken together with the effects of corticosteroids on PII, and the incidence of phasic chin muscle activity in patients with congenital adrenal hyperplasia and nephrotic syndrome, ACTH is hypothesized to suppress the spasms in WS patients not only through corticosteroids, but also through a direct action on the pontine tegmentum. Since PII has been reported to be elevated in patients with an autistic tendency, the appearance of an autistic tendency is also hypothesized to be involved in the functional disturbance of the pontine tegmentum.

Brain↗

Disturbance of phasic chin muscle activity during rapid-eye-movement sleep.

In patients with Rett syndrome (RS), a peculiar type of disturbance in phasic chin muscle activity during rapid-eye-movement sleep (REMS) (e.g. an elevation of phasic inhibition index (PII) without an affection of tonic inhibition index (TII)) has been reported. The similar disturbance in REMS was reported not only in child patients with infantile spasms, severe myoclonic epilepsy in infancy (SMEI), severe nocturnal enuresis, and autism but also in adult patients with Parkinson's disease (PD). Except for SMEI and PD, patients with the other four clinical entities including RS could express autistic tendency. Since the responsible lesion for the occurrence of an elevation of PII with a normal TII value is likely to be in the pontine tegmentum, this subcortical structure is hypothesized to be involved in the appearance of autistic tendency.

Adolescent↗

Brain from bone: efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent.

Bone marrow stromal cells are able to differentiate into adipogenic, chondrogenic, myogenic, osteogenic, and cardiomyogenic lineages, all of which are limited to a mesoderm-derived origin. In this study, we showed that neurons, which are of an ectoderm-origin, could be generated from marrow-derived stromal cells by specific inducers, fibronectin/ornithine coating, and neurosphere formation. The neurons generated from marrow stroma formed neurites, expressed neuron-specific markers and genes, and started to respond to depolarizing stimuli as functional mature neurons. Among stromal cells, isolated mature osteoblasts which had strong in vivo osteogenic activity could be efficiently converted into functional neurons. This transdifferentiation or meta-differentiation was enhanced by Noggin, an inhibitor of bone morphogenetic proteins, in comparison with 5-azacytidine, a demethylating agent capable of altering the gene expression pattern. Marrow stroma is therefore a potential source of cells for neural cell transplantation.

Animals↗

Asynchronous breathing during sleep.

BACKGROUND: Children rarely complain of symptoms associated with sleep disordered breathing (SDB). Paradoxical inward rib cage movement (PIRCM) during sleep might prove useful for detecting SDB. AIMS: (1) To determine the correlation between the degree of PIRCM and other measures of disordered breathing during sleep. PIRCM occurs physiologically throughout rapid eye movement sleep in neonates, while no PIRCM has been reported during sleep in adolescents. (2) To determine the chronological changes in the degree of PIRCM. METHODS: PIRCM was quantified by means of the laboured breathing index (LBI). LBI was determined by respiratory inductive plethysmography; PIRCM accompanies a high LBI. Sleep recordings obtained for 101 subjects for various reasons (aged from 3.5 months to 19 years) were analysed. RESULTS: In 22 records, the minimum SaO2 value was 90% or more and no obstructive apnoea of more than 10 seconds was observed. In these 22 records, LBI during rapid eye movement sleep decreased significantly with age, reaching the mature low level at 3.3 years of age. In the other 79 records, LBI correlated well with measures of obstructed breathing during sleep. CONCLUSIONS: By paying more attention to PIRCM, more obstructed breathing during sleep might be found among children aged 3 years or more.

Adolescent↗

[Efficacy of anticonvulsants on acute encephalitis with refractory, repetitive partial seizures (AERRPS)].

The first purpose of this study is to propose a new clinical entity, acute encephalitis with refractory, repetitive partial seizures (AERRPS), which satisfy the following five criteria: 1. a prolonged acute phase of more than 2 weeks; 2. partial seizures of the same seminology persisting from the acute phase to the convalescence; 3. seizures frequently evolving into convulsive status especially during the acute phase; 4. marked intractableness of seizures; 5. exclusion of related disorders such as known viral encephalitis or metabolic disorders. The second purpose is to evaluate the efficacy of therapeutic agents on AERRPS. We reviewed 21 cases reported previously, as well as one patient seen by us. Based on the data, we recommend that patients with AERRPS should be under a high dose intravenous barbiturate during the acute phase, followed by a high dose of phenobarbital or phenytoin in the convalescence. Clonazepam, zonisamide, and potassium bromide were sometimes effective during the recovery phase.

Acute Disease↗

REM sleep atonia: from basic background to clinical application.

Muscle tone is profoundly suppressed during rapid-eye-movement sleep (REMS). Two indices that quantify this muscle activity suppression were introduced; the tonic inhibition index (TII) and the phasic inhibition index (PII). TII expresses the shortness of phasic chin muscle activity, and PII indicates the weakness of rapid eye movements-related phasic chin muscle activity loss. TII increased significantly with age, while PII decreased significantly. These chronological changes were concluded to indicate that the activity of the human nervous systems involved in both tonic and phasic inhibition in REMS increases with age. TII was found to reach the adult level at 12.3 years of age, while PII decreased to the adult value at 0.4 years. According to this difference in age between their maturation, the human nervous systems involved in muscle activity suppression during REMS are hypothesized to comprise at least 2 independent systems. TII and PII are also hypothesized to be affected by the activity of the brainstem inhibitory/facilitatory centers, which might be implicated in the control of muscle activity during wakefulness as well.

Adult↗

REM sleep atonia: responsible brain regions, quantification, and clinical implication.

Muscle tone is profoundly suppressed during rapid-eye-movement sleep. Two indices that quantify this muscle activity suppression were introduced: the tonic inhibition index (TII) and the phasic inhibition index (PII). TII expresses the shortening of phasic chin muscle activity, and PII indicates the degrees of suppression of the occurrence of phasic chin muscle activity in the period of the burst of rapid eye movements. TII increased significantly with age, while PII decreased significantly. TII was found to reach the adult level at 12.3 years of age, while PII decreased to the adult value at 0.4 years. According to this difference in age between their maturation, the human nervous systems involved in muscle activity suppression are hypothesized to comprise at least two independent systems. TII and PII are also hypothesized to be affected by the activity of the brainstem inhibitory centers, which might be implicated in the suppression of muscle activity during wakefulness as well.

Age Factors↗

ACTH activates rapid eye movement-related phasic inhibition during REM sleep in patients with infantile spasms.

OBJECTIVES: Phasic inhibition index (PII) is the rate of the simultaneous occurrence of phasic chin muscle activity (PCMA) and rapid eye movement bursts during rapid-eye-movement sleep (REMS). In naive patients with infantile spasms (IS), the PII value was found to reflect their prognosis. We studied the effects of adrenocorticotropic hormone (ACTH) on REMS components including PII in IS. METHODS: REMS parameters were examined in 18 IS patients before and after ACTH treatment. The effects of corticosteroids (CSs) were examined in 3 patients with congenital adrenal hyperplasia (CAH) and 3 with nephrotic syndrome (NS). RESULTS: ACTH decreased PII and PCMA in IS patients. In CAH patients, physiological doses of CSs corrected the increased intrinsic ACTH level and increased PII. In NS patients, therapeutic doses of CSs suppressed PCMA without affecting PII. CONCLUSION: ACTH suppressed PCMA through CSs, and reduced PII directly. ACTH was hypothesized to eliminate IS through these dual modes of action.

Adolescent↗

Sleep disordered breathing during REM sleep in Freeman-Sheldon syndrome.

OBJECTIVES: To examine the sleep-disordered breathing in patients with Freeman-Sheldon syndrome (FSS). MATERIAL AND METHODS: One night polysomnography was performed for 2 teenage FSS patients. RESULTS: They showed frequent obstructive sleep apnea exclusively during rapid-eye-movement sleep. CONCLUSION: FSS is a risk factor for the occurrence of sleep disordered breathing.

Abnormalities, Multiple↗

Immunohistochemical analysis of brainstem lesions in infantile spasms.

Whether the cerebral or subcortical lesions are involved in the pathogenesis in infantile spasms (IS) remains to be determined. To investigate the functional lesions of the subcortical structures in IS, the brainstem expression of neurotransmitters, neuropeptides and calcium-binding proteins in IS autopsy cases of lissencephaly and of perinatal hypoxic ischemic encephalopathy (HIE/IS) was investigated. The IS patients consisted of four subjects each of lissencephaly and HIE. They suffered from both West and Lennox-Gastaut syndromes. The healthy and disease controls were composed of four subjects without neuromuscular disorders and six cases of HIE (HIE/C), neither of whom had the epileptic syndrome. In these subjects the expressions of tryptophan hydroxylase (TrH), tyrosine hydroxylase (TH), parvalbumin (PV), methionine-enkephalin (ME) and substance P (SP) were immunohistochemically determined in serial sections of the midbrain, pons and medulla oblongata. The immunoreactivity of neurons and neuronal processes for TH was altered in the mesencephalic periaqueductal gray matter, locus ceruleus, and dorsal vagal nucleus in the patients. The HIE/IS cases showed reduced TrH-immunoreactivity in the medullary raphe nuclei. The brainstem auditory tract was poorly discernible on anti-PV immunostaining in the IS patients. The immunoreactivity for ME in the spinal trigeminal nucleus was severely affected in the IS patients, while that for SP was comparatively well preserved. It is suggested that the presence of common brainstem lesions in IS is irrespective of etiologies. It is intriguing that some of the changes seemed to be interrelated with the neurophysiological abnormalities being reported in IS patients.

Adolescent↗

Quantitative analysis of paradoxical inward rib cage movement during sleep in children.

Paradoxical inward rib cage movement in children is quantified by the labored breathing index (LBI) on the respiratory inductive plethysmography. Labored breathing index during rapid eye movement sleep (REMS) in 59 children without obvious sleep disordered breathing (SDB) declined with age, and decreased to the mature low level at 35 months of age. The LBI was also found to reflect well the severity of SDB. Paradoxical inward rib cage movement, which was quantified by LBI, is concluded to be an important finding in diagnosing SDB in child patients.

Adolescent↗

Nocturnal enuresis and the pontine reticular formation.

OBJECTIVES: To assess the previously proposed hypothesis that enuretic patients have a dysfunction in the pontine reticular formation. METHODS: In 18 patients with intractable nocturnal enuresis, rapid eye movement (REM)-related phasic chin muscle activity loss in REM sleep was examined by means of a single-night polysomnography. RESULTS: In 5 of 18 patients, this physiologically seen phenomenon was found to be disturbed. CONCLUSIONS: Since REM-related phasic chin muscle activity loss is disturbed by the functional impairment in the pontine reticular formation, some enuretic patients could be considered as presenting a dysfunction in this structure.

Adolescent↗

Rapid eye movement sleep in breath holders.

One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.

Brain Stem↗

REM sleep components predict the response to initial treatment of infantile spasms.

PURPOSE: The phasic inhibition index (PII) is the rate of the simultaneous occurrence of rapid eye movement bursts (RBs) and phasic chin muscle activity (PCMA) during rapid eye movement sleep (REMS). PII is low insofar as physiologically occurring REM-related phasic inhibition acts on chin muscles. Previously we found that PII was significantly higher in patients with infantile spasms (ISs) who had a recurrence of convulsions than in patients with ISs who exhibited no recurrence. We aimed to predict the response of patients with ISs to conventional anticonvulsants (AEDs) by means of REMS components including PII, expecting to facilitate avoidance of potentially hazardous hormonal therapy. METHODS: REMS, recorded before the beginning of any medication, was retrospectively examined in 15 patients with ISs. The patients were classified into two groups according to the response to initial treatment with conventional AEDs. Conventional AEDs were enough to control the spasms in six good responders (GRs), whereas further hormonal therapy was required in nine poor responders (PRs) to control the spasms. RESULTS: The amount of REMS was significantly lower in patients with ISs than in controls. GRs had less REMS than did PRs, although no significant difference was observed. Although the frequencies of RB and PCMA showed no significant differences among GRs, PRs, and controls, the average PII value in PRs (12.6+/-3.4; mean+/-SD) was significantly (p < 0.001) higher than that in GRs (6.1+/-1.7). CONCLUSIONS: PII is a useful parameter for differentiating GRs from PRs.

Anticonvulsants↗