Mitochondrial DNA mutations in diabetes mellitus and heart disease.
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DNA, Mitochondrial↗
Biomedical subjects
N Takeda
Publications and source records attributed to N Takeda.
Responses of locus coeruleus neurons to caloric stimulation in rats.
We examined the effects of caloric stimulation on the neuronal activity of the locus coeruleus (LC) and of the vestibular nucleus complex (VNC) in urethan-anesthetized rats. The single unit activity of neurons in the LC and VNC was extracellularly recorded. A polyethylene tube for caloric stimulation was inserted into the middle ear cavity on the ipsilateral side. Through the tube, the middle ear was irrigated by hot (44 degrees C), cold (30 degrees C), and ice (4 degrees C) water. The majority of neurons in the VNC showed excitation by middle ear irrigation with hot water and inhibition by ice-water irrigation. The responses occurred during caloric stimulation and disappeared immediately after the cessation of the stimulation. The results suggest that the responses of VNC neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. On the other hand, the predominant effect of caloric stimulation with hot and cold water on LC neuronal activity was inhibitory. The suppression of LC neuronal activity occurred approximately 1 min after the cessation of the caloric stimulation and persisted for 3-5 min. The results suggest that LC neurons receive processed vestibular signals. Motion sickness and vestibular dysfunction induced by caloric stimulation cause emesis, which is known as vestibulo-autonomic response. The vestibulo-autonomic syndrome can be prevented by amphetamine, a noradrenaline releaser. Therefore, the inhibitory response of noradrenergic LC neurons to vestibular stimulation may be involved in the vestibulo-autonomic response.
Afferent Pathways↗
Clinical investigation of the vestibular cortex.
This study attempted to identify the vestibular cortex that is involved in the perception of vestibular vertigo in the human brain. We used single-photon emission computed tomography (SPECT) to measure regional cerebral blood flow (rCBF) in two cerebrovascular patients with nystagmus-sensation dissociation, which is known as brisk caloric nystagmus without simultaneous sensation of vertigo. Both patients had ischemic lesions involving mainly the parieto-temporal lobe in the nondominant hemisphere. It is suggested that the parieto-temporal lobe in the nondominant hemisphere contains the vestibular cortex which is a center for the perception of vertigo due to vestibular stimulation.
Aged↗
Nystagmus measured by ENG after stapes surgery.
Much attention has been paid to hearing results after stapes surgery, but the risks of vestibular disturbance has not been extensively studied. Postoperative spontaneous nystagmus was measured daily at bedside by portable ENG in order to evaluate the vestibular damage from stapes surgery. Thirteen patients underwent primary stapedotomy or stapedectomy from August 1, 1992 to June 30, 1993. Nystagmus toward the operated ear was observed in 3 cases, that toward the opposite ear in 2 cases, that changing from toward the operated ear to toward the opposite ear in 2 cases, that changing from toward the opposite ear to toward the operated ear in 2 cases and no nystagmus in 4 cases. There was no relationship between duration of nystagmus and that of dizziness. Nystagmus was thought to be due to the following: i) inner ear damage by operation, ii) postoperative perilymphatic fistula, iii) floating footplate, and iv) stimulation of hair cells by high potassium ion in the perilymph due to blood flow into the inner ear.
Adolescent↗
Vestibular modulation of the septo-hippocampal cholinergic system of rats.
Effects of vestibular stimulation on the in vivo release of hypothalamic histamine and hippocampal acetylcholine (ACh) were investigated in urethan-anesthetized rats, using a brain microdialysis method. Changes in glutamate concentration in the medial vestibular nucleus (MVN) were also monitored by a microbiosensor technique using a glutamate oxidase-embodied platinum electrode. Caloric stimulation with hot water increased the glutamate release in the MVN, while that with ice water decreased it. It is evidenced that glutamate is a neurotransmitter between afferent vestibular nerve and the MVN. Electrical stimulation of the round window evoked the release of hypothalamic histamine and hippocampal ACh and these effects were inhibited by the blockade of second-order vestibular neurons by the pre-injection of 6,7-dinitroquinoxaline-2,3-dione (DNQX), an antagonist of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, into the ipsilateral vestibular nucleus. Caloric stimulation with both hot and ice water increased the release of hypothalamic histamine and hippocampal ACh. It is suggested that both the histaminergic and cholinergic systems were activated by the imbalance of intervestibular activities. Depletion of neuronal histamine by alpha-fluorometylhistidine (FMH), an irreversible inhibitor of histamine synthesis, did not suppress the vestibular evoked release of hippocampal ACh. In contrast, caloric stimulation did not evoke hypothalamic histamine release in rats treated with ethylcholine aziridiniun ion (AF64A), a putative cholinotoxin. All these findings suggest that the vestibular information activated the histaminergic neurons via the activation of the cholinergic neurons and this neuronal circuit was involved in the vestibulo-autonomic response.
Acetylcholine↗
Changes in Fos and Jun expression in the rat brainstem in the process of vestibular compensation.
By means of immunohistochemical technique, we examined the changes in Fos and Jun expression after unilateral labyrinthectomy (UL) in the rat brainstem. We observed Fos-like immunoreactivity (-LIR) in the ipsilateral medial vestibular nucleus (ipsi-MVe), the contralateral prepositus hypoglossal nucleus (contra-PrH) and the contralateral inferior olive beta subnucleus (contra-IOb) 1 h after UL. Then, Fos expression in the contra-PrH and the contra-IOb disappeared 3 days after surgery. However, we still found the residual expression in the ipsi-MVe, which disappeared within 7 days. On the other hand, no Jun-LIR was detected in the vestibular or vestibular-related nuclei before or after the operation. Fos expression in the MVe, PrH and IOb was induced immediately after UL. Then, the Fos expression disappeared in accordance with the development of the vestibular compensation. These findings suggest that the transient Fos expression in the vestibular and vestibular related nuclei is a trigger of vestibular compensation.
Animals↗
Assessment of auditory and vestibular functions after vestibular neurectomy for Menière's disease.
Fourteen patients (12 Meniere's disease, one delayed endolymphatic hydrops and one labyrinthitis) suffering from intractable vertigo were treated with retrosigmoid vestibular neurectomy (RSVN) in our institute. Dizziness was controlled completely in all patients. Hearing was preserved in 91.7% of the cases with pure tone threshold deteriorating by more than 10 dB in one case, remained unchanged in 10 cases and improved in one case during long term observation. Substantial decrease of tinnitus was observed in 78.6%. Vestibular compensation was chronologically analyzed with a stabilometer, ENG and vestibular rotation test (0.01-0.64 Hz). Vestibular compensation under static conditions was accomplished within 2 weeks, except for spontaneous nystagmus measured in the dark. Asymmetry of vestibulo-ocular reflex was noted 2 weeks after the operation but had disappeared after 4 weeks. However, for over 2 years the VOR time constant remained lower (4.3-5.2 s) than the pre-operative value (8.2 s). Electro-cochleogram (ECoG) was recorded before and after RSVN. The -SP/AP ratio tended to increase after RSVN in the operated ear, though there was no change in the contralateral ear. The efferent olivo-cochlear bundle was thought to play a potential role in this increase of the -SP/AP ratio.
Adult↗
Natural history of intracranial cavernous malformations.
The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations.
Adolescent↗
[Multivariate analysis of everyday handicap of patients with dizziness].
A preliminary questionnaire consisting of 30 questions was developed to evaluate handicaps in everyday life for 105 patients with dizziness. Factor analysis divided the questions into 5 principal factors of handicap due to dizziness: 1) disturbance of social activity, 2) body motion precipitating dizziness, 3) limitation of physical activity, 4) emotional disturbance, and 5) disturbance of interpersonal communications. The score of each factor was calculated as the sum of the scores of three principal questions in the corresponding factor. There was no contribution of clinical diagnosis, patient's age or gender, or duration of the disease to the score of each factor. Thus, it is concluded that the reorganized questionnaire which consists of three principal questions in 5 factors can be used for evaluating dizziness handicaps in everyday life. The score of the emotional factor in patients with Meniere's disease was higher than that for other vestibular disease. The score of the body motion factor in patients with vestibular neuronitis was higher than that for vertebro-basilar artery insufficiency. Thus, the re-organized questionnaire can also be used for evaluating the contribution of each factor to dizziness handicaps in everyday life.
Activities of Daily Living↗
[Diagnostic and therapeutic problems in vestibular neuronitis: clinical implications for sudden vertigo].
We defined sudden vertigo as a sudden, unilateral peripheral vestibular dysfunction. The criterion for its diagnosis is a single episode of vertigo without cochlear and central symptoms. Among 20 patients with sudden vertigo there was no difference in clinical aspects between those with CP (canal paresis) (CP% > or = 25%) and those without CP (CP% < 25%). This suggests that sudden vertigo with CP is due to sudden vestibular dysfunction with predominant involvement of the lateral semicircular canal. Basically, vestibular neuronitis is considered to be due to acute unilateral neuropathy of the vestibular nerve. However, since we have no routine examination for evaluating vestibular nerve function, sudden vertigo with CP should be diagnosed as vestibular neuronitis. We then assessed the prognosis of sudden vertigo with CP (vestibular neuronitis). About two years after the onset of CP 4 of 10 patients had recovered. However, patients with persistent CP had a handicap in their everyday life because of the dizziness induced by head movements. The possibility of recovery of vestibular function in response to steroid therapy may improve the prognosis in vestibular neuronitis.
Adult↗
[Features of eating behaviour and their psychological background in simple obesity patients].
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Feeding Behavior↗
[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas].
Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.
Antineoplastic Agents↗
Neuropharmacological mechanisms of emesis. I. Effects of antiemetic drugs on motion- and apomorphine-induced pica in rats.
The effects of diphenhydramine, domperidone, ondansetron, and diphenidol on motion- and apomorphine-induced pica (i.e., kaolin ingestion) in rats as the measure analogous to emesis in other species were examined. Diphenhydramine (10 and 20 mg/kg) and diphenidol (30 mg/kg) inhibited kaolin intake induced by 60-min double rotation, while domperidone and ondansetron did not. Kaolin intake induced by apomorphine (10 mg/kg) was inhibited by domperidone (2 mg/kg) and diphenidol (30 mg/kg), but not by diphenhydramine or ondansetron. These findings suggest that the emetic pathways through the inner ear (double rotation) and the chemoreceptor trigger zone (apomorphine) are pharmacologically independent and are mediated by histamine H1 receptors and dopamine D2 receptors, respectively. Diphenidol may inhibit a common locus of emesis.
Animals↗
Synergism of Ce (IV) and Pr(III) for the fastest non-enzymatic DNA hydrolysis ever.
By the synergistic catalysis of Ce4+ and Pr3+, DNA is efficiently hydrolyzed at so far the highest rate. When [Ce4+] = 10 mM and [Pr3+] = 5 mM, the half-life of dinucleotide hydrolysis at pH 7 and 50 degrees C is only 24 min. This catalytic activity is 9 times as large as that of Ce4+, which is the only prominent catalyst hitherto reported. The Ce(4+)-Nd3+ combination is also effective. These bimetallic catalytic systems are eminent tools for the future molecular biology and biotechnology.
Catalysis↗
Neuropharmacological mechanisms of emesis. II. Effects of antiemetic drugs on cisplatin-induced pica in rats.
The effects of diphenhydramine, domperidone, ondansetron, and diphenidol on cisplatin-induced pica (i.e., kaolin ingestion) in rats as the measure analogous to emesis in other species were examined. Ondansetron (2 mg/kg) and diphenidol (30 mg/kg) inhibited kaolin intake induced by cisplatin (10 mg/kg), but diphenhydramine and domperidone did not. Diphenhydramine and diphenidol have been shown to inhibit kaolin intake induced by double rotation, while domperidone and ondansetron did not, and kaolin intake induced by apomorphine was inhibited by domperidone and diphenidol, but not by diphenhydramine or ondansetron. These observations, together with the present findings, suggest that the emetic pathways through the inner ear (double rotation), chemoreceptor trigger zone (apomorphine) and visceral afferent (cisplatin), are pharmacologically independent and are mediated by histamine H1 receptors, dopamine D2 receptors and serotonin 5-HT3 receptors, respectively. It is conceivable that diphenidol may inhibit the emetic center itself, although the receptor on which it acts is not known.
Animal Feed↗
Alterations in G-proteins in congestive heart failure in cardiomyopathic (UM-X7.1) hamsters.
In order to explain the attenuated sympathetic support during the development of heart failure, the status of beta-adrenergic mechanisms in the failing myocardium was assessed by employing cardiomyopathic hamsters (155-170 days old) at moderate degree of congestive heart failure. The norepinephrine turnover rate was increased but the norepinephrine content was decreased in cardiomyopathic hearts. The number and the affinity of beta receptors in the sarcolemmal preparations were not changed in these hearts at moderate stage of congestive heart failure. While the basal adenylyl cyclase activity was not altered in sarcolemma, the stimulation of enzyme activity by NaF, forskolin, Gpp(NH)p or epinephrine was depressed in hearts from these cardiomyopathic hamsters. Since G-proteins are involved in modifying the adenylyl cyclase activity, the functional and bioactivities as well as contents of both Gs and Gi proteins were determined in the cardiomyopathic heart sarcolemma. The functional stimulation of adenylyl cyclase by cholera toxin, which activates Gs proteins, was markedly depressed whereas that by Pertussis toxin, which inhibits Gi proteins, was markedly augmented in cardiomyopathic hearts. The cholera toxin and pertussis toxin catalyzed ADP-ribosylation was increased by 37 and 126%, respectively; this indicated increased bioactivities of both Gs and Gi proteins in experimental preparations. The immunoblot analysis suggested 74 and 124% increase in Gs and Gi contents in failing hearts, respectively. These results suggest that depressed adenylyl cyclase activation in cardiomyopathic hamsters may not only be due to increased content and bioactivity of Gi proteins but the functional uncoupling of Gs proteins from the adenylyl cyclase enzyme may also be involved at this stage of heart failure.
Adenosine Diphosphate Ribose↗