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Biomedical subjects

A Noda

Publications and source records attributed to A Noda.

At least 55 records · Page 3Linked to original sources

Clinical safety and performance of Sugita titanium aneurysm clips.

BACKGROUND: In spite of advantages for neuro-imaging, titanium aneurysm clips are not yet chosen for routine use for clipping of intracranial aneurysms, probably because their reliability has not been demonstrated in large numbers of cases. We assess reliability and safety of Sugita titanium aneurysm clips for routine clinical use in a large number of operated cases. METHOD: Intra-operative performance and safety of Sugita titanium aneurysm clips were evaluated in 347 patients in our institutions. Aneurysms in 261 patients had ruptured: 86 patients had unruptured aneurysms. RESULTS: A total of 441 clips of 52 different types were used. No early or delayed complications occurred in relation to the titianium clips, such as deformity or slippage of a clip. Patient outcome according to the Glasgow Outcome Scale was similar to that when conventional cobalt-based aneurysm clips were used. INTERPRETATION: Reliability and safety of Sugita aneurysm clips were demonstrated in a large number of patients. The clips are suitable for routine use in aneurysm surgery.

Adult↗

Elevation of nitric oxide metabolites in the cerebrospinal fluid of patients with moyamoya disease.

BACKGROUND: To investigate whether nitric oxide (NO) contributes to formation of abnormal collateral circulation in patients with moyamoya disease. METHODS: Cerebrospinal fluid (CSF) samples were obtained from the subarachnoid space of the Sylvian fissure during combined bypass surgery for moyamoya disease and kept frozen until NO metabolites, nitrate and nitrite, were measured using a Griess method. RESULTS: Compared with control CSF obtained from 18 patients with hemifacial spasm, unruptured aneurysm, etc., concentrations of NO metabolites in 26 CSF samples of 18 patients with moyamoya disease were significantly higher (mean +/- SE; 17.6 +/- 1.2 vs. 10.5 +/- 1.0 microM, p < 0.01). In eight patients, the CSF samples from both the first and second operation could be obtained. NO metabolite concentrations (20.5 +/- 2.3 microM) in CSF obtained from the first surgery decreased to 15.7 +/- 1.8 microM (p < 0.01) in CSF obtained from the second, contralateral procedure. The cases of moyamoya disease with greater development of moyamoya vessels at angiographic stage 3 and 4 tended to show higher concentrations of NO metabolites than cases at earlier or later stages with a few moyamoya vessels. INTERPRETATION: Nitric oxide concentrations in CSF are chronically elevated in moyamoya disease, probably reflecting development of abnormal collateral circulation. i.e. moyamoya vessels. Vascular bypass surgery can reduce abnormal collateral circulation with reduced production of nitric oxide.

Adolescent↗

Effects of sigma receptor agonists on the impairment of spontaneous alternation behavior and decrease of cyclic GMP level induced by nitric oxide synthase inhibitors in mice.

In this study, we investigated the involvement of the interaction between sigma receptors and the nitric oxide/cyclic GMP pathway in short term memory in mice, assessed through spontaneous alternation behavior in a Y-maze. N(G)-Nitro-L-arginine methyl ester and 7-nitro indazole, both nitric oxide synthase inhibitors, impaired the spontaneous alternation behavior. These impairments were attenuated by (+) SKF 10,047 and (+) pentazocine, sigma(1) receptor agonists. Further, the sigma(1) receptor antagonist, NE-100, reversed the improvements made by sigma receptor agonists. Cyclic GMP levels and nitric oxide synthase activity in the hippocampus were reduced by treatment with N(G)-nitro-L-arginine methyl ester. The suppressive effects of N(G)-nitro-L-arginine methyl ester on the cyclic GMP levels were reversed by co-treatment with (+) SKF 10,047, but the decline in nitric oxide synthase activity was not. These results suggest that the nitric oxide/cyclic GMP pathway in the hippocampus is responsible for spontaneous alternation behavior in a Y-maze. Further, the ameliorating effects of (+) SKF 10,047 on the impairment of spontaneous alternation behavior may be mediated through activation of guanylate cyclase, but not nitric oxide synthase in the hippocampus of mice.

Analgesics, Opioid↗

Cutaneous primary paracoccidioidomycosis.

Paracoccidioidomycosis is a common fungal infection in Latin America. Few cases have been described in non-endemic countries and their diagnosis without the correct suspicion, bearing in mind that the latency period might be up to 60 years, may not be easy. We report the case of a 59-year-old man who worked as a taxi driver for 25 years in Venezuela. Cutaneous paracoccidioidomycosis was diagnosed one year after he returned to Spain. No internal signs or symptoms of the disease were found and cell-mediated immunity showed no depression. Our case suggested us to consider direct cutaneous infection, although respiratory tract is believed to be the most frequent portal of entry for this infection.

Humans↗

Different beta-adrenergic regulation of myocardial contraction and relaxation between apical and nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The impaired adrenergic control of both inotropic and lusitropic reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM) but not in those with apical HCM (APH). OBJECTIVES: We examined the influence of increases in heart rate and adrenergic stimulation on inotropic and lusitropic reserves in HCM and APH with normal resting left ventricular (LV) systolic function. METHODS: We evaluated LV isovolumic contraction and relaxation during atrial pacing and during supine leg exercise in 7 patients with APH and in 8 patients with HCM. RESULTS: Heart rate was significantly correlated with LV isovolumic contraction and relaxation during pacing and exercise in all patients. In all patients with APH, the increase in LV isovolumic contraction was greater during exercise (101%) than pacing alone (27%) for similar increase in heart rate. In 5 patients with HCM, the increase in LV isovolumic contraction was greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with HCM the increase in LV isovolumic contraction was similar between during exercise (25%) and during pacing alone (22%). In all patients with APH, relaxation was shorter during exercise (39%) than pacing alone (16%). Conversely, in patients with HCM relaxation was similarly shortened between during pacing alone (20%) and during exercise (19%). CONCLUSIONS: The force-frequency and the relaxation-frequency relations were well-preserved in all patients. In patients with HCM, the adrenergic enhancement of force-frequency relation and/or relaxation-frequency relation was impaired. In patients with APH, however, adrenergic control of both force-frequency and relaxation-frequency relations was well-preserved, which may indicate a preserved beta-adrenergic signaling pathway.

Adult↗

Influence of movement arousal on circadian rhythm of blood pressure in obstructive sleep apnea syndrome.

OBJECTIVE: To investigate the hypothesis that repeated arousals at the termination of apnea/hypopnea in obstructive sleep apnea syndrome (OSAS) are related to abnormal circadian rhythm of blood pressure (BP). DESIGN AND METHODS: We performed polysomnography (PSG) with pulse oximetry in 26 middle-aged patients with OSAS aged 42-58 years (mean age 51.8 years). The intensity of arousal on PSG was graded into two levels: grade 1 (EEG arousal, EA), an abrupt shift in EEG frequency, and grade 2 (movement arousal, MA), EEG arousal with an increase in electromyogram activity lasting at least 3 s. The number of apnea/hypopneas per hour (apnea/hypopnea index, AHI), and length of time during which nocturnal oxygen saturation decreased below 90% (oxygen desaturation time, ODT) were also evaluated. Percentage EA and %MA were assessed by the ratio of the number of apneas and hypopneas with EA or MA to the number of apneas and hypopneas in total. The 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively. Multiple regression analysis was performed among AHI, ODT, %EA and %MA or among age, body mass index and %MA. RESULTS: The %MA was the most significant factor contributing to the elevated 24 h SBP (r= 0.46, P< 0.05); oxygen desaturation (r= 0.44, P< 0.05) was the next most important contributing factor. The level and pattern of 24 h BP differed significantly between the patients with %MA 85% and %MA < 85% (mean 24 h SBP: 147 +/- 16.8 versus 125 +/- 19.6 mmHg, P< 0.01; mean 24 h DBP: 97.5 +/- 14.3 versus 85.6 +/- 14.6 mmHg, P< 0.01), and also differed between those with severe OSAS, i.e. ODT > or = 130 min, and mild to moderate OSAS, i.e. ODT < 130 min, (mean 24 h SBP: 149 +/- 15.8 versus 132 +/- 20.6 mmHg, P < 0.01; mean 24 h DBP: 100 +/- 14.1 versus 87.4 +/- 14.0 mmHg, P < 0.01). CONCLUSION: Our findings suggest that MA and oxygen desaturation in OSAS make an important contribution to abnormal circadian rhythm of BP. We conclude that repeated end-apneic arousal and/or hypoxic asphyxia and the subsequent sleep fragmentation may contibute to nocturnal and diurnal elevation of BP.

Adult↗

Chromosomal mapping of genes for epilepsy in NER: a rat strain with tonic-clonic seizures.

PURPOSE: NER is a mutant rat strain that exhibits spontaneous tonic-clonic convulsions accompanied by epileptic discharges on ictal EEG and serves as a model for generalized tonic-clonic seizures in humans. Our previous experiments have suggested that a major autosomal recessive gene and several minor genes regulate the inheritance of tonic-clonic seizures in NER. The purpose of this study was to confirm the mode of inheritance and to locate the causative genes for epilepsy in NER on the rat genetic map. METHODS: We developed F1 hybrid (F1) and reciprocal back-cross progenies of NER with a seizure-resistant strain, F344, and evaluated their seizure susceptibility under tossing-stimulated and nonstimulated conditions. Backcross animals were genotyped using simple sequence length polymorphism markers for polymerase chain reactions. Linkage between seizure susceptibility and marker loci was analyzed by chi2 statistic tests and by the computer programs MAPMAKER/EXP and MAPMAKER/QTL. RESULTS: Under tossing-stimulating conditions, tonic-clonic seizures were provoked in 90% of NER and 66% of (F1 x NER) backcross animals, but no seizures occurred in the F344, F1, or (F1 x F344) backcross animals. Routine monitoring of nonstimulated animals revealed spontaneous tonic-clonic convulsions in 100% of NER and 64.2% of (F1 x NER) backcross animals, but no seizures in F344 or F1. Gender effect on seizure susceptibility was negligible in (F1 x NER) backcross in both conditions. Preliminary genome-wide scanning and subsequent precise location of the causative genes revealed seizure susceptibility loci, designated Ner1 and Ner2, on rat chromosomes 1 and 3, respectively. CONCLUSIONS: Ner1 is a locus that controls the inheritance of spontaneous tonic-clonic seizures in an autosomal recessive mode, whereas Ner2 affects the occurrence of tossing-induced seizures. Orthologous genes in the vicinity of these loci may be related to epileptogenesis in other species, including humans.

Animals↗

An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults.

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

Adult↗

Age related differences in electroencephalographic and cardiac arousal at the termination of sleep apnea/hypopnea.

OBJECTIVE: The purpose of the present study was to determine whether electroencephalographic (EEG) and cardiac arousal, i.e. heart rate elevation at the termination of apnea/hypopnea are related to aging. METHODS: The subjects were 13 middle-aged (40-60 years of age, 47.8+/-5.35 years) and 10 elderly (>60 years of age, 69.8+/-5.31 years) male patients with obstructive sleep apnea syndrome. We evaluated the number of apneas per an hour of sleep (apnea index: AI), the number of hypopneas per an hour of sleep (hypopnea index: HI), the summation of HI and AI (apnea/hypopnea index: AHI), sleep stage, the amount of time during which nocturnal oxygen saturation was decreased below 90% (oxygen desaturation time: ODT), and EEG and cardiac arousal at the termination of apnea/hypopnea using polysomnography with pulse oximetry. RESULTS: There was no significant difference in AHI, duration of apnea/hypopnea, and sleep stage distribution between the two groups. However, the ratio of apnea/hypopnea with EEG and cardiac arousal was significantly higher in middle-aged than in elderly patients. The ratio of HI to AHI was significantly lower in middle-aged than in elderly patients. In middle-aged patients, EEG and cardiac arousal were significantly correlated with AI, AHI, and ODT, whereas, in elderly patients, these parameters were not similarly correlated. CONCLUSION: Our findings suggest that the differences in EEG and cardiac arousal, and the pattern of sleep-disordered breathing (SDB) between middle-aged and elderly patients with SDB might be a physiological phenomenon of aging.

Adult↗

Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats.

OBJECT: In Japan fasudil hydrochloride (HA1077), a protein kinase inhibitor, is widely administered to prevent vasospasm in patients after subarachnoid hemorrhage. The effects of fasudil on experimental spinal cord injury (SCI) were investigated and compared with those obtained using methylprednisolone. METHODS: Spinal cord contusion was induced in rats by applying an aneurysm clip extradurally to the spinal cord at T-3 for 1 minute. After injury three groups of rats were treated with intravenously administered saline (control), intraperitoneally administered fasudil (10 mg/kg), or intravenously administered methylprednisolone (four 30 mg/kg injections). Neurological recovery was evaluated periodically over 1 month by using a modified combined behavioral scale and histopathological examination. Leukocyte infiltration near the injury site was evaluated by measuring myeloperoxidase (MPO) activity at 24 hours. Spinal cord blood flow was measured at intervals up to 3 hours after injury by using laser Doppler flowmetry. In rats in the fasudil-treated group significant improvement in modified combined behavioral score was demonstrated at each time point, whereas in the methylprednisolone-treated rats no beneficial effects were shown. In the fasudil-treated group, reduction of traumatic spinal cord damage was evident histologically in the caudal portion of the injured areas, and tissue MPO activity in tissue samples was reduced. Spinal cord blood flow was not significantly different between fasudil-treated and control group rats. CONCLUSIONS: Fasudil hydrochloride showed promise of effectiveness in promoting neurological recovery after traumatic SCI. Possible mechanisms of this effect include protein kinase inhibition and decreased infiltration by neutrophils.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Detection of reperfusion injury using PET in a monkey model of cerebral ischemia.

UNLABELLED: Several studies of focal ischemia and reperfusion in animal models have proposed that reperfusion contributes to brain damage. However, the extent to which reperfusion affects the brain, especially in acute stroke patients, remains unclear. Our purpose in this study was to determine whether reperfusion injury can be detected with PET and to clarify the extent to which reperfusion contributes to brain damage. METHODS: The right middle cerebral artery (MCA) of cynomolgus monkeys was occluded for 3 h (n = 8) or permanently (n = 5) by a transorbital device. Four consecutive PET studies were performed to assess cerebral blood flow (CBF), oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2). RESULTS: The extent of necrotic brain damage 8 h after MCA occlusion was significantly (P < 0.05) greater in the transient model than in the permanent model. Cortical damage was greater in the transient model. The MCA occlusion decreased CBF and CMRO2 in deep MCA territory and increased OEF in the cortex. In the permanent model, these changes continued throughout the experiment. In the transient model, the reperfusion induced postischemic hyperperfusion in the cortex, which showed necrotic damage at the end of the experiment. In this area, OEF and CMRO2 were decreased by reperfusion. CONCLUSION: The results suggest that reperfusion may strongly contribute to cortical damage. PET studies revealed that reperfusion decreased OEF and CMRO2 in the hyperperfused cortex. These changes may indicate reperfusion injury.

Animals↗

Three-dimensional stereotactic surface projection analysis of macaque brain PET: development and initial applications.

UNLABELLED: To characterize better the local brain functions of conscious rhesus macaques, we developed automated image analysis techniques for monkey PET images, examined the cerebral glucose metabolism of monkeys, and compared it with that of humans. METHODS: Glucose metabolic PET images from 11 monkeys were obtained using a high-resolution animal PET scanner after intravenous administration of FDG. T1-weighted MR images were obtained from 6 of the monkeys. Referencing a bicommissural stereotactic macaque brain atlas, we created a PET brain template using coregistered MR images. Each individual PET image set was transformed to the PET template through an automated affine transformation, followed by nonlinear warping along the directions of the major neuronal fiber bundles in the brain. For minimization of residual anatomic variability, metabolic activities were extracted using 3-dimensional stereotactic surface projections. The effects of anatomic standardization were evaluated using MR images. Patterns of cerebral glucose metabolism of young versus aged monkeys were examined. The metabolic activities of aged monkeys were compared with those of elderly healthy human volunteers that had been analyzed similarly. RESULTS: Anatomic standardization reduced individuals' anatomic variability as evidenced by a reduction in the number of MR pixels with higher SDs calculated across monkeys. Coefficient-of-variation maps of conscious monkeys revealed that the greatest metabolic variances were near the central sulci and occipital cortices. Age-associated glucose metabolic reductions were most pronounced in the occipital lobe, caudate nucleus, and temporal lobe. Compared with human brains, the monkey frontal lobe and posterior cingulate gyrus had significantly less metabolic activity and the supramarginal gyrus and vermis had significantly more metabolic activity. CONCLUSION: The proposed method permits pixel-by-pixel characterization of the metabolic activities of rhesus macaque brains in the stereotactic coordinate system. Greater metabolic variances in the central sulcus region and occipital lobe suggest potential difficulties in controlling sensory input and motor output or planning in conscious monkey experiments. The analyses revealed age-related metabolic reductions in monkeys and marked differences in metabolic patterns between aged monkey brains and aged human brains. The proposed brain-mapping technique enables reproducible and observer-independent analyses and will serve as an important investigative tool for primate brain imaging research.

Aging↗

Elevated neuropeptide Y and corticotropin-releasing factor in the brain of a novel epileptic mutant rat: Noda epileptic rat.

Noda epileptic rat (NER) is a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar. In the present study, possible changes of two neuropeptides, neuropeptide Y (NPY) and corticotropin-releasing factor (CRF), in the brains of NER were investigated. Increased contents of immunoreactive (IR) NPY were found in the striatum and amygdala of 8-week NERs with partial seizure, while these changes extended to the limbic region including hippocampus in 16-week NERs with fully developed generalized tonic-clonic seizure. IR-CRF were elevated only in the entorhinal and pyriform cortex of both 8-week and 16-week NERs. Generalized tonic-clonic seizure in NERs induced a transient increase of NPY mRNA in the granular layer of dentate gyrus. These results suggest that NPY metabolism in the limbic brain contributes to the seizure susceptibility in this model of epilepsy.

Animals↗

FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, restores the regional cerebral blood flow response abolished by scopolamine but not by HA-966: a positron emission tomography study with unanesthetized rhesus monkeys.

The interactions of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, with cholinergic and glutamatergic neuronal systems were evaluated with respect to its effects on the regional cerebral blood flow (rCBF) response to vibrotactile stimulation in unanesthetized rhesus monkeys with [15O]H2O and high resolution positron emission tomography (PET). Under a saline condition, the vibrotactile stimulation given on the right forepaw induced a significant increase in the rCBF response in the contralateral somatosensory cortex of the monkey brain. Systemic administration of scopolamine (50 microg/kg, i.v.), a muscarinic cholinergic receptor antagonist, completely abolished the rCBF response to the stimulation, and the abolishment lasted, at least, up to 4 h after scopolamine injection. The scopolamine-induced abolishment of rCBF response was restored by the administration of FK960 at relatively wide dosing range from 1 to 1000 microg/kg (i.v. ), and the recovery by FK960 on the rCBF response lasted for 1 h following the administration of FK960 at doses of 100 and 1000 microg/kg. On the other hand, the rCBF response abolished by 1000 microg/kg of (+)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), an antagonist of the glycine modulatory site on the N-methyl-d-aspartate (NMDA) receptors, was not restored by FK960 (1000 microg/kg, i.v.). These findings suggest that FK960 reverses the abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission but not via the glutamatergic one.

Animals↗

Regional excitatory and inhibitory amino acid concentrations in Noda epileptic rat (NER) brain.

We measured regional concentrations of excitatory and inhibitory amino acids in Noda epileptic rat (NER) brains to investigate the mechanisms responsible for spontaneous generalized seizures. Compared with Fisher 344 (F344) rats and F1 hybrid (female NER x male F344 rat) rats, NERs had significantly higher concentrations of glycine in the cerebellum. NERs and F1 hybrid rats had significantly lower concentrations of taurine in the cerebellum than did F344 rats. Although our findings do not explain sufficiently the mechanisms directly responsible for spontaneous seizures, they suggest that the cerebellum of NER may be in an excited state to dampen seizures, while the cerebellum of F1 hybrid rats may also be slightly excited to inhibit milder forms of seizures. Further studies, including microdialysis and receptor binding assays, will be required to elucidate these mechanisms.

Amino Acids↗

Mitochondrial and intracellular free-calcium regulation of radiation-induced apoptosis in human leukemic cells.

PURPOSE: To investigate the mechanisms and pathways of X-ray apoptosis in Molt-4 cells, focusing on mitochondrial and cytosolic Ca2+ ([Ca2+]i) regulation. MATERIALS AND METHODS: X-irradiated Molt-4 cells and cell extract (CE) were used to analyse: (1) induced apoptosis (Giemsa stain), (2) p53, Bcl-2 and Bax expressions (immunoblot), (3) mitochondrial potential deltapsi(m) and (4) [Ca2+]i (flow cytometry), (5) caspase-3 activity, and (6) roles of [Ca2+]- and caspase-3-mediated pathways by inhibiting either or both pathways for induced apoptosis. RESULTS: Molt-4 cells were sensitive to apoptosis since 5 Gy induced 57 and 94% apoptosis at 6 and 24 h. After 5Gy, p53 was accumulated that upregulated Bax but which repressed Bcl-2 with time, resulting in a 7-fold increase in Bax/Bxl-2 at 6 h. Predominant Bax reduced deltapsi(m), and low-deltapsi(m) cells increased 45 min earlier than apoptosis after 5 Gy. Caspase-3 was activated in apoptotic CE. The caspase-3 inhibitor Ac-DEVD-CHO inhibited apoptosis and DNA-ladder formation by approximately 50%, suggesting a approximately 50% role of caspase-3-activated DNase (CAD). [Ca2+]i was increased after 5 Gy. [Ca2+]i-chelating BAPTA-AM (5 microM) and/or DNase gamma-inhibiting Zn2+ (0.5 mM) inhibited approximately 50% of induced apoptosis and DNA-laddering, indicating a 50% participation of Ca2+/Mg2+-dependent DNase gamma. CONCLUSIONS: The p53-Bax-mitochondria-caspase-3-CAD pathway and the [Ca+2]i-mediated DNase gamma pathway were involved in the regulation of X-ray apoptosis in sensitive Molt-4 cells.

Animals↗