Biomedical subjects

Y Manabe

Publications and source records attributed to Y Manabe.

At least 37 records · Page 2Linked to original sources

PubMed2001

Expressions of nitrotyrosine and TUNEL immunoreactivities in cultured rat spinal cord neurons after exposure to glutamate, nitric oxide, or peroxynitrite.

Although excitotoxic and oxidative stress play important roles in spinal neuron death, the exact mechanism is not fully understood. We examined cell damage of primary culture of 11-day-old rat spinal cord by addition of glutamate, nitric oxide (NO) or peroxynitrite (PN) with detection of nitrotyrosine (NT) or terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL). With addition of glutamate, NOC18 (a slow NO releaser) or PN, immunoreactivity for NT became stronger in the cytoplasm of large motor neurons in the ventral horn at 6 to 48 hr and positive in the axons of the ventral horn at 24 to 48 hr. TUNEL positive nuclei were found in spinal large motor neurons from 24 hr, and the positive cell number greatly increased at 48 hr in contrast to the vehicle. Pretreatment of cultures with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor antagonist, NO-suppressing agent, and antioxidant protected the immunoreactivity for NT or TUNEL. The present results suggest that both excitotoxic and oxidative stress play an important role in the upregulation of NT nitration and the apoptotic pathway in cultured rat spinal neurons.

Animals↗

PubMed2001

A novel SOD1 gene mutation in familial ALS with low penetrance in females.

We identified a novel missense mutation in the Cu/Zn superoxide dismutase gene in a family with amyotrophic lateral sclerosis (ALS). The mutation was a transition of T to C, resulting in a substitution of leucine 126 to serine in exon 5. The family had very unique clinical features of extremely mild severity only in the legs of two male patients with onset of 42 and 52 years old, and their mothers did not develop any symptom even after reaching the age of 80 and carrying the same mutation. The present study suggests that there are other factors that delay or prevent the disease.

Adult↗

PubMed2001

Impaired retrograde axonal transport of adenovirus-mediated E. coli LacZ gene in the mice carrying mutant SOD1 gene.

A replication-defective recombinant adenoviral vector containing E. coli lacZ gene was injected into the gastrocnemius muscles of transgenic mice carrying mutant Cu/Zn superoxide dismutase (SOD1) gene and non-transgenic wild-type mice at 40 weeks of age. After 60 and 90 h of the injection, lacZ staining was observed at the distal ends of the sciatic nerves in both mice groups, with the number and the distances greatly reduced in the transgenic mice. Mean velocities of retrograde transport for lacZ was estimated to be 2.1 and 0.05 mm/24 h in non-transgenic and transgenic mice, respectively. These results indicate that the retrograde axonal transport of foreign gene product is impaired in the mice model for familial amyotrophic lateral sclerosis.

Adenoviridae↗

PubMed2001

Expression of polysialylated neural cell adhesion molecule in rat brain after transient middle cerebral artery occlusion.

The highly polysialylated form of neural cell adhesion molecule (PSA-NCAM) is important for neurite outgrowth. With this molecule as a marker of plastic change in neurons, we investigated its temporal expression in rat brain after transient middle cerebral artery (MCA) occlusion. In sham-control brain, only subependymal neurons showed a positive immunoreactivity for PSA-NCAM. After 90 min of transient MCA occlusion, neurons in the piriform cortex began to be positively stained at 1 h, while neurons in the cortex and caudate of the MCA territory became positive after 8 h. The stainings persisted for 1 and 3 days after reperfusion. The present results indicate that neurons in the cerebral cortex and caudate have the capability of plastic change in the adult brain, and that those in the piriform cortex rapidly undergo plastic change probably in response to transneuronal injury.

Animals↗

PubMed2001

Time dependent amelioration against ischemic brain damage by glial cell line-derived neurotrophic factor after transient middle cerebral artery occlusion in rat.

Time dependent influence of glial cell line-derived neurotrophic factor (GDNF) was examined after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Treatment with GDNF significantly reduced the infarct volume stained with 2,3,5-triphenyltetrazolium chloride (TTC) when GDNF was topically applied at 0 and 1 h of reperfusion, but became insignificant at 3 h as compared to vehicle group. The protective effect of GDNF was closely related to the significant reduction of the number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) positive cells as well as immunofluorescently positive cells for active forms of caspases, especially active caspase-3 but not -9. Thus, the present study showed that topical application of GDNF significantly reduced infarct size in a time-dependent manner, while the therapeutic time window was shorter than other chemical compounds such as an NMDA receptor antagonist (MK-801) and a free radical scavenger (alpha-phenyl-tert-butyl-nitrone, PBN). The effect of GDNF was stronger in suppressing active caspase-3 than active caspase-9.

Animals↗

PubMed2001

Induction of highly polysialylated neural cell adhesion molecule (PSA-NCAM) in postischemic gerbil hippocampus mainly dissociated with neural stem cell proliferation.

We investigated a possible expression of highly polysialylated neural cell adhesion molecule (PSA-NCAM) in gerbil hippocampus after 5 min of transient global ischemia in association to the proliferation of neural stem cell labeled with bromodeoxyuridine (BrdU). The number of PSA-NCAM positive cells increased in the granule cell layer (GCL) of dentate gyrus (DG) by 1.9 to 2.7-fold at 10 and 20 days after the reperfusion. The number of BrdU-labeled cells increased mainly in the subgranular zone of DG by 7.2 to 8.0-fold at 5 and 10 days after the reperfusion. Immunofluorescence for PSA-NCAM and BrdU showed that the majority of DG cells were not double labeled, while one or two cells per section were double labeled in the deepest portion of the GCL only at 10 days after the reperfusion. These results suggest different predominant spatial distribution and chronological change of PSA-NCAM positive and BrdU-labeled cells in DG after transient ischemia.

Animals↗

PubMed2001

Clinical usefulness of the branched DNA assay version 2 in predicting the efficacy of Interferon treatment in a group of chronic HCV patients based on serotype.

Interferon (IFN) response depends upon pretreatment viral loads and viral genotype/serotype. This study investigated the difference in response to IFN in different viral load groups of 96 chronic hepatitis C patients and compared version 1 (bDNA1.0) and version 2 (bDNA2.0) of the branched DNA assay, according to serotype. On univariate analysis, viral load (P=0.0001, by bDNA 1.0; P=0.0020, by bDNA 2.0,), serotype (P=0.0053) and age (P=0.0073) were significant predictors of IFN response. On multivariate analysis, serotype (odds ratio, 5.44; 95% confidence interval, 1.94-15.24; P<0.01) was a stronger predictor of IFN response than age or viral load (by bDNA2.0). In very high (>6.7 log eq/ml), high (6.0 approximately 6.69 log eq/ml) and low (<6 log eq/ml) viral load groups (by bDNA2.0), complete response was 25, 55 and 92.6% in serotype 2 (sero-2), and 10, 20 and 71.4% in serotype 1 (sero-1), respectively. In sero-2, bDNA2.0 can detect high viral loads underestimated by bDNA1.0. In a low viral load group (by bDNA2.0), IFN response is dependent upon serotype; sero-2 responded better than sero-1. However, in high and very high viral load groups, sensitivities of bDNA1.0 and bDNA2.0 are not effective in clinically distinguishing CR from non-response, and aid in patient selection for IFN therapy.

Journal Article↗

PubMed2001

Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice.

In order to clarify a possible role of oxidative stress in motoneuron death in amyotrophic lateral sclerosis (ALS), we examined a presence of 8-hydroxy-2-deoxyguanosine (8-OHdG), one of the best markers of the oxidative DNA damage, in the spinal cord of transgenic mice harboring a mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunocytochemistry showed a progressive accumulation of 8-OHdG in ventral horn neurons from early and presymptomatic stage (25 weeks) before significant loss of ventral horn neurons, while no detectable 8-OHdG in non-transgenic control mice. At the late and symptomatic stage (35 weeks), the 8-OHdG-like immunoreactivity spread over the posterior horn of spinal cord in Tg mice. The immunoreactivity for 8-OHdG was not localized in the nucleus but in cytoplasm with small granular pattern. These data suggest that an oxidative damage to mitochondrial DNA is happening in spinal motoneurons of the Tg mice from very early stage of the disease, and may be involved in the mechanism of the subsequent motoneuron death in this model.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Induction of polysialic acid-neural cell adhesion molecule in surviving motoneurons of transgenic amyotrophic lateral sclerosis mice.

The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is recognized as a marker of neurogenesis or neural plasticity in adult nervous system. PSA-NCAM expression was examined in the spinal cord of transgenic mice harboring a mutant Cu/Zn superoxide dismutase (SOD1) gene. Immunohistochemistry showed a progressive expression of PSA-NCAM in surviving motoneurons of spinal ventral horns from an early and presymptomatic stage (25 weeks) before significant loss of ventral horn neurons, while no detectable PSA-NCAM in the ventral horn of non-transgenic littermates during the ageing process. The present data suggest that a specific expression of PSA-NCAM may be involved in the survival of spinal motoneurons under pathological conditions such as amyotrophic lateral sclerosis.

Age Factors↗

PubMed2001

Expressions of caspase-3, Tunel, and Hsp72 immunoreactivities in cultured spinal cord neurons of rat after exposure to glutamate, nitric oxide, or peroxynitrite.

Although excitotoxic and oxidative stress play important roles in spinal neuron death, the exact mechanisms are not fully understood. We examined cell damage of primary culture of 11 day-old rat spinal cord by addition of glutamate, nitric oxice (NO) or peroxynitrite (PN) with detection of caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) or 72 kDa heat shock protein (HSP72). With addition of glutamate, NOC18 (a slow NO releaser) or PN, immunoreactivity for caspase-3 became stronger in the cytoplasm of large motor neurons in the ventral horn at 6 to 24 hr. TUNEL positive nuclei were found in spinal large motor neurons from 24 h and the positive cell proportion greatly increased at 48 h in contrast to the vehicle. On the other hand, the immunoreactivity of HSP72 in the ventral horn was already positive at 0 h, and gradually decreased in the course of time with glutamate, NOC18 or PN than vehicle treatment. In the dorsal horn, the proportion of caspase-3 positive small neurons greatly increased at 6 to 48 h after addition of glutamate. The present results suggest that both excitotoxic and oxidative stress play important roles in the apoptotic pathway in cultured spinal neurons.

Journal Article↗

PubMed2001

Long-term optional ingestion of corn oil induces excessive caloric intake and obesity in mice.

Corn oil is well tolerated by mice but tolerance may decrease with excessive ingestion. In the present study, we compared the effects of optional ingestion of excessive corn oil with ingestion of water (control) or a 20% sucrose solution in mice. During the entire study, mice consistently ingested 100% corn oil and incrementally ingested 20% sucrose. Food intake in the corn-oil group was approximately constant but that in the sucrose group was slightly decreased. Body-weight gains in the corn-oil group were higher than those in the control and sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were present, especially in the corn-oil group, and the visceral fat of mice fed corn oil increased significantly compared with the other two groups. These results suggest that mice, when given a choice, will continue to overeat corn oil over the long term, inducing excessive caloric intake and obesity.

Animals↗

PubMed2001

Early decrease of survival signal-related proteins in spinal motor neurons of presymptomatic transgenic mice with a mutant SOD1 gene.

The mechanisms of motor neuronal death in amyotrophic lateral sclerosis (ALS) remain to be unclear. Phosphatidy-linositol 3-kinase (PI3-K) and its main downstream effector, Akt/protein kinase B (PKB) have been shown to play a central role in neuronal survival against apoptosis supported by neurotrophic factors. In order to investigate a possible impairment of survival signaling, we examined expressions of PI3-K and Akt in the spinal cord of the transgenic mice overexpressing a mutant Cu/Zn superoxide dismutase (SOD1) gene, a valuable model for human ALS. Immunoblotting and immunohistochemical analyses showed that the majority of spinal motor neurons lost the immunoreactivities for both PI3-K and Akt in the early and presymptomatic stage that preceded significant loss of the neurons. The present results suggest that an early decrease of survival signal proteins in the spinal motor neurons may account for the subsequent motor neuronal loss in this animal model of ALS.

Amyotrophic Lateral Sclerosis↗

PubMed2001

Long-term follow-up results of electrogustometry and subjective taste disorder after middle ear surgery.

OBJECTIVES: The present study compares the long-term follow-up results of electrogustometry with patient reports of taste dysfunction after middle ear surgery. STUDY DESIGN: Retrospective review of 371 patients who underwent middle ear surgery. METHODS: Patients were divided into the following groups depending on the degree of manipulation or surgical damage to the chorda tympani nerves: the no-touch group (group 1 [n = 109]); the touch group (group 2 [n = 149]); and the severed nerve group (group 3 [n = 113]). Electrogustometry was periodically performed over the course of several years. RESULTS: The incidences of postoperative subjective taste disorder in groups 1, 2, and 3 were 2.8%, 25.5%, and 38.9%, respectively. Although the subjective taste disorder usually recovered within 1 to 2 years after surgery in all groups, it persisted for more than 2 years in 2.7% of the touch group and 5.3% of the severed nerve group. Concerning postoperative electrogustometric results, in the no-touch group, 8.3% of patients showed threshold elevation on electrogustometry, but the elevated thresholds completely recovered in all cases. In the touch group, 45% of patients exhibited elevated electrogustometric thresholds on their first postoperative test, including 32.9% who subsequently had complete electrogustometric recovery, 10.1% who subsequently had incomplete recovery, and 2% who failed to recover during the follow-up period. In the severed nerve group, none of the patients was responsive to the electrical stimulus on the first postoperative test, including 8.8% of patients who subsequently exhibited complete electrogustometric recovery, 32.7% who later had incomplete electrogustometric recovery, and 58.4% who never recovered any electrogustometric responsiveness. Nerve repair in the severed nerve group produced better recovery, as measured electrically. CONCLUSIONS: The incidence of postoperative subjective taste disorder was low, although inconsistent with the high incidence of threshold elevation on electrogustometry, especially in the severed nerve group. Preservation or repair of the chorda tympani nerve is recommended in order to maintain or recover gustatory function.

Adult↗

PubMed2001

Glutamate enhances DNA fragmentation in cultured spinal motor neurons of rat.

The role of glutamate in the mechanism of spinal motor neuron death is not fully understood. With addition of glutamate to primary culture of 11-day-old rat spinal cord, terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) positive nuclei were found in spinal large motor neurons from 24 h, and the number of TUNEL positive large motor neurons greatly increased at 48 h. In contrast, only a small number of large motor neurons became TUNEL positive at 48 h with addition of vehicle to the primary spinal cord culture. The present results show that excessive amount of glutamate enhances DNA fragmentation in developing large motor neuron of cultured spinal cord by involving in apoptotic process of the neurons.

Animals↗

PubMed2001

Fractal dimension analysis of static stabilometry in Parkinson's disease and spinocerebellar ataxia.

The static stabilometry patterns associated with Parkinson's disease (PD, n = 15) and spinocerebellar ataxia (SCA, n = 15) were compared with those of normal control (n = 15) by measuring the fractal dimensions. Fractal dimensions were estimated using the modified pixel dilation (mPD) method. The fractal dimensions with closed eyes showed a significant correlation with Environmental area for SCA group (p < 0.05). The fractal dimension for SCA group was significantly higher with closed eyes than that with open eyes (p < 0.05). The fractal dimension with closed eyes was significantly higher in PD and SCA groups than that in normal group (p < 0.05). The fractal dimension with closed eyes was higher when the clinical stage was more severe with PD and SCA group while Environmental and Longitude/Environmental areas were not. These findings suggest that the fractal dimension is more sensitive than traditional stabilometric analysis in an evaluation of postural instability in PD and SCA.

Aged↗

PubMed2001

Attenuation of oxidative DNA damage with a novel antioxidant EPC-K1 in rat brain neuronal cells after transient middle cerebral artery occlusion.

EPC-K1, L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl-hydrogen phosphate] potassium salt, is a novel antioxidant. In this study, we investigated a reduction of oxidative neuronal cell damage with EPC-K1 by immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG) in rat brain with 60 min transient middle cerebral artery occlusion, in association with terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) and staining for total and active caspase-3. Treatment with EPC-K1 (20 mg kg(-1) i.v.) significantly reduced infarct size (p < 0.05) at 24 h of reperfusion. There were no positive cells for 8-OHdG and TUNEL in sham-operated brain, but numerous cells became positive for 8-OHdG, TUNEL and caspase-3 in the brains with ischemia. The number was markedly reduced in the EPC-K1 treated group. These reductions were particularly evident in the border zone of the infarct area, but the degree of reduction was less in caspase-3 staining than in 8-OHdG and TUNEL stainings. These results indicate EPC-K1 attenuates oxidative neuronal cell damage and prevents neuronal cell death.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2001

Different expression of glycogen synthase kinase-3beta between young and old rat brains after transient middle cerebral artery occlusion.

Ischemia is a common stress to human brain and is difficult to cure in older individuals. To examine the differences of the response to cerebral ischemia between young and old rat brains, distributions of glycogen synthase kinase-3beta (GSK3beta) and tau proteins were analyzed after 90 min of transient middle cerebral artery occlusion (MCAO) in young (10-11 weeks) and old (15 months) rats by immunohistochemical analyses. At 4 h of reperfusion, strong cytoplasmic and nuclear immunoreactivity for GSK3beta was induced in neurons of lamina I, II, V and VI of the cerebral cortex and dorsal caudate in young brains, while the induction was not observed in lamina I and II of old cerebral cortex. The staining in lamina V and VI and dorsal caudate then gradually decreased until seven days of reperfusion in both animal groups. The staining of tau protein and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) did not show any positive signals in the control brain, but showed positive signals after ischemia with a peak at 24 h and 3 days, respectively. No significant difference was observed in the temporal and spatial patterns of tau and TUNEL stainings between these two groups. These data suggest that GSK3beta may have a role in ischemic neuronal cell death, and that the different spatial expression of GSK3beta between young and old rat brains may partly explain the vulnerability of older neurons after ischemia.

Aging↗

PubMed2001

Serial MRI findings in patient with chronic cryptococcus meningo-encephalitis.

We describe the serial changes of magnetic resonance imaging (MRI) in a patient with chronic cryptococcus meningo-encephalitis. In the subacute phase, MRI revealed a focal lesion with hyperintensity on T2-weighted image (WI) in the left thalamus. At 11 months after the onset, MRI showed a focal lesion with hyperintensity on T2-WI in the right pons that was enhanced with gadolinium (Gd). At 13 months after the onset, the lesion in the left thalamus became rim enhanced with Gd. After antifungal therapy (amphotericin B and 5-flucytosine), the rim enhancement in the left thalamus and the high signal intensity area in the right pons decreased. Cryptococcoma should be in the differential from other ring enhancing lesions.

Chronic Disease↗