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Isao Nagano

Publications and source records attributed to Isao Nagano.

47 records · Page 3Linked to original sources
PubMed2003

[A case of neuro-Behçet's disease with repeating isolated thoracic spinal cord lesion].

We reported a 45-year-old man who had repeated isolated thoracic spinal cord lesion on MRI in the clinical course of seven years. He had transient bilateral plantar numbness and urinary retention on December, 1994. Then, spastic paraplegia, total anesthesia of feet, and severe sphincter disturbance struck him on May, 1995. He was diagnosed as incomplete Behçet's disease and neuro-Behçet's disease on June, 1995 because of recurrent oral aphta, genital ulceration, and foliculitis. T2-weighted magnetic resonance imaging showed high intensity enhanced with Gd-DTPA in thoracic spinal cord from Th 5 to 8 level. Any other abnormal lesion on brain or spinal MRI was not observed. He was treated with corticosteroids and recovered incompletely. Another two big attacks occurred to him. No new lesion but thoracic spinal cord lesion was observed. We conclude that this case is the first reported example of neuro-Behçet's disease with repeating isolated thoracic spinal cord lesion.

Behcet Syndrome↗
PubMed2002

Coordinate expression of survival p-ERK and proapoptotic cytochrome c signals in rat brain neurons after transient MCAO.

In order to determine possible coordinate expression of major survival and proapoptotic signals, immunofluorescent analyses for phosphorylated ERK (p-ERK) and cytochrome c were carried out after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Strong induction of p-ERK was primarily expressed in the ischemic penumbra, while that of cytosolic cytochrome c signal was strongly induced in the ischemic core from 3 min to 3 h of reperfusion. The double-stained cells with strong p-ERK/weak cytochrome c became most apparent at 3 min primarily expressed in the ischemic penumbra, whereas the cells with weak p-ERK/strong cytochrome c were predominantly found in the ischemic core at 3 h. The proportion of double positive cells among the total number of single positive cells decreased in the ischemic core, and increased in the ischemic penumbra. These findings suggest that the coordinate expression of p-ERK and cytochrome c is fundamentally involved in cell survival or death at the early stage of reperfusion, and that they could play roles in different temporal and spatial profiles.

Animals↗
PubMed2002

Early decrease of survival factors and DNA repair enzyme in spinal motor neurons of presymptomatic transgenic mice that express a mutant SOD1 gene.

The primary pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS) have been elusive. Some of the mechanisms would be implicated in an imbalance between death and survival factors, and impairment of DNA repair possibly caused by oxidative stress. Phosphatidylinositol 3-kinase (PI3-K) and its downstream effector, Akt/protein kinase B (PKB), have been shown to play a pivotal role in neuronal survival against apoptosis supported by neurotrophic factors. To elucidate the mechanisms of motor neuron death in ALS, we examined the expression of PI3-K, Akt, and the DNA repair enzyme redox factor-1 (Ref-1) protein in the spinal cord of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene, a valuable model for human ALS. Immunoblotting and immunocytochemical analyses showed that most spinal motor neurons lost immunoreactivity for PI3-K, Akt, and Ref-1 in the presymptomatic stage that preceded a significant loss of neurons. These results suggest that an early decrease of survival signal proteins and a DNA repair enzyme in the spinal motor neurons may account for the mutant SOD1-mediated motor neuron death in this animal model of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Change in superoxide dismutase 1 protein localization towards mitochondria: an immunohistochemical study in transgenic G93A mice.

Localization of superoxide dismutase1 (SOD1) and mitochondrial glucose-regulated protein 75 (Grp75), were examined in the spinal cords of transgenic (Tg) mice expressing human mutant SOD1 protein (G93A) and wild-type (Wt) controls at 8, 20 and 32 weeks. SOD1 showed a progressive increase of dot-like deposits in the neuropil of anterior horn of Tg mice, and a late decrease of signal intensity in the white matter and motor neurons. Colocalization of Grp75 and SOD1 signals was demonstrated in Wt and presymptomatic Tg animals, while it was lost in Tg mice at a symptomatic age. The present results suggest that loss of SOD1 protein from mitochondria could contribute to motor neuron damage.

Animals↗
PubMed2002

Selective colocalization of transglutaminase-like activity in ubiquitinated intranuclear inclusions of hereditary dentatorubral-pallidoluysian atrophy.

To investigate the role of transglutaminase (TG) in the pathophysiology of dentatorubral-pallidoluysian atrophy (DRPLA), the distributions of ubiquitin-positive neuronal intranuclear inclusions (Ub-NII) and TG activity were studied in three patients with DRPLA and four disease controls. In the cerebellar granule cells of DRPLA, 2.5-4.9% of neurons had Ub-NII, and 7.5-9.8% of them were TG positive. In the frontal cortex; however, the ratio of neurons with Ub-NII was relatively low compared with those in the cerebellar cortex, and no Ub-NII was TG positive. There was no distinct difference in the ratio of neurons with Ub-NII and their TG positivity between the cases with homozygous or heterozygous DRPLA patients. The selective and good colocalization of Ub-NII and TG in the cerebellar granule cells may reveal a role of TG in the neurodegenerative process in DRPLA.

Adult↗
PubMed2002

Potentiation of Akt and suppression of caspase-9 activations by electroacupuncture after transient middle cerebral artery occlusion in rats.

Electroacupuncture (EA) is an effective curative method for diseases including cerebral ischemia. In the current study, we investigated the effects of EA treatment on the activations of survival Akt and proapoptotic caspase-9 after 90 min of transient middle cerebral artery occlusion (tMCAO) in rat. Immunoreactivity of phospho-Akt (p-Akt) increased in the ipsilateral hemisphere after tMCAO with a peak at 8 h, and EA enhanced the Akt expression both in the number and the staining strength mainly in the ischemic penumbra (IP) at 8 and 24 h. Cleaved caspase-9 was strongly induced at 8 h in IP, which was suppressed with EA. The number of terminal deoxynucleotidyl transferase-mediated uridine 5' triphosphate-biotin nick end labelling positive cells reduced at 24 h in the cerebral cortex. These results suggest that EA potentiated the Akt and suppressed the caspase-9 activations, and may have a potential to reduce the number of neuronal cells undergoing apoptotic cell death.

Animals↗
PubMed2002

Changes of localization of highly polysialylated neural cell adhesion molecule (PSA-NCAM) in rat hippocampus with exposure to repeated kindled seizures.

Highly polysialylated neural cell adhesion molecules (PSA-NCAMs) are involved in migration of neural stem cells as well as neural plasticity. Immunoreactive PSA-NCAM expression was examined in rat with repeated exposure to amygdaloid kindled generalized seizures (GS). The number of PSA-NCAM positive cells in bilateral dentate gyrus (DG) increased significantly at GS. Although total positive cell number was not significantly different between 3 times GS (3 GS) and 30 times GS (30 GS) groups, a greater number of positive cells was located in the outer granule cell layer (GCL), and the immunopositive dendrite greatly extended to the molecular layer in the 30 GS group. These observations indicate that increased migration of newly generated cells as well as plastic change of originally-existed neural cells may occur in response to the recurrent GS, which may contribute to abnormal reconstruction of synaptic network in hippocampus and epileptogenisity in kindling.

Animals↗
PubMed2002

Expression of excretory and secretory protein genes of Trichinella at muscle stage differs before and after cyst formation.

By adapting a semi-quantitative reverse transcriptase-PCR (RT-PCR) method, we investigated kinetics of gene expression at different developmental stages of Trichinella spiralis and T. pseudospiralis. The analyzed genes included four kinds of excretory and secretory (ES) proteins, a heat shock protein (HSP) and a DNA binding protein and showed that T. spiralis and T. pseudospiralis expressed ES proteins in a stage-specific manner. The gene encoding a 43 kDa ES protein was expressed by muscle larvae, either pre-cyst or post-cyst larvae. The genes encoding: the 53 kDa ES protein of T. spiralis; 53 kDa ES protein of T. pseudospiralis; and 19.6 kDa ES protein of T. spiralis were expressed by post-cyst larvae and adult worms, but not expressed by pre-cyst larvae or newborn larvae. The results showed that pre-cyst larvae and post-cyst larvae are similar but different in the expression of 53 and 19.6 kDa ES proteins. On the other hand, genes of housekeeping proteins, such as HSP and the DNA binding protein, were expressed at all stages although there were some differences in the expression level.

Animals↗
PubMed2002

Three steps of neural stem cells development in gerbil dentate gyrus after transient ischemia.

The stage of neurogenesis can be divided into three steps: proliferation, migration, and differentiation. To elucidate detailed relations between these three steps after ischemia, the authors evaluated the three steps in the adult gerbil dentate gyrus (DG) after 5 minutes of transient global ischemia using bromodeoxyuridine (BrdU), highly polysialylated neural cell adhesion molecule (PSA-NCAM), and neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) as markers for proliferation, migration, and differentiation, respectively. Bromodeoxyuridine-labeled cells increased approximately sevenfold, and PSA-NCAM-positive cells increased approximately threefold in the subgranular zone (SGZ) with a peak 10 days after ischemia. Bromodeoxyuridine-labeled cells with PSA-NCAM expression were first detected both in the SGZ and the granule cell layer (GCL) 20 days after ischemia and gradually decreased after that, whereas BrdU-labeled cells with NeuN gradually increased in the GCL until 60 days after ischemia. A few BrdU-labeled cells with GFAP expression were detected in DG after ischemia; no PSA-NCAM-positive cells with GFAP expression were detected, but the radial processes of glial cells were partly in contact with PSA-NCAM-positive cell bodies and dendrites. These results suggest that neural stem cell proliferation begins at the SGZ, and that the cells then migrate into the GCL and differentiate mainly into neuronal cells. The majority of these three steps finished in 2 months after transient global ischemia.

Animals↗
PubMed2002

Clinical Features of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks, strokes, and vascular dementia. Various mutations in the Notch3 gene cause the disease, whereas the mechanism of how they cause the disorder remains unknown. We recently identified two Japanese CADASIL families with an R141C mutation. The mean age of onset was 44.6, and the main symptoms were recurrent strokes and progressive motor disturbances in extremities, as well as pseudobulbar palsy. Besides those in white matter and basal ganglia, ischemic lesions in temporal edge and corpus callosum were present on magnetic resonance images, which seemed to be characteristic of CADASIL. Moreover, in our cases, nocturnal arterial blood pressure fall was significantly lower in patients compared with control subjects, suggesting that it might be partly associated with ischemic lesions in deep white matter in CADASIL. We also compared Japanese and Caucasian CADASIL cases and found that dementia and pseudobulbar palsy were observed more frequently in Japanese patients, although typical migraine was rather rare. In the present study, we describe the clinical features of CADASIL, hoping to help reveal the mechanism of chronic ischemic brain diseases, including leukoaraiosis or Binswanger's disease.

Adult↗