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Biomedical subjects

Eizo Iseki

Publications and source records attributed to Eizo Iseki.

At least 37 records · Page 2Linked to original sources
PubMed2004

Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule-binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl-insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.

Aged↗
PubMed2004

Serum adiponectin concentrations during treatment with olanzapine or risperidone: a pilot study.

Adiponectin is a recently identified adipocyte-derived protein, which is associated with glucose metabolism, insulin sensitivity and adiposity. The aim of this study was to explore the alterations in serum adiponectin concentration during treatment with olanzapine or risperidone. Serum concentrations of adiponectin were investigated in body mass index (BMI, kg/m2)- and age-matched groups of non-diabetic, non-obese schizophrenic patients receiving a stable dose of olanzapine (n = 18) or risperidone (n = 15) for 4 weeks or more, and of mentally and physically healthy volunteers (n = 17). Patients undergoing treatment with olanzapine or risperidone had significantly higher adiponectin concentrations than the healthy volunteers, even after controlling for BMI. Adiponectin concentrations decreased with increasing BMI in patients taking olanzapine, while elevated levels were observed in patients taking risperidone, regardless of adiposity. This preliminary cross-sectional study indicates that adiponectin is involved in the regulation of glucose metabolism and weight in schizophrenic patients during treatment with olanzapine or risperidone, presumably showing a normalizing effect on metabolic abnormality.

Adiponectin↗
PubMed2004

Dementia with Lewy bodies: reclassification of pathological subtypes and boundary with Parkinson's disease or Alzheimer's disease.

The present study is an attempt to reclassify the pathological subtypes of DLB based on both Lewy pathology and Alzheimer pathology, and to clarify the pathological boundary between DLB and Parkinson's disease (PD) or Alzheimer's disease (AD) in autopsied cases, using pathological and immunohistochemical methods. Dementia with Lewy bodies was classified into the limbic type and neocortical type according to the degree of Lewy pathology, including Lewy bodies (LB) and LB-related neurites, by our staging and was classified into the pure form, common form and AD form according to the degree of Alzheimer pathology including NFT and amyloid deposits by Braak staging. These combined subtypes were lined up on a spectrum not only with Lewy pathology but also with other DLB-related pathologies including Alzheimer pathology, neuronal loss in the substantia nigra, spongiform change in the transentorhinal cortex and LB-related neurites in the CA2-3 region. There were some similarities in both Lewy pathology and other DLB-related pathologies between PD and DLB, although Lewy pathology of PD was below the lowest stage of Lewy pathology. In contrast, AD did not meet the stages of Lewy pathology, and there were also no similarities in other DLB-related pathologies between AD and DLB. In addition, LB of AD showed the characteristics different from those of DLB on the coexistence of LB with NFT. These present findings suggest that DLB has pathological continuity with PD, but can be pathologically differentiated from AD. The present study clarified the pathological entity of DLB, compared with PD and AD.

Aged↗
PubMed2004

Ubiquitin and ubiquitin-related proteins in neurons and dendrites of brains of atypical Pick's disease without Pick bodies.

Nine cases of atypical Pick's disease without Pick bodies were investigated immunohistochemically. Ubiquitin (ub)-positive and tau-negative structures were mainly found in the cerebral cortex and hippocampal dentate gyrus. In the cerebral cortex, most of the ub-positive structures had ub-positive dendrites in the neuropil, although some also showed diffuse ub-positive staining in the neuronal cytoplasm. These ub-positive structures were distributed throughout layers II-IIIab and layers V-VI. Granular cells of the dentate gyrus had ub-positive intraneuronal inclusions. When the numbers of ub-positive neurons and dendrites were evaluated in relation to the degree of neuronal loss in the cerebral cortex, the number of ub-positive neurons was significantly lower in regions showing very mild neuronal loss and higher in regions showing moderate neuronal loss. In contrast, ub-positive dendrites were detected even in cortical regions showing very mild neuronal loss. Immunoelectron-microscopically, ub-positive structures contained ub-positive ribosome-like granular components in the neuronal cytoplasm and dendrites, which were occasionally related to the rough endoplasmic reticulum and accompanied by a few filamentous components. Almost all ub-positive structures were positive for ub-binding protein p62 in double-immunostaining method. Some ub-positive or negative neurons in the cerebral cortex were positively immunolabeled with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase antibodies, whereas dendrites were not labeled by these antibodies. From the present study, it is suggested that in the cerebral cortex, these ubiquitinated proteins may firstly accumulate in the dendrites at the onset of neuronal degeneration, then appear in the neuronal cytoplasm before finally disappearing with neuronal loss.

Aged↗
PubMed2004

Ubiquitin and ubiquitin-related proteins in the brains of patients with atypical Pick's disease without Pick bodies and dementia with motor neuron disease.

Nine cases of atypical Pick's disease without Pick bodies (aPiD) and seven cases of dementia with motor neuron diseases (D-MND) were compared using immunohistochemistry of ubiquitin (ub) and ub-related proteins. All cases showed rostral-dominant atrophy in the temporal and frontal lobes, although the degree of atrophy with neuronal loss was much more severe in the aPiD cases. In both aPiD and D-MND cases, ub-positive and tau-negative structures were found mainly in the hippocampal dentate gyrus and cerebral cortex. Granular cells of the dentate gyrus showed similar ub-positive intraneuronal inclusions in both cases. In the aPiD cases, most of the ub-positive cortical structures were ub-positive dendrites in layers II-IIIab and layers V-VI, although some neurons also showed diffuse ub-positive staining in the cytoplasm. In the D-MND cases, some neurons showed ub-positive inclusions in layers II-IIIab, and ub-positive dendrites were unremarkable. The number of ub-positive neurons and dendrites in relation to the degree of neuronal loss in the cerebral cortex were then evaluated. The number of ub-positive neurons in the regions showing very mild to mild neuronal loss was significantly greater in the D-MND cases than in the aPiD cases. However, in the aPiD cases, the number of ub-positive neurons was significantly greater in the regions showing moderate neuronal loss. When double-immunostained, almost all ub-positive structures were positive for ub-binding protein p62. Some ub-positive or negative neurons in the cerebral cortex were immunostained with anti-ub ligase (Parkin) and anti-ub C-terminal hydrolase (UCH-L1) antibodies. Granular cells of the dentate gyrus were weakly positive for UCH-L1. There could be some differences in the mechanism by which neurons in the cerebral cortex accumulate ub between aPiD and D-MND.

Adult↗
PubMed2004

Habitual self-mutilation in Japan.

The purpose of the present study was to clarify the relationship between bulimic behavior, dissociative phenomenon and sexual/physical abuse histories in Japanese subjects with habitual self-mutilation. Subjects consisted of 34 female outpatients who had cut their wrists or arms on more than 10 occasions. Two age-matched groups, which consisted of 31 general psychiatric outpatients and 26 non-clinical volunteers, served as controls. They were assessed with the Beck Depression Inventory-II, Bulimia Investigatory Test of Edinburgh, Adolescent Dissociative Experience Scale, and an original self-reporting questionnaire concerning various problematic behaviors and sexual/physical abuse histories. The habitual self-mutilation and the two control groups were compared. The habitual self-mutilation group had significantly higher scores on the Beck Depression Inventory-II, Bulimia Investigatory Test of Edinburgh, and Adolescent Dissociative Experience Scale than either of the two control groups (P < 0.001). Furthermore, the habitual self-mutilation group more frequently had a history of illicit psychoactive drug use (P = 0.001), shoplifting (P < 0.001), suicide attempts (P < 0.001), overdosing with medicine (P < 0.001), sexual abuse (P = 0.011), and childhood physical abuse (P = 0.001) than the general psychiatric controls. These results are consistent with those in Western studies. Habitual self-mutilation is likely to coexist with depression, bulimia, and dissociation. Such patients frequently have clinical features similar to those of 'multi-impulsive bulimia'. Evidence supports the association between habitual self-mutilation and sexual/childhood physical abuse in Japan.

Adolescent↗
PubMed2004

Patterns of self-cutting: a preliminary study on differences in clinical implications between wrist- and arm-cutting using a Japanese juvenile detention center sample.

The present study was aimed to clarify the differences in clinical implications between wrist- and arm-cutting. Subjects were 201 delinquent adolescents (178 males and 23 females) who had been admitted to a detention center from February to March 2003. A self-reporting questionnaire and the Adolescent Dissociative Experience Scale (ADES) were given. Traumatic events and other self-injurious behavior were compared among four groups. In total, 33 (16.4%) subjects reported wrist- and/or arm-cutting. Of the females, 60.9% (n = 14) had experienced self cutting behaviors compared to 10.7% of males (n = 19). Subjects were divided into four groups; 'non-cutting' (NC: n = 168, 83.6%), 'wrist-cutting' (WC: n = 5, 2.5%), 'arm-cutting' (AC: n = 19, 9.5%), and 'wrist- and arm-cutting' (WAC: n = 9, 4.5%). WC, AC, and WAC groups reported early separation, bulling in school, and histories of sexual/physical abuse more frequently than NC group. WC and WAC groups reported suicidal ideation and suicide attempts more frequently than NC and AC groups. The ADES scores in AC and WAC groups were significantly higher than in those in NC group (P < 0.001), while the scores in WC were not different from NC groups. WC and WAC groups self-cut due to suicide idea more frequently than the AC group, while AC group self-cut due to anger expression more frequently than WC or WAC groups. Self-cutters experienced early separation, bullying in school, and sexual/physical abuse more frequently than-non-self-cutters. Arm-cutting behavior may predict dissociation, while wrist-cutting may involve with suicidality.

Adolescent↗
PubMed2004

Psychomotor retardation correlates with frontal hypoperfusion and the Modified Stroop Test in patients under 60-years-old with major depression.

Frontal hypoperfusion and frontal dysfunction have been reported in patients with major depression. It was also found that frontal hypoperfusion correlated with frontal dysfunction evaluated by neuropsychological tests in depressive patients aged 60 or over. These findings suggested that depression may cause frontal dysfunction and frontal hypoperfusion, and that these pathophysiological changes are manifested as psychomotor retardation. We performed single photon emission computed tomography and Modified Stroop Test on 35 patients with depression aged 25-83 to investigate association of depressive symptoms and psychological tests with cerebral blood perfusion. Additionally, we divided the patients into a younger (less than 60 years old) and an older (60 or over) group to examine the effect of age. Significant correlations were found between frontal perfusion, interference measure on Modified Stroop Test, and psychomotor retardation in all patients. These correlations were also found in the younger group. There was no significant difference on frontal perfusion, interference measure of the Modified Stroop Test, and psychomotor retardation between the two groups. The present findings suggest that frontal hypoperfusion, frontal dysfunction, and psychomotor retardation were associated with one another in not only the old but also the young patients with depression.

Adult↗
PubMed2004

Nitric oxide pathways in Alzheimer's disease and other neurodegenerative dementias.

Nitric oxide (NO) is an enzymatic product of nitric oxide synthase (NOS). NO has significant physiological functions and an increasing body of evidence suggests that NO pathways are implicated in a number of neurological disorders, including Alzheimer's disease (AD) and other neurodegenerative dementias. NO is continuously released by endothelial cells in the vascular system, whereas advanced age in the presence of vascular risk factor causes a decrease in cerebral blood flow, involving microvasculopathy with impaired NO release, which in turn results in regional metabolic dysfunction. This finding suggests that vascular pathology plays a crucial role in the pathogenesis of so-called neurodegenerative dementias. Inflammatory responses are commonly found in the brain under a variety of neurodegenerative dementias, including AD and dementia with Lewy bodies, in which up-regulation of NOS expression, suggesting overproduction of NO, is found in neurons and glia. NO is thought to be involved in such neuroinflammation due to its free radical properties, which compromise cellular integrity and viability via mitochondrial damage. Further studies to elucidate NO pathways in neurodegenerative dementias could lead to a better understanding of their pathogenesis and improved therapeutic strategies, and therefore are certainly warranted.

Alzheimer Disease↗
PubMed2004

[A case with late-onset MELAS with hallucination and delusion].

We report a 53-year-old male patient with late onset mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes(MELAS) with hallucination and delusion. The patient manifested various neurological symptoms including perceptive deafness, muscle weakness of limbs with loss of consciousness, sensory abnormalities in hands, feet and a face, abnormal sense of taste, tremor, palsy of upward eye movement and weak deep tendon reflexes prior to the psychotic episode. He was diagnosed as MELAS, because of high serum lactic acid and pyruvic acid, and the point mutation in the mitochondrial DNA 3243. SPECT imaging showed decreased perfusion in occipital cortex and thalamus. These SPECT changes improved after disappearing visual hallucination. Hallucination might be caused by delirium due to stroke-like episode. Dysfunction in the occipital cortex and thalamus might be involved with this perfusion change.

Delusions↗
PubMed2003

Expression of BRI, the normal precursor of the amyloid protein of familial British dementia, in human brain.

Familial British dementia (FBD) is characterized neuropathologically by deposition of a unique amyloid-forming protein, ABri. It is a fragment of an abnormal form of a precursor protein, BRI. In FBD, BRI is elongated by 11 amino acids due to a point mutation that prevents recognition of the normal stop codon. We have investigated the expression of normal BRI in non-FBD cases. Three antibodies were raised against sequences of BRI and were used for immunoblotting and immunohistochemistry. Each of these antibodies detected a band at approximately 35 kDa by Western blotting. In postmortem human brain tissues, BRI was detected as fine granules in the neuronal cytoplasm. Pyramidal neurons in CA3 and CA4 of the hippocampus as well as Purkinje cells in the cerebellar cortex were most intensely stained for BRI. Such a distribution of neurons strongly expressing BRI parallels the reported occurrence of ABri deposits in patients with FBD. In pathological cases, BRI was detected in dystrophic neurites in senile plaques, around lesions in ischemic cases, in torpedo and glumose changes in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in hypoxic cases. These results suggest that BRI is transported in neuronal processes and is possibly involved in some role in nerve terminals. While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein, which is the source of the beta-amyloid protein of Alzheimer's disease.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Serum ghrelin concentrations in patients receiving olanzapine or risperidone.

RATIONALE: Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanism is poorly understood. OBJECTIVES: To test the hypothesis that ghrelin, a gastrointestinal hormone that enhances appetite, is involved in increased food intake and weight gain during treatment with antipsychotics. METHODS: Serum ghrelin concentrations were investigated in schizophrenic patients receiving olanzapine or risperidone, and in healthy volunteers. RESULTS: Serum ghrelin concentrations did not increase, but rather decreased, in patients treated with olanzapine or risperidone in comparison with healthy volunteers. No significant difference was found in serum ghrelin concentration between patients treated with olanzapine and risperidone. CONCLUSIONS: Our results indicate that ghrelin is not a direct cause of increased food intake and weight gain during treatment with olanzapine or risperidone, whereas ghrelin is associated with metabolic change in patients receiving these agents.

Adult↗
PubMed2003

Siah-1 facilitates ubiquitination and degradation of synphilin-1.

Parkinson's disease is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and appearance of Lewy bodies, cytoplasmic inclusions that are highly enriched with ubiquitin. Synphilin-1, alpha-synuclein, and Parkin represent the major components of Lewy bodies and are involved in the pathogenesis of Parkinson's disease. Synphilin-1 is an alpha-synuclein-binding protein that is ubiquitinated by Parkin. Recently, a mutation in the synphilin-1 gene has been reported in patients with sporadic Parkinson's disease. Although synphilin-1 localizes close to synaptic vesicles, its function remains unknown. To investigate the proteins that interact with synphilin-1, the present study performed a yeast two-hybrid screening and identified a novel interacting protein, Siah-1 ubiquitin ligase. Synphilin-1 and Siah-1 proteins were endogenously expressed in the central nervous system and were found to coimmunoprecipitate each other in rat brain homogenate. Confocal microscopic analysis revealed colocalization of both proteins in cells. Siah-1 was found to interact with the N terminus of synphilin-1 through its substrate-binding domain and to specifically ubiquitinate synphilin-1 via its RING finger domain. Siah-1 facilitated synphilin-1 degradation via the ubiquitin-proteasome pathway more efficiently than Parkin. Siah-1 was found to not facilitate ubiquitination and degradation of wild type or mutant alpha-synuclein. Synphilin-1 inhibited high K+-induced dopamine release from PC12 cells. Siah-1 was found to abrogate the inhibitory effects of synphilin-1 on dopamine release. Such findings suggest that Siah-1 might play a role in regulation of synphilin-1 function.

Animals↗
PubMed2003

Developmental stages of cortical Lewy bodies and their relation to axonal transport blockage in brains of patients with dementia with Lewy bodies.

We investigated 10 dementia with Lewy bodies (DLB) brains showing various degrees of Lewy pathology using alpha-synuclein-immunohistochemistry, and morphologically divided cortical Lewy bodies (LB) into six developmental stages. Further, we demonstrated the ultrastructure of each stage of cortical LB using alpha-synuclein-immunoelectron microscopy. In the initial stage, alpha-synuclein accumulated in part of the neuronal cytoplasm without filamentous components, then formed LB and LB-related neurites composed of granulo-filamentous components. Finally, LB degraded to extracellular LB composed of loose filamentous components with involved astroglial processes. In addition, we immunohistochemically investigated the accumulation of axonal transported substances in cortical LB, and showed that APP, chromogranin-A, synphilin-1 and synaptophysin accumulated in cortical LB from stages 1, 2, 3 and 4, respectively. These findings suggest that chronic axonal transport blockage is implicated in the development of cortical LB in DLB brains.

Amyloid beta-Protein Precursor↗
PubMed2003

4-repeat tauopathy sharing pathological and biochemical features of corticobasal degeneration and progressive supranuclear palsy.

We report a 67-year-old man with 4-repeat (4R) tauopathy sharing both features of corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). Although CBD and PSP have a common pathological feature that 4R tau accumulates in neurons and glia, recent pathological studies have confirmed differences between the two disorders. Clinical features of the present case were asymmetrical apraxia, parkinsonism, memory disturbance, disorientation and left limb myoclonus with a 5-year history. Pathological features were the widespread occurrence of 4R tau-positive structures including pre-tangles, neurofibrillary tangles, astrocytic plaques, tufted astrocytes, coiled bodies and argyrophilic threads. Biochemically, immunoblotting of insoluble tau demonstrated the low molecular fragments of 37 kDa and 33 kDa observed in typical CBD and PSP, respectively, in addition to the presence of 4R tau isoforms. The present case shared tau-related pathological and biochemical features of CBD and PSP. These findings support that CBD and PSP are closely associated disorders having a pathogenesis common to 4R tauopathy.

Aged↗
PubMed2003

Degeneration of tyrosine hydroxylase-immunoreactive neurons in the cerebral cortex and hippocampus of patients with dementia with Lewy bodies.

We immunohistochemically investigated the degeneration of tyrosine hydroxylase (TH)-positive neurons in the cerebral cortex and hippocampus of dementia with Lewy bodies (DLB) brains. TH-positive neurons in the cerebral cortex and hippocampus were decreased in number, and were rarely associated with Lewy bodies (LB) or neurofibrillary tangles (NFT). A mild to moderate loss of TH-positive neurons was observed in both the cerebral cortex and substantia nigra. In addition, most brains showing low NFT stages and lacking amyloid deposits (AM), corresponding to pure-form DLB brains, demonstrated a moderate to severe loss of TH-positive neurons. These findings suggest that TH-positive neurons in the cerebral cortex degenerate by a pathomechanism similar to that in the substantia nigra, and that the degeneration of these neurons is partly related to LB or NFT formation in either the substantia nigra or cerebral cortex.

Aged↗
PubMed2003

Neuronal accumulation of alpha- and beta-synucleins in the brain of a GM2 gangliosidosis mouse model.

Sandhoff disease (SD) is a heritable lysosomal storage disease resulting from impaired degradation of GM2 ganglioside. The hallmark pathology of the SD model mouse brain is GM2 ganglioside accumulation in neurons. In the present study, we immunohistochemically investigated the neuronal pathology in SD mouse brains, and demonstrated neuronal accumulation of alpha- and beta-synucleins in addition to GM2 ganglioside. Synuclein-positive neurons were extensively observed throughout SD mouse brains, although the distribution of beta-synuclein was less extensive than that of alpha-synuclein. Synuclein-positive neurons were negative to ubiquitin and PHF-tau. These findings suggest that neuronal synucleins may accumulate secondarily to GM2 ganglioside in SD mouse brains, and that neuronal accumulation of synucleins may be more critical than that of GM2 ganglioside for SD mice.

Animals↗