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Biomedical subjects

Hideo Mori

Publications and source records attributed to Hideo Mori.

At least 19 recordsLinked to original sources
PubMed2006

Nuclear localization of the 20S proteasome subunit in Parkinson's disease.

Considering the involvement of ubiquitin-proteasome system (UPS) in Parkinson's disease (PD), the aim of the present study was to determine the distribution of proteasomes in PD brains. Immunohistochemical studies showed localization of 20S proteasome in the nuclei of neurons of the putamen and substantia nigra of PD. In contrast, no nuclear staining was observed in the same areas of brains of controls. Our results suggest that nuclear localization of 20S proteasome seems to be associated with the pathogenesis of PD.

Adult↗
PubMed2006

Up-regulation of hMUTYH, a DNA repair enzyme, in the mitochondria of substantia nigra in Parkinson's disease.

There is ample evidence for the involvement of oxidative stress in mitochondrial DNA damage and repair mechanisms in Parkinson's disease (PD). The human MutY homolog (hMUTYH) which removes misincorporated adenine opposite 8-oxoG in DNA functions in post-replication, and is localized in the nuclei and mitochondria. We hypothesized that hMUTYH is involved in the disease process of PD. To test our hypothesis, we performed immunohistochemical and biochemical studies on brains of patients with PD and those of control patients. Our results showed up-regulation of hMUTYH in the mitochondria of the SN of PD patients. Western blot analysis also revealed high hMUTYH levels in PD patients and expression of a 47-kDa molecule in the brains as the major isoform. This molecule was localized within the mitochondria as confirmed by double staining with a mitochondrial marker. To confirm the presence of this molecule, we examined the mRNAs of isoforms that translate to the 47-kDa molecule. Based on the amount of mRNAs, the major molecule was alpha4. Interestingly, this molecule lacks the mitochondria targeting sequence. Our results suggest that hMUTYH might be a useful marker of oxidative stress and that oxidative stress and genomic instability are important in the PD disease process.

Aged↗
PubMed2006

An efficient method for quantitative determination of cellular ATP synthetic activity.

The authors have developed an efficient method to measure cellular activity of ATP synthesis. Although ATP is a major energy source of biological reactions, it has been difficult to measure cellular ATP synthetic activity quantitatively. In this report, bioluminescence from the luciferin-luciferase reaction was used for the quantitative measurement. Under the used condition, bioluminescence from standard ATP solution showed no attenuation within several minutes, and the intensity corresponded proportionally to ATP concentrations of the standards. To measure dynamic cellular ATP synthetic activity, combination of osmotic shock and detergent treatment was used to make Escherichia coli cells permeable. ATP was discharged from permeable cells and reacted with externally added luciferase. Because permeable cells used glucose to synthesize and accumulate ATP without further growth, intensity of bioluminescence was increasing during the cellular consumption of glucose. Cellular ATP biosynthetic activity was calculated form the slope of linearly increasing bioluminescence. This permeable cell assay could be applied to high-throughput measuring for dynamic cellular activity of glycolytic ATP synthesis.

Adenosine Triphosphate↗
PubMed2006

Oral care reduces incidence of ventilator-associated pneumonia in ICU populations.

OBJECTIVE: To examine whether oral care contributes to preventing ventilator-associated pneumonia (VAP) in ICU patients. DESIGN: Nonrandomized trial with historical controls. SETTING: A medical-surgical ICU in a university hospital. PATIENTS: 1,666 mechanically ventilated patients admitted to the ICU. INTERVENTION: Oral care was provided to 1,252 patients who were admitted to the ICU during period between January 1997 and December 2002 (oral care group), while 414 patients who were admitted to the ICU during period between January 1995 and December 1996 and who did not receive oral care served as historical controls (non-oral care group). MEASUREMENTS AND RESULTS: Incidence of VAP(episodes of pneumonia per 1000 ventilator days) in the oral care group was significantly lower than that in the non-oral care group (3.9 vs 10.4). The relative risk of VAP in the oral care group compared to that in the non-oral care group was 0.37, with an attributable risk of -3.96%. Furthermore, length of stay in ICU before onset of VAP was greater in the oral care than in the non-oral care group (8.5+/-4.6 vs 6.3+/-7.5 days). However, no significant difference was observed in either duration of mechanical ventilation or length of stay between the groups (5.9+/-10.8 vs 6.0+/-8.8 days and 7.5+/-11.5 vs 7.2+/-9.5 days, respectively). Pseudomonoas aeruginosa was the most frequently detected bacteria in both groups. Number of potentially pathogenic bacteria in oral cavity was significantly reduced by single oral care procedure. CONCLUSION: Oral care decreased the incidence of VAP in ICU patients. DESCRIPTOR: Pulmonary nosocomial infection.

Chi-Square Distribution↗
PubMed2006

Prognosis of Parkinson's disease: time to stage III, IV, V, and to motor fluctuations.

We report a long-term outcome on a large cohort of Japanese patients with Parkinson's disease (PD). A total of 1,768 (793 men, 975 women) consecutive patients visited our clinic from 1 January 1989 to 31 December 2002. Among them, 1,183 patients (531 men, 652 women) came to our clinic within 5 years from the onset of disease and at the Hoehn & Yahr Stage III or less at the first visit. Long-term outcome was evaluated in this subcohort of the patients. We examined the duration to reach Stage III, IV, and V, and the duration to develop wearing off and dyskinesia. Time to reach Stage III was slightly but significantly shorter in women, in that 23.8% of men and 35.3% of women reached Stage III by the end of the 5th year; 49.7% of men and 63.3% of women reached Stage III by the end of the 10th year, and 88.9% of men and 79.9% of women by the end of the 15th year (P < 0.001). Also, durations to develop wearing off and dyskinesia were shorter in women compared to men. These data suggest that the disease progression may be slightly faster for women. Young-onset patients showed significantly longer duration to reach Stage III, IV, and V but shorter duration to develop wearing off and dyskinesia. Not many studies are available in the literature on the long-term outcome of PD, and our data would be useful as a reference.

Adult↗
PubMed2006

Pathological and biochemical studies on a case of Pick disease with severe white matter atrophy.

We report on a male patient with Pick disease who had shown severe white matter atrophy and dilatation of the lateral ventricle in the frontal lobe from an early stage. Upon admission to our hospital 2 years after disease onset, the patient showed apathy, and MRI revealed severe atrophy of the cortex and white matter of the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy revealed severe atrophy of the frontal and temporal lobes, severe loss of white matter in the frontal lobe, dilatation of the lateral ventricles, and cortical thinning. Histopathological examination showed severe loss of myelinated fibers in the frontal white matter and severe neuronal loss with gliosis in the frontal and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of Pick disease predominantly affecting the frontal lobe with severe involvement of the white matter from an early stage. This case suggests that myelinated fibers in the white matter as well as cerebral neurons are primarily affected in Pick disease.

Aged↗
PubMed2006

[An 81-year-old man with personality change, dementia, and gait disturbance with diffuse leukoaraiosis of the cerebral white matter].

We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.

Aged, 80 and over↗
PubMed2006

[An 80-year-old woman with progressive stroke, who had rheumatoid arthritis and antiphospholipid syndrome].

We report an 80-year-old woman who had rheumatoid arthritis and antiphospholipid syndrome. She was treated for rheumatoid arthritis since her thirties. At 76 years of age, she was diagnosed antiphospholipid syndrome serologically. She felt It. limb weakness and dysarthria and was admitted to the hospital on July 18, 2003. The brain MRI showed T2 hyperintensity signal on the rt. pre-central lobe. She was treated by the argatroban, edaravone, glycerol, and aspirin. However, she became bedridden and fed by NG-tube because her symptoms progressed in spite of the therapy. Progression of stroke stopped by adding heparin at last. After that, she repeated pneumonia. She was found dead on the bed August 2, 2003. The patient was discussed in a CPC. The chief discussant arrived at a conclusion that the cause of infarction was angitis due to rheumatoid arthritis. Other possibilities were multiple thrombus due to antiphospholipid syndrome, amyloid angiopathy, and atherosclerotic infarction. Post-mortem study revealed sputum obstruction in her bronchus, string deposition in her organs. The brain showed infarction on the rt. pre-central lobe. There were multiple thrombus in the leptomeningeal artery, but few atherosclerotic changes of the small arteries. Amyloid didn't deposit in the brain artery and the parenchyma. Pathologist concluded that her infarction was induced with multiple thrombus due to antiphospholipid syndrome.

Aged, 80 and over↗
PubMed2005

Positive immunoreactivity for vesicular monoamine transporter 2 in Lewy bodies and Lewy neurites in substantia nigra.

Vesicular monoamine transporter 2 (VMAT2) is responsible for packing dopamine into vesicles, and reduces the effects of neurotoxins by sequestering them into vesicles. In this report, we tested the hypothesis that VMAT2 is associated with Lewy body (LB) formation by immunohistochemical staining of midbrain and cortical sections of autopsied brains of patients with Parkinson's disease (PD) and diffuse Lewy body disease (DLBD) for VMAT2 using a polyclonal antibody against VMAT2. LBs in the substantia nigra (SN) of PD and DLBD were immunoreactive for VMAT2, especially in the peripheral zone. Previous electron microscopic studies also revealed the presence of numerous dense core vesicles around the LBs, suggesting that these vesicles are related to LB formation. Indeed, the presence of a few vesicle-linked proteins such as synaptophysin and chromogranin A in LBs has been reported. Together with the low expression of VMAT2 in the SN of PD, the involvement of VMAT2 in LBs of the SN suggests the association of this protein in the neurodegeneration of nigral neurons in PD.

Aged↗
PubMed2005

A possible role for humoral immunity in the pathogenesis of Parkinson's disease.

The pathogenesis of idiopathic Parkinson's disease is unknown, but nigral degeneration and depigmentation are associated with microglial inflammation and anti-inflammatory medications appear to protect against the disease. The possibility that humoral immunity may play a role in initiating or regulating the inflammation has been suggested by experimental studies triggering dopamine cell death using a variety of transfer strategies and the observation of CD8+ T lymphocytes and complement in the nigra in Parkinson's disease. We analysed the association between degeneration and humoral immune markers in brain tissue of patients with idiopathic (n = 13) or genetic (n = 2 with alpha-synuclein and n = 1 with parkin mutations) Parkinson's disease and controls without neurological disease (n = 12) to determine the humoral immune involvement in Parkinson's disease. Formalin-fixed tissue samples from the substantia nigra and primary visual cortex for comparison were stained for alpha-synuclein, major histocompatibility complex II (HLA), immunoglobulin M (IgM), immunoglobulin G (IgG), IgG subclasses 1-4 and IgG receptors FcgammaR I-III. Antigen retrieval and both single immunoperoxidase and double immunofluorescence procedures were employed to determine the cell types involved and their pattern and semiquantitative densities. Significant dopamine neuron loss occurred in all patients with Parkinson's disease, negatively correlating with disease duration (r = -0.76, P = 0.002). Although all patients had increased inflammatory HLA immunopositive microglia, the degree of inflammation was similar throughout the disease (r = 0.08, P = 0.82). All patients with Parkinson's disease had IgG binding on dopamine neurons but not IgM binding. Lewy bodies were strongly immunolabelled with IgG. A mean 30 +/- 12% of dopamine nigral neurons were immunoreactive for IgG in Parkinson's disease with the proportion of IgG immunopositive neurons negatively correlating with the degree of cell loss in the substantia nigra (r = -0.67, P < 0.0001) and positively correlating with the number of HLA immunopositive microglia (r = 0.51, P = 0.01). Most neuronal IgG was the IgG1 subclass with some IgG3 and less IgG2 also found in the damaged substantia nigra. The high affinity activating IgG receptor, FcgammaRI, was expressed on nearby activated microglia. The low affinity activating IgG receptor, FcgammaRIII was expressed on cells morphologically resembling lymphocytes, whereas immunoreactivity for the inhibitory IgG receptor FcgammaRII was absent in all cases. This pattern of humoral immune reactivity is consistent with an immune activation of microglia leading to the targeting of dopamine nigral neurons for destruction in both idiopathic and genetic cases of Parkinson's disease.

Aged↗
PubMed2005

Functional coupling between vanillate-O-demethylase and formaldehyde detoxification pathway.

Pseudomonas putida vanillate-O-demethylase consisting of VanA and VanB was expressed in Escherichia coli strain K-12. Recombinant E. coli strain K-12 cells expressing VanAB efficiently converted vanillate into protocatechuate with glucose consumption. Mutant lacking either pgi or zwf showed higher or lower converting activity than the parental strain, respectively. Formaldehyde, which is the by-product of the demethylation, was converted into formate in the cellular reaction. Formate accumulation was blocked by gene disruption of the E. coli frmA that coded glutathione-dependent formaldehyde dehydrogenase.

DNA, Recombinant↗
PubMed2005

Myoclonic tremulous movements in multiple system atrophy are a form of cortical myoclonus.

We prospectively studied the clinical and electrophysiological features of myoclonic tremulous movements in patients with multiple system atrophy (MSA). Among 42 consecutive patients, 12 MSA-p (parkinsonian type) and 3 MSA-c (cerebellar type) patients showed small-amplitude myoclonic movements. These movements occurred in the distal part of the arms and fingers, particularly in posture or during voluntary movements. We conducted detailed electrophysiological studies in 11 patients. Electromyographic recordings showed irregular bursts of brief duration often synchronously involving the antagonistic muscles. Somatosensory evoked responses were slightly enlarged in some patients. Long-latency reflexes were enhanced in 7 patients. A jerk-locked averaging technique revealed premyoclonic cortical potentials in 9 patients. These findings suggest that small-amplitude myoclonic movements in MSA are a form of cortical myoclonus.

Aged↗
PubMed2005

Relationship between Parkinson disease with dementia and dementia with Lewy bodies.

Parkinson disease (PD) and dementia with Lewy bodies (DLB) are considered Lewy body diseases (LBDs). To clarify the relation between PD with dementia (PDD) and DLB, 30 patients with LBD were divided into pathological subtypes according to the consensus guidelines for DLB. Patients with PDD showed neocortical and limbic type of LBD as well as patients with DLB. Dementia had not been noted in 2 patients with neocortical type. Our results indicate that PDD and DLB share a common pathological substrate and that the pathological subtypes of LBD show considerable overlap in clinical manifestations.

Age of Onset↗
PubMed2005

Pathological substrate of dementia in Parkinson's disease--its relation to DLB and DLBD.

The pathological background of dementia in Parkinson's disease (PD) has been a matter of controversy. Recent studies have revealed the appearance of many Lewy bodies in the cerebral cortex of PD with dementia (PDD). This pathological change corresponds to the neocortical type, which was originally reported as diffuse Lewy body disease (DLBD), or a transitional type of dementia with Lewy bodies (DLB). Clinical differentiation between DLBD and the transitional type of Lewy body disease (LBD) is sometimes difficult because the symptoms overlap. Therefore, it is appropriate, at least at present, that DLB and PDD are used as clinical diagnoses and that DLBD and the transitional- and brainstem-types of LBD are used as neuropathological diagnoses.

Cerebral Cortex↗
PubMed2005

Functional analysis of 1440 Escherichia coli genes using the combination of knock-out library and phenotype microarrays.

Escherichia coli is one of the best elucidated organisms. However, about 40% of E. coli genes have not been assigned to their function yet. We analyzed 1440 single gene knock-out mutants using the GN2-MicroPlate, which permits assay of 95 carbon-source utilizations simultaneously. In the knock-out library there are 1044 of so called y-genes with no apparent function. The raw dataset was analyzed and genes were interrelated by the clustering method of the GeneSpring software. In the resulted dendrogram of genes, a group of genes with known and related function tended to be assembled into a cluster. Our clustering method would be useful for functional assignment of so called y-genes with no apparent function, since the resulted dendrogram could connect y-genes to phenotype and function of well-studied genes.

Escherichia coli↗
PubMed2005

New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.

Adult↗