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Biomedical subjects

S Tanimukai

Publications and source records attributed to S Tanimukai.

At least 19 recordsLinked to original sources
PubMed2001

Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease.

BACKGROUND: Although the APOE epsilon 4 allele increases the risk of developing AD, the effects of the epsilon 4 allele on brain atrophy in clinical AD patients are controversial. OBJECTIVE: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. METHODS: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the epsilon 3/3 allele, one group (n = 46) had the epsilon 3/4 allele, and one group (n = 46) had the epsilon 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE epsilon 4 allele was also examined. RESULTS: The normalized hippocampal volume was correlated with the number of APOE epsilon 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE epsilon 4 alleles (r = -0.178, p = 0.037). The number of APOE epsilon 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). CONCLUSIONS: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

Aged↗
PubMed2001

Microglial signaling by amyloid beta protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS.

Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic protein associated with cell motility and phagocytosis, is activated upon phosphorylation by protein kinase C (PKC) and proline-directed protein kinases. In Alzheimer disease (AD), activated microglia expressing MARCKS migrates around senile plaques. We reported that amyloid beta protein (A beta), a major component of senile plaques, activated MARCKS through a tyrosine kinase and PKC-delta. We have now identified another A beta signaling pathway through a mitogen-activated protein kinase (MAPK) involved in the phosphorylation of MARCKS and analysed cross-talk between PKC and MAPK pathways in primary cultured rat microglia. A selective inhibitor for MAPK kinase, PD098059, significantly inhibited the phosphorylation of MARCKS induced by A beta. Extracellulary regulated kinases, the activities of which were induced by A beta, directly phosphorylated a recombinant MARCKS in vitro. The MAPK pathway was sensitive to wortmannin, but not to a PKC inhibitor or to tyrosine kinase inhibitors. The activation of PKC by A beta was not sensitive to wortmannin. Our findings suggest involvement of the MAPK pathway through phosphoinositol 3-kinase in the phosphorylation of MARCKS in rat cultured microglia, an event may be associated with mechanisms activating microglia in AD.

Amyloid beta-Peptides↗
PubMed2001

Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.

The increased accumulation of activated microglia containing amyloid beta protein (Abeta) around senile plaques is a common pathological feature in subjects with Alzheimer's disease (AD). Much less is known, however, of intracellular signal transduction pathways for microglial activation in response to Abeta. We investigated intracellular signaling in response to Abeta stimulation in primary cultured rat microglia. We found that the kinase activity of PKC-delta but not that of PKC-alpha or -epsilon is increased by stimulation of microglia with Abeta, with a striking tyrosine phosphorylation of PKC-delta. In microglia stimulated with Abeta, tyrosine phosphorylation of PKC-delta was evident at the membrane fraction without an overt translocation of PKC-delta. PKC-delta co-immunoprecipitated with MARCKS from microglia stimulated with Abeta. Abeta induced translocation of MARCKS from the membrane fraction to the cytosolic fraction. Immunocytochemical analysis revealed that phosphorylated MARCKS accumulated in the cytoplasm, particularly at the perinuclear region in microglia treated with Abeta. Taken together with our previous observations that Abeta-induced phosphorylation of MARCKS and chemotaxis of microglia are inhibited by either tyrosine kinase or PKC inhibitors, our results provide evidence that Abeta induces phosphorylation and translocation of MARCKS through the tyrosine kinase-PKC-delta signaling pathway in microglia.

Amyloid beta-Peptides↗
PubMed2000

Visuoperceptual impairment in dementia with Lewy bodies.

BACKGROUND: In dementia with Lewy bodies (DLB), vision-related cognitive and behavioral symptoms are common, and involvement of the occipital visual cortices has been demonstrated in functional neuroimaging studies. OBJECTIVES: To delineate visuoperceptual disturbance in patients with DLB in comparison with that in patients with Alzheimer disease and to explore the relationship between visuoperceptual disturbance and the vision-related cognitive and behavioral symptoms. DESIGN: Case-control study. SETTING: Research-oriented hospital. PATIENTS: Twenty-four patients with probable DLB (based on criteria of the Consortium on DLB International Workshop) and 48 patients with probable Alzheimer disease (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) who were matched to those with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. MAIN OUTCOME MEASURES: Four test items to examine visuoperceptual functions, including the object size discrimination, form discrimination, overlapping figure identification, and visual counting tasks. RESULTS: Compared with patients with probable Alzheimer disease, patients with probable DLB scored significantly lower on all the visuoperceptive tasks (P<.04 to P<.001). In the DLB group, patients with visual hallucinations (n = 18) scored significantly lower on the overlapping figure identification (P = .01) than those without them (n = 6), and patients with television misidentifications (n = 5) scored significantly lower on the size discrimination (P<.001), form discrimination (P = .01), and visual counting (P = .007) than those without them (n = 19). CONCLUSIONS: Visual perception is defective in probable DLB. The defective visual perception plays a role in development of visual hallucinations, delusional misidentifications, visual agnosias, and visuoconstructive disability charcteristic of DLB.

Aged↗
PubMed2000

Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer's disease.

Repeated falls are reported as one of the clinical characteristics in dementia with Lewy bodies (DLB). We examined the incidence of fall-related injuries in 561 dementia patients with various clinical diagnoses, including DLB and Alzheimer's disease (AD), in a ward established for dementia research. The incidence of fall-related injuries was significantly higher in DLB patients (10.7%) than in AD patients (1.1%) (P < 0.001). The high incidence in those patients with DLB cannot be attributed to Parkinsonism because none of the DLB patients with injuries showed extrapyramidal sign. Our observations suggest that patients with a clinical diagnosis of DLB have a high risk of fall-related injuries, even though they do not show Parkinsonism. An appropriate clinical discrimination between DLB and AD is recommended to manage and prevent fall-related injuries.

Accidental Falls↗
PubMed2000

Effect of the apolipoprotein E epsilon4 allele on white matter hyperintensities in dementia.

BACKGROUND AND PURPOSE: The clinical significance of the apoE epsilon4 allele in white matter changes in patients with dementia has been a subject of debate. We studied the association between the apoE epsilon4 allele and white matter hyperintensities (WMHs) before and after control for (1) potential vascular risk factors and (2) the presence of lacunar infarcts in patients with dementia. METHODS: The subjects were 131 patients with dementia who had either Alzheimer's disease or vascular dementia, or a combination of these 2 types of dementia, with or without WMHs, lacunar infarcts, or both. The association of the epsilon4 allele with WMHs was examined before and after control for age, sex, duration of symptoms, education level, severity of dementia, presence of lacunar infarcts, and potential vascular risk factors, including hypertension, diabetes mellitus, lipid disorders, smoking habit, drinking habit, and cardiac diseases. RESULTS: WMHs were observed in 73 (55.7%) of the patients. Neither the number of apoE epsilon4 alleles nor their presence was significantly associated with WMHs before or after control for the potential confounding factors. Multiple logistic regression analyses revealed that age, the presence of hypertension, and the presence of lacunar infarcts were independently associated with WMHs. CONCLUSIONS: The apoE epsilon4 allele was not associated with WMHs in patients with dementia. The fact that WMHs were significantly associated with hypertension and lacunar infarcts may indicate an ischemic origin of WMHs.

Aged↗
PubMed2000

Impact of emotion on memory. Controlled study of the influence of emotionally charged material on declarative memory in Alzheimer's disease.

BACKGROUND: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake. AIMS: To test our previous findings in a controlled experimental study. METHOD: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not. RESULTS: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls. CONCLUSIONS: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia.

Aged↗
PubMed2000

A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto)

Exonic and intronic mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Here, we describe a new mutation, consisting of a C-to-T transition at position +12 of the intron following exon 10 of the tau gene in the Kumamoto pedigree, showing frontotemporal dementia. The mutation caused a marked reduction in melting temperature of the tau exon 10-splicing regulatory element RNA and a large increase in exon 10-containing transcripts. Brain tissue from affected individuals showed an abnormal preponderance of exon 10-containing transcripts that was reflected at the protein level by an overproduction of tau isoforms with four microtubule-binding repeats. Immunostaining revealed the presence of tau aggregates in degenerating neurons and glial cells. Isolated tau filaments had a twisted ribbon-like morphology and were made of hyperphosphorylated four-repeat tau isoforms. The additional mutation located dose to the splice-donor site of the intron following exon 10 of the tau gene supports the view that intronic mutations exercize their pathogenic effect by destabilizing RNA secondary structure.

Brain↗
PubMed1999

A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration.

We detected a missense mutation in exon 10 of tau that causes a substitution at codon 279 (N279K) in a Japanese patient with a familial background of parkinsonism and dementia originally described as pallido-nigro-luysian degeneration. This mutation is the same as one seen in a Caucasian family with pallido-ponto-nigral degeneration. The similarities between these two families suggest a common genetic mechanism that may account for the peculiar distribution of neuroglial degeneration with tauopathy.

Amino Acid Sequence↗
PubMed1999

Visual hallucinations and regional cerebral metabolism in dementia with Lewy bodies (DLB).

To investigate the neurobiological bases of visual hallucinations in dementia with Lewy bodies (DLB), regional cerebral glucose metabolism was compared among three patient groups; DLB with visual hallucinations, DLB without visual hallucinations and Alzheimer's disease (AD) without visual hallucinations. The regional metabolism was significantly lower in both DLB groups than in the AD group in the primary visual area and the posterior temporal, parietal and lateral occipital association areas. The hypometabolism in the right posterior temporal and parietal areas was significantly milder in DLB with visual hallucinations than in DLB without hallucinations. The hypometabolism in the primary visual cortex and the relatively preserved metabolism in the right temporoparietal association cortices may be associated with the occurrence of visual hallucinations in DLB patients.

Aged↗
PubMed1999

Lack of effect of apolipoprotein E E4 allele on neuropsychiatric manifestations in Alzheimer's disease.

The association between the apolipoprotein E epsilon 4 (APOE E4) allele and a wide spectrum of behavioral symptoms of Alzheimer's disease (AD) was investigated. Neither the severity nor the presence of any behavioral changes was associated with the number of APOE E4 alleles, even after controlling for the effects of age at onset, sex, education level, duration of illness, and severity of dementia. The findings do not support the hypothesis that neuropsychiatric manifestations of AD are different in patients with the APOE E4 allele.

Aged↗
PubMed1999

Distinctive neurobehavioral features among neurodegenerative dementias.

The distinctive neuropsychiatric features of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) were investigated by using the Neuropsychiatric Inventory. The patients with FTD had significantly more euphoria, aberrant motor activity, and disinhibition and significantly fewer delusions compared with the patients with AD or DLB. The patients with DLB had significantly more hallucinations compared with the AD or FTD patients. The findings clearly demonstrate that AD, DLB, and FTD have distinctive neuropsychiatric features, which may correspond to different patterns of cerebral involvement characteristic of these three major degenerative dementias.

Aged↗
PubMed1998

Cognitive loss in dementia with Lewy bodies and Alzheimer disease.

BACKGROUND: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. Some preliminary evidence exists that the pattern of cognitive impairment in DLB is different from that in Alzheimer disease (AD). OBJECTIVE: To delineate features of cognitive impairment of DLB on standardized neuropsychological tests. METHODS: We performed neuropsychological assessments of 26 patients with probable DLB (based on criteria of the consortium on DLB international workshop) and of 52 patients with probable AD (based on criteria of the National Institute of Neurological and Communicative Disorders and Stroke [now the National Institute of Neurological Disorders and Stroke])-Alzheimer's Disease and Related Disorders Association) who were matched to the patients with DLB 2:1 by age, sex, education, and Mini-Mental State Examination score. RESULTS: Compared with the group with probable AD, the group with probable DLB scored significantly lower on the picture arrangement, block design, object assembly, and digit symbol substitution subtests of the Wechsler Adult Intelligence Scale-Revised and on the Raven Colored Progressive Matrices test and significantly higher on the Mini-Mental State Examination locational orientation subtest and the Alzheimer's Disease Assessment Scale word recall subtest. A discriminant analysis revealed that the word recall score on the Alzheimer's Disease Assessment Scale and the block design score on the Wechsler Adult Intelligence Scale-Revised were the best discriminant factors. CONCLUSIONS: The disproportionately severe visuoperceptual, visuoconstructive, and visuospatial dysfunction and the disproportionately mild memory impairment in DLB compared with AD, which likely reflect the distribution of the pathologic changes in DLB, can help to differentiate DLB from AD.

Aged↗
PubMed1998

Regional metabolism: associations with dyscalculia in Alzheimer's disease.

OBJECTIVES: The ability to calculate, which is an important aspect of social daily living, is commonly impaired in patients with Alzheimer's disease even early in the course of the disease. Dyscalculia is often accompanied by focal brain damage, and has been argued to be an independent sign localised around the left temporoparietal region. However, the region most responsible for dyscalculia in Alzheimer's disease has not been determined. The relation between calculation ability and regional cerebral glucose metabolism in Alzheimer's disease was therefore examined. METHODS: The calculation ability, In 91 patients with probable Alzheimer's disease of minimal to moderate severity, was assessed using the arithmetic subtest of the Wechsler adult intelligence scale-revised and the performance correlated with regional cerebral glucose metabolism determined by "F-fluorodeoxyglucose and PET. RESULTS: Regional glucose metabolism in the left inferior parietal lobule and in the left inferior temporal gyrus was significantly correlated with the calculation performance irrespective of age, sex, education, and severity of disease. CONCLUSIONS: The results suggest that dysfunction of the left inferior parietal lobule and the left inferior temporal gyrus plays an important part in producing dyscalculia in patients with Alzheimer's disease.

Aged↗
PubMed1998

Medial temporal and whole-brain atrophy in dementia with Lewy bodies: a volumetric MRI study.

OBJECTIVE: Dementia with Lewy bodies (DLB) is emerging as a common cause of degenerative dementia. A recent pathologic study has indicated that the medial temporal lobe in patients with DLB was less atrophic than that in patients with AD. The purpose of this study was to examine whether medial temporal MRI volumetry was useful to differentiate DLB from AD clinically. METHODS: We compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in 27 patients with probable DLB (based on the criteria of the Consortium on DLB International Workshop), 27 patients with probable AD (based on criteria of the National Institute of Neurological Disease and Stroke/Alzheimer's Disease and Related Disorders Association), and 27 normal elderly subjects using an MRI-based volumetric technique. The three groups were matched for age and sex. Severity of cognitive disturbances represented by their Mini-Mental State Examination score was comparable between the DLB and AD groups. RESULTS: Hippocampal volume (normalized to intracranial volume) in the DLB group was significantly larger than that in the AD group, but significantly smaller than that in the normal control group. There were no significant differences in the amygdala and whole-brain volume between the DLB group and the AD group, but the atrophies of the amygdala and whole brain were more severe in the DLB group than those in the control group. CONCLUSIONS: These findings indicate the usefulness of MRI hippocampal volumetry in clinically discriminating patients with DLB from patients with AD.

Aged↗
PubMed1998

[Successful double peripheral blood stem cell transplantation for patient with malignant lymphoma of primary induction failure].

Three patients with non-Hodgkin's lymphoma of intermediate-grade histologies, who had failed to achieve a complete remission (CR) after more than several courses of conventional chemotherapy were treated with two cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (double PBSCT). All patients received regimen A with carboplatin 1g/m2, etoposide 1.2g/m2 and cyclophosphamide 120mg/kg prior to 1st PBSCT and obtained a partial remission. One patients received regimen A and two patients received regimen B with MCNU 500mg/m2, etoposide 750mg/m2 and L-PAM 140mg/m2 prior to 2nd PBSCT and all patients obtained CR. Second PBSCT was performed 3 to 5 months after the 1st PBSCT. At a median follow-up of 36 (range; 29 to 54) months, all patients remained in continuous CR. The period after reinfusion of PBSCT to achieve a neutrophil count more than 500/microliters ranged between 7 and 9 days and to achieve a platelet count more than 5 x 10(4)/microliters ranged 12 and 22 days. Grade 3 nonhematologic toxicity (mucositis) was seen in one patient after 2nd PBSCT. Double PBSCT could be well tolerated with a high response rate in patients with malignant lymphoma of primary induction failure.

Adult↗
PubMed1998

[Pryce type I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein].

A 50-year-old woman was examined because of chest discomfort. Chest X-ray films disclosed a tumorous shadow behind the heart. Chest computed tomography (CT) scans revealed a mass connected to the descending aorta, with increased blood flow in the left basal segment. The patient was admitted for further examination. Chest CT scans and cardioscintigrams were very useful as diagnostic tools, but the final diagnosis was made on the basis of angiography. An anomalous tortuous artery ran from the descending aorta into the left basal segment and returned to the left inferior pulmonary vein. The left pulmonary arterial trunk had no basal branch (A8-A10). A loop corresponding to the superior vein (V6) ran beneath the anomalous tortuous artery. To our knowledge, this is the second case of Pryce type-I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein to be reported in Japan. A left inferior lobectomy was performed. Histological finding from the excised tissues showed prominent interstitial fibrosis, atypical adenomatous hyperplasia, and atherosclerosis. Following surgery, the patient's PaO2 increased from 80.4 Torr to 95.8 Torr, suggesting that left inferior lobectomy was an appropriate treatment.

Bronchopulmonary Sequestration↗