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Biomedical subjects

Masaru Takasaki

Publications and source records attributed to Masaru Takasaki.

At least 19 recordsLinked to original sources
PubMed2003

Effect of age on regional cerebral blood flow patterns in Alzheimer's disease patients.

The purpose of this study was to explore the influence of age on regional cerebral blood flow (rCBF) patterns in patients with Alzheimer's disease (AD). Single photon emission computed tomography (SPECT) was performed in 79 patients with AD, including 31 younger and 48 older patients divided according to age at examination (<70 and > or = 70 years), and the SPECT data were analyzed using three-dimensional stereotactic surface projection. Although no significant differences in severity and duration of disease between the two groups were found, there were some differences in rCBF patterns. Patients with younger AD had a more severe decrease of rCBF in the parietotemporal and posterior cingulate cortex, while patients with older AD had a more severe decrease of rCBF in the medial temporal region and medial frontal lobe. This observer-independent analysis of SPECT data provides an objective assessment of cortical rCBF abnormalities in patients with AD and is useful in demonstrating the differences in rCBF patterns between younger and older patients with AD.

Age Factors↗
PubMed2003

Cerebral microbleeds in Binswanger's disease: a gradient-echo T2*-weighted magnetic resonance imaging study.

We investigated the incidence and the number of microbleeds (MBs) on T2*-weighted gradient-echo magnetic resonance imaging in 30 Binswanger's disease (BD) patients with diffuse white matter lesions and a varying degree of lacunar infarction, 51 multiple lacunar stroke (MLS) patients with multiple lacunar infarction and no or mild white matter lesions, and 59 elderly controls. MBs were found in 23 (77%) patients with BD, 26 (51%) patients with MLS, and 5 (8%) controls, and the incidence and the number of MBs were significantly greater in the BD group compared with MLS and control groups. Patients with BD had a more widespread location of MBs. More specifically, MBs were commonly found in areas within or surrounded by white matter lesions of the patients with BD. When 81 patients from both the BD and MLS groups were analyzed, logistic regression analysis showed that number of lacunar infarct, severity of white matter hyperintensity, and use of antiplatelet agents were significantly associated with MBs. Patients with BD exhibited a high frequency and number of MBs, indicating advanced bleeding-prone microangiopathy within the brain, which should be taken into account in treatment and management.

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PubMed2003

Regional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease.

We attempted to identify the characteristic patterns in regional cerebral blood flow (rCBF) of patients with Alzheimer's disease who responded to donepezil therapy. Sixty-one patients treated with donepezil were divided into two groups (responders and nonresponders) on the basis of changes in their Mini Mental State Examination (MMSE) scores from baseline to study endpoint. We analyzed single-photon emission computed tomography data (SPECT) at baseline using three-dimensional stereotactic surface projections and compared differences in rCBF between the two groups. Statistical maps showed a significantly lower rCBF of the lateral and medial frontal lobes in the nonresponders than in the responders. There was a significant inverse correlation between the relative rCBF reduction in the frontal lobe and the MMSE change. These results suggest that frontal function, as assessed by SPECT, affects the patient's response to treatment with donepezil. Measuring rCBF may aid in the selection of possible treatment responders.

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PubMed2003

Atrophy of the substantia innominata on magnetic resonance imaging predicts response to donepezil treatment in Alzheimer's disease patients.

To investigate whether atrophy of the substantia innominata as shown on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, predicts response to donepezil treatment in patients with Alzheimer's disease (AD), we studied correlations between the thickness of the substantia innominata and clinical efficacy. Eighty-two patients were divided into responders, including transiently and continuously responding groups, and nonresponders, based on the changes in the Mini-Mental State Examination (MMSE) score from baseline at 3 months and at 12 months. Atrophy of the substantia innominata was more pronounced in transiently and continuously responding groups than nonresponders, but no significant change in the thickness between transiently and continuously responding groups was found. The MMSE score changes from baseline at 3 months and at 12 months significantly inversely correlated with the thickness of the substantia innominata. Logistic regression analysis revealed that the overall discrimination rate with the thickness of the substantia innominata was 70% between responders and nonresponders. We conclude that atrophy of the substantia innominata on MRI helps to predict response to donepezil treatment in patients with AD.

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PubMed2003

[Characteristics of MRI features in Alzheimer's disease patients predicting response to donepezil treatment].

We attempted to investigate whether morphological features as shown on magnetic resonance imaging (MRI) predict response to donepezil treatment in patients with Alzheimer's disease (AD). Sixty-three patients with AD were divided into responders (n = 16) and non-responders (n = 47) based on the changes in the MMSE score between baseline and endpoint. Atrophy of the substantia innominata was more pronounced in responders than non-responders. Although no significant difference in the medial temporal lobe atrophy between responders and non-responders was found, magnetization transfer ratios (MTRs) of the hippocampus and parahippocampus, indicators of structural damage, in the non-responder group were significantly reduced compared to those in the responder group. There were no significant differences in the severity of white matter lesions between the two groups. Logistic regression analysis revealed that the overall discrimination rate was 81%, with 85% of non-responders and 69% of responders, through measurement of the thickness of the substantia innominata and MTR of the hippocampus and parahippocampus. These results suggest that AD patients who show more severe cholinergic dysfunction and less severe structural damage of the hippocampus and parahippocampus as shown on MRI are likely to respond to donepezil treatment.

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PubMed2003

[Marked decrease of intracranial atherosclerosis in contrast with unchanged coronary artery stenosis in Japan].

We conducted comparative studies on intracranial atherosclerosis and coronary artery stenosis over the past 28 years. Two-year consecutive autopsy case studies from an urban geriatric hospital between 1974-1975 (Group I. 484 cases). 1986-1987 (Group II, 504 cases) and 2000-2001 (Group III, 273 cases) were employed. Atherosclerotic changes of the bilateral middle cerebral arteries and basilar artery were semiquantitatively evaluated as none (0), mild (1), moderate (2) and severe (3) and values of the 3 arteries were totalled to give a value of 0-9 which was taken as the intracranial atherosclerotic index (ICAI). The coronary stenotic index was calculated as previously reported (Sugiura et al 1969). ICAI and CSI were directly compared with each other, together with risk factors for each, including mean blood pressure (BP), serum level of total cholesterol (Tch) and the history of diabetes mellitus (DM+). Chronologically ICAI decreased dramatically but CSI did not change at all. There was continuous lowering of BP, elevation of Tch and increased incidence of DM+. There was a significant positive correlation in BP in relation to both ICAI and CSI (p < 0.01). DM+ vs. CSI (p < 0.01) and ICAI (p < 0.05), and Tch vs. CSI (p < 0.01) but not ICAI. Regression analysis highlighted age and BP as major risk factors for ICAI. Our study provides the first morphological confirmation of marked decrease of the intracranial atherosclerosis in the recent 28 years, in contrast with unchanged coronary stenosis in Japanese elderly subjects.

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PubMed2003

Changes in carotid atherosclerosis patterns detected by ultrasonography in Japanese elderly patients with aortic aneurysm.

To clarify current changes in the patterns of carotid atherosclerosis in Japan, carotid ultrasonographic findings in Japanese male patients with aortic aneurysm were compared between two groups examined in different periods. The first group was recruited from 42 consecutively examined patients in 1997, while the second group consisted of 40 consecutive patients from September, 2001 to January, 2002. Carotid lesions were analyzed by computer, and classified into three types based on the texture: echolucent, hyperechoic, and heterogeneous types. The mean age of the first group was 72 years, similar to that of the second group. In the first group, cigarette smoking was frequently noted, while the mean BMI was greater and IHD and CVD were frequent in the second group. Fifty carotid lesions were seen in each group. Severe stenosis and hypoechoic type lesions were more frequent in the second group than in the first group. These findings indicated that hypoechoic-type lesions, which are considered to be lipid deposition, hemorrhage, or loose fibrous tissue, and severe stenosis, were increased in the more recent group. This predicted that circulatory disturbance due to unstable atherosclerotic lesions may increase in the future among the elderly because carotid lesions reflect vascular change in other organs.

Age Factors↗
PubMed2003

Apolipoprotein E genotype and early Alzheimer's disease: a longitudinal SPECT study.

BACKGROUND AND PURPOSE: To determine the association of the apolipoprotein E (APOE) genotype and longitudinal changes of regional cerebral blood flow (rCBF) in Alzheimer's disease (AD). Previous reports have yielded conflicting results concerning this association. METHODS: A retrospective cohort study was performed. rCBF was noninvasively measured using 99mTc-ethyl cysteinate dimer single-photon emission computed tomography in 23 patients with probable AD at the very early stage and at a mean interval of 24 months, as well as in 55 age-matched healthy volunteers. Patients were classified into 2 groups according to the presence of the epsilon 4 allele: 11 epsilon 4 carriers and 12 noncarriers. Correction for partial volume effects (PVEs) was performed in all patients using gray matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of absolute rCBF data and the adjusted rCBF images of relative flow distribution. RESULTS: In the baseline study, both carriers and noncarriers showed significant decreases of absolute and adjusted rCBF in the psoterior cingulate gyri and precunei. After PVE correction, carriers showed a greater spread of areas with significant rCBF reduction from the parietotemporal to the frontal area than noncarriers during the follow-up period compared to healthy volunteers. Moreover, carriers showed a significant decline of absolute rCBF in the frontal cortex from the baseline to the follow-up study. CONCLUSIONS: The authors' study suggests that the APOE epsilon 4 allele is associated with the faster progression of AD, and PVE correction may be necessary for accurate assessments of SPECT studies of AD.

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PubMed2002

Abnormal incorporation and utilization of alpha-tocopherol in erythrocyte membranes of streptozotocin-induced diabetic rats.

Alpha-tocopherol is a well-known lipophilic-free radical scavenger that is mainly localized in biomembranes. In this study, we investigated the changes in the incorporation and utilization of alpha-tocopherol in erythrocyte membranes of streptozotocin-induced diabetic rats and the effects of insulin to control hyperglycemia on these changes. Diabetes was experimentally induced by the injection of streptozotocin (60 mg/kg, i.v.). Blood was collected to determine the concentrations of alpha-tocopherol and its oxidative metabolite (alpha-tocopherolquinone) in plasma or erythrocyte membranes after streptozotocin injection. In streptozotocin-induced diabetic rats, alpha-tocopherol concentrations were decreased in erythrocyte membranes and increased in plasma. The ratio of alpha-tocopherol in erythrocyte membranes to that in plasma, which reflects the incorporation of alpha-tocopherol into erythrocyte membranes, was dramatically decreased in streptozotocin-induced diabetic rats. Moreover, the ratio of alpha-tocopherolquinone to alpha-tocopherol in erythrocyte membranes, which reflects the utilization of alpha-tocopherol, was increased in streptozotocin-induced diabetic rats. These changes were prevented by insulin to control hyperglycemia. These findings suggest that the abnormalities in the incorporation and utilization of alpha-tocopherol in erythrocyte membranes of streptozotocin-induced diabetes can be restored to normal by insulin therapy to control hyperglycemia.

Animals↗
PubMed2002

Molecular cloning and characterization of the mouse thymocyte protein gene.

Chicken thymocyte protein (cThy28) has recently been identified and implicated to be involved in apoptosis of avian lymphocytes, while its functional role remains undefined. To elucidate the role of Thy28, we have molecularly cloned the mouse Thy28 (mThy28) cDNA and clarified its genomic organization in the present study. The mThy28 cDNA encodes a 226 amino acid protein, whose sequence is highly conserved among bacteria, yeast and plants as well as vertebrates. Northern blot analysis revealed abundant expression of approximately 1 kb mRNA in testis, liver, brain and kidney with lower levels of the expression in thymus, spleen, heart and stomach. The mThy28 gene spans at least 7 kb of genomic DNA, and contains eight exons and seven introns. The 5'-flanking region of the mThy28 gene does not contain a typical TATA box, but contains a putative CCAAT box and presumably multiple transcription initiation sites. Potential Sp1, GATA-1, -2, -3, AP-1, and p300 binding sites were found in the 5'-flanking region of the mThy28 gene. The gene was mapped to mouse chromosome 9.

3T3 Cells↗
PubMed2002

Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease.

Atrophy of the substantia innominata on magnetic resonance imaging (MRI), reflecting degeneration of cholinergic neurons in the nucleus basalis of Meynert, may be an in vivo marker of cholinergic damage. We attempted to investigate whether the MRI features of the substantia innominata predict response to donepezil treatment in Alzheimer's patients. The thickness of the substantia innominata was measured on the coronal T2-weighted MRI through the anterior commissure. Seventy-two patients treated with donepezil were divided into the two groups (responders and non-responders) based on changes in Mini-Mental State Examination (MMSE) scores from baseline to study endpoint. Atrophy of the substantia innominata was more pronounced in responders than non-responders. There was a significant inverse correlation between thickness of the substantia innominata and MMSE changes. MRI analysis of the substantia innominata may be a simple and practical method for the selection of possible treatment responders.

Acetylcholine↗
PubMed2002

Increased blood-brain barrier permeability in white matter lesions of Binswanger's disease evaluated by contrast-enhanced MRI.

We investigated blood-brain barrier (BBB) permeability in white matter lesions of Binswanger's disease (BD) with contrast-enhanced MRI. Three subject groups were studied: 17 patients with BD and periventricular hyperintensities (PVH) on MRI, 10 patients with ischemic cerebrovascular events and with PVH but no dementia, and 14 age-matched control subjects without PVH. BBB permeability was quantified by calculation of T(1) change defined as [(T(1post) - T(1pre))/T(1pre)] x100, where T(1pre) and T(1post) represent the T(1) relaxation times before and after Gd-DTPA administration. T(1) change in PVH of BD patients significantly decreased in comparison with that observed in PVH of the nondemented patients and in normal white matter of the control subjects, but no significant T(1) change was observed between the PVH of the nondemented patients and normal white matter of the controls. There was a significant correlation between the Mini-Mental State Examination score and T(1) change for areas of PVH in BD. These results suggest that BBB permeability increases in areas of PVH in BD and that a BBB dysfunction is related to a progression of cognitive impairment.

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PubMed2002

Effects of novel phenoxazine compounds, 2-amino-4, 4a-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one and 3-amino-1, 4alpha-dihydro-4alpha, 8-dimethyl-2H-phenoxazine-2-one on proliferation of phytohemagglutinin- or anti-human IgM-activated human peripheral blood mononuclear cells.

We examined the in vitro effects of 2-amino-4, 4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one(Phx 1)and 3-amino-1, 4alpha-dihydro-4a, 8-dimethyl-2H-phenoxazine-2-one (Phx 2) on the proliferation of phytohemagglutinin (PHA)- or anti-human IgM-activated human peripheral blood mononuclear cells (PBMC). Phx 1 and Phx 2 inhibited the incorporation of 3H-thymidine of PHA-activated PBMC by as much as 75% and 40%, respectively, at a concentration of 40 microM. The inhibition was dependent on the dose of Phx 1 and Phx 2. These results strongly suggest that Phx 1 and Phx 2 inhibit proliferation of T cells, because PHA specifically activates the T cells among PBMC. On the other hand, when PBMC were activated by anti-human IgM, which specifically stimulates B cells, the incorporation of 3H-thymidine was rather increased in the presence of 15.8 microM Phx 1 or Phx 2. However, at a higher concentration of Phx 1 or Phx 2 (50 microM), the incorporation of 3H-thymidine was increased by Phx 1, but was inhibited by Phx 2. These results suggest different effects of Phx 1 and Phx 2 on proliferation of human T and B cells.

Animals↗
PubMed2002

Prognosis of the elderly with asymptomatic atherosclerotic plaques of the carotid arteries.

OBJECTIVE: To elucidate the prognosis of the elderly with neurologically asymptomatic atheromatous plaques of the carotid arteries. METHODS: A total of 228 subjects aged 60 years or older, examined by carotid ultrasonography and platelet aggregation test, were studied. They were divided into 3 groups based on plaque morphology: the no lesion group (n=110), the nodular plaque group (n=47), and the mural plaque group (n=71). Platelet aggregability was assessed as suppressed, normal, or accelerated. RESULTS: During the 4.0 years of mean follow-up period, 31 subjects died, and 16 of the deaths were due to vascular events such as cerebral infarction or ischemic heart disease. The annual mortality rate due to vascular events was 0.5% in the no lesion group, 1.4% in the nodular plaque group, and 4.1% in the mural plaque group, and Kaplan-Meier survival curve showed poor prognosis of the mural plaque group (logrank statistics: 12.8, Df=2, p=0.0017). According to the Cox proportional hazard model, a high hazard ratio (HR) was seen in the mural plaque group (5.3) and also the accelerated platelet aggregability group (4.0). CONCLUSION: These findings suggested that subjects with mural plaques and accelerated platelet aggregability, even when asymptomatic, have a poor prognosis due to vascular events. Antiplatelet therapy and exercise stress test for detecting coronary artery disease should be considered in these subjects.

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PubMed2002

[Evaluation of outcome based on platelet function in elderly patients with various diseases].

This study was conducted to clarify the relationship between the outcome of various diseases in elderly patients and platelet function. The outcome in 347 consecutive patients aged 60 or older, who were treated without antiplatelet drugs on registration, was retrospectively studied after platelet aggregability tests. The mean age was 77.5 years (161 men and 186 women). The grading curve (GC) type, as an index of platelet aggregability, was determined spectrophotometrically with an aggregometer and adenosine-5'-diphosphate as an agonist. They were classified into three groups according to GC type: Group I with a GC type of -2 or -1 (n = 40), group II with a GC type of 0 or +1 (n = 208), and group III with a GC type of +2 or +3 (n = 99). The mean follow-up period was 3.9 years. There were 3 deaths in group I, 33 in group II, and 30 in group III. Mean annual mortality rate was 2.1% in group I, 4.0% in group II, and 7.5% in group III. Among causes of death, vascular events was seen in 15 patients of group III, although the most common cause of death was pneumonia in the three groups. The annual mortality rates due to vascular events were 0.7% in group I, 0.6% in group II, and 4.2% in group III, indicating a significantly higher mortality rate in group III. Antiplatelet therapy was performed in approximately 15% of each group during their clinical course, and, when they were excluded for survival analyses, annual mortality rate was also higher in group III than in groups I and II. Cox proportional hazards models for vascular death yielded a hazard ratio of 2.3 and 2.2 in the increased GC type and diabetes, respectively. These findings indicated that elderly patients with accelerated aggregability had higher mortality rates due to vascular events. Therefore, accelerated aggregability in the elderly suggested not only the progress of arteriosclerosis, but indications of antiplatelet therapy to prevent vascular events.

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PubMed2002

[Relationship between aging and vitamin E].

We investigated the pathophysiological significance in biomembranes of the redox dynamics of Vitamin E (alpha-tocopherol) which is lipophilic radical scavenger related to aging or pathologic status such as non-insulin-dependent diabetes mellitus or primary hyperlipidemia. Vitamin E eliminates lipid peroxyl radicals by the peroxidation chain reaction of the membrane lipid, and it becomes Vitamin E radical. Furthermore, the Vitamin E radical becomes Vitamin E quinone which is an oxidic metabolite of Vitamin E. Therefore, it was needed to determine the alpha-tocopherol and alpha-tocopherolquinone simultaneously to evaluate the antioxidative status of alpha-tocopherol in biomembranes exactly. For this purpose, we developed the assay method for the simultaneous determination of the two substances using HPLC system. Then we applied this method to basic and clinical research. 1) For the simultaneous determination of alpha-tocopherol and alpha-tocopherolquinone, highly-sensitive measurement system by HPLC-multiple coulometric ECD was developed. This system is useful to estimate the redox dynamics of alpha-tocopherol in biomembranes. 2) The utilization rate of alpha-tocopherol in the erythrocyte membrane of 10- to 120-week-old rats was significantly increased, whereas alpha-tocopherol uptake in the erythrocyte membrane decreased age-dependently. Furthermore, a significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of the erythrocyte membrane were seen with age. 3) There was a strongly significant positive correlation between age and the utilization rate of alpha-tocopherol in the erythrocyte membrane of healthy volunteers aged between 23 and 103. 4) The alpha-tocopherol uptake in erythrocyte membrane was significantly lower in elderly non-insulin-dependent diabetes mellitus patients (average 68.1 years old) than in healthy subjects (average 71.8 years old). 5) The utilization rate of alpha-tocopherol in erythrocyte membrane and the alpha-tocopherol uptake in erythrocyte membrane were significant lower in elderly patients with primary hyperlipidemia (average 74.1 years old) compared to healthy subjects (average 71.2 years old). These findings suggest that the redox dynamics of alpha-tocopherol in biomembranes should be investigated with special regard to the onset, aggravation and complications of several diseases or aging as a result of oxidative stress. In addition redox dynamics were suggested to be useful to evaluate the grade of aging.

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PubMed2002

[Bone lesions in elderly multiple myeloma].

We investigated the incidence of bone lesions in elderly cases of multiple myeloma (MM) and the course of those lesions, and also evaluated the relationships of skeletal symptoms with prognostic factors, and prognosis. The subjects were 146 patients, aged 65 years or more (median age 74, range 65-97 year), who were admitted to 11 institutions between January, 1988 and December, 1997. They consisted of 64 men and 82 women. The disease type was IgG type in 88 patients, IgA type in 37 patients, Bence-Jones (BJ) type in 17 patients, IgD type in three patients, and non-secretory type in one patient. Bone lesions in elderly MM patients were compared with those in 65 non-elderly MM patients. Skeletal symptoms were noted in 104 patients, and bone pain in 75 patients at the time of diagnosis. The bone lesions were evaluated as only osteolytic lesions in 26 patients, osteolytic lesions + osteoporosis in 23 patients, only osteoporosis in 2 patients and pathologic bone fractures in 53 patients. The occurrence rate of osteoporosis plus osteolytic lesion was higher in elderly patients (63.5%) than that in non-elderly patients (NE-MM group) (28.3%) (p < 0.0001). The bone lesions were most often observed in lumbar vertebrae (58.7%), cranial bone (56.7%), thoracic vertebrae (40.4%) and ribs (27.9%). The occurrence rate of bone lesion in lumbar vertebrae was higher in elderly patients (58.7%) than that in non-elderly patients (22.6%) (p < 0.0001). The life activities were limited in 71 patients because of the bone lesions. The relationship between the prognostic factors of MM and bone lesions was evaluated. There was a significant difference in the serum Ca level between patients with and without bone pain (P < 0.0001) and between those with and without pathologic bone fracture (P < 0.01). There was a significant difference in the appearance rate of plasma cells in the bone marrow between the patients with and without bone lesions (P < 0.05), between those with and without bone pain (P < 0.01), and between those with and without pathologic fracture (P < 0.05). There was a significant difference in the serum beta 2-microglobulin level between the patients with and without bone pain, and between those with and without pathologic fracture. There were no significant differences in survival times between elderly MM patients with and without bone lesions, bone pain and pathological bone fractures, while significant differences of survival times were found between non-elderly MM patients with and without bone lesions, bone pain and pathological bone fractures (P < 0.05, each). These data suggest that there are some differences in bone lesions between elderly and non-elderly MM patients.

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