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T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 19 recordsLinked to original sources
PubMed2006

G-protein beta-3 subunit C825T polymorphism, sodium and arterial blood pressure: a community-based study of Japanese men and women.

Epidemiological evidence on gene-environment effects of the G-protein beta-3 subunit C825T polymorphisms and sodium on blood pressure in the free-living general population is limited. We examined the associations between the C825T polymorphism and blood pressure levels, stratified by the sodium variables estimated by 24-h urinary sodium excretion and a dietary questionnaire, among 1,471 men and women aged 30-74 from a community in Japan. Our a priori hypothesis was that individuals with the 825T allele have elevated blood pressure among subjects with a high sodium intake. Among the whole group, the systolic blood pressure level was +2.2 mmHg (p = 0.10) higher in TT than CC genotype individuals after adjustment for sex, age, antihypertensive medication use, body mass index, and alcohol consumption. This difference was more evident among individuals with low sodium excretion (+4.5 mmHg, p = 0.01), low present sodium intake (+3.2 mmHg, p = 0.11), and low past sodium intake (+4.8 mmHg, p = 0.02). No associations were observed among those with high sodium variables. Our results indicate that the G-protein beta-3 subunit C825T polymorphism is associated with higher systolic blood pressure levels in a large free-living Japanese population, and more specifically in women with a low sodium intake. This finding helps to explain part of the discrepancy between the previously reported genetic association among different ethnic groups.

Adult↗
PubMed2004

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women.

AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between type 2 diabetes and risk of ischaemic stroke in Asian populations. METHODS: We conducted a 17-year prospective cohort study in 10,582 Japanese individuals (4287 men and 6295 women) aged 40-69 years living in five communities in Japan. All subjects were free of stroke and CHD at baseline. Diabetes was defined as a fasting glucose level of >/=7.0 mmol/l, a non-fasting glucose of >/=11.1 mmol/l, or receiving medication for diabetes. RESULTS: The risk of non-embolic ischaemic stroke was approximately two-fold higher in diabetic subjects than in subjects with normal glucose levels. The multivariate relative risk after adjustment for age, community, hypertensive status, BMI, triceps and subscapular skinfold thickness (TSF and SSF), and other known cardiovascular risk factors was 1.8 (95% CI 1.0-3.2) for men and 2.2 (1.2-4.0) for women. This excess risk was primarily observed among non-hypertensive subjects and individuals with higher values for measures of adiposity (BMI, TSF and SSF values above the median), particularly those with higher values for SSF. The association between non-embolic ischaemic stroke and glucose abnormality was particularly strong among non-hypertensive subjects with higher SSF values: the multivariate relative risk was 1.9 (1.0-3.7) for borderline diabetes and 4.9 (2.5-9.5) for diabetes. CONCLUSIONS/INTERPRETATION: In this cohort, type 2 diabetes was a significant risk factor for non-embolic ischaemic stroke, particularly in non-hypertensive and non-lean individuals. Due to the nationwide decrease in blood pressure and increase in mean BMI among the Japanese population, with current levels approaching those observed in Western countries, the impact of glucose abnormalities on risk of ischaemic stroke represents a forthcoming public health issue in Japan.

Adult↗
PubMed2002

Elevated plasma level of differentiation inhibitory factor nm23-H1 protein correlates with risk factors for myelodysplastic syndrome.

We measured plasma nm23-H1 level (nm23-H1), a differentiation inhibitory factor, by an enzyme-linked immunosorbent assay (ELISA) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The nm23-H1 in AA was not significantly elevated when compared to normal subjects (6.66 +/- 1.20 ng/ml vs 5.13 +/- 0.81 ng/ml; P = 0.274). In contrast, MDS patients had significantly high levels of nm23-H1 compared not only to normal subjects (11.16 +/- 1.42 vs 5.13 +/- 0.81 ng/ml; P = 0.0004) but also to those of the AA group (11.16 +/- 1.42 ng/ml vs 6.66 +/- 1.20 ng/ml; P = 0.018). In the MDS group of patients, no significant difference was observed in the nm23-H1 levels between patients with refractory anemia (RA) and RA with excess blasts (RAEB)/RAEB in transformation (10.71 +/- 1.61 ng/ml vs 9.24 +/- 2.66 ng/ml; P = 0.672). Of the patients with RA, patients with low risk according to the International Prognostic Scoring System (IPSS) had significantly low levels of nm23-H1 compared to those of IPSS INT-1 level cases (6.40 +/- 1.36 ng/ml vs 13.05 +/- 2.50 ng/ml; P = 0.0028), suggesting that nm23-H1 may be useful as a prognostic marker for MDS, especially in low risk patients.

Acute Disease↗
PubMed2001

An improved method for the rapid preparation of 2-amino-4,4a-dihydro-4a,7-dimethyl-3H-phenoxazine-3-one, a novel antitumor agent.

A simple and rapid preparation method for a novel antitumor agent, 2-amino-4,4a-dihydro-4a,7-dimethyl-3H-phenoxazine-3-one (Phx) was described. The procedure included (1) the reaction of bovine hemolysates with 2-amino-5-methylphenol, (2) one-shot denaturation of hemoglobin and proteins by methanol, and removal of the denatured hemoglobin and proteins, (3) concentration of the reaction products, and (4) purification by a Sephadex column. These procedures yielded Phx in 34% yield.

Animals↗
PubMed2001

Serum triglycerides and risk of coronary heart disease among Japanese men and women.

To examine the relation of triglycerides with coronary heart disease among populations with low mean total cholesterol, the authors conducted a 15.5-year prospective study ending in 1997 of 11,068 Japanese aged 40-69 years (4,452 men and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03 mmol/liter, respectively), initially free of coronary heart disease or stroke. There were 236 coronary heart disease events comprising 133 myocardial infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The coronary heart disease incidence was greater in a dose-response manner across increasing quartiles of nonfasting triglycerides for both sexes. The multivariate relative risk of coronary heart disease adjusting for coronary risk factors and time since last meal associated with a 1-mmol/liter increase in triglycerides was 1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95% CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial infarction, angina pectoris, and sudden cardiac death. The relation of triglycerides with coronary heart disease was not influenced materially by total cholesterol levels or, in a subsample analysis (51% of total sample), by high density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict the incidence of coronary heart disease among Japanese men and women who possess low mean values of total cholesterol. Further adjustment for high density lipoprotein cholesterol suggests an independent role of triglycerides on the coronary heart disease risk.

Adult↗
PubMed2001

Anaplastic large-cell lymphoma which showed severe inflammatory status and myelodysplasia with increased VEGF and IL-6 serum levels after long-term immunosuppressive therapy.

We report a patient with anaplastic large-cell lymphoma (ALCL) who has been given immunosuppressive therapy for Evans syndrome for 10 years. He was admitted with spike fever, intra-abdominal lymphadenopathy, and multiple liver masses. Examination of biopsy specimens obtained by para-aortic lymph nodes and liver masses resulted in a diagnosis of ALCL. Immunohistochemically, these cells were reactive to anti-CD30 antibody but were not of B- or T-lineage. Bone marrow aspiration demonstrated the invasion of giant neoplastic cells and trilineage myelodysplasia. Because the patient showed severe inflammatory symptoms, we examined serum levels of various cytokines. Pretreatment levels of IL-6 and VEGF in this patient were significantly elevated compared to those of normal controls. He was treated with combination chemotherapy (ABVD regimen), achieving complete remission. Myelodysplasia and serum IL-6 and VEGF also normalized after treatment. We assumed that ALCL resulted from long-term immunosuppressive therapy and that the up-regulation of IL-6 and VEGF played a role in pathogenesis of this type of lymphoma.

Abdominal Pain↗
PubMed2001

Successful treatment with cyclosporin A for myelodysplastic syndrome with erythroid hypoplasia associated with T-cell receptor gene rearrangements.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia, a rare form of MDS, has not yet been clearly defined. We report four patients with MDS with erythroid hypoplasia who received immunosuppressive therapy. All were elderly, had severe transfusion-dependent anaemia, morphological evidence of myelodysplasia and a low percentage (3.2-13.6%) of erythroid precursors. Administration of cyclosporin A (CsA) improved their anaemia; all transfusion-dependent patients achieved transfusion-independence. An inverted CD4/8 ratio was seen in three patients who also demonstrated T-cell receptor (TCR)-beta and -gamma gene rearrangements by Southern blotting and clonality by polymerase chain reaction. Treatment with CsA can be an attractive alternative treatment for patients with MDS with erythroid hypoplasia, which may be associated with a clonal abnormality in T cells.

Aged↗
PubMed2001

A cryptic melibiose transporter gene possessing a frameshift from Citrobacter freundii.

Wild-type Citrobacter freundii cannot grow on melibiose as a sole source of carbon. The melibiose transporter gene melB was cloned from a C. freundii mutant M4 that could utilize melibiose as a sole carbon source. Although the cloned melB gene is closely similar to the melB genes of other bacteria, it is cryptic because of a frameshift mutation. Site-directed mutagenesis was used to construct a functional melB gene by deleting one nucleotide, resulting in the production of an active melibiose transporter. The active MelB transporter could utilize Na(+) and H(+) as coupling cations to melibiose transport. The amino acid sequence of the C. freundii MelB was found to be most similar to those of Salmonella typhimurium and Escherichia coli MelB. These facts are consistent with the phylogenetic relationship of bacteria and the cation coupling properties of the melibiose transporters.

Amino Acid Sequence↗
PubMed2001

The R3 region, one of three major repetitive regions of human herpesvirus 6, is a strong enhancer of immediate-early gene U95.

An immediate-early (IE) gene of human herpesvirus 6 (HHV-6), U95, has similarity at the amino acid level to the murine cytomegalovirus (MCMV) IE2 gene and is related to the human cytomegalovirus (HCMV) US22 gene family. Sequence analyses of U95 cDNA clones revealed that the transcription start site was located about 1.6 kbp upstream of the putative initiating ATG and that the transcript consisted of two exons. A single intron extended from nucleotides 142589 to 144229, which contained ORF U94. A protein with a molecular mass of about 120 kDa was translated from this cDNA clone in an in vitro transcription-translation assay. The transcription start site was found to be 220 bp downstream of the R3 region by primer extension analysis. HHV-6 has three repetitive elements, R1, R2, and R3, in or near the IE-A locus. R3 is composed of 24 copies of a 104- to 107-bp sequence element, which contains multiple putative binding sites for cellular transcription factors such as AP2 and NF-kappaB, and its biological significance has yet to be elucidated. The region between -710 and +46 relative to the transcription start site of U95 was analyzed in this study. Deletion from -710 to -396, corresponding to three copies of an R3 unit, decreased the promoter activity by 15-fold, and coexpression of IkappaBalpha(S32A/S36A) repressed it to almost the same level. Electrophoretic mobility shift assays showed that NF-kappaB family members p50 and c-Rel bound to NF-kappaB sites derived from the R3 region. These results demonstrate that R3 strongly enhances the U95 promoter activity and that NF-kappaB and binding sites for NF-kappaB in the R3 region play an important role in its activation. Because U95 promoter activity correlated with the number of R3 units, which each contained an NF-kappaB site, the repetitive organization of R3 is important for regulating U95 transcription.

Base Sequence↗
PubMed2001

Prospective study of depressive symptoms and risk of stroke among japanese.

BACKGROUND AND PURPOSE: We sought to examine the relationship between depressive symptoms and the incidence of stroke among Japanese men and women. METHODS: A 10.3-year prospective study on the relationship between depressive symptoms and the incidence of stroke was conducted with 901 men and women aged 40 to 78 years in a rural Japanese community. Depressive symptoms were measured at baseline with the use of the Zung Self-Rating Depression Scale (SDS). The incidence of stroke was ascertained under systematic surveillance. RESULTS: During the 10-year follow-up, 69 strokes (39 ischemic strokes, 10 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 10 unclassified strokes) occurred. Age- and sex-adjusted prevalence of mild depression (SDS scores >/=40) at baseline was 25% among subjects with incident stroke and 12% among subjects without stroke (P<0.01). Persons with SDS scores in the high tertile had twice the age- and sex-adjusted relative risk of total stroke as those with scores in the low tertile. The excess risk was confined to ischemic stroke. After we adjusted for body mass index, systolic blood pressure level, serum total cholesterol level, cigarette smoking, current treatment with antihypertensive medication, and history of diabetes mellitus, these relative risks remained statistically significant for total stroke (1.9; 95% CI, 1.1 to 3.5) and ischemic stroke (2.7; 95% CI, 1.2 to 6.0). CONCLUSIONS: Depressive symptoms predict the risk of stroke, specifically ischemic stroke among Japanese.

Adult↗
PubMed2001

Long-term prognosis after stroke: a community-based study in Japan.

Stroke is the leading cause of severe disability in the elderly. Under the national insurance for care and assistance for the elderly starting in 2000, data must be obtained on the prognostic status of stroke patients in communities. We identified 322 incident strokes in six communities (total census population=71,610) during the two- or three-years survey period between 1987 and 1990, and we completed a follow-up of the respective prognoses of most of these patients at one, three, and five years after the onset (n=315 stroke patients) (98%). One year after stroke, 33% of the 315 strokes were dead, 13% were dependent, and 54% were independent. After three years, 44% were dead, 13% were dependent, and 43% were independent. After five years, 52% were dead, 9% were dependent, and 39% were independent. The long-term prognosis was poorer with increased age, and poorer for women than for men except in the case of men ages less than 55 years old at onset. Among patients who were dependents, the proportion of taken care at home was approximately 30% one year after onset, and 50% three to five years after onset. It is estimated that approximately 17 dependents from 127 incident strokes in a population of around 70,000 every year. Because the average survival time of dependents was about 4 years, the prevalence of dependents is estimated to be 68, indicating that the prevalence is about 10 persons per 10,000. Over the period of this study, and as compared with the reported proportions in community-based studies in the 1970's, the proportion of deaths declined and that of independents increased, probably due to reduced severity of stroke. However, the proportion of dependents did not change significantly over time. Thus, under the terms of the new national insurance, it is essential for family and communities to cooperate in taking care of dependent stroke patients.

Activities of Daily Living↗
PubMed2001

Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation.

Myelodysplastic syndromes (MDS) are characterized by cytopenias in the blood and dysplastic features in the hematopoietic cells. Although the impact of cytogenetic abnormalities is considerable for prognosis, the exact genetic mechanism of MDS remains undetermined. In this study we assessed cytogenetic changes, microsatellite alterations, and telomere dynamics in order to obtain further insight into the pathogenesis of MDS. Thirty-three percentage of MDS patients and 60% of post-MDS acute leukemia (post-MDS AML) had de novo microsatellite changes. In the MDS phase, however, > 60% of patients showed reduction of telomere lengths without microsatellite changes, indicating that telomere reduction in most MDS patients does not seem to be directly linked to genome instability, or that reduction of telomere length does not induce microsatellite changes in the MDS phase. Some MDS patients had microsatellite changes without telomerase elevation, indicating that genome instability might accumulate during the disease progression in some MDS patients, and this condition (cellular senescence) may be related to ineffective hemopoiesis in MDS patients. In contrast, 40% of post-MDS AML patients had elevated telomerase activity with microsatellite changes, indicating that approximately 40% of patients with post-MDS AML patients had accumulation of genome instability resulting in elevated telomerase activity in an attempt to obtain genetic stability. However, the remaining MDS patients had microsatellite changes without telomerase up-regulation, suggesting that some MDS had genome instability even after leukemic transformation. Most MDS patients with elevated telomerase activity in the AML phase had elevated telomerase activity even in the MDS phase without apparent change in telomere length before and after leukemic transformation. These findings indicate that telomerase activity in the MDS phase may be independent of telomere length, although telomere shortening seems to be related to genomic instability, and this process may be linked to apoptosis of MDS cells.

Cell Transformation, Neoplastic↗
PubMed2001

[Prediction of mortality from findings of annual health checkups utility for health care programs].

OBJECT: To clarify relationships between the findings of annual health checkups and mortality in men and women living in Ibaraki prefecture. METHOD: The subjects were 32,705 men and 63,959 women aged 40 to 79 years who participated in annual health checkups in 1993. They were followed up until November 30, 1998, with a systemic review of resident registration and death certificates. The Cox's proportional hazards model was used to estimate relative risk, after adjustment for age, smoking status, usual alcohol intake, hypertension category, serum total cholesterol, HDL cholesterol, blood glucose, serum creatinine, body mass index (BMI) and urinary protein. RESULTS: During the 5.2-year follow-up, there were 2,937 deaths (including 384 deaths from stroke, 242 from coronary heart disease and 1,305 from cancer). Significant predictors of mortality from all causes were smoking, usual alcohol intake, hypertension, low serum total cholesterol, low BMI, high blood glucose level, proteinuria for men and women, and low HDL cholesterol for men, and high serum creatinine for women. Significant predictors of mortality from all cardiovascular diseases were smoking, hypertension, low BMI, high serum creatinine, proteinuria for men and women, usual alcohol intake and low HDL cholesterol for men, and serum total cholesterol and high blood glucose level for women. Significant predictors of mortality from stroke were hypertension, low BMI, high serum creatinine for men and women, and proteinuria for women. Significant predictors of mortality from coronary heart disease were smoking, high serum total cholesterol, high blood glucose level, proteinuria for men and women, hypertension, low HDL cholesterol for men. Significant predictors of mortality from cancer were smoking, usual alcohol intake, BMI for men and women, low serum total cholesterol, low HDL cholesterol and proteinuria for men, and high blood glucose level for women. Smoking, usual alcohol intake, low HDL cholesterol and proteinuria were significant predictors of mortality from lung cancer for men. CONCLUSION: Smoking, usual alcohol intake, hypertension, BMI, serum level of total cholesterol, HDL cholesterol, blood glucose, creatinine, and urinary protein are significantly associated with mortality. We obtained the new finding that serum creatinine level is a significant predictor of mortality from all cardiovascular diseases in Japanese men and women, and that the multivariate relative risk in female moderate alcohol drinkers (46-68 g ethanol intake/day) vs non-drinkers is significantly elevated for death from all causes. The results of our study are useful for planning of health care education and services.

Adult↗