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T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 55 records · Page 3Linked to original sources
PubMed2001

Phenotypic and functional change of cytokine-activated neutrophils: inflammatory neutrophils are heterogeneous and enhance adaptive immune responses.

Polymorphonuclear leukocytes (PMN) are the most abundant leukocytes, comprising about two-thirds of peripheral blood leukocytes, and play major roles in innate immunity. In addition, PMN play critical roles in the development of adaptive immunity. Recently, defensins and other peptides pre-stored in PMN granules were shown to attract monocytes, dendritic cells, and T cells, leading to the hypothesis that the release of PMN granular peptides may link innate and adaptive immunity. During the past several years, we have focused on an alternative hypothesis that activated PMN further differentiate and acquire new phenotypes and functions that enable them to link the two responses. To test our hypothesis, we have taken local and global approaches and have shown several key findings that support the hypothesis. The findings include the requirement for priming PMN by cytokines to induce the delayed expression of MCP-1/CCL2, a signal for mononuclear cells, and the expression of new cell-surface markers by such cytokine-activated PMN. In the present manuscript, we focus on the phenotypic and functional changes that occur during PMN activation with selected cytokines. The results of our study indicate that inflammatory PMN are heterogeneous and play roles in not only innate but also adaptive immunity in response to stimuli released in injured tissues.

Animals↗
PubMed2001

[Detection of underlying causes of death among the deceased of Yusho patients by linkage to the national vital statistics data].

As of January 31, 1996, 292 deaths among registered patients of Yusho were identified by three follow-up studies conducted in 1986, 1990, and 1996. In this study, we attempted to identify underlying causes of death by linkage of the registered data to the National Vital Statistics Data provided by the Management and Coordination Agency of Japan, which included 15 million deaths between 1978 and 1996. The two datasets were linked by matching for six variables; birth year/month/day, death year/month, and sex, along with a variable of death day or death place, or both. The matched cases were 203 among 235 deaths between 1978 and 1996 (matching rate was 86%). Among the 203 deaths, 58 underlying causes of death were newly identified, 146 causes of death were already grasped by the follow-up studies, and 31 deaths did not have matching pair in the National Vital Statistics data. Among the 146 deaths, 110 causes of death were concordant with each other, however, 35 causes of death were completely discord. The reason of the discordance and the unmatched deaths might be due to difference in information of the matching variables in the two datasets. In order to conduct an efficient follow-up study of Yusho patients, identification of underlying causes of death by linkage to the National Vital Statistics Date is evitable. For that, we need to substitute basic information in the Yusho database to those compatible to the National civil registration system.

Cause of Death↗
PubMed2001

[Influential factors in the elevation of serum creatine phosphokinase for the patients with Kanemi Yusho--freeze fracture study of rat muscle plasma membrane].

We studied the factors of the elevation of serum creatine phosphokinase (CK) using the data from the routine medical checkup of Kanemi Yusho patients during 1995 and 1999. We also studied rat muscle plasma membrane by the freeze fracture method, which were given the polychlorinated biphenyls (PCB) and controls. The patients with elevation of serum CK showed significant elevation of PCB in their blood but not in polychlorinated quanterphenyls (PCQ). The rat muscle plasma membrane showed a slight increase of orthognal array density but it was not statistically significant. The densities of caveolae and particles were not changed. Accordingly, PCB were thought to be a factor in the elevation of CK in the serum.

Animals↗
PubMed2001

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance.

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824, P<0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539, P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

Adult↗
PubMed2001

Arsenic contamination of groundwater and prevalence of arsenical dermatosis in the Hetao plain area, Inner Mongolia, China.

An investigation was carried out on arsenic contamination of groundwater and prevalence of arsenical dermatosis in the Hetao plain of Inner Mongolia Autonomous Region, China. Based on the screening of water samples from 96 randomly selected wells in this Region, two areas (Wuyuan and Alashan) were chosen as highly contaminated areas because arsenic in the water samples was higher than 50 microg/l. Arsenic was measured using an arsenic silver diethyl dithiocarbamate method for 326 water samples from all the wells in these areas. The results show arsenic contaminated groundwater from tubule-type wells of depths about 15-30 m was serious compared with open-type wells where depth is about 3-5 m. In the Wuyuan area, 96.2% of water samples from tubule-type wells contained arsenic above 50 microg/l and 69.3% in Alashan area; the highest value was 1354 microg/l and 1088 microg/l, respectively. In these two areas, a health survey was carried out for arsenical dermatosis. The results show the prevalence of arsenical dermatosis in the Wuyuan area was 44.8%, higher than 37.1% prevalence of arsenical dermatosis in the Alashan area. The prevalence of arsenical dermatosis was highest in the over 40-year-old age group. There was no sex difference in the prevalence. Further investigation is needed to clarify the actual situation of arsenic pollution of groundwater in Inner Mongolia, China in order to reduce the adverse health effect among residents exposed to arsenic.

Adolescent↗
PubMed2000

Expression of CCR6 and CD83 by cytokine-activated human neutrophils.

Polymorphonuclear leukocytes (PMNLs) are thought to be terminally differentiated, short-lived, and unable to actively synthesize new proteins or to interact with T cells. In the current study, it was found that PMNLs incubated with supernatants of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup) expressed high levels of CCR6 mRNA. Neutralization with IgG against several cytokines revealed that tumor necrosis factor (TNF)-alpha was largely responsible for the PHA-sup-induced CCR6 mRNA expression. Among recombinant cytokines, TNF-alpha induced high levels of CCR6 mRNA expression, whereas interferon (IFN)-gamma induced low levels. The 2 cytokines together exhibited a considerable synergy. Cytokine-activated PMNLs expressed functional CCR6, as detected by the binding of sodium iodide I 125-labeled liver and activation-regulated chemokine (LARC) and dose-dependent migration toward LARC. The induction of CCR6 suggested that these cytokine-activated PMNLs have more similarities with dendritic cells (DCs) that express CCR6 in an immature stage. In fact, the activation of PMNLs with TNF-alpha and IFN-gamma induced the expression of CD83, a dominant cell-surface marker of DCs. When PMNLs were activated with granulocyte macrophage-colony-stimulating factor, TNF-alpha, and IFN-gamma, these cells expressed CD40 and HLA-DR in addition to CD83. Taken together, PMNLs, under appropriate conditions, can undergo a differentiation process characterized by the acquisition of new phenotypes and functions, and such differentiated PMNLs may play more active roles in the adaptive immune response. (Blood. 2000;96:3958-3963)

Antigens, CD↗
PubMed2000

Syntheses and structural analysis of 10-monoxy- and -dioxy-5-N-substituted iminothianthrene derivatives and the stereochemical change on their sulfur atom under acidic and thermal conditions.

5-(N-p)-Toluenesulfonyl)iminothianthrenes, whose sulfur atoms are oxidized to a sulfoxide or sulfone at the 10-position, were hydrolysed readily in high yield to N-unsubstituted-sulfilimines by using concentrated H2SO4. During hydrolysis, 10-monoxy-5-N-unsubstituted-sulfilimines were obtained as a separable mixture of the cis and trans isomers. The stereochemical interconversion of these compounds was studied under both hydrolytic and thermal conditions and their structures were elucidated by using X-ray crystallography.

Journal Article↗
PubMed2000

Replication protein A1 reduces transcription of the endothelial nitric oxide synthase gene containing a -786T-->C mutation associated with coronary spastic angina.

We recently reported that a mutation (-786T-->C) in the promoter region of the endothelial nitric oxide synthase (eNOS) gene reduced transcription of the gene and was strongly associated with coronary spastic angina and myocardial infarction. To elucidate the molecular mechanism for the reduced eNOS gene transcription, we have now purified a protein that specifically binds to the mutant allele in nuclear extracts from HeLa cells. The purified protein was identical to replication protein A1 (RPA1), known as a single-stranded DNA binding protein essential for DNA repair, replication and recombination. In human umbilical vein endothelial cells, inhibition of RPA1 expression using antisense oligonucleotide restored transcription driven by the mutated promoter sequence, whereas, conversely, overexpression of RPA1 further reduced it. RPA1 was similarly detected in placenta and eNOS mRNA levels in placentas carrying the -786T-->C mutation were significantly lower than in placentas without it. The functional importance of the diminished eNOS expression was revealed by the finding that serum nitrite/nitrate levels among individuals carrying the -786T-->C mutation were significantly lower than among those without the mutation. RPA1 thus apparently functions as a repressor protein in the -786T-->C mutation-related reduction of eNOS gene transcription associated with the development of coronary artery disease.

Alleles↗
PubMed2000

Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis.

BACKGROUND: Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N:(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1 in this process is not known. METHODS AND RESULTS: We investigated the effect of a specific monoclonal anti-MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions. Cotreatment with an anti-MCP-1 antibody, but not with control IgG, prevented the L-NAME-induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti-MCP-1 antibody did not decrease the development of perivascular fibrosis, the expression of transforming growth factor (TGF)-beta(1) mRNA, or systolic pressure overload induced by L-NAME administration. CONCLUSIONS: These results suggest that MCP-1 is necessary for the development of medial thickening as well as monocyte recruitment. In contrast, the pathogenesis of fibrosis may involve other factors, such as TGF-beta(1).

Animals↗
PubMed2000

Evaluation of dietary intake using carbon and nitrogen isotope analysis of human hair of Chinese living in southern part of China.

We examined dietary intakes among 69 people of three ethnic groups (Yao Chinese, Zhung Chinese and Han Chinese) in the autonomous country of Bama in China where many elderly people have a long life span in 1998. Dietary intake was evaluated using carbon and nitrogen isotope ratios of human hair (delta 13C, delta 15N) standardized by standard gas. The distributions of delta 13C in Yao Chinese and Han Chinese were scattered from -21 to -17/1000, which were close to that of C4 plants such as corn and millet. The distribution of delta 13C in Zhung Chinese was located from -25 to -22/1000, which was near that of C3 plants such as rice, wheat and potato. These values showed a much wider range when compared with delta 13C in Chinese living in urban areas. On the other hand, delta 15N in each group was distributed in the area ranged from 8 to 11/1000. The result of delta 13C was consistent with data obtained from a nutritional survey, but that of delta 15N was a little higher than expected. The carbon and nitrogen isotope ratios of human hair among three ethnic groups showed characteristic distributions, although the relation between these isotope ratios and longevity is uncertain.

Adolescent↗
PubMed2000

Human T-cell leukemia virus type I tax activates transcription of the human monocyte chemoattractant protein-1 gene through two nuclear factor-kappaB sites.

Infection by human T-cell leukemia virus type (HTLV) I leads to adult T-cell leukemia and is also associated with the neurodegenerative disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Leukocytes are attracted to sites of inflammation by chemokines. One such chemokine is monocyte chemoattractant protein (MCP)-1, a member of the C-C subfamily of chemokines. We investigated whether HTLV-I infection causes up-regulation of MCP-1, which may in turn cause recruitment of leukocytes to HTLV-I-infected areas. We now report that MCP-1 mRNA levels are elevated in HTLV-I-infected T-cell lines, when compared with uninfected ones. We further confirmed secretion of MCP-1 by HTLV-I-infected T-cell lines. MCP-1 mRNA was also expressed in leukemic cells from patients with adult T-cell leukemia. The 5' transcriptional regulatory region of the MCP-1 gene was activated by the HTLV-I-encoded transactivator Tax in the human T-cell line Jurkat, in which endogenous MCP-1 is induced by Tax. By using site-specific point mutations, we have identified two closely spaced nuclear factor (NF)-kappaB sites, A1 and A2, to be important for Tax-mediated transactivation of the MCP-1 gene. Through the use of an electrophoretic mobility shift assay, we demonstrated that Tax induced NF-kappaB binding to both MCP-1 kappaB sites. This is the first report to demonstrate that Tax can transactivate the MCP-1 gene through the induction of NF-kappaB. Our results thus reveal how Tax disrupts the normally regulated MCP-1 gene and leads to its constitutive expression in HTLV-I-infected cells. These findings may have important implications for our understanding of HTLV-I-associated diseases.

Binding Sites↗
PubMed2000

Molecular analysis of avian circadian clock genes.

Unlike mammals, avian circadian rhythms are regulated by a multiple oscillatory system consisting of the retina, the pineal and the suprachiasmatic nucleus in the hypothalamus. To understand avian circadian system, we have cloned Clock and Period homologs (qClock, qPer2 and qPer3) and characterized these genes in Japanese quail. Overall, qCLOCK, qPER2 and qPER3 showed approximately 79%, approximately 46% and approximately 33% amino acid identity to mCLOCK, mPER2, mPER3, respectively. Clock was mapped to quail chromosome 4 and chicken chromosome 4q1.6-q2.1. Per2 and Per3 genes were both localized to microchromosomes. qClock mRNA was expressed throughout the day, while qPer2 and qPer3 showed robust circadian oscillation in the eye and the pineal gland. All three genes were expressed in various tissues. In addition, qPer2 mRNA was induced by light, but neither qClock nor qPer3 was induced. These results can explain the molecular basis for circadian entrainment in Japanese quail and also provide new avenues for molecular understanding of avian circadian clock and photoperiodism.

Animals↗
PubMed2000

Transport of 1,5-anhydro-D-glucitol into insulinoma cells by a glucose-sensitive transport system.

The uptake of 1,5-anhydro-D-glucitol (1,5-AG) occurs by passive mechanisms in cells or tissues that have passive glucose transporters. It is known that serum 1,5-AG concentrations are reduced in patients with diabetes mellitus. To elucidate the metabolism of this substance and its physiological role in pancreatic beta-cells, we assayed 1,5-AG transport in the insulinoma-derived cell lines, RINr and MIN6. Both cell lines showed an insulin-insensitive, concentration-dependent uptake of 1,5-AG with a saturation time of approximately 120 min, and most of the 1,5-AG in the cytoplasm was in the free form. A biphasic saturation curve was obtained using a wide range of 1,5-AG concentrations, suggesting that accumulation was mediated by a high affinity and a low affinity transporter. The high affinity transporter had a K(m) of 10.4 in RINr cells and 13.0 mM in MIN6 cells, and the low affinity transporter had a K(m)100 times, being much higher than the physiological concentrations of 1,5-AG. These results indicate that the 1,5-AG carrier system in insulinoma cells is distinct from that in either the somatic cells or renal tubular cells. These findings also suggest that a unique 1,5-AG transport system is present in pancreatic beta-cells.

Carbon Radioisotopes↗
PubMed2000

cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase. Candidate for selenium delivery protein in selenoprotein synthesis.

Selenocysteine lyase (SCL) (EC 4.4.1.16) is a pyridoxal 5'-phosphate-dependent enzyme that specifically catalyzes the decomposition of L-selenocysteine to L-alanine and elemental selenium. The enzyme was proposed to function as a selenium delivery protein to selenophosphate synthetase in selenoprotein biosynthesis (Lacourciere, G. M., and Stadtman, T. C. (1998) J. Biol. Chem. 273, 30921-30926). We purified SCL from pig liver and determined its partial amino acid sequences. Mouse cDNA clones encoding peptides resembling pig SCL were found in the expressed sequence tag data base, and their sequences were used as probes to isolate full-length mouse liver cDNA. The cDNA for mouse SCL (mSCL) was determined to be 2,172 base pairs in length, containing an open reading frame encoding a polypeptide chain of 432 amino acid residues (M(r) 47, 201). We also determined the sequence of the N-terminal region of putative human SCL. These enzymes were shown to be distantly related in primary structure to NifS, which catalyzes the desulfurization of L-cysteine to provide sulfur for iron-sulfur clusters. The recombinant mSCL overproduced in Escherichia coli was a homodimer with the subunit M(r) of 47,000. The enzyme was pyridoxal phosphate-dependent and highly specific to L-selenocysteine (the k(cat)/K(m) value for L-selenocysteine was about 4,200 times higher than that for L-cysteine). Reverse transcriptase-polymerase chain reaction and Western blot analyses revealed that mSCL is cytosolic and predominantly exists in the liver, kidney, and testis, where mouse selenophosphate synthetase is also abundant, supporting the view that mSCL functions in cooperation with selenophosphate synthetase in selenoprotein synthesis. This is the first report of the primary structure of mammalian SCL.

Amino Acid Sequence↗
PubMed2000

Important role of local angiotensin II activity mediated via type 1 receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats.

BACKGROUND: The chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) upregulates the cardiovascular tissue angiotensin II (Ang II)-generating system and induces cardiovascular inflammatory changes in rats. METHODS AND RESULTS: We used a rat model to investigate the role of local Ang II activity in the pathogenesis of such inflammatory changes. Marked increases in monocyte infiltration into coronary vessels and myocardial interstitial areas, monocyte chemoattractant protein-1 (MCP-1) expression, and nuclear factor-kappaB (NF-kappaB, an important redox-sensitive transcriptional factor that induces MCP-1) activity were observed on day 3 of L-NAME administration. Along with these changes, vascular superoxide anion production was also increased. Treatment with an Ang II type 1 receptor antagonist or with a thiol-containing antioxidant, N-acetylcysteine, prevented all of these changes. CONCLUSIONS: Increased Ang II activity mediated via the type 1 receptor may thus be important in the pathogenesis of early cardiovascular inflammatory changes in this model. Endothelium-derived NO may decrease MCP-1 production and oxidative stress-sensitive signals by suppressing localized activity of Ang II.

Angiotensin II↗
PubMed2000

Allelic imbalance and mutations of the PTEN gene in ovarian cancer.

The PTEN/MMAC1/TEP1 tumor-suppressor gene, which maps to chromosome 10q23.3, is mutated and homozygously deleted in a variety of human tumors, including endometrioid-type ovarian tumors. We examined 33 primary ovarian cancers and 3 ovarian borderline tumors for allelic imbalance (AI) of the 10q23.3 region using 5 polymorphic markers, including an insertion/deletion-type polymorphic marker identified in intron 4 of the PTEN gene. AI at one or more loci was detected in 12 of 31 (39%) informative ovarian cancers and none of 3 ovarian borderline tumors. The commonly deleted region was mapped between the D10S215 and D10S541 loci, including the PTEN locus. Moreover, the incidence of AI at the PTEN locus (38%) was the highest among the 5 loci examined. Therefore, we searched for mutations in the entire coding region of the PTEN gene by PCR-SSCP and sequencing analyses in these tumors and 7 ovarian cancer cell lines. Mutations were detected in 3 of the 33 (9%) ovarian cancers: 2 cases with double mutations and 1 case with a mutation on 1 allele accompanied by deletions on both alleles in the poly T tract preceding the splice acceptor site in intron 7. An intragenic deletion was detected in 1 of the 7 (14%) ovarian cancer cell lines. PTEN mutations were detected not only in the endometrioid type but also in the serous and mucinous types of ovarian cancer. However, PTEN was not mutated in the 12 tumors that showed AI of the PTEN locus. Our results suggest that the PTEN gene plays an important role in the development of a subset but diverse histological types of ovarian tumors. However, it is possible that another tumor-suppressor gene in the close vicinity of the PTEN gene is also inactivated by AI of the 10q23.3 region.

Chromosome Mapping↗
PubMed2000

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition.

The adult T cell leukemia-derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N-acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia-reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia-reoxygenation (H-R) injury model was developed using a murine endothelial cell line, cultured in a thiol-free medium. In this condition, cells became much more vulnerable to H-R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 microM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol-free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 microM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H-R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol-free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically.

Acetylcysteine↗