Biomedical subjects

K Matsui

Publications and source records attributed to K Matsui.

At least 55 records · Page 3Linked to original sources

PubMed2001

Roles of chromosomal and episomal dinB genes encoding DNA pol IV in targeted and untargeted mutagenesis in Escherichia coli.

DNA polymerase IV (pol IV) in Escherichia coli is a member of a novel family of DNA polymerases (the DinB/UmuC/Rad30/Rev1 super-family or the DNA polymerase Y family). Although expression of the dinB gene encoding DNA pol IV is known to result in an enhancement of untargeted mutagenesis, it remains uncertain whether DNA pol IV is involved in a variety of lesion-induced mutagenesis (targeted mutagenesis), and the relationship between expression levels of dinB and the mutagenesis that DNA pol IV promotes has not been investigated thoroughly. Here, we report that DNA pol IV is involved in -1 frameshift mutagenesis induced by 4-nitroquinoline N-oxide (4-NQO) and that the expression level of the chromosomal pol IV gene is 6-12 times higher than those for other SOS-inducible DNA polymerases in E. coli, i.e., DNA pol II (PolB) or DNA pol V (UmuDC), respectively. Interestingly, the dinB gene is present not only on the chromosome but also on the F' plasmid in the E. coli CC108 strain. In this strain, 750 molecules of DNA pol IV are expressed from the F' dinB gene in the uninduced state and 250 molecules are expressed from the chromosomal gene. These cellular expression levels strongly affect -1 frameshifts induced by 4-NQO in runs of six guanine bases: mutagenicity was highest in the strain CC108, followed by strains YG2242 (chromosome deltadinB/F' dinB+), YG2247 (chromosome dinB+/F' deltadinB) and FC1243 (chromosome deltadinB/F' deltadinB). The incidence of untargeted -1 frameshifts was reduced by two-thirds on deletion of dinB from the F' episome. The chromosomal dinB gene appeared to have little or no effect on the untargeted mutagenesis. These results suggest that DNA pol IV efficiently mediates targeted mutagenesis by 4-NQO, and that the cellular levels of expression substantially affect targeted and untargeted mutagenesis.

4-Nitroquinoline-1-oxide↗

PubMed2001

Expression of matrix metalloproteinases in invasive pulmonary adenocarcinoma with bronchioloalveolar component and atypical adenomatous hyperplasia.

To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. Immunostaining for type IV collagen MMP-2 is useful in evaluating the prognosis of the lung.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2001

Human xanthine dehydrogenase cDNA sequence and protein in an atypical case of type I xanthinuria in comparison with normal subjects.

To investigate the properties of xanthine dehydrogenase/xanthine oxidase (XDH/XO) deficiency in a patient with atypical type I xanthinuria, as indicated by oxypurine data, a cDNA sequence encoding XDH, XDH/XO immunoblot analysis and a competitive PCR assay were performed, and the results were compared with those of normal subjects. The xanthine dehydrogenase cDNA sequence of the patient was consistent with the controls, while immunologically reactive 150 kD XDH/XO protein was not present in the xanthinuric duodenal mucosa, unlike the control duodenal mucosa. In addition, a decrease in XDH/XO messenger RNA was found by competitive PCR. These results suggest that atypical type I xanthinuria is due to a decrease in messenger RNA of XDH/XO. Furthermore, it was considered that this decrease could explain the normal plasma level and near normal urinary excretion of hypoxanthine seen in this case of xanthinuria, though XDH/XO activity and protein were not detected spectrophotometrically and immunologically, respectively.

Base Sequence↗

PubMed2001

Differences in management and outcomes of acute myocardial infarction among four general hospitals in Japan.

OBJECTIVE: To ascertain the differences among hospitals in Japan in the management patterns and outcomes of patients with acute myocardial infarction (AMI). DESIGN: Retrospective cohort study by means of patient chart review. SETTING: Four tertiary-care teaching hospitals in Japan observed over a 1-year period. STUDY PARTICIPANTS: Consecutive patients (N=482) admitted for AMI. MAIN OUTCOME MEASURES: Clinical characteristics, rates of diagnostic and therapeutic procedures performed, cardiac complications, and length of stay. RESULTS: Patients' clinical characteristics differed significantly among the four hospitals in terms of age, gender, and prior cardiac history, but not in terms of comorbidity or infarct location. The frequency and type of diagnostic and therapeutic procedures were different, and in-hospital mortality varied (4-14%, P=0.022). Average length of hospital stay ranged from 15.8+/-12.6 days to 41.0+/-19.4 days (P=0.0001). After adjustment for the clinical characteristics, these differences remained significant among hospitals. CONCLUSION: Considerable differences in the management and outcomes of patients with AMI exist in Japan.

Aged↗

PubMed2001

Yeast-immobilized SPV device for koji quality control in sake brewing process.

The malted rice, koji, is an indispensable material for the brewing of sake. It saccharifies rice starch and supplies vitamins for the yeast in sake brewing. Since the quality of sake depends strongly on the quality of koji, quality control of koji is very important in the brewing. There are some methods to measure the activity of enzymes and the quantity of vitamins with the quality of koji. None of these methods, however, directly relate to the yeast metabolism. We constructed a sensor system to monitor the yeast metabolism in sake brewing by use of immobilized Saccharomyces cerevisiae and a Surface PhotoVoltage device (SPV). In this system, S. cerevisiae K701 and K9, designed for use in sake brewing by the Brewing Society of Japan, were employed as immobilized microbe. The pH change due to the production of organic acids in sake brewing is measured using the SPV. A linear relationship was observed between decrease in the photocurrent (the metabolism response) and the concentration to less than 60 mM of glucose (r=0.990). Then we measured the koji extract and observed the difference of response between K701 and K9 which corresponded to the productivity of acidic substances by batch test.

Acids↗

PubMed2001

Restriction of proliferation of primordial germ cells by the irradiation of Japanese quail embryos with soft X-rays.

Primordial germ cells (PGCs) are the progenitor cells for the gametes. Avian PGCs are located in the central region of the area pellucida at the blastoderm stage. Shortly after further incubation, they migrate to the extra-embryonic germinal crescent, and then as soon as the blood vessels form, they enter the circulation and finally settle in the gonadal primordium. We have developed a simple method using soft X-ray irradiation (18 kV power, 20 cm distance) to reduce the number of PGCs in Japanese quail embryos, which should be useful in preparing recipient embryos for PGC-transfer studies. When embryos were exposed to the soft X-rays for 40 s before incubation, the concentration of circulating PGCs was less than one-fifth that in controls after 2 days of incubation. Embryos at day 6 of incubation contained approximately half the number of PGCs compared to controls when they were exposed before or at day 2 of incubation. Irradiation for 40 s is recommended taking into consideration the restriction of proliferation of PGCs, and viability and hatchability.

Animals↗

PubMed2001

Effect of overexpression of fatty acid 9-hydroperoxide lyase in tomatoes (Lycopersicon esculentum Mill.).

To modify the flavor properties of tomato fruits, cucumber fatty acid hydroperoxide lyase (HPL), which can act on 9-hydroperoxides of fatty acids to form volatile C9-aldehydes, was introduced to tomato plants. Through enzyme assay, high activity of the introduced HPL could be found in either the leaves or fruits of transgenic tomatoes; however, the composition of volatile short-chain aldehydes and alcohols in the transgenic tomato fruits was little modified. This was unexpected because tomato fruits have high lipoxygenase activity to form 9-hydroperoxides. When linoleic acid was added to a crude homogenate prepared from the transgenic tomato fruits, a high amount of C9-aldehyde was formed, but the amount of C6-aldehyde was almost equivalent to that in nontransgenic tomatoes. Through quantification of fatty acid hydroperoxides, it has been revealed that 13-hydroperoxides of fatty acids are preferably formed from endogenous substrate, whereas 9-hydroperoxides are formed from fatty acids added exogenously. From these observations, possible mechanisms to regulate metabolic flow of the lyase pathway are discussed.

Aldehydes↗

PubMed2001

Effects of SM-20550, a selective Na+-H+ exchange inhibitor, on the ion transport of myocardial mitochondria.

The effect of a novel Na+-H+ exchange inhibitor, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate] (SM) on the ion transport of myocardial mitochondria was studied using ion fluorometry and superfusion techniques. Isolated mitochondria from the guinea-pig heart were pre-loaded with fluoroprobes of either BCECF AM for H+, SBFI AM for Na+ or fura-2 AM for Ca2+. Initially, the treated mitochondria were superfused with a normal medium (MOPS-buffer, pH 7.4, 24 degrees C), subsequently fluorometric experiments on the Na+, H+, Ca2+ mobilization across the mitochondrial membrane were performed. The intramitochondrial pH (pHm) was increased by the superfusion of Na+ at physiological cytosolic concentrations of 10 mM, indicating the existence of a Na+-H+ exchange in mitochondrial membranes. The Na+ induced elevation of pH was dose-dependently inhibited by SM 1 microM (delta pHm; 45% as drug-free 100%), and 10 microM (delta pHm; 70%), as observed in our experiments with the myocardial sarcolemmal membrane. The selective Na+-H+ exchange inhibitor SM reduced such pHm elevations more markedly than that of EIPA [5-(N-ethyl-N-isopropyl) amiloride]. The Na+-H+ exchange inhibitors, SM and EIPA suppressed the intramitochondrial Ca2+ elevation ([Ca2+]m) brought on by external Ca2+ concentration changes: The pretreatment with SM 1 microM, 10 microM and EIPA 10 microM reduced the [Ca2+]m influx by 28.3, 56.5 and 63%, respectively. Additionally, the [Ca2+]m elevation induced by acidification of the perfusate was reduced by the prior infusion of SM and EIPA. Pretreatment of mitochondria with SM or EIPA which had beneficial effects on the left ventricular developed pressure (LVDP) in the ischemia-reperfusion injury of Langendorff hearts, reduced the intramitochondrial Na+ and pHm levels, indicating interplay of the inhibitory mechanism of Ca2+-uptake into mitochondria coupled with Na+-H+ exchange. These findings suggested that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due in part to the Ca2+-paradox at the mitochondria level.

Amidines↗

PubMed2001

Immunohistochemical study of the phosphorylated and activated form of c-Jun NH2-terminal kinase in human aorta.

c-Jun NH2-terminal kinase is a key enzyme mediating the cellular response to a variety of extracellular stimuli. In the present study, we performed immunohistochemical studies of the expression of the phosphorylated form of the kinase in 51 human aortas of various ages. The phosphorylated kinase immunoreactivity was strongly detected in vascular smooth muscle cells of the medial vessel layer of atherosclerotic lesions from adults. Immunoreactivity was also strongly detected in similar cells of the intima. On the other hand, immunoreactive phosphorylated kinase was only weakly defected in the medial vascular smooth muscle cells of non-atherosclerotic lesions from adults. We also investigated the expression of the phosphorylated kinase in infant aortas. In contrast to its weak immunoreactivity in adult non-atherosclerotic lesions, the kinase immunoreactivity was detected in high amounts in vascular smooth muscle cells of non-atherosclerotic lesions from infants. Thus, the abundant expression of the phosphorylated kinase in these cells in atherosclerotic lesions of adults and non-atherosclerotic lesions of infants suggests that the activation of c-Jun NH2-terminal kinase may be an important element initiating the proliferation of vascular smooth muscle cells during atherogenesis and aortic development.

Adult↗

PubMed2001

Tumor cell lysis syndrome resulting from transient abnormal myelopoiesis in a neonate with Down's syndrome.

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Down Syndrome↗

PubMed2001

Immunolocalisation of the janus kinases (JAK)--signal transducers and activators of transcription (STAT) pathway in human epidermis.

The janus kinases (JAK) and signal transducers and activators of the transcription (STAT) pathway have been shown to be activated by a number of cytokines or growth factors and to play significant roles in the differentiation of various cell types. In the present study, we investigated the distribution of the JAK-STAT pathway using immunohistochemistry in the human epidermis. Each element of the pathway showed abundant and differential expression in the epidermis. The differential distribution of the elements was most strikingly observed in the horny keratinised cell and granular layers of the epidermis. JAK2, JAK3, STAT1 and STAT5 were expressed in high amounts, and JAK1, TYK2, STAT2, STAT3, STAT4 and STAT6 to a much lesser extent in the horny cell layer. JAK3, TYK2, STAT2, STAT3, STAT4 and STAT6 were more abundantly expressed in the granular layer than the lower layers of the epidermis. JAK1, STAT1 and STAT5 were expressed at almost the same levels in the various layers of the epidermis. These results show that elements of the JAK-STAT pathway are abundantly and differentially expressed in the epidermis. It is suggested that each element of the pathway may play a role at a distinct stage of keratinocyte differentiation.

Adult↗

PubMed2001

Possible involvement of Fyn kinase in ethanol-stimulated Cas tyrosine phosphorylation in rat cerebellum and cerebral cortex.

In the present study, we have investigated the effect of intraperitoneal injection of ethanol (3.5 g/kg) on tyrosine phosphorylation in rat brain. Immunoblot analysis using an antiphosphotyrosine antibody revealed that a 130-kDa protein band was detected in the brain extract in response to ethanol administration. This ethanol-stimulated tyrosine phosphorylation of the 130-kDa protein was found in the brain but not in the heart, liver or thymus. The 130-kDa phosphotyrosine-containing protein was identified by immunoprecipitation to be Cas, a crk-associated src substrate. This ethanol-stimulated tyrosine phosphorylation of Cas was observed most prominently in the cerebellum and the cerebral cortex. We further examined the possible involvement of Fyn kinase in ethanol-stimulated Cas tyrosine phosphorylation. Immunecomplex kinase assay showed that Fyn was activated in the cerebellum and cerebral cortex of ethanol-administered rats. Immunoprecipitation experiments also showed that Fyn was co-immunoprecipitated with an anti-Cas antibody in these regions from ethanol-administered rats. Furthermore, exogenous Fyn was shown to phosphorylate Cas from cerebellum and cerebral cortex in vitro. These findings indicate that ethanol stimulates tyrosine phosphorylation of Cas in rat cerebellum and cerebral cortex, and that Fyn may be involved in the process.

Animals↗

PubMed2001

Immunolocalization of the mitogen-activated protein kinase signaling pathway in Hassall's corpuscles of the human thymus.

In the present study, we investigated the immunohistochemical localization of mitogen-activated protein kinase (MAPK) signaling pathway in the human thymus. Three members of MAPK, the extracellular signal-regulated kinase (ERK), the c-Jun N-terminal kinase (JNK) and the p38 kinase, showed differential expression patterns in the thymus medulla. The phosphorylated form of ERK (p-ERK) was abundantly present in the outer layer of Hassall's corpuscles, and the phosphorylated form of p38 kinase (p-p38 kinase) was present in the entire Hassall's corpuscles. The phosphorylated form of JNK (p-JNK) was expressed in medullary thymocytes. We also examined localization of MAPK kinases (MAPKK or MEK) which specifically activate MAPK. MEK1, an activator of ERK, was found in the outer layer of Hassall's corpuscles where p-ERK was expressed. MEK3, an activator of p38 kinase, was also expressed in the outer layer. MEK4 and MEK7, which are activators of JNK, were present in the entire Hassall's corpuscles. Thus, differential expression of MAPK in the thymus supports the concept that the MAPK signaling pathway controls the specificity of functional thymic responses to extracellular stimuli. Furthermore, the abundant expression of various elements of the pathway in Hassall's corpuscles suggests that the pathway is involved in thymic medullary epithelial maturation.

Child, Preschool↗

PubMed2001

Lipopolysaccharide of Haemophilus influenzae induces interleukin-5 mRNA expression in human peripheral blood mononuclear cells.

Haemophilus influenzae is the bacterial species most often isolated from sputum of patients with chronic obstructive pulmonary disease (COPD). In this study, we examined the induction of interleukin-5 (IL-5) mRNA expression in human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) from H. influenzae to try to predict the effect of H. influenzae infection on the eosinophilic inflammation in COPD. Detection of IL-5 mRNA by RT-PCR showed that LPS from H. influenzae induced IL-5 mRNA expression in PBMC at a concentration of 1 microg/ml. Furthermore, the level of expression of IL-5 mRNA induced by LPS correlated with the amount of IL-5 protein in the culture supernatant. Inhibition of LPS-induced IL-5 mRNA expression by anti-CD14 antibody and diminution of this in a CD3(+) -cell-depleted fraction of PBMC, respectively, suggested that CD14 molecules were required for the increase in IL-5 mRNA and that T lymphocytes were the principal source of IL-5 mRNA expression in PBMC. Briefly, the IL-5 mRNA expression induced by LPS would be based on LPS-activated monocytes interacting with T lymphocytes to produce IL-5. These results may explain the role that colonization with H. influenzae plays in eosinophilic inflammation in patients with COPD.

Base Sequence↗

PubMed2001

Prognostic significance of pulmonary lymphangioleiomyomatosis histologic score.

Correlations were made between clinical and follow-up data and histopathologic findings in 105 women (mean age +/- standard deviation, 38.3 +/- 9.0 years) with pulmonary lymphangioleiomyomatosis (LAM). The actuarial survival (to pulmonary transplantation or death) of the patients from the time of lung biopsy was 85.1% and 71.0% after 5 and 10 years respectively. The histologic severity of LAM, graded as a LAM histologic score (LHS), was determined on the basis of semiquantitative estimation of the percentage of tissue involvement by the two major features of LAM: the cystic lesions and the infiltration by abnormal smooth muscle cells (LAM cells) in each case: LHS-1, <25%; LHS-2, 25% to 50%; and LHS-3, >50%. Analysis using the Kaplan-Meier method revealed significant differences in survival for patients with LHS-1, -2, and -3 (p = 0.01). The 5-and 10-year survivals were 100% and 100% for LHS-1, 81.2% and 74.4% for LHS-2, and 62.8% and 52.4% for LHS-3. Increased degrees of accumulation of hemosiderin in macrophages also were associated with higher LHS scores (p = 0.029) and a worse prognosis (p = 0.0012). Thus, the current study suggests that the LHS may provide a basis for determining the prognosis of LAM.

Adolescent↗

PubMed2001

Protective effect of SM-20550, a selective Na+ - H+ exchange inhibitor, on ischemia-reperfusion-injured hearts.

The protective effects of Na+ - H+ exchange inhibitors SM-20550 (SM) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) against ischemia-reperfusion injury were investigated in guinea pig Langendorff hearts. The changes in intracellular pH (pHi), high-energy phosphates, and biologic intracellular active ions ([Na+]i and [Ca2+]i) were regarded using the 31P-NMR and specific fluorescent signals from the heart tissues together with simultaneous recordings of the left ventricular developed pressure (LVDP). The recovery rate of LVDP from ischemia (40 min) by reperfusion was 36.8% in the control experiments, whereas in the presence of SM 10(-7) M, a gradual increase to 75.9% (55.5% with 10(-8) M), in contrast to EIPA (10(-7) M), 47.5% was observed. SM 10(-7) M restored the ATP level by 70% in 40-min reperfusion, which was already higher than the control in the latter half (20-40 min) of the ischemic period. The recovery rate of phosphocreatine by pretreatment of the heart with SM 10(-7) M was 75% in 40 min reperfusion. The pHi estimated from Pi/phosphocreatine chemical shift became highly acidic in ischemic heart so that SM 10(-7) M caused slight but significant pHi reduction from control pHi of 5.89 to 5.75. The level returned to pHi at around 7.38 during 30-40 min reperfusion, and the recovery was significantly greater than the control pHi of 7.24. The fura-2 Ca2+ or SBFI-Na+ signals during Langendorff ischemia heart increased, and rapidly returned to the control level after the reperfusion. SM suppressed the [Na+]i or [Ca2+]i elevation induced in the late stage during ischemia, resulting in LVDP restoration after reperfusion; Diastolic Ca2+ in the end period of ischemia, SM 10(-7) M 194% versus drug-free 220.7%. Na+: SM 10(-7) M 121.6% versus drug-free 128.0%. The present results suggest that the selective Na+ - H+ exchange inhibitor SM is promising as a potent and specific protective agent against ischemia-reperfusion injuries with Ca2+ overload induced via Na+ - H+, Na+ - Ca2+ exchange.

Adenosine Triphosphate↗

PubMed2001

Na+/H+ exchange inhibitor SM-20220 attenuates leukocyte adhesion induced by ischemia-reperfusion.

Leukocytes play a key role in ischemia-reperfusion-induced tissue injuries. It has been suggested that blocking the Na+/H+ exchanger improves ischemic injuries such as stroke. In this study, we investigated the effect of the Na+/H+ exchanger inhibitor SM-20220 (N-[aminoiminomethyl]- 1-methyl-1H-indole-2-carboxamide methanesulfonate) on leukocyte-endothelial cell interactions during ischemia-reperfusion. SM-20220 (0.3-1.0 mg/kg i.v.) given after ischemia significantly attenuated the leukocyte adhesion in the mesenteric postcapillary venules that was induced by transient superior mesenteric artery occlusion. At 60 min after reperfusion, the numbers of adherent leukocytes in groups treated with vehicle or SM-20220 (0.3 mg/kg) were 15.1+/-2.9 cells/100 microm/3 min and 3.0+/-0.7 cells/100 microm/3 min (p < 0.01), respectively. In a transient middle cerebral artery occlusion model, i.v. infusion of SM-20220 (0.4 mg/kg per hour) for 1 h, beginning 1 h after the start of occlusion, significantly reduced both the infarct size and the increase in brain myeloperoxidase activity, compared with the vehicle group (p < 0.01 and p < 0.05, respectively). In summary, this is the first evidence that the leukocyte adhesion to the endothelium that is induced by ischemia-reperfusion is attenuated by the inhibition of Na+/H+ exchanger activity in vivo. Our results suggest that Na+/H+ exchanger inhibitors may prevent ischemia-reperfusion injuries such as stroke partly through the attenuation of leukocyte-endothelial cell interactions.

Amides↗

PubMed2001

Repression domains of class II ERF transcriptional repressors share an essential motif for active repression.

We reported previously that three ERF transcription factors, tobacco ERF3 (NtERF3) and Arabidopsis AtERF3 and AtERF4, which are categorized as class II ERFs, are active repressors of transcription. To clarify the roles of these repressors in transcriptional regulation in plants, we attempted to identify the functional domains of the ERF repressor that mediates the repression of transcription. Analysis of the results of a series of deletions revealed that the C-terminal 35 amino acids of NtERF3 are sufficient to confer the capacity for repression of transcription on a heterologous DNA binding domain. This repression domain suppressed the intermolecular activities of other transcriptional activators. In addition, fusion of this repression domain to the VP16 activation domain completely inhibited the transactivation function of VP16. Comparison of amino acid sequences of class II ERF repressors revealed the conservation of the sequence motif (L)/(F)DLN(L)/(F)(x)P. This motif was essential for repression because mutations within the motif eliminated the capacity for repression. We designated this motif the ERF-associated amphiphilic repression (EAR) motif, and we identified this motif in a number of zinc-finger proteins from wheat, Arabidopsis, and petunia plants. These zinc finger proteins functioned as repressors, and their repression domains were identified as regions that contained an EAR motif.

Amino Acid Motifs↗