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N Yamada

Publications and source records attributed to N Yamada.

At least 145 records · Page 8Linked to original sources
PubMed2000

Detailed motion analysis of the left ventricular myocardium using an MR tagging method with a dense grid.

Detailed analysis of myocardial deformation through a whole cardiac cycle was accomplished using a tagging method with a high-density grid. Four sets of tagged images with a 4-mm-spacing grid were measured by generating four tagging pulses arranged at regular intervals in the cardiac cycle. Through each set of images, tag intersections were tracked semi-automatically. The estimated motions of tag intersections were concatenated so that sequential positions of myocardium were connected through a whole cardiac cycle. In vitro evaluation of the precision of this technique showed that the mean error of tracked 4-mm tag intersections was less than 0.47 +/- 0.17 mm, even on the quite low-contrast images, and the concatenation error caused by double concatenation was comparable to the interpolation error in the subendocardial area obtained with 8-mm tag intersection motion. The small difference between the two mean distance curves of the in vivo evaluation indicated that the method is useful for analyzing heart wall abnormalities. Magn Reson Med 44:73-82, 2000.

Algorithms↗
PubMed2000

Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia-reperfusion injury.

The mitogen-activated protein kinase (MAPK) family is considered to be activated by stress, but the role of the MAPK family is still unknown in cardiac pathology. In the present study, not only the localization of MAPKs such as the extracellular responsive kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK (p38), but also ultrastructural changes were investigated in the ischemia-reperfusion model of Wistar rats. At 5, 10, 30, 60, and 180 min reperfusion after 30 min ischemia by occluding the coronary artery, the expression of these MAPKs was increased in blood vessels and cardiomyocytes by Western blotting and immunohistochemical methods. In addition, after ischemia reperfusion, various ultrastructural changes such as decreased glycogen granules, mitochondrial swelling, and myolysis were observed in the blood vessels and cardiomyocytes. These results suggest that protein kinases may regulate numerous biological processes, including the regulation of contraction and ion transport.

Animals↗
PubMed2000

The 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene is associated with severe preeclampsia.

Preeclampsia is associated with thrombosis of the intervillous or spiral artery. A deletion/insertion polymorphism (4G or 5G) in the promoter of the plasminogen activator inhibitor type 1 (PAI-1) gene is suggested to be involved in regulating the synthesis of the inhibitor, 4G allele, being associated with the enhanced gene expression and plasma PAI-1 levels. We assessed the association between preeclampsia and the 4G/5G polymorphism of the PAI-1 gene in 115 preeclamptic patients, 210 pregnant controls, and 298 healthy volunteer controls. The frequency of the homozygotes for the 4G allele was significantly higher in the patients than in the control pregnant women (P = 0.04) or in the healthy volunteers (P = 0.02). The 4G allele frequency was also significantly higher in the patients than in the control group of pregnant women (P = 0.03) and in the healthy volunteers (P = 0.02). These results suggest that the presence of the 4G/4G genotype of the PAI-1 gene is one of the risk factors for preeclampsia.

Alleles↗
PubMed2000

Preoperative demonstration of the Adamkiewicz artery by magnetic resonance angiography in patients with descending or thoracoabdominal aortic aneurysms.

OBJECTIVE: Investigating the possibility of magnetic resonance angiography (MRA) to visualize the Adamkiewicz artery of as a preoperative study of thoracic aortic aneurysms. METHODS: From February 1998 to March 1999, 26 consecutive patients who had aneurysms of the thoracoabdominal or descending aorta underwent preoperative MRA to visualize the Adamkiewicz artery. Mean age was 60.5+/-11.5 years. Fifteen patients had non-dissecting aneurysm and 11 had aortic dissections. Nineteen patients underwent replacement of the aneurysms, four patients underwent endovascular stent-graft repair, and three patients were discharged without treatment of aneurysm. MRA was performed on a 1.5-T system (Magnetom, Siemens) and data acquisition was repeated two times following injection of gadolinium-DTPA. Source images were reconstructed with multiplanar reconstruction and maximum intensity projection. Criteria for the Adamkiewicz artery of were that the artery ascends from the dorsal branch of the intercostal or lumbar artery to the anterior mid-sagital surface of the spinal cord in the early phase. RESULTS: The Adamkiewicz arteries were demonstrated in 18 patients (69%). These arteries were originated from the left intercostal or lumbar arteries in 13 (72.2%) patients and from the right in 5 (27.8%) and from the Th8 branch in three, Th9 in seven, Th10 in two, Th11 in four, and L1 in two. All patients had graft replacement of the aorta using a partial bypass. All intercostal or lumber arteries, which were visualized as the origin of the Adamkiewicz artery, were reattached to the grafts. No spinal cord injury occurred. CONCLUSION: Preoperative detection the Adamkiewicz artery was possible by MRA and was very useful to reduce the incidence of ischemic injury of the spinal cord during surgery of the thoracoabdominal or descending aorta.

Adult↗
PubMed2000

An electrospray-ionization mass spectrometry analysis of the pH-dependent dissociation and denaturation processes of a heterodimeric protein.

Electrospray ionization mass spectrometry (ESI-MS) was applied to the analysis of the dissociation and denaturation processes of a heterodimeric yeast killer toxin SMKT. The two distinct subunits of SMKT noncovalently associate under acidic conditions, but become dissociated and denatured under neutral and basic conditions. In order to understand the unique pH-dependent denaturation mechanism of this protein, a pH titration was performed by utilizing ESI-MS. The molecular ions of the heterodimer which possesses the highly ordered structure, were mainly observed below pH 4.6. However, the two subunits immediately dissociated at this pH. The spectra measured with various settings of the mass spectrometer indirectly demonstrated that the pH-dependent dissociation occurs in the liquid phase. The current result as well as the three-dimensional structure of SMKT suggest that the deprotonation of a specific carboxyl group triggers a cooperative dissociation process of this protein. In conclusion, the pH titration of a protein by ESI-MS is particularly effective, when the unfolding process or the biological function of the protein is related to the interaction with other molecules.

Fungal Proteins↗
PubMed2000

On-line parameter estimation of industrial fermentation process with an alkaliphilic cellulase-producing bacterium by exhaust gas analysis.

A method for on-line estimation of the fermentation parameters (substrate, product, and cells) of an alkaliphilic Bacillus sp. by utilizing data on the O2 and CO2 tensions in the exhaust gas and the pH of the fermentation broth was investigated. The estimation was based on the stoichiometric relations concerning the weight of CO2 formed, O2 consumed, product formed, and substrate consumed by the bacterium and on the ratio of the mass of the product to that of the cell biomass. During the fermentation, in which the pH range was 7.8-8.8, the parameters were successfully estimated by considering the reactions of CO2 to produce HCO3- and/or CO3(2-) in the liquid-phase as well as the desorption of CO2 to the aeration gas. It was verified that the proposed estimation method is applicable to industrial-scale fermentation using an alkaliphilic cellulase-producing Bacillus sp. The correlation coefficients between the estimated and observed fermentation parameters exceeded 0.990, indicating that the method is capable of evaluating fermentation parameters with an accuracy satisfactory for industrial use.

Journal Article↗
PubMed2000

Bile acids increase intracellular Ca(2+) concentration and nitric oxide production in vascular endothelial cells.

The effects of bile acids on intracellular Ca(2+) concentration [Ca(2+)](i) and nitric oxide production were investigated in vascular endothelial cells. Whole-cell patch clamp techniques and fluorescence measurements of [Ca(2+)](i) were applied in vascular endothelial cells obtained from human umbilical and calf aortic endothelial cells. Nitric oxide released was determined by measuring the concentration of NO(2)(-). Deoxycholic acid, chenodeoxycholic acid and the taurine conjugates increased [Ca(2+)](i) concentration-dependently, while cholic acid showed no significant effect. These effects resulted from the first mobilization of Ca(2+) from an inositol 1,4,5-triphosphate (IP(3))-sensitive store, which was released by ATP, then followed by Ca(2+) influx. Both bile acids and ATP induced the activation of Ca(2+)-dependent K(+) current. Oscillations of [Ca(2+)](i) were occasionally monitored with the Ca(2+)-dependent K(+) current in voltage-clamped cells and Ca(2+) measurements of single cells. The intracellular perfusion of heparin completely abolished the ATP effect, but failed to inhibit the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO(2)(-) production concentration-dependently, while cholic acid did not enhance it. The bile acids-induced nitric oxide production was suppressed by N(G)-nitro-L-arginine methyl ester, exclusion of extracellular Ca(2+) or N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium, calmodulin inhibitors. These results provide novel evidence showing that bile acids increase [Ca(2+)](i) and subsequently nitric oxide production in vascular endothelial cells. The nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in liver diseases including cirrhosis.

Animals↗
PubMed2000

Ultrastructure of early phase hepatic metastasis of human colon carcinoma cells with special reference to desmosomal junctions with hepatocytes.

To demonstrate ultrastructural events in the early phase of hepatic metastasis of human colon carcinoma, we intrasplenically injected a highly metastasizable, human colon carcinoma cell line LM-H3 (1 x 10(6) cells) into nude mice, and electron microscopically investigated the hepatic metastasis. At 24 h, tumor cells adhered to the endothelial wall of terminal portal venules and periportal sinusoids. At 48-72 h, after extravasation, they deeply invaded the hepatic cell plate and the interstitial tissue of the portal tract, in which they underwent proliferation and made the metastatic foci. Tumor cells were linked with each other or with surrounding hepatocytes by desmosomes. Desmosomes were maintained during the mitosis. When invading tumor cells were exposed to the bile canaliculi, they generated microvilli on the surface. Microvilli were also formed at the luminal surface of intracytoplasmic inclusions. In the interstitial tissue of the portal tract, tumor cells were closely associated with fibroblasts. However, no junctional specializations were seen between them. The present study demonstrated that human colon carcinoma cell line LM-H3 formed desmosomes with hepatocytes soon after invasion of the hepatic cell plate, suggesting the regulatory role of an interaction with hepatocytes in the growth of metastatic foci within the liver parenchyma.

Animals↗
PubMed2000

Increased hemostatic molecular markers in patients undergoing anticoagulant therapy.

We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 +/- 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.

Adult↗
PubMed2000

Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.

Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT)n repeat and susceptibility to the development of CPE, we screened the frequencies of alleles with varying numbers of (GT)n repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)n repeat were grouped into three classes: class S alleles (<25 repeats), class M alleles (25-29 repeats), and class L alleles (>/=30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT)n repeats (n=16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)16 or (GT)20 but did not do so with (GT)29 or (GT)38. These findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.

Aged↗
PubMed2000

Glaucoma screening using the scanning laser polarimeter.

PURPOSE: To determine the ability of scanning laser polarimetry (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies, Inc., San Diego, CA) to separate normal eyes and those considered likely to have glaucoma in a public glaucoma screening. METHODS: A 2-day public glaucoma screening program was held at two different institutions. Each subject underwent ophthalmologic examination, Humphrey perimetry (24-2 Fastpac program), and imaging using scanning laser polarimetry (GDx) in each eye for allocation into a diagnostic category: normal, ocular hypertensive, glaucoma suspect, or glaucoma. Results from the normal and glaucoma groups were analyzed, using modulation parameters calculated from a measurement band located 1.8 disc diameters from the disc, and selected parameters provided automatically by GDx software. Receiver operating characteristic curves were used to depict the sensitivity/specificity relationship at different GDx parameter cutoff levels. RESULTS: Of 200 subjects, 197 were classified; 122 were classified as normal, 23 were classified with ocular hypertension, 30 were classified as glaucoma suspects, and 22 were classified with definite glaucoma. Three subjects had ocular diseases other than glaucoma. The maximum area under the receiver operating characteristic curve for modulation parameters was 0.935, and for the GDx software parameters was 0.901. CONCLUSIONS: Scanning laser polarimetry may be useful in glaucoma screening.

Diagnostic Techniques, Ophthalmological↗
PubMed2000

Changes in the nerve fiber layer thickness following a reduction of intraocular pressure after trabeculectomy.

PURPOSE: To assess changes in the nerve fiber layer thickness after trabeculectomy using scanning laser polarimetry. METHODS: The authors prospectively enrolled 46 eyes from 46 patients with primary open-angle glaucoma in whom intraocular pressure had been reduced by more than 30% after trabeculectomy without significant ophthalmic complications and from whom good quality images were obtained by a scanning laser polarimetry preoperatively and at 3 to 6 months after trabeculectomy. In each enrolled eye, changes in the nerve fiber layer thickness after surgery in the defined ring (1.8 disc diameters) around the optic disc were calculated in 10 degrees intervals (36 sectors in total) and in the following 4 quadrants (the sum of 9 10 degrees sectors): superior, nasal, inferior, and temporal. RESULTS: The mean intraocular pressure was 22.6 +/- 6.9 mm Hg preoperatively and 10.2 +/- 3.7 mm Hg postoperatively (P < 0.01). According to the analyses in every 10 degrees, the postoperative nerve fiber layer thickness was significantly greater than the preoperative nerve fiber layer thickness in the superotemporal region (10-50 degrees) and inferotemporal region (290-340 degrees) of the optic disc (P < 0.05). A stepwise multiple regression analysis showed that only the preoperative mean deviation in the Humphrey visual fields was a significant independent factor associated with changes in the nerve fiber layer thickness in the nasal and inferior quadrants. CONCLUSIONS: The thickness of the nerve fiber layer, as measured by scanning laser polarimetry, may increase after trabeculectomy, especially in the superotemporal and inferotemporal regions, and can be expected in cases in the early stage of glaucoma that have a better mean deviation.

Diagnostic Techniques, Ophthalmological↗
PubMed2000

Regulation of dihydropyrimidine dehydrogenase and pyrimidine nucleoside phosphorylase activities by growth factors and subsequent effects on 5-fluorouracil sensitivity in tumor cells.

Dihydropyrimidine dehydrogenase (DPD) and pyrimidine nucleoside phosphorylase (PyNPase) are the first and rate-limiting enzymes that regulate 5-fluorouracil (5-FU) metabolism, and tumoral DPD activity appears to be a promising predictor of 5-FU sensitivity. However, the regulatory mechanisms determining these enzyme activities have not been fully understood. We investigated the biological effects of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha on cell growth and tumoral DPD and PyNPase activities, and the subsequent effects on 5-FU sensitivity in uterine cervical carcinoma SKG-IIIb cells. The treatment of tumor cells with EGF or TGF-alpha resulted in a concentration-dependent increase in tumor cell growth and PyNPase activity, whereas tumoral DPD activity was inhibited. Their stimulatory effects on tumor cell growth correlated well with PyNPase activity, but were inversely related to DPD activity (P < 0.01). 5-FU sensitivity of tumor cells increased in the presence of EGF or TGF-alpha. These growth factors were shown to stimulate the first, rate-limiting enzyme activity in 5-FU anabolism and to inhibit that in 5-FU catabolism, leading to enhancement of the antiproliferative action of 5-FU at achievable therapeutic levels. The tumor environmental factors, EGF and TGF-alpha, may act as intrinsic regulators of DPD and PyNPase activities that affect the 5-FU sensitivity of individual tumors.

Antimetabolites, Antineoplastic↗
PubMed2000

In vivo and in vitro interactions between human colon carcinoma cells and hepatic stellate cells.

Stromal reaction is important for the growth of cancer both in primary and metastatic sites. To demonstrate this reaction during the hepatic metastasis of human colon carcinoma, we histologically investigated alterations to the distribution and phenotype of hepatic stellate cells (HSCs), the only mesenchymal cells in the liver parenchyma, using a nude mouse model. Intrasplenically injected colon carcinoma LM-H3 cells migrated into the space of Disse and underwent proliferation, in close association with hepatocytes and HSCs, at 2 days. At 14 days, HSCs were accumulated around the tumor mass and expressed alpha-smooth muscle actin, a marker for HSC activation. We next investigated in vitro the growth factors involved in the interactions between LM-H3 cells and HSCs. Conditioned medium of rat HSCs which underwent culture-induced activation contained platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta, and could augment LM-H3-cell proliferation and migration. Neutralizing antibodies against PDGF-AA and PDGF-BB and those against PDGF-BB and HGF inhibited proliferation and migration, respectively, of LM-H3 cells, whereas antibody against TGF-beta had no effect. LM-H3 cells expressed PDGF receptors-alpha and -beta and c-met. Conditioned medium of LM-H3 cells contained PDGF-AB, and could enhance HSC proliferation and migration. This augmenting effect was suppressed by treatment with anti-PDGF-AB antibody. The present study has demonstrated that bidirectional interactions involving PDGF and HGF take place in vitro between colon carcinoma cells and HSCs, raising the possibility that similar interactions might be involved in the stromal reaction during hepatic metastasis.

Adenocarcinoma↗
PubMed2000

Animal models for hyperinsulinemia and insulin resistance.

The direct effect of endogenous insulin on the atherosclerotic process has not been well understood. To clarify this question, we performed pancreas transplantation in Wistar Shionogi (WS) rats. Hyperinsulinemia was not related to coronary risk factors such as dyslipidemia and hypertension in transplanted rats. After 9 months of transplantation, the cholesterol ester contents of the aortas of transplanted WS rats were significantly higher than in the control rats. The effects of insulin resistance on coronary risk factors were examined in mice deficient in insulin substrate-1-deficient (IRS-1) mice, a non-obese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1-deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1-deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis was involved in the increased plasma triglyceride levels under insulin-resistant conditions.

Animals↗
PubMed2000

Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells.

To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the expression of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, on epithelial cells, and it increased the production of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha in supernatants. Dexamethasone reduced the viral titers of supernatants and cell lysates, viral RNA of infected cells, and susceptibility of RV14 infection in association with inhibition of cytokine production and ICAM-1 induction. In contrast to RV14 infection, dexamethasone did not alter RV2 infection, a minor group of RVs. These results suggest that dexamethasone may inhibit RV14 infection by reducing the surface expression of ICAM-1 in cultured human tracheal epithelial cells. Glucocorticoid may modulate airway inflammation via reducing the production of proinflammatory cytokines and ICAM-1 induced by rhinovirus infection.

Aged↗
PubMed2000

The heparin-binding proteins apolipoprotein E and lipoprotein lipase enhance cellular proteoglycan production.

Apolipoprotein E (apoE) and lipoprotein lipase (LPL), key proteins in the regulation of lipoprotein metabolism, bind with high affinity to heparin and cell-surface heparan sulfate proteoglycan (HSPG). In the present study, we tested whether the expression of apoE or LPL would modulate proteoglycan (PG) metabolism in cells. Two apoE-expressing cells, macrophages and fibroblasts, and LPL-expressing Chinese hamster ovary (CHO) cells were used to study the effect of apoE and LPL on PG production. Cellular PGs were metabolically labeled with (35)[S]sulfate for 20 hours, and medium, pericellular PGs, and intracellular PGs were assessed. In all transfected cells, PG levels in the 3 pools increased 1.6- to 3-fold when compared with control cells. Initial PG production was assessed from the time of addition of radiolabeled sulfate; at 1 hour, there was no difference in PG synthesis by apoE-expressing cells when compared with control cells. After 1 hour, apoE-expressing cells had significantly greater production of PGs. Total production assessed with [(3)H]glucosamine was also increased. This was due to an increase in the length of the glycosaminoglycan chains. To assess whether the increase in PGs was due to a decrease in PG degradation, a pulse-chase experiment was performed. Loss of sulfate-labeled pericellular PGs was similar in apoE and control cells, but more labeled PGs appeared in the medium of the apoE-expressing cells. Addition of exogenous apoE and anti-human apoE antibody to both non-apoE-expressing and apoE-expressing cells did not alter PG production. Moreover, LPL addition did not alter cell-surface PG metabolism. These results show that enhanced gene expression of apoE and LPL increases cellular PG production. We postulate that such changes in vascular PGs can affect the atherogenic potential of arteries.

Animals↗