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Biomedical subjects

Y Ueno

Publications and source records attributed to Y Ueno.

At least 19 recordsLinked to original sources

Ischaemic stroke with malignancy may often be caused by paradoxical embolism.

BACKGROUND: Although ischaemic stroke with malignancy occasionally occurs, the mechanisms of stroke in such cases have not been investigated in detail. OBJECTIVE: To examine the mechanisms of ischaemic stroke with malignancy, particularly in relation to right-to-left shunt (RLS). METHODS: Consecutive patients with ischaemic stroke within 24 h of stroke onset were prospectively studied. Contrast saline transcranial Doppler examination was carried out for all patients, to investigate the presence of RLS. When patients with stroke had RLS, deep venous thrombosis (DVT) or pulmonary embolism was assessed to diagnose paradoxical brain embolism. RESULTS: Participants comprised 184 consecutive patients (115 men and 69 women) with a mean (standard deviation (SD)) age of 73 (11.8) years and mean (SD) National Institutes of Health Stroke Scale (NIHSS) score of 8 (7.4). RLS was detected in 32 of 184 (18%) patients. Malignancy was present in 11 (5%) patients. RLS was more frequent in patients with malignancy than in patients without malignancy (55% v 15%, respectively; p = 0.001). All six patients with RLS and malignancy displayed DVT or pulmonary embolism with severe disability (modified Rankin Scale 4-5) before stroke onset. CONCLUSION: Paradoxical brain embolism should be considered to be an important mechanism in patients with stroke and malignancy.

Aged↗

Association between a functional polymorphism in the renin-angiotensin system and completed suicide.

Suicide has been suggested to involve disturbances in the stress response system and to be related to genetics. The renin-angiotensin system (RAS) has been shown to affect the stress response, and several functional polymorphisms in RAS-related genes have been predicted to alter protein function. We hypothesized that the dysregulation of RAS was involved in suicide, and examined the association between completed suicides and four functional polymorphisms of RAS-related genes: the angiotensinogen M235T, angiotensin-converting enzyme (ACE) insertion(I)/deletion(D), angiotensin type-1 receptor A1166C, and G-protein-beta3 C825T gene polymorphisms. The I allele of the ACE I/D polymorphism was found to be more frequent in completed suicides than in controls (P = 0.014). The I allele was also found to be more frequent in male completed suicides (P = 0.022) than in male controls, while this was not the case in females. These results suggest that the alteration of RAS function caused by the genetic polymorphism is involved in the susceptibility to suicide in males.

Adult↗

Changes in bacterial community during fermentative hydrogen and acid production from organic waste by thermophilic anaerobic microflora.

AIMS: Changes in fermentation pattern during the treatment of organic wastes containing solid materials by thermophilic anaerobic microflora were investigated with respect to product formation and bacterial community structure during hydrogen production. METHODS AND RESULTS: Anaerobic microflora enriched from sludge compost was cultivated using artificial garbage slurry in a continuous flow-stirred tank reactor. Product formation varied depending on pH and hydraulic retention time (HRT) applied. Community analysis by terminal restriction fragment length polymorphism and clone library analysis of polymerase chain reaction-amplified bacterial 16S rDNA indicated that difference in the fermentative product distribution could be caused by different populations of micro-organisms in the microflora. CONCLUSION: Hydrogen fermentation with acetate/butyrate formation was optimized at <1.0 d HRT at pH 5.0 and 6.0. Thermoanaerobacterium thermosaccharolyticum was the dominant hydrogen-producing micro-organism. Conversely, unidentified organisms became dominant after 4.0 d HRT at pH 7.0 and 8.0, where relatively high-solubilization efficiency of solid materials was observed with no production of hydrogen. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report describing product formation in the fermentation of solid organic wastes by a mixed population of micro-organisms. Various fermentation patterns including hydrogen fermentation were characterized and evaluated from engineering and microbial aspects.

Acids↗

Re-oxygenation improves hypoxia-induced pulp cell arrest.

Dental pulp cells can be exposed to hypoxia during severe inflammation or restorative procedures, though their response to hypoxia is not well-understood. We hypothesized that hypoxia has effects on the growth of pulp cells in vitro. When the cells were exposed to hypoxia for 48 hr, cell growth was suppressed, and cell death was detected by Hoechst staining. Western blot analysis revealed that phosphorylation of retinoblastoma protein was inhibited in cells exposed to hypoxia. Analyses of the molecules involved in retinoblastoma protein phosphorylation revealed that hypoxia suppressed cyclin D2 and activated p21(CIP1/WAF1). Further, hypoxia-exposed pulp cells showed improvement of cell viability, cell-cycle progression, and expression of cyclin D2 with re-oxygenation. These findings indicate that hypoxia-induced cell cycle arrest in pulp cells is reversible, while cyclin D2 may play an essential role in the improvement of cell proliferation with re-oxygenation.

Analysis of Variance↗

Promotive effects of hyperthermia on the inhibition of DNA synthesis in ehrlich ascites tumor cells by eicosapentaenoic and docosahexaenoic acids.

AIM: To evaluate inhibitory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on DNA synthesis in combination with hyperthermia in vitro. METHODS: A suspension of Ehrlich ascites tumor cells (EAT) was mixed with DHA or EPA in a glass tube, heated at 37 degrees C, 40 degrees C, or 42 degrees C for 1 h in a water bath, and cultured at 37 degrees C for 19 or 96 h. DNA synthesis was assayed by monitoring of the incorporation of [3H]-thymidine into the acid-insoluble fraction. DHA or EPA incorporated into EAT cells was extracted and measured by thin-layer chromatography and gas-liquid chromatography. RESULTS: The inhibition of DNA synthesis by EPA or DHA increased markedly upon the treatment at 42 degrees C and 40 degrees C compared to that at 37 degrees C. At 37 degrees C, inhibitory action of EPA was more potent than that of DHA at low concentrations (at 50 microM -- DNA synthesis level: EPA, 63.1%; DHA, 87.9%), whereas inhibitory action of DHA was higher at 150 muM (16.7%, 4.4%, ibid.). The effect of DHA compared to EPA was more marked at 40 degrees C (29.0%, 19.2% at 100 microM) or 42 degrees C (19.7%, 10.6% at 100 microM). Evaluation of DNA synthesis rate in the cells treated for 1 h by EPA or DHA with the next culturing of EAT cells for 19 h resulted in the enhanced inhibitory activity of EPA even at concentrations as low as 50 microM at either 37 degrees C (0.5%, 11.3%) or 42 degrees C (0.6%, 4.5%), which in these conditions was higher than that of DHA. At the same time the rate of incorporation of EPA in EAT cells at 37 degrees C or 42 degrees C was lower than that of DHA. CONCLUSION: Administration of DHA or EPA in vitro significantly inhibit DNA synthesis, and such effect is enhanced by combination of PUFAs with hyperthermia.

Animals↗

Seasonal variation of chromophore composition in the eye of the Japanese dace, Tribolodon hakonensis.

The relationship between seasonal variation and the effect of several different environmental factors on chromophore composition was investigated in the eye of the Japanese dace, Tribolodon hakonensis which lives either in rivers or in the sea. Eyes obtained from river and sea populations had both retinal (A1) and 3,4-didehydroretinal (A2) all through the year but the ratio of these chromophores showed seasonal variation the relative amount of A2 was higher in winter and lower in summer. Besides seasonal variation, A2 showed marked differences depending on habitat: the highest proportion of A2 was 67% in January and the lowest 13% in July, in the river population, whereas in the sea population the highest and the lowest values were only 30 and 6%, respectively, during the same months. The seasonal variation in gonadosomatic index showed no correlation to variations in A2 proportion, and the maximum difference in water temperature between summer and winter was ca. 15 degrees C for both habitats. Because spectral conditions at the locations of capture of both river and sea populations were similar, we conclude that Japanese dace eyes are affected by exogenous factors related to differences between freshwater and seawater environments.

Animals↗

Selective inhibition of TNF-alpha-induced activation of mitogen-activated protein kinases and metastatic activities by gefitinib.

We have reported that the selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib ('Iressa', ZD1839), suppressed intrahepatic metastasis of hepatocellular carcinoma CBO140C12 cells. In this study, we focused on the tumour necrosis factor-alpha (TNF-alpha) signalling pathways. Real-time reverse transcription-polymerase chain reaction showed that TNF-alpha mRNA was expressed in large quantities in the implanted tumour. Gefitinib inhibited EGF- but not hepatocyte growth factor (HGF)-induced activation of mitogen-activated protein kinase (MAPK) cascades, suggesting selectivity of the inhibitor. However, gefitinib inhibited the TNF-alpha-induced activation of MAPKs and Akt. In addition, TNF-alpha-induced metastatic properties including adhesion to fibronectin, mRNA expression of integrin alpha v, production of matrix metalloproteinase-9 and invasion were inhibited by gefitinib without affecting cell proliferation. Furthermore, the TNF-alpha-induced responses except for NF-kappaB activation were blocked by metalloprotease inhibitors, suggesting that gefitinib inhibited the transactivation of EGFR induced by TNF-alpha. These results suggest that the TNF-alpha signalling pathway is a possible target of gefitinib in suppressing the intrahepatic metastasis of hepatocellular carcinoma.

Animals↗

Styrene monomer primarily induces CYP2B1 mRNA in rat liver.

To determine the cytochrome P450 (CYP) primarily expressed after styrene exposure, seven forms of hepatic CYP mRNA in rats treated with 600 mg kg(-1) styrene were examined. CYP1A2, CYP2B1/2, CYP2E1 and CYP3A2 mRNA were observed using real-time LightCycler PCR. The amount of CYP2B1 mRNA was significantly increased, 47-fold compared with controls, suggesting that this CYP is the primary cytochrome P450 in rats exposed to styrene. Significant increases in the amount of CYP2E1, CYP1A2 and CYP2B2 mRNA were also observed after styrene exposure, and their increase levels were 3.1-, 1.7- and 1.7-fold higher than controls, respectively. Western blot analysis also indicated that the protein levels of CYP2B1, CYP2B2, CYP2E1 and CYP1A2 showed clear increases after styrene treatment, corresponding to their mRNA expression. CYP2C11 mRNA decreased significantly in rats after styrene exposure. CYP1A1 was detected at the mRNA level in rat liver, but it was not detected at the protein level. The expression of epoxide hydrolase (EH), involved in Phase I drug metabolism, was also examined. EH mRNA increased 2-fold compared with controls after styrene exposure. Styrene thus appears to be a chemical compound that induces multiple CYPs. The results demonstrate that CYP2B1 is the primarily induced CYP form by styrene treatment to rats at acute toxic level.

Animals↗

Cysteinyl leukotrienes induce monocyte chemoattractant protein 1 in human monocytes/macrophages.

BACKGROUND: Monocytes/macrophages have a cysteinyl leukotriene 1 (CysLT1) receptor, but its function is poorly understood. Objective To elucidate the biological function of the CysLT1 receptor of human monocytes/macrophages. METHODS: We examined the production of TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), and eotaxin induced by CysLTs (leukotriene (LT)C4, -D4, and -E4) in THP-1 cells, a human monocytic leukaemia cell line, and peripheral blood CD14+ monocytes/macrophages. Moreover, we examined the effect of CysLTs on the expression of beta-chemokine receptor 2B (CCR2B) as the receptor of MCP-1 by Western blot analysis. RESULTS: ELISA revealed that CysLTs induced MCP-1 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages, but not other cytokines. PCR demonstrated that CysLTs increased MCP-1 mRNA expression in THP-1 cells, and Western blotting showed that CysLTs increased the expression of CCR2B in THP-1 cells. Moreover, we demonstrated that pranlukast, a CysLT1 receptor antagonist, blocked MCP-1 production by CysLTs in THP-1 cells almost completely, and partially inhibited MCP-1 release by CysLTs in peripheral blood CD14+ monocytes/macrophages and CCR2B expression by CysLTs in THP-1 cells. CONCLUSION: CysLTs induce MCP-1 and increase CCR2B expression in human monocytes/macrophages.

Blotting, Western↗

Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss.

Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%), while no interferon-gamma production was observed in non-responders (NR) (n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells specific for all the peptides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-gamma production by CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8(+) T cell response in controlling HCV infection.

Adult↗

[Two-stage repair of the transposition of great arteries with interruption/coarctation of the aorta].

We report on 10 patients who underwent two-stage repair of transposition of the great arteries (TGA) with interruption (IAA) or coarctation (CoA) of the aorta. First, an operation for aortic arch reconstruction was performed: Blalock-Park with pulmonary artery banding (PAB) for IAA (5 patients), subclavian flap with PAB for CoA (4 patients) and end-to-end anastomosis without PAB (1 patient). All survived the first operation and had no significant pressure gradient with good growth of the ascending aorta, except for the 1 case without PAB. Half of the 8 patients who underwent PAB developed migration of the PAB. The arterial switch operation (ASO) was performed 0.7-12.6 (5.6+/-4.7) months after the first surgery. One patient with an abnormal coronary artery tract was lost after ASO. Five developed pulmonary artery stenosis and 1 developed supra-aortic stenosis late after ASO. Two patients need reoperation, 1 for supra-aortic stenosis, and the other for reCoA. Two-stage repair for TGA with IAA/CoA is still a useful method with a good operative result. However, strict follow-up is necessary because of the high frequency of late morbidity.

Aorta, Thoracic↗

Drug-incorporating calcium carbonate nanoparticles for a new delivery system.

We devised a simple method for incorporating drugs into solid calcium carbonate nanoparticles (nano-CaCO3). The size of nano-CaCO3 was controlled by mixing speed. Washing the nanoparticles released little incorporated drug but much drug that was adsorbed on the surface. In an in vitro releasing test, granulocyte colony-stimulating factor incorporated in nano-CaCO3 was chemically stable and released very slowly. Subcutaneous injection of nano-CaCO3 incorporating betamethasone phosphate (BP) resulted in a smaller initial increase in plasma concentration and a subsequent sustained release in compared with betamethasone phosphate solution. Nano-CaCO3 may be useful to deliver hydrophilic drugs and bioactive proteins.

Animals↗

Intravenous immunoglobulin does not increase FcgammaRIIB expression on monocytes/macrophages during acute Kawasaki disease.

OBJECTIVES: Intravenous immunoglobulin (IVIG) therapy has been reported to be effective for reducing the incidence of coronary artery lesions in Kawasaki disease (KD), an acute febrile vasculitis of unknown aetiology. Regarding the mechanism of IVIG in immune thrombocytopenic purpura (ITP), it has been reported that IVIG increases the expression of the inhibitory Fc receptor, FcgammaRIIB (CD32B), on splenic macrophages in a murine ITP model. Regarding the mechanism of IVIG during acute KD, we investigated whether or not IVIG increases the expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages. METHODS: The expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages was determined before and after IVIG therapy in 13 patients with acute KD by flow cytometry. RESULTS: The percentage of CD14+ CD32B+ monocytes/macrophages among peripheral blood mononuclear cells, the absolute number of CD14+ CD32B+ monocytes/macrophages and the percentage of CD14+ CD32B+ monocytes/macrophages among CD14+ monocytes/macrophages in patients with acute KD before IVIG therapy were significantly increased compared with those after IVIG therapy and in controls. CD14+ CD32B+ monocytes/macrophages decreased to within the normal range soon after IVIG therapy. CONCLUSIONS: IVIG therapy in patients with KD did not increase the expression of FcgammaRIIB in peripheral blood CD14+ monocytes/macrophages during the acute stage.

Acute Disease↗

An immunoglobulin agent (IVIG) inhibits NF-kappaB activation in cultured endothelial cells of coronary arteries in vitro.

OBJECTIVE: Kawasaki disease (KD) is an acute febrile vasculitis of unknown etiology that may lead to cardiovascular disorders. High-dose intravenous immunoglobulin (IVIG) therapy is well established as a standard therapy for KD. Tumor necrosis factor-alpha (TNF-alpha) is responsible for the pathogenesis of acute KD. We examined whether or not IVIG inhibits TNF-alpha-induced activation of transcription factor NF-kappaB, a factor that is essential for the expression of proinflammatory cytokines, in human coronary artery endothelial cells (CAEC). METHODS: The inhibitory effect of IVIG on NF-kappaB activation induced by TNF-alpha was evaluated by Western blot analysis and ELISA. Moreover, the inhibitory effects of IVIG on IkappaBalpha degradation, interleukin-6 (IL-6) production, and E-selectin expression induced by TNF-alpha were evaluated by Western blot analysis, ELISA, and flow cytometry, respectively. RESULTS: Western blot analysis and ELISA demonstrated that IVIG inhibits NF-kappaB activation induced by TNF-alpha in CAEC. Moreover, IVIG inhibited IkappaBalpha degradation, IL-6 production, and E-selectin expression induced by TNF-alpha in CAEC. CONCLUSION: The data suggest that IVIG inhibits NF-kappaB activation induced by TNF-alpha in CAEC, thereby possibly modulating IL-6 production and E-selectin expression.

Arteries↗

Trends of fumonisin contamination and animal intoxication through monitoring 1991 to 1997 corn crop in the State of Paraná, Brazil.

Eleven feed samples associated with six animal (horse and poultry) intoxication outbreaks (1991) in the state of Paraná, Brazil, were evaluated for fungal and fumonisin contamination. In order to estimate the trend of livestock intoxication, fumonisin contamination was monitored in corn produced both at the commercial level (1991, 1995 crop), and in an experimental field at a local Agronomy Institute (1997 crop). The total mould count in the feed samples ranged from 2.9 x 10(3) to 1.9 x 10(7) CFU/g, with Fusarium verticillioides as the predominant species, at a high count of 2.4 x 10(4)-6.5 x 10(5) CFU/g. Fumonisins (FB1 + FB2) were detected in all corn-based feed samples at levels ranging from 2.89 to 14.54 microg/g. All 27 Northern corn samples (1991 crop) were contaminated with fumonisins at levels ranging from 2.32 to 16.64 microg/g. Twenty-six (96.3%) out of 27 corn samples from the Central-Southern region (1995 crop) were positive for fumonisins (FB1+FB2), with the range of 0.07-3.66 microg/g, while all 37 Northern samples (1995 crop) were contaminated with fumonisins ranging from 0.57 to 9.97 microg/g. Twenty-one out of 37 corn samples from the Northern region (1997 crop) were positive for fumonisins, but at low level (range of 0.05-2.67 microg/g). The results showed a decreasing trend in fumonisin contamination over the years. Nowadays animal intoxication outbreaks rarely occur in this State, as both animal producers and feed industries have become conscious about monitoring of corn and other raw materials at the quality control level.

Animal Feed↗

Vigorous response of cytotoxic T lymphocytes associated with systemic activation of CD8 T lymphocytes in fulminant hepatitis B.

BACKGROUND: Fulminant hepatitis is a clinical syndrome characterized by sudden and severe liver dysfunction. METHODS: We analyzed two patients with a superacute form of fulminant hepatitis B and compared findings with those of four patients with acute self-limited hepatitis B, two patients with acute exacerbation of chronic hepatitis B and four healthy individuals. RESULTS: In fulminant hepatitis, an increased population of human leukocyte antigen (HLA)-DR(+) CD8(+) lymphocytes was observed in peripheral blood by flow cytometry, which was accompanied by the presence of HLA-DR(hi) lymphocytes. The phenotype of CD8(+) T lymphocytes from patients with fulminant hepatitis was mostly that of the effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA(-) CCR7(-) phenotype dominated in the liver of these patients. A larger population of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) appeared in peripheral circulation of the fulminant hepatitis patients compared with that in a patient with acute hepatitis. HBV-specific CTLs were highly concentrated in the liver, although epitopes recognized by these CTLs in the peripheral blood and in the liver were similar. Peripheral CTLs were mostly functional as indicated by intracellular perforin and interferon-gamma. CONCLUSIONS: These results suggest the presence of vigorous activation of CD8(+) T cells in vivo in fulminant hepatitis and the necessity of extensive therapy in patients with this disease.

Adult↗