Biomedical subjects

N Ide

Publications and source records attributed to N Ide.

At least 19 recordsLinked to original sources

PubMed2005

Comparative study of survival of patients with hepatocellular carcinoma predicted by different staging systems using multivariate analysis.

AIMS: In a previous pilot study, we reported the usefulness of the modified the Cancer of the Liver Italian Program (CLIP) score for patients with hepatocellular carcinoma (HCC). To determine the best staging system for predicting the survival of HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 210 Japanese HCC patients who underwent hepatic resection. METHODS: We compared the survival as predicted by various staging systems, including tumour node metastasis (TNM) stage of the American Joint Commission on Cancer (AJCC) and the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), CLIP score and our modified CLIP score using protein induced by vitamin K absence or antagonist II (PIVKA-II). RESULTS: Univariate analysis showed that discrimination of disease-free survival in the early and advanced stages by the JIS score and modified CLIP score was clearer than by the Japanese or AJCC TNM or the original CLIP score. Discrimination between stages of overall survival by all staging systems was significant. Multivariate analysis showed that the JIS, CLIP and modified CLIP scores were better staging systems for predicting survival than the Japanese and AJCC TNM. The modified CLIP score showed the lowest Akaike information criteria statistical value for disease-free and overall survival, which means the best discrimination ability for patient survival compared with the JIS score and CLIP score. CONCLUSIONS: A staging system that combines tumour factors, sensitive tumour marker(s) and hepatic function is the best predictor of prognosis of HCC patients.

Adult↗

PubMed2004

The Japanese integrated staging score using liver damage grade for hepatocellular carcinoma in patients after hepatectomy.

AIMS: The new Japanese staging system for hepatocellular carcinoma (HCC), the Japan integrated staging (JIS) score, accounts for both Child-Pugh classification and Japan tumour node metastasis (TNM) staging. However, in HCC patients who undergo hepatectomy, liver function is relatively good and a better prognostic classification of hepatic function is necessary. METHODS: The present study was designed to analyse the modified JIS score using liver damage grade by the Liver Cancer Study Group of Japan instead of the Child-Pugh classification (using the category indocyanine green retention rate at 15 min [ICG(R15)] instead of encephalopathy), and to compare the Japan TNM stage in 101 patients who underwent resection of HCC. RESULTS: The liver damage grade showed significantly better discrimination of disease-free and overall survival than did the Child-Pugh classification. The modified JIS score system showed significant differences of disease-free and overall survivals in each score and this system was superior for discriminating survivals compared with the TNM staging. CONCLUSIONS: The combined staging system of hepatic function, particularly ICG(R15), and tumour stage provides a better prediction of prognosis. The JIS score using the liver damage grade was a useful predictor of prognosis of HCC patients who underwent hepatic resection.

Adult↗

PubMed2001

S-allyl cysteine reduces oxidant load in cells involved in the atherogenic process.

Oxidation of low-density lipoprotein (LDL) and activation of the pleiotropic transcription factor nuclear factor kappa B (NF-kappaB), are often the chemical and molecular alterations associated with the development of the atherosclerotic lesion. We have reported previously on the antioxidant properties of a garlic compound, S-allyl cysteine (SAC), and its ability to inhibit damage caused by oxidative stress in bovine endothelial cells. In this study, the antioxidant effects of SAC were further determined, using several in vitro assay systems. First, we determined the effect of SAC on Cu2+-induced oxidation of LDL. Varying concentrations of SAC were co-incubated with a standardized Cu2+/LDL solution, and LDL-oxidation was then ascertained by determining the formation of thiobarbituric acid reactive substances (TBARS). SAC inhibited LDL-oxidation at an optimum concentration of 1 mM. In another experiment, we determined the effects of SAC on oxidized-LDL (ox-LDL) activation of J774 murine macrophages and human umbilical vein endothelial cells (HUVEC). Cells were grown on 96-well plates, preincubated with SAC at 37 degrees C and 5% CO2 for 24 h, washed, and exposed to ox-LDL for 24 h. Levels of hydrogen peroxide (H2O2) were determined by a fluorometric assay. In both cell lines, SAC exhibited dose-dependent inhibition of H2O2 formation. We also studied the effects of SAC on NF-kappaB activation in HUVEC using tumor necrosis factor-a (TNF-alpha) or H2O2 as stimulators. Cells were grown in 75 cm2 flasks at 37 degrees C and 5% CO2 and were preincubated with SAC 24 h before stimulation with TNF-alpha or H2O2. Nuclear extracts were then prepared and NF-kappaB activation was determined using an electrophoretic mobility shift assay with a 32P-labeled probe. SAC exhibited dose-dependent inhibition of NF-kappaB activation. Our data suggest that SAC may act via antioxidant mechanisms to inhibit the atherogenic process.

Animals↗

PubMed2001

Garlic compounds minimize intracellular oxidative stress and inhibit nuclear factor-kappa b activation.

Oxidative modification of LDL has been recognized as playing an important role in the initiation and progression of atherosclerosis. In this study, we determined the effects of aged garlic extract (AGE) and its major compound, S-allylcysteine (SAC), on oxidized LDL (Ox-LDL)-induced injury in endothelial cells (EC). Lactate dehydrogenase (LDH) release as an index of membrane damage, methylthiazol tetrazoium (MTT) assay for cell viability and thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation were measured. Ox-LDL caused an increase of LDH release, loss of cell viability and TBARS formation. Both AGE and SAC prevented all of these changes. To elucidate the mechanism, effects of AGE or SAC on intracellular glutathione (GSH) level in EC, and release of peroxide from EC and macrophages (M Phi) were determined. Ox-LDL depleted intracellular GSH and increased release of peroxides. Both AGE and SAC inhibited these changes. Effects of SAC on hydrogen peroxide (H(2)O(2)) or tumor necrosis factor (TNF)-alpha-induced nuclear factor (NF)-kappa B activation were determined. Pretreatment of EC with SAC inhibited NF-kappa B activation. We demonstrated that both AGE and SAC can protect EC from Ox-LDL-induced injury by preventing intracellular GSH depletion in EC and by minimizing release of peroxides from EC and M Phi. SAC also inhibited H(2)O(2)- or TNF-alpha-induced NF-kappa B activation. Our data suggest that AGE and its main compound, SAC, may be useful for prevention of atherosclerosis.

Animals↗

PubMed2001

N alpha-(1-deoxy-D-fructos-1-yl)-L-arginine, an antioxidant compound identified in aged garlic extract.

Aged garlic extract (AGE) has been shown to have antioxidant activity. The organosulfur compounds, S-allyl-L-cysteine and S-allylmercapto-L-cysteine, are responsible, at least in part, for the antioxidant activity of AGE. To identify major active components, we fractionated AGE, using hydrogen peroxide scavenging activity as an antioxidative index. Strong activity in the amino acid fraction was found and the major active compound was identified as N alpha-(1-deoxy-D-fructos-1-yl)-L-arginine (Fru-Arg). Antioxidant activity of Fru-Arg was comparable to that of ascorbic acid, scavenging hydrogen peroxide completely at 50 micromol/L and 37% at 10 micromol/L. Quantitative analysis using the established HPLC system revealed that AGE contained 2.1-2.4 mmol/L of Fru-Arg, but none was detected in either raw or heated garlic juice. Furthermore, it was shown that a minimum of 4 mo aging incubation was required for Fru-Arg to be generated. These findings indicate that the aging process is critical for the production of the antioxidant compound, Fru-Arg. These results may explain some of the variation in benefits among different commercially available garlic preparations.

Antioxidants↗

PubMed2001

[The examination of usefulness of the disposable pump in case of cancer pain relaxation and the economic problem].

Recently, an increasing number of cancer patients being taken care of at home has been able to use morphine to treat their pain by themselves. The most suitable administration method for individual patients-oral, intravenous, subcutaneous or depository--is being investigated. When oral intake becomes difficult, the subcutaneous via of administration is best option because it is the less dangerous and easier to use compared with the other two options. These are also thought to be less useful because it is difficult to judge the exact dosage. The use of pumps might be an economic problem to some patients. We will examine this problem.

Analgesia, Patient-Controlled↗

PubMed2000

Unusual core histones specifically expressed in male gametic cells of Lilium longiflorum.

We have cloned three novel histone genes using antibodies that recognize only nuclei of the male gametic (generative and sperm) cells of Lilium longiflorum. The deduced amino acid sequence of each clone shows only between 40% and 50% identity with the H2A, H2B and H3 somatic core histones of other plant species. Transcripts of these genes were first detected in bicellular pollen soon after microspore mitosis, and their mRNAs, as revealed by in situ hybridization, were observed only in the cytoplasm of the generative cells. As expression of these three genes was specific to generative cells within the bicellular pollen, we designated the clones gH2A, gH2B and gH3. Immunocytochemistry further revealed that the proteins encoded by these genes accumulated in the elongating and condensing generative nucleus during development of bicellular pollen, and were most abundant in the two sperm nuclei within an elongated pollen tube. We therefore propose that these male gamete-specific core histones contribute to chromatin condensation of male gametes or to chromatin remodeling, and result in the repression of gene expression in male gametes.

Amino Acid Sequence↗

PubMed2000

Complex PTSD: a review of current issues.

The diagnostic formulation of PTSD has made a great advance since its inception in the early 1980s. Yet it may be argued that PTSD as now formulated does not go far enough in capturing the psychological response to traumatic events. The notion of "complex PTSD" is reviewed as an extension of the current formulations of PTSD. Complex PTSD transcends current formulations of PTSD in three main areas of disturbance: 1) complex symptom presentations, 2) characterological issues, and 3) vulnerability to repeated trauma. These issues are reviewed and support is provided for a formal recognition of "complex PTSD".

Humans↗

PubMed1999

Localization of membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 at tight junctions of epithelial cells.

Membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 and Synapse-associated protein (SAP) 97/human Discs-large tumor suppressor gene (hDLG) are ubiquitous isoforms of synaptic scaffolding molecule (S-SCAM) and Postsynaptic density (PSD)-95/SAP90, both of which are implicated in the structures of synapses, respectively. SAP97/hDLG is localized at epithelial junctions and may function as a scaffolding protein, but the subcellular localization or the function of MAGI-1/BAP1 has not been clarified. In intestinal epithelial cells, MAGI-1/BAP1 was localized at tight junctions, whereas SAP97/hDLG was localized diffusely at cell - cell junctions. In Madine Darby canine kidney (MDCK) cells, MAGI-1/BAP1 was colocalized with ZO-1, whereas SAP97/hDLG was colocalized with E-cadherin. In MDCK cells, dominant active and negative mutants of Rac1 small G protein changed the amounts of SAP97/hDLG at cell - cell junctions, but not that of MAGI-1/BAP1. When MDCK cells were switched to a low Ca2+ medium, E-cadherin disappeared from the plasma membrane, and cells were dissociated. The phorbol 12-myristate 13-acetate-treatment after the low Ca2+ switch induced a tight junction-like structure. MAGI-1/BAP1 was recruited with ZO-1 to this structure, but SAP97/hDLG or E-cadherin was not. These findings suggest that MAGI-1/BAP1 is a component of tight junctions of epithelial cells, and that its role is different from that of SAP97/hDLG.

Adaptor Proteins, Signal Transducing↗

PubMed1999

nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP).

Postsynaptic density (PSD)-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are synaptic membrane-associated guanylate kinases. Both the proteins interact with SAP90/PSD-95-associated protein (SAPAP) (also called guanylate kinase-associated protein/Dlg-associated protein). SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures. We found here a novel SAPAP-interacting protein, which was specifically expressed in neural tissue and was present in the postsynaptic density fraction in brain. This protein had a sorbin homology domain in the N terminus, a zinc finger motif in the middle region, and three src homology (SH) 3 domains in the C terminus and was homologous to the ponsin/ArgBP2/vinexin family proteins. We named this protein nArgBP2 because it was the most homologous to ArgBP2. nArgBP2 is a neural member of a growing family of SH3-containing proteins. nArgBP2 bound to the proline-rich region of SAPAP via its third SH3 domain and was coimmunoprecipitated with SAPAP from the extract of rat brain. Furthermore, nArgBP2 was colocalized with SAPAP at synapses in cerebellum. nArgBP2 bound to not only SAPAP but also vinculin and l-afadin, known to bind to ponsin and vinexin. nArgBP2 may be implicated in the protein network around SAPAP in the PSD.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Synamon, a novel neuronal protein interacting with synapse-associated protein 90/postsynaptic density-95-associated protein.

Guanylate kinase-associated protein (GKAP)/SAP90/PSD-95-associated protein (SAPAP)/DLG-associated protein (DAP) is a protein of the postsynaptic density (PSD), and binds to the guanylate kinase domain of PSD-95/synapse-associated protein (SAP) 90 and synaptic scaffolding molecule. GKAP/SAPAP/DAP recruits PSD-95/SAP90 and its interacting protein, brain-enriched guanylate kinase-interacting protein, into the Triton X-100-insoluble fraction in transfected cells, suggesting that GKAP/SAPAP/DAP may link several PSD components to the Triton X-100-insoluble structures in the PSD. We have identified here a novel neuronal GKAP/SAPAP/DAP-binding protein and named it synamon. Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-A/ZO-1 domain, and several proline-rich regions at the carboxyl terminus. Synamon interacts with the COOH-terminal region of GKAP/SAPAP/DAP via the middle region containing a PSD-95/Dlg-A/ZO-1 domain. Synamon was coimmunoprecipitated with SAPAP from rat crude synaptosomes and colocalized with SAPAP in primary cultured rat hippocampal neurons. Because synamon is composed of various protein-interacting modules, it may also interact with proteins other than GKAP/SAPAP/DAP to organize the architecture of the PSD.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.

In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.

Amino Acid Sequence↗

PubMed1999

MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein.

Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases. Because PSD-95/SAP90 and S-SCAM function as synaptic scaffolding proteins, identification of ligands for these proteins is important to elucidate the structure of synaptic junctions. Here, we report a novel protein interacting with the PDZ domains of PSD-95/SAP90 and S-SCAM and named it MAGUIN-1 (membrane-associated guanylate kinase-interacting protein-1). MAGUIN-1 has one sterile alpha motif, one PDZ, and one plekstrin homology domain. MAGUIN-1 is localized at the plasma membrane via the plekstrin homology domain and the C-terminal region and interacts with PSD-95/SAP90 and S-SCAM via a C-terminal PDZ domain-binding motif. MAGUIN-1 has a short isoform, MAGUIN-2, which lacks a PDZ domain-binding motif. MAGUINs are expressed in neurons and localized in the cell body and neurites and are coimmunoprecipitated with PSD-95/SAP90 and S-SCAM from rat crude synaptosome. MAGUIN-1 may play an important role with PSD-95/SAP90 and S-SCAM to assemble the components of synaptic junctions.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Interaction of S-SCAM with neural plakophilin-related Armadillo-repeat protein/delta-catenin.

Synaptic scaffolding molecule (S-SCAM) is a multiple PDZ domain-containing protein, which interacts with neuroligin, a cell adhesion molecule, and the NMDA receptor. In this study, we searched for S-SCAM-interacting proteins and obtained a neuralplakophilin-related armadillo-repeat protein (NPRAP)/delta-catenin. NPRAP/delta-catenin bound to the last PDZ domain of S-SCAM via its carboxyl-terminus in three different cell-free assay systems, was coimmunoprecipitated with S-SCAM from rat crude synaptosomes, and was localized at the excitatory synapses in rat hippocampal neurons. NPRAP/delta-catenin may be implicated in the molecular organization of synaptic junctions through the interaction with S-SCAM.

Adaptor Proteins, Signal Transducing↗

PubMed1999

nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM).

Synaptic scaffolding molecule (S-SCAM) has six PDZ domains through which it interacts with N-methyl-d-aspartate receptors and neuroligin at synaptic junctions. We isolated here a novel S-SCAM-binding protein. This protein has one PDZ, one Ras association, one Ras GDP/GTP exchange protein (Ras GEP) domain, and one C-terminal consensus motif for binding to PDZ domains. We named it nRap GEP (neural Rap GEP). nRap GEP moreover has an incomplete cyclic AMP (cAMP)-binding (CAB) domain. The domain organization of nRap GEP is similar to that of Epac/cAMP-guanine nucleotide exchange factor (GEF) I, except that Epac/cAMP-GEFI has complete CAB and Ras GEP domains but lacks the other two domains and the C-terminal motif. nRap GEP showed GEP activity for Rap1 but did not bind cAMP. nRap GEP was specifically expressed in rat brain. Immunohistochemical analysis revealed that nRap GEP and S-SCAM were localized at synaptic areas of the cerebellum. These results suggest that nRap GEP is a novel neural Rap1-specific GEP which is associated with S-SCAM.

Adaptor Proteins, Signal Transducing↗

PubMed1999

Aged garlic extract attenuates intracellular oxidative stress.

Oxidation of low density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. We recently reported that aged garlic extract (AGE) inhibited LDL oxidation and minimized oxidized LDL-induced cell injury. In this study, the antioxidant effects of AGE were further examined using bovine pulmonary artery endothelial cells (PAEC) and murine macrophages. Lactate dehydrogenase (LDH) release, as an index of membrane injury, and intracellular glutathione (GSH) levels were determined. Oxidized LDL (Ox-LDL) caused an increase of LDH release and depletion of GSH. Pretreatment with AGE prevented these changes. AGE exhibited an inhibition of Ox-LDL-induced peroxides in PAEC. AGE suppressed peroxides in murine Macrophage (J774 cells) dose-dependently. The J774 cells were also incubated with AGE, interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) and nitric oxide (NO) production was measured. AGE inhibited NO production in J774 cells. In a cell free system, AGE was shown to scavenge H2O2 dose-dependently. Our data demonstrate that AGE can protect the endothelial cells from oxidized LDL-induced injury by preventing depletion of intracellular GSH and by removing peroxides. AGE also reduces levels of NO and peroxides in macrophages. These data suggest that AGE is a useful protective agent against cytotoxicity associated with Ox-LDL and NO, and it may thus be useful for the prevention of atherosclerosis and cardiovascular diseases.

Animals↗

PubMed1999

Antioxidant effects of fructosyl arginine, a Maillard reaction product in aged garlic extract.

The amino-carbonyl (Maillard) reaction of amino acids with sugars is a nonenzymatic browning reaction that takes place during the processing, cooking, and storage of foods. Maillard reaction products (MRPs) have been shown to possess interesting chemical and biological properties including antimutagenic and antioxidant activity. In this study, we determined the antioxidant effects of fructosyl arginine (Fru-Arg), a MRP in aged garlic extract. Low density lipoprotein (LDL) was incubated with Cu(2+) at 37 degrees C and 5% CO(2) for 24 hours, which resulted in an increase of thiobarbituric acid reactive substances (TBARS) indicating lipid peroxidation. Coincubation of Cu(2+) with Fru-Arg and LDL resulted in a significant inhibition of TBARS formation. Pulmonary artery endothelial cells (PAEC) were exposed to 0.1 mg/mL oxidized LDL (Ox-LDL) at 37 degrees C and 5% CO(2) for 24 hours. Lactate dehydrogenase (LDH) release, as an index of cell membrane damage, and TBARS were measured. Ox-LDL caused an increase of LDH release and TBARS formation. Pretreatment of PAEC with Fru-Arg inhibited these changes. Murine macrophages were incubated with Ox-LDL, and the release of peroxides was measured using a fluorometric assay. Ox-LDL caused an increased release of peroxides. Coincubation of macrophages with Fru-Arg and Ox-LDL inhibited the release of peroxides dose-dependently. In a cell free system, Fru-Arg was shown to scavenge hydrogen peroxide. These data suggest that Fru-Arg is a potent antioxidant, and thus may be useful for the prevention of atherosclerosis and other disorders associated with oxidative stress.

Journal Article↗

PubMed1999

S-allylcysteine attenuates oxidative stress in endothelial cells.

Oxidation of low-density lipoprotein (LDL) has been recognized as playing an important role in the initiation and progression of atherosclerosis. We recently reported that S-allylcysteine (SAC), one of the major compounds in the aged garlic extract (AGE), inhibited LDL oxidation and minimized oxidized LDL-induced cell injury. In this study, the antioxidant effects of SAC were further determined using several in vitro assay systems. Pulmonary artery endothelial cells (PAECs) were preincubated with SAC at 37 degrees C and 5% CO2 for 24 hr, washed, and then exposed to 0.1 mg/ml oxidized LDL for 24 hr. Lactate dehydrogenase (LDH) release, as an index of membrane injury, and intracellular glutathione (GSH) level were determined. Oxidized LDL caused an increase of LDH release and depletion of GSH. Pretreatment with SAC prevented these changes. Peroxides were measured directly in 24-well plates using a fluorometric assay. SAC dose-dependently inhibited oxidized LDL-induced release of peroxides in PAEC. In a cell-free system, SAC was shown to scavenge hydrogen peroxide. Our data demonstrate that SAC can protect endothelial cells from oxidized LDL-induced injury by removing peroxides and preventing the intracellular GSH depletion and suggest that this compound may be useful for the prevention of atherosclerosis.

Animals↗