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      • Slide Session : OS-END-04 ; Diabetes : Correlation Between Plasma Levels of Carboxyme-thyl-Lysine and the Severity of Diabetic Neuropathy

        ( Masayuki Kitagawa ),( Jiro Akiba ),( Yukihiro Shikama ),( Ikuro Ohta ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: Advanced glycation end products such as carboxymethyl-lysine are produced by a nonenzymatic reaction between proteins and sugar in patients with long-term hyperglycemia. Advanced glycation end products in the matrix of the walls of small blood vessels are thought to have an effect on the development of diabetic complication. We hypothesized that plasma levels of caroxymethyl-lysine were re- flected by the severity of diabetic neuropathy. Methods: 1) Patients: The 84 patients with type 2 diabetes mellitus (mean age 61.8±9.5 years, duration of diabetes 12.4±8.6, mean HbA1c 7.7±1.4%) were included. 2) Carboxymethl-lysine: The plasma levels of carboxymethyl-lysine were measured by ELISA method. 3) Motor Nerve Conduction Velocity: We measured motor nerve conduction velocity of tibial nerve as marker of the severity of diabetic neuropathy. 4) Statistical Analyses: Correlation was assessed by linear regression analysis and multiple regression analysis using Stat View 5 for Macintosh. Results: In 53 type 2 diabetic patients with normal renal function (serum creatinine <1.0 mg/dl), we measured motor nerve conduction velocity of tibial nerve, and at the same time, we measured plasma levels of carboxymethyl-lysine. Motor nerve conduction velocity was correlated negatively with plasma levels of carboxymethyl-lysine in 25 male patients (r = 0.228, p = 0.29), but motor nerve conduction velocity was significantly correlated with plasma levels of carboxymethyl-lysine in 28 female patients (r =-0.632, p < 0.0003). Multiple regression analysis revealed an in dependent influence of plasma levels of carboxmethyl-lysine on motor nerve conduction velocity of tibial nerve in 28 female patients (r² = 0.375, p < 0.05). Conclusions: Our data suggests that plasma levels of carboxymethyl-lysine may be one of the etiology of diabetic neuropathy in female diabetic patients. We presumed this result is concerned with female lipid peroxidation of carboxymethyl-lysine.

      • Poster Session : PS 0159 ; Diabetes : A Case of Limbic System Atrophy in a Patient with Type 2 Diabetes Mellitus

        ( Masayuki Kitagawa ),( Jiro Akiba ),( Yukihiro Shikama ),( Ikuro Ohta ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

        Background: It is thought that there is close relation in glucose metabolism and brain damage. It is presumed that brain damage is caused for hypoglycemia. A limbic system exists in the inside of the cerebral cortex. It has been reported that limbic system atrophy tends to receive damage with hypoglycemia. We evaluated brain MR imaging changes of limbic system in a patient with type 2 diabetes mellitus with hypoglycemia. This case was considered to be a precious case when considering the relevance of glucose metabolism and brain damage. Case Report: The patient was 86-year-old female diagnosed with type 2 diabetes mellitus 20 years ago. She was brought to the emergency department in our hospital due to consciousness disturbance. In the emergency room, the blood glucose level was 16 mg/dl, and consciousness disorder was not recovered although intravenous injection of glucose was performed. It was presumed that the badness of a general state and unsuitable use of the oral hypoglycemic agent caused unstable glycemic control. Evaluation of change of brain MRI was made for 98 days. Results: Evaluation of change of brain MRI was made for 98 days. The appearance of limbic system atrophy was observed. Limbic system atrophy advanced gradually. It was thought that this case was a precious case in which picture change of the limbic system was able to be caught. Conclusions: It is presumed that hypoglycemia brings about activation of a glutamic acid receptor, and causes oxidant stress, and it is presumed that they make brain damage induce. Also in this case, we thought the damage of the limbic system was based on hypoglycemia. This case was considered to be a precious case when considering the relevance of glucose metabolism and brain damage.

      • Regulation of Major Histocompatibility (MHC) Class Ⅱ Human Leukocyte Antigen-DRα Gene Expression in Thyrocytes by Single Strand Binding Protein-1, a Transcription Factor That Also Regulates Thyrotropin Receptor and MHC Class I Gene Expression

        BALDUCCI-SILANO, PINA L.,SUZUKI, KOICHI,OHTA, MASANORI,SAITO, JUN,OHMORI, MASAYUKI,MONTANI, VALERIA,NAPOLITANO, GIORGIO,SHONG, MINHO,TANIGUCHI, SHIN-ICHI,PIETRARELLI, MICHELE,LAVARONI, STEFANO,MORI, A 충남대학교 생물공학연구소 1999 생물공학연구지 Vol.7 No.-

        The single strand binding protein (SSBP-1) is a positive regulator of TSH receptor gene expression and binds to an element with a GXXXXG motif. The S box of the mouse major histocompatibility classⅡ gene has multiple GXXXXG motifs and can also bind SSBP-1. The S box is one of four highly conserved elements on the 5'-flanking region of classⅡ genes that are necessary for interferon-γ (IFNγ) to overcome the normally suppressed state of the gene and induce aberrant classⅡ expression. In this report we show that SSBP-1, when overexpressed in FRTL-5 thyroid cells, is a positive regulator of human leukocyte antigen (HLA)-DRα classⅡ gene expression, as is IFNγ or the classⅡ trans-activator (CIITA). This is evidenced by increased exogenous promoter activity, increased endogenous RNA levels, and increased endogenous antigen expression after transfecting full-length SSBP-1 complementary DNA together with a HLA-DRα promoter-reporter gene chimera into TSH-treated FRTL-5 thyroid cells whose endogenous SSBP-1 levels are low. IFNγ reverses the ability of TSH to decrease endogenous SSBP-1 RNA levels. Also, whereas SSBP-1 transfection does not cause any increase in IFNγ-induced exogenous promoter activity, transfection of SSBP-1 and CIITA additively increases endogenous classⅡ RNA levels to levels measured in cells treated with IFNγ. Further, competition studies show that SSBP-1 binding is necessary for formation of the double strand protein/DNA complexes that are seen in electrophoretic mobility shift assays when the classⅡ 5'-flanking region is incubated with extracts from IFNγ-treated FRTL-5 cells and that have been previously associated with IFNγ-induced aberrant classⅡ expression. These data suggest that SSBP-1 is involved in the action of IFNγ to overcome the normally suppressed state of the classⅡ gene; it functions together with CIITA, whose expression is independently increased by IFNγ. The effect of SSBP-1 as a positive regulator of classⅡ promoter activity is lost in cells maintained without TSH, in which endogenous SSBP-1 RNA levels are already high in the absence of aberrant classⅡ gene expression. These data suggest that high levels of endogenous SSBP-1 are insufficient to cause aberrant classⅡ expression, but, rather, TSH or IFNγ treatment additionally modulates the cell, albeit differently, such that transfected or endogenous SSBP-1, respectively, can express its positive regulatory activity. The effect of TSH is consistent with reports indicating that TSH enhances the ability of IFNγ to increase classⅡ gene expression despite the fact IFNγ increases endogenous SSBP-1 to only the same levels as in cells untreated with TSH. Finally, the effect of SSBP-1 as a positive regulator is lost when GXXXXG motifs, which exist on both the coding and noncoding strands of the S box, are mutated. Consistent with this, mutation and oligonucleotide competition studies show that GXXXXG motifs are necessary for either strand of the S box to bind protein/DNA complexes containing SSBP-1 in FRTL-5 cell extracts or to bind to recombinant SSBP-1. They also suggest that the SSBP-1-binding sites on either strand of the HLA-DRα S box are functionally distinct. We conclude from these data that the positive regulatory action of SSBP-1 on classⅡ gene expression involves GXXXXG motifs on each strand of the highly conserved S box of the classⅡ 5'-flanking region. As SSBP-1 is modulated by IFNγ and is involved in classⅠ and TSH receptor as well as classⅡ gene expression in FRTL-5 cells, the sum of the data supports the hypotheses that common transcription factors regulate all three genes, and their altered activities may contribute to the development of autoimmunity. (Endocrinology 139: 2300-2313, 1998)

      • SCISCIESCOPUS

        Antioxidant effects of citrus pomace extracts processed by super-heated steam

        Wang, Lei,Jo, Min-Ji,Katagiri, Riho,Harata, Kaori,Ohta, Moemi,Ogawa, Ayane,Kamegai, Masayuki,Ishida, Yasuyuki,Tanoue, Shota,Kimura, Sojiro,Lee, Seung-Cheol,Jeon, You-Jin Elsevier 2018 FOOD SCIENCE AND TECHNOLOGY -ZURICH- Vol.90 No.-

        <P>This study was performed to investigate the enhanced antioxidant effects of citrus pomace (CP) extracts processed by super-heated steam (SHS). CP extracts were obtained using a closed SHS system at three different temperatures (100, 200, and 300 degrees C) with an extraction time of 10 or 20 min. These extracts were evaluated for their antioxidant activities by measuring their DPPH, alkyl, and hydroxyl radical scavenging activity using Electron Spin Resonance (ESR) spectroscopy and for their protective effects against H2O2-induced oxidative stress in Vero cells. All extracts exhibited strong radical scavenging activities and protective effects against H2O2-induced Vero cell damage. Especially, the SHS-CP extracts obtained at 300 degrees C with extraction times of both 10 min and 20 min exhibited antioxidant activities that were significantly higher than those of ethanol extracts and SHS-CP extracts obtained at other temperatures. The total phenolic and flavonoid contents of SHS-CP extracts and their antioxidant activities were found to be increased with elevated processing temperatures. Moreover, gas chromatography/mass spectrometry (GC/MS) in the presence of a methylating reagent revealed that some characteristic polyphenols and polyhydroxycyclohexanes were present in the SHS-CP extracts. Thus, this study demonstrated that SHS extraction is an efficient and environmentally friendly method for extracting antioxidants from CP.</P>

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