• Title/Summary/Keyword: Molecular medicine

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A Comparative Coagulopathic Study for Treatment of Vasospasm by Using Low- and High-molecular Weight Hydroxyethyl Starches

  • Hwang, Sung-Ho;Won, Yu-Sam;Yu, Jang-Sun;Yang, Jae-Young;Choi, Chun-Sik
    • Journal of Korean Neurosurgical Society
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    • v.42 no.5
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    • pp.377-381
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    • 2007
  • Objective : High-molecular-weight hydroxyethyl starch (HES) compromises blood coagulation more than does low-molecular-weight HES. We compared the effects of low- and high-molecular-weight HES for the treatment of vasospasm and investigated the dose relationship with each other. Methods : Retrospectively, in a series of consecutive 102 patients with subarachnoid hemorrhage (SAH), 35 patients developed clinical symptoms of vasospasm of these fourteen patients were treated with low-molecular weight HES for volume expansion while the other 21 received high-molecular-weight HES as continuous intravenous infusion. Prothrombin time (PT), partial thromboplastin time (PIT), fibrinogen level, and platelet count were all measured prior to initiation, during treatment and after termination of therapy for symptomatic vasospasm. The total dose of HES ranged from 5 L to 14 L and median infusion duration was 10 days. Results : A more pronounced PTT prolongation was observed in high-molecular-weight HES group compared with low-molecular-weight HES group. No other coagulation parameters were altered. Dosage (=duration) shows a positive correlation with PTT. Clinically, significant bleeding episodes were noted in four patients who received high-molecular-weight HES. Conclusion : Coagulopathy was developed in direct proportion to molecular weight of starch and dosages. We propose the extreme caution in the administration of HES solution for the vasospasm treatment.

Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes

  • Kim, Hyo Jung;Yoon, Bo Kyung;Park, Hyounkyoung;Seok, Jo Woon;Choi, Hyeonjin;Yu, Jung Hwan;Choi, Yoonjeong;Song, Su Jin;Kim, Ara;Kim, Jae-woo
    • BMB Reports
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    • v.49 no.2
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    • pp.111-115
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    • 2016
  • Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.

Polymorphism of Ghrelin Gene in Twelve Chinese Indigenous Chicken Breeds and Its Relationship with Chicken Growth Traits

  • Li, C.C.;Li, K.;Li, J.;Mo, D.L.;Xu, R.F.;Chen, G.H.;Qiangba, Y.Z.;Ji, S.L.;Tang, X.H.;Fan, B.;Zhu, M.J.;Xiong, T.A.;Guan, X.;Liu, Bang
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.2
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    • pp.153-159
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    • 2006
  • A 2,656 bp fragment of chicken ghrelin gene was cloned and SNPs were detected by PCR-RFLP and Allele Specific PCR (ASP) in 12 Chinese indigenous chicken breeds and a commercial chicken population. The results showed that there were 23 base variations and an amino acid change ($Gln{\rightarrow}Arg$) in cloned chicken ghrelin gene. Three SNPs were confirmed in 13 populations and associations between this gene and growth traits of Tibetan chicken (TC) and Recessive White chicken (RW) were investigated. The results of haplotype analysis revealed that 26 haplotype genotypes were composed of eight haplotypes. The results of $x^2$ tests indicated that there were significant differences between genotypes or haplotype genotype frequencies in some of the breeds or sexes at 0.05 or 0.01 levels. The results of ANOVA revealed that there were significant differences between genotypes or haplotype genotypes on some growth traits of TC and RW chicken breeds at 0.05 or 0.01 levels. Multiple comparisons showed that there were significant associations between genotype CT at site 71 and some growth traits of two chicken breeds and between genotype AG at site 1,215 and body weight at 16 wk of two chicken breeds, and there was a significant association between haplotype genotype CAA/CAG and body weight and shank girth at 16 wk of two chicken breeds.

Carboxypeptidase E, Identified As a Direct Interactor of Growth Hormone, Is Important for Efficient Secretion of the Hormone

  • Mizutani, Akiko;Inoko, Hidetoshi;Tanaka, Masafumi
    • Molecules and Cells
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    • v.39 no.10
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    • pp.756-761
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    • 2016
  • We have identified 88 interactor candidates for human growth hormone (GH) by the yeast two-hybrid assay. Among those, we focused our efforts on carboxypeptidase E (CPE), which has been thought to play a key role in sorting prohormones, such as pro-opiomelanocortin (POMC), to regulated secretory vesicles. We found that CPE colocalizes with and interacts with GH in AtT20 pituitary cells. Downregulation of CPE led to decreased levels of GH secretion, consistent with involvement of CPE in GH sorting/secretion. Our binding assay in vitro with bacterially expressed proteins suggested that GH directly interacts with CPE but in a manner different from POMC.

$^{18}F$-FDG PET/CT Finding in a Case of Xanthogranulomatous Pyelonephritis (황색육아종성 신우신염 환자의 $^{18}F$-FDG PET/CT 소견 1예)

  • Choi, Bong-Hoi;Hong, Sun-Pyo;Yoon, Joon-Kee;Pai, Ki-Soo;Hong, Jeong;Yim, Hyun-Ee
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.2
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    • pp.150-153
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    • 2009
  • Xanthogranulomatous pyelonephritis is an uncommon chronic renal infection, which is usually found on middle-aged women and is rare in infant. Sometimes it forms focal mass like lesion of kidney with pathologically characteristic lipid-laden macrophage. A 1-month female infant was admitted for fever and moaning sound. On work-up of urinary tract infection, abdomen ultrasonography and computed tomography revealed a large mass on the upper portion of right kidney and PET/CT showed homogeneously increased $^{18}F$-FDG uptake. The radical nephrectomy of right kidney was performed and histology revealed a focal xanthogranulomatous pyelonephritis. To our knowledge, this is the first report presenting the finding of $^{18}F$-FDG PET/CT in the childhood xanthogranulomatous pyelonephritis.

Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells

  • Jiang, Qian;Li, Feng;Shi, Kejian;Yang, Yang;Xu, Caimin
    • BMB Reports
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    • v.45 no.3
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    • pp.194-199
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    • 2012
  • Autophagy has been suggested as a possible mechanism for non-apoptotic death despite evidence from many species that autophagy represents a survival strategy of cells under stress. From our previous findings that supranutritional doses of sodium selenite induced apoptosis in human leukemia cells, now we show autophagic cell death occurred after selenite exposure in HL60, suggested an alternative mechanism for the potential therapeutic properties of selenite. Additionally, Death-associated Protein Kinase (DAPK) performed a significantly increased expression during this process, concomitantly with gradually decreased phosphorylation at $Ser^{308}$. We further reveal that the up-regulation of DAPK which depends on selenite-activated ERK had no effect on autophagy. However, activation of DAPK via PP2A-mediated dephosphorylation at $Ser^{308}$ serves as a new strategy for autophagy induction. In conclusion, these results indicate that PP2A-mediated activated DAPK sensitizes HL60 cells to selenite, ultimately triggers autophagic cell death pathway to commit cell demise.

Expression of Endoplasmic Reticulum Membrane Kinases by Thyroid Stimulating Hormone in the FRTL-5 Cells

  • Jin, Cho-Yi;Kwon, Ki-Sang;Han, Song-Yi;Goo, Tae-Won;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.14 no.1
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    • pp.59-62
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    • 2008
  • This experiment was performed to study the effect of TSH (thyroid-stimulating hormone) on the expression of endoplasmic reticulum (ER) chaperones in the rat thyrocytes FRTL-5 cells. Although the expressions of ER membrane kinases (ATF6, IRE1 and PERK) were specially enhanced under absence of TSH, no remarkable up- or down regulations of ER chaperones (BiP, CHOP and Calnexin) were detected by TSH. We firstly report here that TSH by dose up-regulated expression of ER membrane kinases in FRTL-5 culture thyrocytes.

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Synthesis of dimeric fluorescent TSPO ligand for detection of glioma

  • Tien Tan Bui;Hee-Kwon Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.7 no.1
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    • pp.56-65
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    • 2021
  • TSPO, an 18-kDa translocator protein, is a peripheral-type benzodiazepine receptor that has been associated to a variety of biological activities such as apoptosis, steroidogenesis, and cell proliferation. Because TSPO overexpression has been found in various forms of cancer, it has recently become one of the most appealing biological targets for cancer therapies and detection. In order to create new optical imaging agents for improved diagnostics, we synthesized a novel dimeric fluorescent TSPO ligand based on PRB28 structure and SCy5.5. Following the preparation of the novel TSPO ligand, in vivo and ex vivo imaging tests were performed to examine the tumor uptake characteristics of the fluorescent TSPO ligand in a glioma animal model, and it was found that novel TSPO ligand was accumulated in glioma. These results suggested that novel dimeric fluorescent TSPO ligand will be applied to detect glioma.

ErbB3 binding protein 1 contributes to adult hippocampal neurogenesis by modulating Bmp4 and Ascl1 signaling

  • Youngkwan Kim;Hyo Rim Ko;Inwoo Hwang;Jee-Yin Ahn
    • BMB Reports
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    • v.57 no.4
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    • pp.182-187
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    • 2024
  • Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

Large scale purification and characterization of recombinant human autotaxin/lysophospholipase D from mammalian cells

  • Song, Yuanda;Dilger, Emily;Bell, Jessica;Barton, William A.;Fang, Xianjun
    • BMB Reports
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    • v.43 no.8
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    • pp.541-546
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    • 2010
  • We utilized a mammalian expression system to purify and characterize autotaxin (ATX)/lysophospholipase D, an enzyme present in the blood responsible for biosynthesis of lysophosphatidic acid. The human ATX cDNA encoding amino acids 29-915 was cloned downstream of a secretion signal of CD5. At the carboxyl terminus was a thrombin cleavage site followed by the constant domain (Fc) of IgG to facilitate protein purification. The ATX-Fc fusion protein was expressed in HEK293 cells and isolated from conditioned medium of a stable clone by affinity chromatography with Protein A sepharose followed by cleavage with thrombin. The untagged ATX protein was further purified to essential homogeneity by gel filtration chromatography with a yield of approximately 5 mg/liter medium. The purified ATX protein was enzymatically active and biologically functional, offering a useful tool for further biological and structural studies of this important enzyme.