The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation

Chung, C.,Yoo, G.,Kim, T.,Lee, D.,Lee, C.S.,Cha, H.R.,Park, Y.H.,Moon, J.Y.,Jung, S.S.,Kim, J.O.,Lee, J.C.,Kim, S.Y.,Park, H.S.,Park, M.,Park, D.I.,Lim, D.S.,Jang, K.W.,Lee, J.E. Academic Press 2016 Biochemical and biophysical research communication Vol.479 No.2

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

Identification of a Novel SNP Associated with Meat Quality in C/EBP${\alpha}$ Gene of Korean Cattle

Shin, S.C.,Kang, M.J.,Chung, E.R. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.4

CCAAT/enhancer binding protein ${\alpha}$($C/EBP{\alpha}$) plays an important role in lipid deposition and adipocyte differentiation. In order to find genetic markers to improve the meat quality of Korean cattle, the bovine $C/EBP{\alpha}$ gene was chosen as a candidate gene to investigate its association with carcass and meat quality traits in Korean cattle. A single nucleotide polymorphism (SNP) was identified at position 271 (A/C substitution) of coding region in the $C/EBP{\alpha}$ gene. A PCR-RFLP procedure with restriction enzyme SmaI was developed for determining the marker genotypes. The frequencies of alleles C and A and were 0.374 and 0.626, respectively. The genotype frequencies for CC, AC and AA were 12.9, 49.0 and 38.1%, respectively, in Korean cattle population. The frequencies of genotype were in agreement with Hardy-Weinberg equilibrium. Association analysis indicated that the gene-specific SNP marker of $C/EBP{\alpha}$ showed a significant association with marbling score (p<0.05). The animals with AA genotype had higher marbling score than those with the AC or CC genotype. Although further studies are needed to validate our results, the $C/EBP{\alpha}$ gene could be useful as a genetic marker for carcass and meat quality traits in Korean cattle.

SNP Detection of Carboxypeptidase E Gene and Its Association with Meat Quality and Carcass Traits in Korean Cattle

Shin, S.C.,Chung, E.R. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.3

Carboxypeptidase E (CPE) plays an important role in the regulation of the body fat content. Therefore, it has been suggested as candidate gene for traits related to meat quality in beef cattle. This study was conducted to identify single nucleotide polymorphisms (SNPs) in the CPE gene and to investigate association of SNP marker with carcass and meat quality traits in Korean cattle. Three SNPs were identified in the intron 4 (A309G SNP and C445T SNP) and exon 5 (C601T SNP) of the CPE gene by sequence analyses of CPE cDNA and genomic DNA samples. The sequences have been deposited in GenBank database with accession numbers AY970664 and AY970663. Genotyping of the gene-specific SNP marker was carried out using the PCR-RFLP with restriction enzymes DdeI for C445T SNP and NlaIII for C601T SNP. The frequencies of C and T alleles were 0.43 and 0.57 for C445T SNP and 0.42 and 0.58 for C601T SNP, respectively. Statistical analysis indicated that the C445T SNP showed a significant effect (p<0.05) on marbling score (MS) and breeding value of backfat thickness (BF-EBV), respectively. Animals with the CT genotype showed higher marbling score and backfat thickness than those with the TT genotype. This marker also showed a significant dominance effect for the MS and BF-EBV (p<0.05). However, no significant associations were observed between C601T SNP genotypes and all traits examined. The results suggest that the CPE gene may be used as a marker for carcass traits in Korean cattle.

Impact of ABCC2, ABCG2 and SLCO1B1 Polymorphisms on the Pharmacokinetics of Pitavastatin in Humans

Oh, E.S.,Kim, C.O.,Cho, S.K.,Park, M.S.,Chung, J.Y. 日本藥物動態學會 2013 DRUG METABOLISM AND PHARMACOKINETICS Vol.28 No.3

Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP) transporter alleles on its disposition, the pharmacokinetic (PK) parameters were compared among the following groups: SLC01B1 (*15 carrier and non-carrier), ABCC2 (G1249A, C3972T, C-24T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUClast was higher in individuals carrying the SLC01B1*15 allele than those not carrying it (144.1+/-55.3 vs 84.7+/-25.7h-ng/mL [mean+/-SD], p=0.002). The AUC<SUB>last</SUB> varied significantly according to the ABCC2 C-24T allele (103.4+/-42.2, 80.2+/-23.8, and 39.0h-ng/mL in CC, CT and TT, respectively; p=0.027). Other SNPs of ABCC2 and ABCG2 were not significant. The effect of these transporters and body weight on the AUC<SUB>last</SUB> and C<SUB>max</SUB> were tested, and only SLC01B1 and ABCC2 C-24T genotypes were significant factors by analysis of covariance. These variants accounted for almost 50% of the variation in AUC<SUB>last</SUB> and C<SUB>max</SUB> of pitavastatin. Therefore, ABCC2 C-24T was significantly associated with pitavastatin human PK when the known effect of SLC01B1 *15 was also considered.

Measurements of surgeons’ exposure to ionizing radiation dose: comparison of conventional and mini C-arm fluoroscopy

Sung, K. H.,Min, E.,Chung, C. Y.,Jo, B. C.,Park, M. S.,Lee, K. SAGE Publications 2016 The journal of hand surgery. journal of the Britis Vol.41 No.3

<P>This study was performed to measure the equivalent scattered radiation dose delivered to susceptible organs while simulating orthopaedic surgery using conventional and mini C-arm fluoroscopy. In addition, shielding effects on the thyroid, thymus, and gonad, and the direct exposure delivered to the patient's hands were also compared. A conventional and mini C-arms were installed in an operating room, and a hand and an operator phantom were used to simulate a patient's hand and a surgeon. Photoluminescence dosimeters were used to measure the equivalent dose by scattered radiation arriving at the thyroid, thymus, and gonad on a whole-body phantom in the position of the surgeon. Equivalent scattered radiation doses were measured in four groups: (1) unshielded conventional C-arm group; (2) unshielded mini C-arm group; (3) lead-shielded conventional C-arm group; and (4) lead-shielded mini C-arm group. Equivalent scattered radiation doses to the unshielded group were significantly lower in the mini C-arm group than those in the conventional C-arm group for all organs. The gonad in the lead-shielded conventional C-arm group showed the highest equivalent dose among operator-susceptible organs, and radiation dose was reduced by approximately 96% compared with that in the unshielded group. Scattered radiation was not detected in any susceptible organ in the lead-shielded mini C-arm group. The direct radiation dose to the hand phantom measured from the mini C-arm was significantly lower than that measured from the conventional C-arm. The results show that the equivalent scattered radiation dose to the surgeon's susceptible organs and the direct radiation dose to a patient's hand can be decreased significantly by using a mini C-arm rather than a conventional C-arm. However, protective lead garments, such as a thyroid shield and apron, should be applied to minimize radiation exposure to susceptible organs, even during use of mini C-arm fluoroscopy.</P>

Campylobacter 장염에 대한 역학적 연구 - 1 . 사람 , 동물 , 식품 및 강물에 있어서 Campylobacter jejuni 의 분포와 분리주의 혈청형

강호조,김용환,정병곤,박종일 경상대학교 축산진흥연구소 1989 畜産振興硏究所報 Vol.16 No.1

To investigate the epidemiological trait of gastroenteritis of human caused by C. jejuni isolation of etiological agent was carried out. Isolated C. jejuni were biotyped and serotyped. A total of 1929 specimens from 438 human, 182 milking cows, 200 cattle, 187 goats, 70 dogs, 426 pigs, 278 chickens, 148 duck, 50 raw milk, 110 chicken meat, 20 duck liver and 50 river water was examined for the presence of C. jejuni, and C. coli by direct plating and enrichment techniques. Isolation rates detected in human, animals food and water were as follows : human 0.796, ducks 54.7%, dogs 37.196, chickens 33.7%, goats 26.7%, cattle 25.5%, pigs 19.9% and milking cows 7.7%. The organism was isolated from 65% of 20 duck livers and from 2096 of 110 chicken west. Campylobacter was not recovered from raw river water. The majority of the isolated 201 strains of C. jejuni was classified as biotype I (53.7%) and biotype II (36.896). 117 strains of C. coli were 59.896 of biotype I , 40.1% biotype II. Isolated C. jejuni stranis showed 13 different serotype, and serotype 4, 5, 26 end 36 were most frequent. C. coli strains howed 7 different serotype, and serotype 21, 25 and 29 were relatively commom.

Continuous lithium mining from aqueous resources by an adsorbent filter with a 3D polymeric nanofiber network infused with ion sieves

Chung, W.J.,Torrejos, R.E.C.,Park, M.J.,Vivas, E.L.,Limjuco, L.A.,Lawagon, C.P.,Parohinog, K.J.,Lee, S.P.,Shon, H.K.,Kim, H.,Nisola, G.M. Elsevier 2017 Chemical Engineering Journal Vol.309 No.-

Electrospun composite nanofiber (NF) was fabricated and employed as an adsorbent membrane filter in a continuous Li<SUP>+</SUP> mining process from seawater. The filter was composed of a hydrophilic polyacrylonitrile (PAN) matrix infused with lithium ion sieves (LIS) H<SUB>1.6</SUB>Mn<SUB>1.6</SUB>O<SUB>4</SUB>. Characterization of the LIS/PAN NF confirmed its favorable structural and surface properties for effective Li<SUP>+</SUP> adsorption. The LIS/PAN NF was mechanically suitable as a microfiltration membrane with high water flux and low pressure requirement. Breakthrough experiments at varied feed concentrations (C<SUB>f</SUB>), seawater flowrates (F), and NF thicknesses (Z) revealed the dynamic adsorption behavior of the filter. The seawater residence time was most critical and must be kept ≥0.12min at any given C<SUB>f</SUB> and Z to maximize the Li<SUP>+</SUP> capacity of the filter. This can be conveniently achieved by adjusting the F of the process. Analogous to a packed bed system, the predictive power of nine breakthrough models were determined through non-linear regression analyses. Results reveal that bed-depth-space-time, Bohart-Adams (BA) and Thomas models adequately predicted the performance of the filter albeit BA exhibited the best agreement. Meanwhile, Wolborska failed to converge with any of the experimental results while Yoon-Nelson, Wang, Clark, dose-response, and modified dose-response were too simple to provide any meaningful information. Cycled Li<SUP>+</SUP> adsorption-desorption runs successfully collected and concentrated Li<SUP>+</SUP> in a mild acid stripping solution. After ten cycles, Li<SUP>+</SUP> was separated 155-1552 times more efficiently than Na<SUP>+</SUP>, K<SUP>+</SUP>, Mg<SUP>2+</SUP> and Ca<SUP>2+</SUP>. Overall results demonstrate the potential of LIS/PAN NF as an adsorbent membrane filter for continuous Li<SUP>+</SUP> mining from aqueous resources.

Rosuvastatin inhibits norepinephrine-induced cardiac hypertrophy via suppression of G_h

Choi, E.Y.,Chang, W.,Lim, S.,Song, B.W.,Cha, M.J.,Kim, H.J.,Choi, E.,Jang, Y.,Chung, N.,Hwang, K.C. North-Holland ; Elsevier Science Ltd 2010 european journal of pharmacology Vol.627 No.1

Statins have recently been shown to produce anti-cardiac hypertrophic effects via the regulation of small GTPases. However, the effects of statins on G protein-mediated cardiac hypertrophy, which is the main pathway of cardiac hypertrophy, have not yet been studied. We sought to evaluate whether statin treatment directly suppresses cardiac hypertrophy through a large G protein-coupled pathway regardless of the regulation of small GTPases. Using neonatal rat cardiomyocytes, we evaluated norepinephrine-induced cardiac hypertrophy for suppressibility of rosuvastatin and the pathways involved by analyzing total protein/DNA content, cell surface area, immunoblotting and RT-PCR for the signal transduction molecule. In a concentration-dependent manner, rosuvastatin inhibited total protein synthesis and downregulated basal and norepinephrine-induced expressions of myosin light chain2 and the c-fos proto-oncogene in cardiomyocytes. Treatment with norepinephrine induced cardiac hypertrophy accompanied by G<SUB>h</SUB> expression and membrane translocation. Rosuvastatin inhibited G<SUB>h</SUB> protein activity in cardiomyocytes by inhibiting basal and norepinephrine-stimulated mRNA transcription, protein expression and membrane translocation; however, norepinephrine-stimulated G<SUB>q</SUB> protein expression was not inhibited. In addition, the norepinephrine-stimulated protein kinase C (PKC)-mitogen-activated protein kinase (MEK 1,2)-extracellular signal-regulated kinases (ERKs) signaling cascade was inhibited by pretreatment with rosuvastatin. Rosuvastatin treatment also helped maintain expression levels of SERCA2a and intracellular calcium concentration. G<SUB>h</SUB> protein is a novel target of statins in myocardial hypertrophy, and statin treatment may directly suppress cardiac hypertrophy through a large G<SUB>h</SUB> protein-coupled pathway regardless of the regulation of small GTPases.

피하성회화결절(Subepidermal Calcified Nodule) 및 음낭부 특발성 석회증(Idiopathic Calcinosis of Scrotum)에 대한 임상 및 병리학적 고찰

崔應鈺,丁銓殷,洪聖鎬 大韓成形外科學會 1983 Archives of Plastic Surgery Vol.10 No.3

Subepidermal calcified nodule and idiopathic calcinosis of scrotum are subdivisions of the calcinosis cutis which calcium salt is deposited abnormally in skin and subcutaneous layer. Author summarized the clinico-histopathological characteristics of 21 cases of subepidermal calcified nodule and 2 cases of idiopathic calcinosis of scrotum at Korea University Hospital from January, 1970 to February, 1982. The results were as follows: 1. Incidence was I case among the about 3,000 surgical specimens. 2. Range of age of subepidermal calcified nodule was 14 to 72 years old and idiopathic calcinosis of scrotum was 25 years old in all cases. 3. Subepidermal calcified nodule occured equally in both sexes. 4. Clinical duration of subepidermal calcified nodule was 4 months to 6 years and there was no co-relation between clinical duration and size of tumor. 5. The gluteal region was the most frequent location of subepidermal calcified nodule and it was found on the trunk, extremities and face in descending order. 6. Subepidermal calcified nodule was single nodule in all cases, but idiopathic calcinosis of scrotum revealed two nodules in 50%, and the size of tumor ranged from 0.2cm to 6.0cm in diameter, but the most tumors measured 1.0 to 2.0cm in diameter. 7. Histopathologically subepidermal calcified nodule was located in dermal layer mostly. 8. Calcification was noted in all cases and foreign body giant cell was noted in most. 9. There was no recurrence or malignant change with simple surgical excision in all cases.

Distal protection device aggravated microvascular obstruction evaluated by cardiac MR after primary percutaneous intervention for ST-elevation myocardial infarction

Yoon, C.H.,Chung, W.Y.,Suh, J.W.,Cho, Y.S.,Youn, T.J.,Chun, E.J.,Choi, S.I.,Chae, I.H.,Choi, D.J. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.167 No.5

Background: Protection of distal embolization by balloon occlusion and thrombus aspiration has not improved microvascular circulation nor decreased myocardial injury during primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI) in randomized trials. In a prospective randomized trial, we investigated the mechanism of the poor effect of distal protection and thrombus aspiration (DP-TA) in 126 patients with STEMI. Methods: Patients with first-diagnosed STEMI were randomly assigned to DP-TA pretreatment or conventional PCI (c-PCI). Primary endpoint was reduced left ventricular end-diastolic volume (LVEDV) measured by MRI at post-PCI and 6months after PCI. Secondary end points were infarct ratio (infarct size to entire LV size) by delayed enhancement (DE), area at risk (AAR) ratio (AAR to entire LV size) by T2 high signal, microvascular occlusion index (MVO) ratio (MVO to entire LV size) by DE, and myocardial salvage index (MSI: (AAR-infarct size)*100/AAR) using cardiac magnetic resonance imaging (MRI) within 3days after PCI. Results: Baseline characteristics of the patients including cardiovascular risk factors and lesion characteristics were similar between the two groups. DT-PA failed to improve LV remodeling at 6months (LVEDV 140+/-39 vs 133+/-37 in c-PCI group, p=0.418). Infarct ratio, AAR ratio and MSI were not statistically different between DP-TA group and c-PCI group. However, MVO ratio was significantly larger in DP-TA group than in c-PCI group (2.4+/-2.7 vs 1.1+/-1.9, p=0.045). Conclusion: DP-TA was potentially hazardous in primary PCI for STEMI by increasing MVO. DP-TA should not be used in STEMI.