• Title/Summary/Keyword: GN

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A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region

  • Piao, Yongwei;Yun, So Yoon;Kim, Hee Soo;Park, Bo Kyung;Ha, Hae Chan;Fu, Zhicheng;Jang, Ji Min;Back, Moon Jung;Shin, In Chul;Won, Jong Hoon;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.529-539
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    • 2022
  • Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

Endoscopic Findings and Treatment of Gastric Neoplasms in Familial Adenomatous Polyposis

  • Sato, Chihiro;Takahashi, Kazuya;Sato, Hiroki;Naruse, Takumi;Nakajima, Nao;Takatsuna, Masafumi;Mizuno, Ken-ichi;Hashimoto, Satoru;Takeuchi, Manabu;Yokoyama, Junji;Kobayashi, Masaaki;Terai, Shuji
    • Journal of Gastric Cancer
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    • v.22 no.4
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    • pp.381-394
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    • 2022
  • Purpose: Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP. Materials and Methods: A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes. Results: Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs.Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014). Conclusions: Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.

Effects of Administration of Oxytocin Antagonist on Implantation and Pregnancy Rates in Patients with Repeated Failure of IVF/ICSI Treatment (체외수정시술의 반복적인 실패 환자에서 옥시토신 길항제 주입이 착상 및 임신에 미치는 영향)

  • Ahn, Jun-Woo;Kim, Chung-Hoon;Kim, So-Ra;Jeon, Gyun-Ho;Kim, Sung-Hoon;Chae, Hee-Dong;Kang, Byung-Moon
    • Clinical and Experimental Reproductive Medicine
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    • v.36 no.4
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    • pp.275-281
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    • 2009
  • Objective: This study was performed to evaluate the effect of oxytocin antagonist on the outcome of IVF/ICSI cycles in infertile patients with repeated failure of IVF/ICSI treatment. Method: Forty patients who had experienced two or more failures of IVF/ICSI treatment without low ovarian reserve, were recruited for this prospective randomized study. All patients received controlled ovarian stimulation (COS) using GnRH antagonist multidose protocol (MDP). For the intervention group, intravenous administration of atosiban (mixed vasopressin $V_{1A}$/oxytocin antagonist) started with a bolus dose 6.75 mg one hour before embryo transfer (ET) and continued at an infusion rate of 18 mg/hour. After ET, administered atosiban was reduced to 6 mg/hour and continued for 2 hours. The main efficacy endpoints were clinical pregnancy rate and implantation rate. Results: Patients' characteristics were comparable in the intervention and control groups. COS parameters and IVF results were also similar. The number of uterine contractions for 3 minutes measured just before ET was significantly lower in the intervention group than control group ($3.5{\pm}1.4$ vs $8.7{\pm}2.2$, p<0.001). While there was no statistically significant difference in the clinical pregnancy rate between control group and intervention group (20.0% and 40.0%, p=0.168), the implantation rate was significantly higher in the intervention group, with 16.9% (11/65) compared with 6.0% (4/67) in the control group (p=0.047). There were no differences in ectopic pregnancy rate and miscarriage rate between the two groups. Conclusion: This study demonstrates that administration of oxytocin antagonist during ET can improve the implantation rate probably by decreasing the frequency of uterine contractions in infertile patients undergoing IVF/ICSI treatment.

Clinicopathologic Features and HBsAg and HBeAg Expressions in Hepatitis B Virus-associated Glomerulopathy (B형 간염 바이러스 감염과 연관된 사구체신염의 임상병리학적 특성과 신 조직내에서 HBs Ag 과 HBe Ag의 발현)

  • Jung Soo-Jin;Kim Young-Joo;Yoon Hye-Kyoung;Chung Woo-Yeong;Kim Young-Hoon;Kim Su-Yung
    • Childhood Kidney Diseases
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    • v.2 no.1
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    • pp.50-59
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    • 1998
  • Purpose : Hepatitis B virus (HBV) infection has been involved in several forms of immune-related glomerulopathy but the pathogenic role of HBV infection is not clear. To evaluate the clinicopathological features of HBV-associated glomerulopathy, a clinicopathological analysis and immunohistochemical stain for HBs Ag and HBe Ag were done. Methods : Clinicopathological features of HBV-associated glomerulopathy were analyzed with renal biopsies in 28 HBsAg seropositive patients from April 1990 to February 1997 at Pusan Paik Hospital, and immunohistochemical evaluation for HBsAg and HBeAg was done in renal tissues. Light microscopic, immunofluorescent and electron microscopic examination and immunohistochemical staining for HBsAg (DAKO) and HBeAg (BIONIKE) of renal tissue were performed. Result ; 1. The age distribution was 6 to 73 years old, and eight were children and 20 were adults. Male : female ratio was 3:1. Nineteen (67.9%) and 21 (75.0%) of 28 cases showed hematuria and proteinuria, respectively at the time of biopsy. Sixteen (57.2%) of them had nephrotic syndrome. 2. Liver function test was performed in 11 patients and seven (63.6%) of them showed increased AST and ALT levels. Liver biopsy was done in three patients and revealed findings of chronic active hepatitis. 3. HBV-associated glomerulopathy was membranous glomerulonephritis (MGN) in 10 (35.7%), mesangiopathy in 8 (28.6%), membranoproliferative glomerulonephritis (MPGN) in 7 (25.0%) and minimal change disease in 3 (10.7%) out of 28 cases. 4. Ultrastructurally HBV-associated MGN showed conspicuous subepithelial deposits with intramembranous, mesangial and subendothelial deposits and proliferation of mesangial cells and matrix, which were suggestive of MPGN. In HBV-associated MPGN, intramembranous and subepithelial deposits were scattered. 5. Immunohistochemical staining revealed no expression for HBsAg, but positive reaction for HBeAg along capillary wall in 8 cases (28.6%), of which 3 cases were checked for serum HBeAg, all showed positivity. Conclusion : HBV-associated glomerulopathy showed a wide morphologic spectrum and overlapping ultrastructural features in MGN and MPGN, and the activity of hepatitis B virus may be related to the development of HBV-associated glomerulopathy but further studies are recommended to confirm this relationship.

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STABILITY OF OBWEGESER II METHOD IN MANDIBULAR PROGNATHIC OR ANTERIOR OPEN BITE PATIENTS (하악전돌증 및 개교합 환자에 있어 Obwegeser Ⅱ method의 안정성)

  • Jung, Chang-Wook;Nam, Jeong-Hun;Lee, Sang-Han;Kwon, Tae-Geon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.30 no.1
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    • pp.25-33
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    • 2004
  • The purpose of this study was to evaluate the postoperative stability of the severe open bite or mandibular prognathic patients after mandibular set back surgery by Obwegeser II method. There were 19 patients who had been undergone Obwegeser II method. The horizontal and vertical position of the cephalometric points were measured preoperation and immediate postoperation, postoperative 1 month, postoperative 6 months ; were analyzed by linear measurement to evaluate changes in skeletal landmark and the relapse was compared between open bite group and prognathism group. By the operation, horizontal change of B was $6.84{\pm}4.35mm$ and vertical change of B was $6.28{\pm}3.25mm$ in open bite group and horizontal change of B was $14.20{\pm}4.81mm$ and vertical change of B was $1.99{\pm}2.66mm$ in prognathism group, horizontal change of Pog was $3.82{\pm}5.71mm$ and vertical change of Pog was $5.38{\pm}2.11mm$ in open bite group and horizontal change of Pog was $13.24{\pm}5.99mm$ and vertical change of Pog was $1.91{\pm}0.94mm$ in prognathism group. Between immediate postoperation and postoperative 1 month, all skeletal landmarks change was no statistical difference (p>0.05) and there were no statistical difference between open bite group and prognathism group except x-Me landmark (p>0.05). Between postoperative 1 month and 6 months, horizontal change of B was $0.12{\pm}1.35mm$ and vertical change of B was $1.47{\pm}1.48mm$ in open bite group and horizontal change of B was $1.43{\pm}1.35mm$ and vertical change of B was $0.82{\pm}1.99mm$ in prognathism group, horizontal change of Pog was $0.13{\pm}1.40mm$ and vertical change of Pog was $0.88{\pm}1.71mm$ in open bite group and horizontal change of Pog was $1.08{\pm}1.74mm$ and vertical change of Pog was $0.47{\pm}1.57mm$ in prognathism group (p>0.05) and there were no statistical difference between open bite group and prognathism group (p>0.05). Between immediate postoperation and postoperative 6months, horizontal change of B was $0.24{\pm}1.17mm$ and vertical change of B was $1.87{\pm}1.63mm$ in open bite group and horizontal change of B was $1.54{\pm}1.55mm$ and vertical change of B was $1.04{\pm}1.96mm$ in prognathism group, horizontal change of Pog was $0.91{\pm}1.46mm$ and vertical change of Pog was $1.18{\pm}2.05mm$ in open bite group and horizontal change of Pog was $0.96{\pm}1.62mm$ and vertical change of Pog was $1.23{\pm}2.35mm$ in prognathism group (p>0.05) and there were statistical difference between open bite group and prognathism group in x-B, x-Pog, x-Gn, x-Me (p<0.05). Obwegeser II method is considered as one of the best operation when surgical correction of severe open bite or severe mandibular prognathism is needed.

A comparative study on head posture and craniofacial morphology between koreans and scandinavian caucasians (한국인과 스칸디나비아계 백인의 두부자세와 두개안면구조의 형태에 관한 비교연구)

  • Oh, Yong-Duck;Yoon, Young-Jooh;Kim, Kwang-Won
    • The korean journal of orthodontics
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    • v.29 no.6 s.77
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    • pp.707-720
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    • 1999
  • The purpose of this study was to evaluate racial differences In head posture and the influence of head posture to the craniofacial morphology. The sample group of this study was made up of 51 Korean males and 120 Scandinavian Caucasian males. From the comparison of the cranio-cervical angle and the variables of craniofacial morphology between them, the following results were obtained. 1. The cranio-cervical angle (NSL/OPT) was on average 9.28 degrees larger In Koreans. 2. The length of the anterior cranial base (N-S) was on average 4.66mm shorter in Koreans. 3. The length of the maxillary base (sp-pm and ss-pm) were on average 2.75mm and 4.65mm shorter in Koreans respectively, the anterior maxillary height (n-sp) was on average 2.60mm longer, the posterior dimension (s-pm) was found to be 2.06mm longer in Koreans, and the maxillary inclination (NSL/NL) was identical in both samples. 4. The mandibular body length (pg-tgo) and ramus height (ar-tgo) were identical in the two groups, but the genial angle (ML/RL) was 3.22 degrees smaller and the mandibular plane inclination (NSL/ML) was 2.44 degrees larger in Koreans 5. The maxillary prognathism (s-n-sp and s-n-ss) and the mandibular prognathism (s-n-sm) were identical in both samples. 6. The sagittal jaw relationship (ss-n-pg) was 1.44 degrees larger in the Korean sample, but the vortical jaw relationship (NL/ML) was not significantly different. 7. The anterior facial height (n-gn) was 5.57mm longer in the Korean sample. 8. The mandibular alveolar prognathism (CL/ML) was 5.71 degrees greater and the interincisal angle (ILs/ILi) was 3.08 degrees more acute in Koreans. Taken together these results, craniofacial morphology can be influenced by the head posture defined by cranio-cervical angulation.

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Empirical Orthogonal Function Analysis of Surface Pressure, Sea Surface Temperature and Winds over the East Sea of the Korea (Japan Sea) (한국 동해에서의 해면기압, 해수면온도와 해상풍의 경험적 직교함수 분석)

  • NA Jung-Yul;HAN Snag-Kyu;SEO Jang-Won;NOH Yi-Gn;KANG In-Sik
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.30 no.2
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    • pp.188-202
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    • 1997
  • The seasonal variability of the sea surface winds over the last Sea of Korea (Japan Sea) is investigated by means of empirical orthogonal function (EOF) analysis. The combined representation of fields of three climatic variables by empirical orthogonal functions is discussed. The eigenvectors are derived from daily sea level pressure, wind speed and 10-day mean sea surface temperature (SST) during 15 years $(1978\~1992)$. The spatial patterns of the mean pressure are characterized by the high pressure in the western part and the low pressure in the eastern part. The spatial distribution of the standard deviation (SD) of pressure are characterized by max SD of 6.6 mb near the Vladivostok, and minima along the coast of the Japan. In Vladivostok, the maxima of SD of SST and south-north wind (WV) were also occurred. The representation of fields of individual meteorological variables by EOF shows that the first mode of the west-east wind (WU) explain over $47.3\%$ of the variance and the second mode of WU represents $30\%$. Especially, the first mode of the WV explain $70.9\%$ of the variance and their time series coefficients show 1-cpy, 0.5-cpy frequency spectrum. The spatial distribution of the first mode eigenvectors of SST are characterized by maximum near Vladivostok. The combined representation of fields of several variables (pressure, wind, SST) reveals that the first mode magnitudes of the variance of the combined eigenvectors (WU-PR) are increased. By means of this result, the 1-year peak and the 6-months peak are remarkable. In the three combined patterns (wind, pressure, SST), the second mode of the eigenvector (wind) is affected by the SST. Their time coefficients of the first mode show noticeable 1-year peak. The spectral analysis of the second mode shows broad seasonal signal with the period of 4-months and a significant peak of variability at 3-month period.

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Molecular Phylogenetic Study of Nesiohelix samarangae Based on Metallothionein Gene (동양달팽이(Nesiohelix samarangae)의 metallothionein 유전자를 기초로 한 분자계통 분류학적 연구)

  • Lee, Jun-Seo;Min, Byung-Jun;Kang, Se-Won;Lee, Jae-Bong;Baek, Moon-Ki;Hwang, Seung-Young;Kim, So-Hee;Kho, Weong-Gyu;Choi, Sang-Haeng;Chae, Sung-Hwa;Park, Hong-Seog;Han, Yeon-Soo;Lee, Jun-Sang;Jeong, Kye-Heon;Lee, Yong-Seok
    • The Korean Journal of Malacology
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    • v.24 no.1
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    • pp.73-80
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    • 2008
  • Numerous morphological studies on N. samarangae have been well conducted over the last ten years. In this context, we have attemtped to do molecular phylogenetic analysis by using metallothionein (MT) gene from N. samarangae. To this end, we cloned the full length cDNA of MT from cDNA library of N. samarangae. The complete cDNA sequences were obtained from the expressed sequence tag (EST) sequencing project of N. samarangae, The coding region of 195 bp gives an amino acid sequence of 65 residues including methionine. There are 5' (61 bp) and 3' (48 bp) untranslated region at both ends of the Ns-MT cDNA sequence. The combined results from BLAST analyses, multiple sequence alignment and molecular phylogenetic study of Ns-MT cDNA indicate that N. samarangae has similarity to land snails such as Helix pomatia, Helix aspersa and Arianta arbustorum.

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Regulation of $LH{\beta}$ subunit mRNA by Ovarian Steroid in Ovariectomized Rats (난소제거된 흰쥐에서 난소호르몬에 의한 $LH{\beta}$ subunit의 유전자 발현조절)

  • Kim, Chang-Mee;Park, Deok-Bae;Ryu, Kyung-Za
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.225-235
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    • 1993
  • Pituitary LH release has been known to be regulated by the hypothalamic gonadotropin releasing hormone (GnRH) and the gonadal steroid hormones. In addition, neurotransmitters and neuropeptides are actively involved in the control of LH secretion. The alteration in LH release might reflect changes in biosynthesis and/or posttranslational processing of LH. However, little is known about the mechanism by which biosynthesis of LH subunits is regulated, especially at the level of transcription. In order to investigate if ovarian steroid hormones regulate the LH subunit gene expression, ${\alpha}\;and\;LH{\beta}$ steady state mRNA levels were determined in anterior pituitaries of ovariectomized rats. Serum LH concentrations and pituitary LH concentrations were increased markedly with time after ovariectomy. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels after ovariectomy were increased in a parallel manner with serum LH concentrations and pituitary LH contents, the rise in $LH{\beta}$ subunit mRNA levels being more prominent than the rise in ${\alpha}\;subunit$ mRNA. ${\alpha}\;and\;LH{\beta}$ subunit mRNA levels in ovariectomized rats were negatively regulated by the continuous treatment of ovarian steriod hormones for $1{\sim}4\;days$ and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback of estradiol than progesterone. Treatment of estrogen antagonist, LY117018 or progesterone antagonist, RU486 significantly restroed LH subunit mRNA levels as well as LH release which were suppressed by estradiol or progesterone treatment. These results suggest that ovarian steroids negatively regulate the LH synthesis at the pretranslational level by modulating the steady state levels of ${\alpha}\;and\;LH{\beta}\;subunit$ mRNA and $LH{\beta}\;subunit$ mRNA seemed to be more sensitive to negative feedback action of estradiol than progesterone.

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Phylogenetic Analysis based on Metallothionein Gene Sequence of an Indigenous Species Pisidium (Neopisidium) coreanum in Korea (한국 고유종 Pisidium (Neopisidium) coreanum (산골조개) 의 metallothionein 유전자를 기초로 한 분자계통 분류학적 연구)

  • Baek, Moon-Ki;Lee, Jun-Seo;Kang, Se-Won;Lee, Jae-Bong;Kang, Hyun-Jung;Jo, Yong-Hun;Noh, Mi-Young;Han, Yeon-Soo;Choi, Sang-Haeng;Chae, Sung-Hwa;Park, Hong-Seog;Lee, Jun-Sang;Lee, Yong-Seok
    • The Korean Journal of Malacology
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    • v.25 no.2
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    • pp.153-160
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    • 2009
  • Pisidium (Neopisidium) coreanum is a freshwater snail and lives in spring water near mountain areas. Interestingly, this snail has been traditionally regarded as medicinal food, and thus has been used as folk remedies for healing broken bones. Recently, alpha classification on Pisidium (Neopisidium) coreanum through redescription has been conducted. However, not much attention has been made in beta classification. In this study, we performed the beta classification based on metallothionein (MT) genes found from various organisms. To this end, the complete cDNA sequences were obtained from the Expressed Sequence Tag (EST) sequencing project of Pisidium (Neopisidium) coreanum. The coding region (315 bp) encoded an amino acid sequence of 105 residues. The combined results from BLAST analyses, multiple sequence alignment and molecular phylogenetic study of Pc-MT gene indicate that Pisidium (Neopisidium) coreanum has similarity to freshwater bivalve such as Dreissena polymorpha (zebra mussel), Unio tumidus (swollen river mussel) and Crassostrea ariakensis (suminoe oyster).

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