• Title/Summary/Keyword: CFTR

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Limb Salvage Using a Combined Distal Femur and Proximal Tibia Replacement in the Sequelae of an Infected Reconstruction on Either Side of the Knee Joint (슬관절 주위 재건물 감염 후유증 시 슬관절 상하부 종양인공관절을 이용한 사지 구제술)

  • Jeon, Dae-Geun;Cho, Wan Hyeong;Park, Hwanseong;Nam, Heeseung
    • Journal of the Korean Orthopaedic Association
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    • v.54 no.1
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    • pp.37-44
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    • 2019
  • Purpose: Tumor infiltration around the knee joint or skip metastasis, repeated infection sequelae after tumor prosthesis implantation, regional recurrence, and mechanical failure of the megaprosthesis might require combined distal femur and proximal tibia replacement (CFTR). Among the aforementioned situations, there are few reports on the indication, complications, and implant survival of CFTR in temporarily arthrodesed patients who had a massive bony defect on either side of the knee joint to control infection. Materials and Methods: Thirty-four CFTR patients were reviewed retrospectively and 13 temporary arthrodesed cases switched to CFTR were extracted. All 13 cases had undergone a massive bony resection on either side of the knee joint and temporary arthrodesis state to control the repeated infection. This paper describes the diagnosis, tumor location, number of operations until CFTR, duration from the index operation to CFTR, survival of CFTR, complications, and Musculoskeletal Tumor Society (MSTS) score. Results: According to Kaplan-Meier plot, the 5- and 10-year survival of CFTR was 69.0%±12.8%, 46.0%±20.7%, respectively. Six (46.2%) of the 13 cases had major complications. Three cases underwent removal of the prosthesis and were converted to arthrodesis due to infection. Two cases underwent partial change of the implant due to loosening and periprosthetic fracture. The remaining case with a deep infection was resolved after extensive debridement. At the final follow-up, the average MSTS score of 10 cases with CFTR was 24.6 (21-27). In contrast, the MSTS score of 3 arthrodesis cases with failed CFTR was 12.3 (12-13). The average range of motion of the 10 CFTR cases was 67° (0°-100°). The mean extension lag of 10 cases was 48° (20°-80°). Conclusion: Although the complication rates is substantial, conversion of an arthrodesed knee to a mobile joint using CFTR in a patient who had a massive bony defect on either side of the knee joint to control infection should be considered. The patient's functional outcome was different from the arthrodesed one. For successful conversion to a mobile joint, thorough the eradication of scar tissue and creating sufficient space for the tumor prosthesis to flex the knee joint up to 60° to 70° without soft tissue tension.

Expression of Anion Exchanger and CFTR in the Hepatocyte and Cholangiocytes in Bile Duct-Ligated Rat (담관 결찰 쥐의 간세포와 담관세포의 anion exchanger와 CFTR 발현)

  • Lee, Jae-Dong;Wang, Joon-Ho;Ki, Seung-Seog;Choe, Won-Hyeok;Park, Jae-Seung;Cho, Won-Kyoo;Park, Jung-Jun;Kim, Hong-Su
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1772-1777
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    • 2011
  • Cystic fibrosis transmembrane conductance regulator (CFTR) gene and sodium-independent $Cl^-/HCO_3^-$ anion exchanger (AE) genes are expressed in a wide variety of mammalian tissues including cholangiocytes. They play an important role in the regulation of intracellular pH (pHi) as well as in transepithelial acid/base transport necessary for biliary bicarbonate secretion. The aim of this study was to examine the expression level of CFTR gene and AE genes (AE1, AE2 and AE3) in the cholangiocytes and the hepatocytes, and also measure AE2 gene expression level after bile duct ligation (BDL). As we previously described, isolated hepatocytes and cholangiocytes from the liver of normal and BDL rats were prepared and gene expression levels were measured by using RT-PCR. We found that AE1, AE2, and AE3 genes were expressed in both hepatocytes and cholangiocytes, but CFTR was only in cholangiocytes. AE2 gene expression level was higher in the BDL hepatocytes than normal hepatocytes, which was significantly different between two groups. AE2 gene expression level was lower in the BDL cholangiocytes than normal cholangiocytes. However, AE2 gene expression level in both hepatocytes and cholangiocytes were not changed with a longer duration of BDL. These results suggest that CFTR and AE2 may play an important role in the pathogenetic mechanism of biliary cholestatic liver disease.

Cell Scheduling for Multicast Traffic in Input-Queueing ATM Switches (멀티캐스트 트래픽을 지원하는 입력 버퍼 ATM 스위치에서의 셀 스케쥴링 기법)

  • Jo, Min-Hui;Song, Hyo-Jeong;Gwon, Bo-Seop;Yun, Hyeon-Su;Jo, Jeong-Wan
    • Journal of KIISE:Information Networking
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    • v.27 no.3
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    • pp.331-338
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    • 2000
  • 온라인 화상회의, VOD 등의 멀티캐스트(multicast)특성을 갖는 서비스를 효율적으로 제공하기 위해서는 스위치 수준에서의 멀티캐스트 트래픽 처리를 위한 연구가 필요하다. ATM 스위치 증 입력 버퍼형은 하드웨어 구현 복잡도가 낮아 고속의 트래픽 처리와 대용량 스위치 구현에 적합한 반면, 높은 성능을 가지기 위해서는 임의접근(random access) 입력버퍼와 좋은 셀 스케쥴링 알고리즘이 필요하다. 본 논문에서는 입혁버퍼형 ATM 스위치에서의 멀티캐스트 셀 스케쥴링 알고리즘인 무충동 시간예약(CFTR)기법을 제안한다. CFTR 기법은 입력버퍼의 셀의 전송시점을 충돌이 없도록 예약함으로써 높은 처리율을 가질 수 있도록 하며, 이를 위해 입력단, 출력단 스케쥴러에 예약 테이블을 둔다. CFTR 기법은 각 출력 단 스케쥴러에서의 예약과정이 간단하고 독립적, 병렬적 수행이 가능하므로 고속 트래픽 처리에 적합하다. CFTR 기법의 성능평가를 위해 시뮬레이션을 통해 기존의 셀 스케쥴링 방식과 비교하며, 약간의 하드웨어 추가로 매우 좋은 성능을 보임을 알 수 있다.

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Korean Red Ginseng aqueous extract improves markers of mucociliary clearance by stimulating chloride secretion

  • Cho, Do-Yeon;Skinner, Daniel;Zhang, Shaoyan;Lazrak, Ahmed;Lim, Dong Jin;Weeks, Christopher G.;Banks, Catherine G.;Han, Chang Kyun;Kim, Si-Kwan;Tearney, Guillermo J.;Matalon, Sadis;Rowe, Steven M.;Woodworth, Bradford A.
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.66-74
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    • 2021
  • Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

Molecular Mechanism of Pancreatic Bicarbonate Secretion

  • Lee, Min-Goo;Kim, Je-Woo;Kim, Kyung-Hwan;Muallem, Shmuel
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.3
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    • pp.131-138
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    • 2002
  • Thanks to recent progress in availability of molecular and functional techniques it became possible to search for the basic molecular and cellular processes that mediate and control $HCO_3{^-}$ and fluid secretion by the pancreatic duct. The coordinated action of various transporters on the luminal and basolateral membranes of polarized epithelial cells mediates the transepithelial $HCO_3{^-}$ transport, which involves $HCO_3{^-}$ absorption in the resting state and $HCO_3{^-}$ secretion in the stimulated state. The overall process of HCO3 secretion can be divided into two steps. First, $HCO_3{^-}$ in the blood enters the ductal epithelial cells across the basolateral membrane either by simple diffusion in the forms of $CO_2$ and $H_2O$ or by the action of an $Na^+-coupled$ transporter, a $Na^+-HCO_3$ cotranporter (NBC) identified as pNBC1. Subsequently, the cells secrete $HCO_3{^-}$ to the luminal space using at least two $HCO_3{^-}$ exit mechanisms at the luminal membrane. One of the critical transporters needed for all forms of $HCO_3{^-}$ secretion across the luminal membrane is the cystic fibrosis transmembrane conductance regulator (CFTR). In the resting state the pancreatic duct, and probably other $HCO_3{^-}$ secretory epithelia, absorb $HCO_3{^-}.$ Interestingly, CFTR also control this mechanism. In this review, we discuss recent progress in understanding epithelial $HCO_3{^-}$ transport, in particular the nature of the luminal transporters and their regulation by CFTR.

Coordination of Pancreatic $HCO_3^-$ Secretion by Protein-Protein Interaction between CFTR and Luminal NHE

  • Wooin Ahn;Kim, Kyung-Hwan;Lee, Jin-Ah;Kim, Joo-Young;Park, Joo-Young;Shmuel Muallem;Lee, Min-Goo
    • Proceedings of the Korean Biophysical Society Conference
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    • 2001.06a
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    • pp.56-56
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    • 2001
  • Increasing evidence suggests that protein-protein interaction is essential in many biological processes including epithelial transport. In this report, we present the significance of protein interactions to HCO$_3$$^{-10}$ secretion in pancreatic duct cells. In pancreatic ducts HCO$_3$$^{-10}$ secretion is mediated by CFTR-activated luminal CUHCO$_3$$^{-10}$ exchange activity and HCO$_3$$^{-10}$ absorption is achieved by Na$^{+}$-dependent mechanism including NHE3.(omitted)

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Antisense Oligonucleotide Therapeutics for Cystic Fibrosis: Recent Developments and Perspectives

  • Young Jin Kim;Adrian R. Krainer
    • Molecules and Cells
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    • v.46 no.1
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    • pp.10-20
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    • 2023
  • Antisense oligonucleotide (ASO) technology has become an attractive therapeutic modality for various diseases, including Mendelian disorders. ASOs can modulate the expression of a target gene by promoting mRNA degradation or changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation. Advances in medicinal chemistry and a deeper understanding of post-transcriptional mechanisms have led to the approval of several ASO drugs for diseases that had long lacked therapeutic options. For instance, an ASO drug called nusinersen became the first approved drug for spinal muscular atrophy, improving survival and the overall disease course. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Although Trikafta and other CFTR-modulation therapies benefit most CF patients, there is a significant unmet therapeutic need for a subset of CF patients. In this review, we introduce ASO therapies and their mechanisms of action, describe the opportunities and challenges for ASO therapeutics for CF, and discuss the current state and prospects of ASO therapies for CF.

Analysis of the Active Compounds and Therapeutic Mechanisms of Yijin-tang on Meniere's Disease Using Network Pharmacology(II) (네트워크 약리학을 활용한 메니에르병에 대한 이진탕(二陳湯)의 활성 성분과 치료 기전 연구(II))

  • SunKyung Jin;HaeJeong Nam
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.36 no.2
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    • pp.1-9
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    • 2023
  • Objectives : This study used a network pharmacology approach to analyze the treatment mechanisms of Yijin-tang on Meniere's disease, and comparative analysis the treatment mechanisms of drugs recommended in the Meniere's disease treatment guidelines. Methods : We collected information on the recommended drugs from the Meniere's disease treatment guidelines and their target proteins were screened via the STITCH database. The intersection targets were obtained through Venny 2.1.0. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using ClueGO. Results : The 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were associated with both Yijin-tang and Meniere's disease related genes. The 10 proteins(AQP2, KCNE1, AQP1, AVP, ACE, HRH1, HRH3, NOS1, CA1, CFTR) were associated with both the recommended drugs in the guidelines and Meniere's disease related genes. The 2 proteins(CFTR, NOS1) were common across all three groups. Further, GO/KEGG pathway analysis of the collected proteins revealed that the common mechanisms of action between Yijin-tang and the recommended drugs in the guidelines were related to pathways involving immune dysfunction and disturbances in lymphatic fluid homeostasis. In addition, the recommended drugs in the guidelines appeared to act through mechanisms that improve blood flow through vasodilation. Conclusions : Pharmacological network analysis can help to explain the treatment mechanisms of Yijin-tang on Meniere's disease.