• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.547-556
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• 2016

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing $K^+$ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward $K^+$ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing $K^+$ channels (TASK-2). NIOK in the presence of $K^+$ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

• Journal of Veterinary Clinics
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• v.24 no.2
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• pp.182-191
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• 2007

Bioabsorbable devices have been utilized and experimented in many aspects of orthopaedic surgery. Depending upon their constituent polymers, these materials can be tailored to provide sufficient rigidity to allow bone healing, retain mechanical strength for certain period of time, and then eventually begin to undergo degradation. The objective of this study was to estimate extent in which Poly-L-latic acid (PLLA) implants had bioabsorbability and biocompatibility with bone and soft tissue in dogs and also to develop bioabsorbable, biocompatible materials with the appropriate strength and degradation characteristics to allow for regular clinical use for treating orthopedic problems in humans as well as animals. Eighteen dogs were used as experimental animals and were inserted two types of PLLA implants. PLLA rods were inserted into subcutaneous tissue of back or the abdomen wall. And the rods were tested for material properties including viscosity, molecular weight, melting point, melting temperature, crystallinity, flexural strength, and flexural modulus over time. PLLA screws were inserted through cortical bone into bone marrow in the femur of the dogs and stainless steel screw was inserted in the same femur. Radiographs were taken after surgery to observe locations of screw. Histological variations including cortical bone response, muscular response, bone marrow response were analyzed over the time for 62weeks. The physical properties of PLLA rods had delicate balances between mechanical, thermal and viscoelastic factors. PLLA screws did not induce any harmful effects and clinical complications on bone and soft tissue for degradation period. These results suggest that PLLA implants could be suitable for clinical use.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.213-221
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• 2017

Baicalein, a natural flavonoid obtained from the rhizome of Scutellaria baicalensis Georgi, has been reported to have anticancer activities in several human cancer cell lines. However, its antimetastatic effects and associated mechanisms in melanoma cells have not been extensively studied. The current study examined the effects of baicalein on cell motility and anti-invasive activity using mouse melanoma B16F10 cells. Within the noncytotoxic concentration range, baicalein significantly inhibited the cell motility and invasiveness of B16F10 cells in a concentration-dependent manner. Baicalein also reduced the activity and expression of matrix metalloproteinase (MMP)-2 and -9; however, the levels of tissue inhibitor of metalloproteinase-1 and -2 were concomitantly increased. The inhibitory effects of baicalein on cell motility and invasiveness were found to be associated with its tightening of tight junction (TJ), which was demonstrated by an increase in transepithelial electrical resistance and downregulation of the claudin family of proteins. Additionally, treatment with baicalein markedly reduced the expression levels of lipopolysaccharide-induced phosphorylated Akt and the invasive activity in B16F10 cells. Taken together, these results suggest that baicalein inhibits B16F10 melanoma cell migration and invasion by reducing the expression of MMPs and tightening TJ through the suppression of claudin expression, possibly in association with a suppression of the phosphoinositide 3-kinase/Akt signaling pathway.

• Journal of Preventive Medicine and Public Health
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• v.39 no.2
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• pp.141-148
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• 2006

Objectives : We wanted to evaluate the medical underutilization for benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) among Korean elderly men and we wanted to determine their associated factors. Methods : This study was conducted on 239 men with LUTS and 116 men with BPH who were compatible with the diagnostic criteria from a total of 641 participants. These participants were over 50 years old and they were randomly chosen in a community-based study for estimating the prevalence of BPH. Using a self-reported questionnaire, we surveyed the sociodemographics, health status, quality of life, lower urinary tract symptoms, medical utilization and reasons for not seeking treatment. Results : Only 27.6% of the men with LUTS and 31.0% of the men with BPH reported having visited a doctor for urinary symptoms. The reasons for not visiting a doctor were, in order of responses from the group with LUTS: 'considered the symptoms as a part of the normal ageing process', 'not enough time to visit a doctor', 'financial difficulty' and 'the symptoms were not severe or bothersome'. Regarding BPH, the responses were the same as those of the group with LUTS however, 'financial difficulty' placed second. Among the men with experience of visiting a doctor for urinary symptoms, 33.3% of those with LUTS and 28.1% of those with BPH were not treated. The most common reason in both groups was 'the symptoms were not severe to be treated'. On a multiple logistic regression analysis, the larger size household (odds ratio (OR) 3.03, 95% confidence interval (CI)=1.40-6.54) and an unsatisfactory quality of life related with urinary symptoms (OR 2.98, 95% CI=1.23-7.21) were associated with medical utilization in the group of LUTS. For BPH, the current employment status was related with the medical utilization (OR 2.80, 95% CI=1.10-7.11), in addition to the larger size household (OR 3.24, 95% CI=1.14-9.21). Conclusions : Many men with urinary symptoms do not visit a doctor. This medical underutilization for people with LUTS and BPH may be associated with economic status in Korea.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.189-196
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• 2003

Purpose : Ureteral duplication is a common urologic anomaly and early diagnosis may prevent irreversible renal damage. We thus aimed to evaluate the benefits of prenatal sonography in early detection. Methods : We retrospectively studied 55 children with duplicated systems who were admitted to Severance Hospital, Yonsei University, Seoul, Korea from January 1998 to July 2003. Results : The mean age at diagnosis was 2.3 years old. 89% of the children had complete duplicated ureter. 47% of the children visited the hospital with an initial complaint of abnormal prenatal sonographic findings. Among these patients, 70.8% had DMSA defects. The mean differential renal function(DRF) in the DMSA scan was 48.2% in the group diagnosed prenatally. In the postnatally-diagnosed group, DMSA defects were found in 67.7% patients and the mean DRF was 45.5%. Conclusion : In comparison with the past studies, the mean age at diagnosis is becoming younger, and the proportion of abnormal prenatal sonography as an initial complaint larger. Other clinical manifestations were similar. The difference of the renal damage between the prenatally diagnosed group and the postnatally diagnosed group was not statistically significant. A multi-center study may help to prove the importance of prenatal sonography in early diagnosis and treatment of ureteral duplication. (J Korean Soc Pediatr Nephrol 2003;7:189-196)

• Annals of Clinical Microbiology
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• v.21 no.4
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• pp.75-79
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• 2018

Background: Urine culture is one of the most frequently requested tests in microbiology. Automated urine analyzers yield much infection-related information. The Sysmex UF-5000 analyzer (Sysmex, Japan) is a new flow cytometry urine analyzer capable of quantifying urinary particles, including bacteria, WBCs, and yeast-like cells (YLCs) and can provide a Gram stainability flag. In this work, we evaluated how many unnecessary urine cultures could be screened out using the UF-5000. Methods: We compared the culture results of 126 urine samples among 453 requested urine cultures (from sources other than the Urology and Nephrology departments) with urinalysis results. Urine cultures were considered positive if bacterial or YLC growth was ${\geq}10^4CFUs/mL$. Results: We used urinalysis cut-off values of $50/{\mu}L$ and $100/{\mu}L$ for bacteria and YLC, respectively. Forty eight of the 126 (38.1%, or 10.6% of 453 requested) cultures were below these cut-off values and did not contain any culture-positive samples. Conclusion: Bacteria and YLC counts generated using the UF-5000 analyzer could be used to screen out negative cultures and reduce urine culture volume by ~10% without sacrificing detection of positive cultures.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.2
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• pp.121-132
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• 2005

연구목적: 본 연구에서는 비폐쇄성 무정자증 환자에서 나타나는 정자형성과정의 이상과 고환세포의 세포자연사와의 연관관계 여부를 확인하였다. 또한 SELDI-TOF MS 분석을 통하여 고환 내 단백질 발현 양상을 확인하고, 질환에 따른 효과적인 biomarker 개발 가능성 여부를 확인하였다. 재료 및 방법: RT-PCR 및 면역조직화학법을 사용하여 고환에서의 Fas, FasL, Bcl-2, Bax와 Caspase-3의 발현 양상을 확인하고, in situ DNA 3'-end-labelling 방법으로 고환세포의 세포자연사 양상을 확인하였다. SELDI-TOF MS 분석법에 의한 고환의 병리학적 소견에 따른 단백질 발현 변화는 소수성 칩 ($H_4$)을 사용하여 분자량 10~100 kDa 범위 내에서 분석하였다. 결 과: 정상적인 정자형성과정을 보이는 폐쇄성 무정자증 환자의 고환에 비해 지주세포 증후군 (Sertoli cell only syndrome)과 성숙정지 (maturation arrest)를 보이는 고환 내 생식세포와 지주세포에서 세포자연사가 현저하게 증가한 것을 확인할 수 있었다. 세포자연사 관련인자들의 발현 양상을 확인한 결과, 지주세포 증후군과 성숙정지 환자군에서 Fas와 FasL mRNA의 발현이 증가하였으나, bcl-2, bax와 caspase-3 mRNA 발현의 경우에는 두 질환 모두에서 유의한 차이를 확인할 수 없었다. FasL 단백질 발현의 경우, 세포자연사의 증가가 관찰되었던 지주세포 증후군과 성숙정지를 보이는 환자의 간질세포와 지주세포에서 증가하는 양상을 나타내었다. SELDI-TOF MS 분석 결과에서 폐쇄성 무정자증 환자군에 비해 전체적인 단백질 발현양이 지주세포 증후군과 성숙정지 환자의 고환에서 감소하는 양상을 보였으며, 특히, 16.730 kDa 단백질의 현저한 감소를 확인할 수 있었다. 결 론: 본 연구결과를 통해 비폐쇄성 무정자증 환자에서 나타나는 정자형성과정의 장애는 생식세포의 비정상적인 세포자연사와 연관되어 있으며, 고환 내 Fas와 FasL의 비정상적인 발현이 주된 원인인 것을 확인할 수 있었다. 또한, SELDI-TOF MS 분석법을 통한 단백질 발현 양상의 연구는 무정자증 환자에서의 다양한 병리학적 소견을 쉽게 파악할 수 있는 biomarker 발굴뿐만 아니라 질환의 원인규명을 위한 연구에도 유용하게 이용될 수 있을 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.3
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• pp.279-286
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• 2005

Objective: Although several genetic factors have been associated with defects in human spermatogenesis, the unambiguous causative genes have not been elucidated. The male infertility by haploinsufficiency of PRM1 or PRM2 has been reported in mouse model. The aim of this study was to identify the single nucleotide polymorphisms (SNPs) of PRM1 and PRM2, related to the genotype of Korean infertile men. Methods: Genomic DNAs were extracted from peripheral bloods of infertile men with oligozoospermia or azoospermia, and analyzed using polymerase chain reaction (PCR) and direct sequencing. We carried out the direct sequencing analysis of amplified fragments in PRM1 (557 nucleotides from -42 to 515) and PRM2 (599 nucleotides from 49 to 648) genes, respectively. Results: Three SNPs of coding region in the PRM1 gene was found in the analysis of 130 infertile men. However, the SNPs at a133g (aa 96.9%, ag 3.1% and gg 0.0%), c160a (cc 99.2%, ca 0.8% and aa 0.0%) and c321a (cc 56.9%, ca 35.4% and aa 7.7%) coded the same amino acids, in terms of silence phenotypes. On the other hand, as results of the PRM2 gene sequencing in 164 infertile men, only two SNPs, g398c (gg 62.2%, gc 31.1% and ga 6.7%) and a473c (aa 63.4%, ac 29.9% and cc 6.7%), were identified in the intron of the PRM2 gene. Conclusions: There was no mutation and significant SNPs on PRM1 and PRM2 gene in Korean infertile men. These results suggest that the PRM1 and PRM2 genes are highly conserved and essential for normal fertility of men.

• Molecules and Cells
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• v.44 no.10
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• pp.770-779
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• 2021

Transgenic Arabidopsis thaliana expressing an anti-rabies monoclonal antibody (mAb), SO57, was obtained using Agrobacterium-mediated floral dip transformation. The endoplasmic reticulum (ER) retention signal Lys-Asp-Glu-Leu (KDEL) was tagged to the C-terminus of the anti-rabies mAb heavy chain to localize the mAb to the ER and enhance its accumulation. When the inaccurately folded proteins accumulated in the ER exceed its storage capacity, it results in stress that can affect plant development and growth. We generated T₁ transformants and obtained homozygous T₃ seeds from transgenic Arabidopsis to investigate the effect of KDEL on plant growth. The germination rate did not significantly differ between plants expressing mAb SO57 without KDEL (SO plant) and mAb SO57 with KDEL (SOK plant). The primary roots of SOK agar media grown plants were slightly shorter than those of SO plants. Transcriptomic analysis showed that expression of all 11 ER stress-related genes were not significantly changed in SOK plants relative to SO plants. SOK plants showed approximately three-fold higher mAb expression levels than those of SO plants. Consequently, the purified mAb amount per unit of SOK plant biomass was approximately three times higher than that of SO plants. A neutralization assay revealed that both plants exhibited efficient rapid fluorescent focus inhibition test values against the rabies virus relative to commercially available human rabies immunoglobulins. KDEL did not upregulate ER stress-related genes; therefore, the enhanced production of the mAb did not affect plant growth. Thus, KDEL fusion is recommended for enhancing mAb production in plant systems.

• 한국노년학
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• v.38 no.4
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• pp.853-869
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• 2018

This study aimed to investigate variables affecting subjective memory impairment in the elderly with benign prostatic hyperplasia. We used 179 survey data collected from the urology department of two metropolitan general hospitals. The subjects were patients with benign prostatic hyperplasia. T-test, one-way analysis of variance, and $Scheff{\acute{e}}^{\prime}s$ test were performed to identify differences among variables. Pearson's correlation-coefficient and stepwise multiple regression were used to identify variables that affect subjective memory impairment. This study revealed that lower urinary tract symptom and activities of daily living were statistically significant variables, with an explanatory power of 30.0%. The lower urinary tract symptom was due to the benign prostatic hyperplasia increasing the risk of subjective memory impairment. Treatment of the lower urinary tract symptom was delayed because as the elderly got older, they increasingly recognized benign prostatic hyperplasia as a reasonable symptom. Timely intervention and early screening are necessary to prevent lower urinary tract symptom. Finally, programs to reduce the incidence of lower urinary tract symptom and educate nurses to assess, evaluate, perform intervention for subjective memory impairment should be developed.