• Title/Summary/Keyword: Stem Cell

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an Influence of Stem Cell Study on Life Insurance Industry (줄기세포연구와 생명보험산업에 대한 고찰)

  • Kim, Han-Su;Cho, Sung-Moon;Park, Sung-Soo
    • The Journal of the Korean life insurance medical association
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    • v.25
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    • pp.49-62
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    • 2006
  • 생명공학의 시대로 일컬어 지고 있는 오늘날, 재생의학 분야에서는 난치성 질환 치료를 목적으로 활발한 연구가 진행되고 있다. 특히, 줄기세포를 이용한 세포 대체치료 관련 연구는 최근 국내 황우석 박사의 체세포 핵이식 배아세포주 확립에 이르기 까지 괄목할 만한 발전을 보여 주고 있다. 이와 관련해 생명보험산업에 적잖은 파장이 예상되며, 생명보험사 내부적으로 기존에 판매된 상품의 사차손 관리와 함께 급속도로 발전하는 줄기세포 연구에 직접적으로 대응하는 상품개발, 언더라이팅, 지급 심사 등 보험사 내외에서의 전방위적인 변화가 필요하다는 문제 제기가 있다. 줄기세포란 조직 분화 과정에서 볼 수 있는 세포이며 근육 뼈 뇌 피부 등 신체의 어떤 기관으로도 전환할 수 있는 만능세포로서, 간 폐 심장 등 구체적 장기를 형성하기 이전에 분화를 멈출 배아 단계의 세포를 말한다. 한편, 성체줄기세포는 조직이나 기관의 분화된 세포들 사이에서 발견되는 미분화 세포로써, 자기 스스로 증식할 수 있으며, 조직이나 기관의 특수한 기능을 가지고 있는 세포로 분화할 수 있는 능력을 가진 신체줄기세포를 말한다. 배아줄기세포와 생체줄기세포를 통한 장기이식 등 난치병 정복은 윤리적, 사회적으로 많은 논란이 예상되며, 기술적으로도 해결해야 할 문제점들이 산적해 있기 때문에 아직은 요원한 것이 사실이다. 현재 유럽 대부분의 나라와 미국에서는 인간 배아의 복제가 금지되어 있으며, 일본 정부는 연구용 배아 복제를 제한적으로 허용하고 있다. 하지만, 우리 나라의 경우 2005년 1월에 '생명윤리 및 안전에 관한 법'이 발효되었지만 정부는 관련 부작용에 대한 깊은 고찰 없이 전폭적인 지원들 약속하고 있는 실정이다. 줄기세포 연구의 발달로 인해 인류가 난치병 치료의 첫 장을 열었다고 하더라도 그 영향이 당장 보험사에 미친다고 할 수는 없다. 왜냐하면 앞으로 이러한 신기술이 실제 의료행위에 적용되기 위해서는 여러 단계의 안정화 작업과 임상시험이 필요한데 이러한 작업이 기술적으로 어렵고 그 시간도 만만치 않게 걸리기 때문이다. 또한, 보험사의 보장은 크게 사망/수술/입원/암/기타보장으로 구별할 수 있는데, 줄기세포 연구의 발달과 관련이 있는 보장이 제한되어 있어 보험사에 미치는 영향이 당장 우려할 만한 수준이라 할 수 없다. 하지만 만약 치료용 줄기세포 배양으로 인한 장기 기관의 이식이나 손상세포의 대체 등과 같은 의학신기술의 예상 외로 급격하게 발전한다면 보험사의 Risk 관리에 상당한 저해요인으로 작용할 것으로 판단된다. 특히 진단 입원 수술로 대표되는 생존보장에 대한 사차 Risk 및 사차손의 급증이나 역선택 증가는 보험사의 경영수지 악화를 유발하여 보험산업 전반에 위험으로 작용할 수도 있다. 따라서, 장기적인 안목으로 업계 공동의 대응이 필요하고, 각 사에서도 상품개발, 언더라이팅, 지급심사 간의 긴밀한 협조가 요구된다. 생명보험산업의 Risk 관리는 기존의 시장환경에 영향을 받는 비차, 이차중심에서 보험회사가 어느 정도 관리를 통해 적정규모를 유지할 수 있는 사차로 그 중심축이 이동하고 있다. 보험산업이 계속 활력을 갖고 성장하기 위해서는 체계적인 Risk나 관리가 핵심일 것이며, 보험사의 사차 Risk의 중요성이 더욱 커져 가고 있는 현실에서 거시적으로 의학신기술 발달 등 위험요인에 대해 미리 분석하고 이에 대한 대비책 마련이 필요할 것으로 판단된다.

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A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

  • Choe, Sang-Min;Kim, Gayeong;Lim, Hyeong-Seok;Cho, Sang-Heon;Ghim, Jong-Lyul;Jung, Jin-Ah;Kim, Un-Jib;Noh, Gyu-Jeong;Bae, Kyun-Seop;Lee, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.273-279
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    • 2012
  • Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

Leukocyte-Endothelial Cell Adhesion Induced by Ischemia and Reperfusion Observed with in vivo Videomicroscopy (허혈-재관류에 의해 유도된 백혈구-혈관내피세포 유착에 대한 Videomicroscopy 영상소견)

  • Lee, Young Bae;Kang, Han Sug;Park, Shin Byung
    • Journal of Korean Neurosurgical Society
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    • v.29 no.10
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    • pp.1289-1295
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    • 2000
  • Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n=10), and (2)those having the arterial occlusion released after 90 minute(n=20). By 4 hours(n=10) and 24 hours(n=10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n=10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

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Effects of NaCl on the Growth and Physiological Characteristics of Crepidiastrum sonchifolium (Maxim.) Pak & Kawano (NaCl 처리가 고들빼기의 생장과 생리적 특성에 미치는 영향)

  • Lee, Kyeong Cheol;Han, Sang Kyun;Yoon, Kyeong Kyu;Lee, Hak bong;Song, Jae Mo
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.1
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    • pp.1-8
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    • 2020
  • Background: This study was conducted to investigate the effects of NaCl concentration on the photosynthetic parameters, chlorophyll fluorescence and growth characteristics of Crepidiastrum sonchifolium. Methods and Results: As treatments, we subjected C. sonchifolium plants to four different concentrations of NaCl (0, 50, 100 and 200 mM). We found that the photosynthetic parameters maximum photosynthesis rate (PN max), net apparent quantum yield (Φ), maximum carboxylation rate (Vcmax), and maximum electron transport rate (Jmax) were significantly reduced at an NaCl concentration greater than 100 mM. In contrast, there was an increase in water-use efficiency with increasing NaCl concentration, although in terms of growth performances, leaf dry weight, root dry weight, stem length, and total dry weight all decreased with increasing NaCl concentration. Furthermore, leakage of electrolytes, as a consequence of cell membrane damage, clearly increased in response to an increase in NaCl concentration. Analysis of the polyphasic elevation of chlorophyll a fluorescence transients (OKJIP) revealed marked decrease in flux ratios (ΦPO, ΨO and ΦEO) and the PIabs, performance index in response to treatment with 200 mM NaCl, thereby reflectings the relatively reduced state of photosystem II. This increase in fluorescence could be due to a reduction in electron transport beyond Q-A. We thus found that the photosynthetic parameters, chlorophyll fluorescence and growth characteristics of C. sonchifolium significantly increased in response to treatment with 200 mM NaCl. Conclusions: Collectively, the findings of this study indicate that C. sonchifolium shows relatively low sensitivity to NaCl stress, although photosynthetic activity was markedly reduced in plants exposed to 200 mM NaCl.

MMP2 Gene-735 C/T and MMP9 gene -1562 C/T Polymorphisms in JAK2V617F Positive Myeloproliferative Disorders

  • Sag, Sebnem Ozemri;Gorukmez, Ozlem;Ture, Mehmet;Gorukmez, Orhan;Topak, Ali;Sahinturk, Serdar;Ocakoglu, Gokhan;Gulten, Tuna;Ali, Ridvan;Yakut, Tahsin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.443-449
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    • 2015
  • Background: Myeloproliferative disorders (MPDs) are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of malignancy progression. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. To our knowledge, this is the first investigation of associations between the -735 C/T and -1562 C/T polymorphisms in the MMP2 and MMP9 genes, respectively, and the risk of essential thrombocytosis (ET), and polycythemia vera (PV). Materials and Methods: The case-control study included JAK2V617F mutation positive 102 ET and PV patients and 111 controls. Polymorphisms were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and electrophoresis. Results: No statistically significant differences were detected between patient (ET+PV) and control groups regarding genotype distribution for MMP2 gene-735 C/T and MMP9 gene -1562 C/T polymorphisms and C/T allele frequency (p>0.050). Statistically borderline significance was observed between PV and control groups regarding genotype distribution for the MMP9 gene -1562 C/T polymorphism (p=0.050, OR=2.26, 95%Cl=0.99-5.16). Conclusions: Consequently this study supported that CC genotype of MMP9 gene -1562 C/T polymorphism may be related with PV even if with borderline significance.

The Effects of Antimicrobial, Antioxidant, and Anticancer Properties of Opuntia humifusa Stems (천년초 줄기의 항균, 항산화 및 항암효과에 관한 연구)

  • Jung, Bok-Mi;Shin, Mi-Ok;Kim, Hyung-Rak
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.1
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    • pp.20-25
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    • 2012
  • This study was performed to investigate antimicrobial, antioxidant, and anticancer properties of Opuntia humifusa (OH) stems. OH stems were extracted with hexane, methanol, butanol and water. The methanol and hexane fraction exhibited strong antimicrobial activities on three strains of microbes, Rhodococcus equi, Staphylococcus aureus, and Clostridium perfringens. In the peroxynitrite scavenging effect ($ONOO^-$) of OH stems, the antioxidative activity of methanol, butanol and water fraction but not hexane fraction showed significant increases in a concentration-dependent manner. The DPPH radical scavenging activities of OH stems were high in the butanol fraction compared with other fractions. Anti-proliferation effects on the B16-F10, HepG2, HT29, and MCF-7 cell lines were significantly higher in the methanol and hexane fractions than in the water and butanol fractions at $100{\mu}g/mL$ concentration of extracts. These results suggest that OH stems can be used for the development of functional foods with biological activity.

Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes

  • Chung, Hee Kyoung;Ko, Eun Mi;Kim, Sung Woo;Byun, Sung-June;Chung, Hak-Jae;Kwon, Moosik;Lee, Hwi-Cheul;Yang, Byoung-Chul;Han, Deug-Woo;Park, Jin-Ki;Hong, Sung-Gu;Chang, Won-Kyong;Kim, Kyung-Woon
    • BMB Reports
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    • v.45 no.12
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    • pp.742-747
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    • 2012
  • Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent ($H_2O_2$). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

A Novel PHKA1 Mutation in a Patient with Glycogen Storage Disease Type IXD (당원 축적병 9D (GSD9D) 환자의 신규 PHKA1 돌연변이)

  • Kim, Hye Jin;Nam, Soo Hyun;Kim, Sang Beom;Chung, Ki Wha;Choi, Byung-Ok
    • Journal of Life Science
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    • v.30 no.8
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    • pp.672-679
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    • 2020
  • Distal myopathy is a clinically and genetically heterogeneous group of degenerative diseases of the distal muscle. Glycogen storage disease type IXD (GSD9D) is a metabolic distal myopathy characterized by muscle deficiency of phosphorylase kinase, a key regulatory enzyme in glycogen metabolism. Affected individuals may develop muscle weakness, degeneration, and cramps, as well as abnormal muscle pain and stiffness after exercise. It has been reported that mutations in the PHKA1 gene which encodes the alpha subunit of muscle phosphorylase kinase cause GSD9D. In this study, we examined a Korean GSD9D family with a c.3314T>C (p.I1105T) mutation in the PHKA1 gene. This mutation has not been previously reported in any mutation database nor was it found in 500 healthy controls. The mutation region is well conserved in various other species, and in silico analysis predicts that it is likely to be pathogenic. To date, only seven mutations in the PHKA1 gene have been documented, and this is the first report of Korean GSD9D patients. This study also describes and compares the clinical symptoms and pathological conditions of previously reported cases and these Korean patients. We believe that our findings will be useful for the molecular diagnosis of GSD9D.

Effects of Diniconazole Application on Anatomical and Biochemical Characteristics Related to Stress Tolerance in Lilum davuricum (날개하늘나리에 있어서 디니코나졸 처리가 스트레스 내성과 관련된 해부학적 및 생화학적 특성에 미치는 영향)

  • Eum, Sun-Jung;Park, Kyeung-Il;Choi, Young-June;Oh, Wook;Kim, Kiu-Weon
    • Horticultural Science & Technology
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    • v.30 no.3
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    • pp.229-235
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    • 2012
  • This study was carried out to examine the effects of foliar-sprayed diniconazole on the morphological characteristics and the contents of polyamines (PA) and proline, and to investigate their relationship with stress tolerance in Lilium davuricum native to Korea. Plants with 5 cm mean height were sprayed with $50mg{\cdot}L^{-1}$ diniconazole or distilled water (control) and grown in a greenhouse maintained at 23/$18^{\circ}C$ (day/night) for 30 days. Diniconazole decreased plant height, leaf length, diameter and length of the pith and cortical cell of the stem, while it increased the thickness and epicuticular wax of leaves measured at 30 days after treatment. In polyamines contents, diniconazole increased spermidine content at 5-10 days after treatment and spermine content after the 10th day of treatment as compared with the control. Diniconazole decreased proline content after the 10th day of treatment as compared with the control. From these results, it was concluded that foliar-sprayed diniconazole might morphologically and biochemically improve the stress tolerance of this plant species.

A Parentage Test using Indel, Microsatellite Markers and Genotypes of MC1R in the Jeju Black Cattle Population (제주 흑우 집단에서 Indel, Microsatellite 마커와 MC1R 유전자형을 이용한 친자 확인)

  • Han, Sang Hyun;Cho, Sang-Rae;Cho, In-Cheol;Cho, Won-Mo;Kim, Sang-Geum;Yang, Sung-Nyun;Kang, Yong-Jun;Park, Yong-Sang;Kim, Young-Hoon;Park, Se-Phil;Kim, Eun-Young;Lee, Sung-Soo;Ko, Moon-Suck
    • Journal of Embryo Transfer
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    • v.28 no.3
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    • pp.207-213
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    • 2013
  • This study was carried out to examine a molecular marker system for parentage test in Jeju Black cattle (JBC). Based on the preliminarily studies, we finally selected for construction of a novel genetic marker system for molecular traceability, identity test, breed certification, and parentage test in JBC and its related industrial populations. The genetic marker system had eight MS markers, five indel markers, and two single nucleotide polymorphisms (SNPs; g.G299T and g.del310G) within MC1R gene which is critical to verify the breed specific genotypes for coat color of JBC differing from those of exotic black cattle breeds such as Holstein and Angus. The results showed lower level of a combined non-exclusion probability for second parent (NE-P2) of $4.1202{\times}10^{-4}$ than those previously recommended by International Society of Animal Genetics (ISAG) of $5.000{\times}10^{-4}$ for parentage, and a combined non-exclusion probability for sib identity (NE-SI) of $2.679{\times}10^{-5}$. Parentage analysis has been successfully identified the JBC offspring in the indigenous population and cattle farms used the certified AI semens for production using the JBC-derived offspring for commercial beef. This combined molecular marker system will be helpful to supply genetic information for parentage test and traceability and to develop the molecular breeding system for improvement of animal productivity in JBC population.