• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.235-245
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• 2008

Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

• Microbiology and Biotechnology Letters
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• v.44 no.3
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• pp.355-362
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• 2016

The phosphomannomutase/phosphoglucomutase gene (pmm/pgm) of Vibrio anguillarum (the causative agent of fish vibriosis) was cloned, and the open reading frame corresponded to a protein with 446 amino acids. The pmm/pgm gene showed a significant degree of sequence homology with the previously reported genes from V. mimicus, V. vulnificus, V. splendidus, and V. harveyi, with 92.3%, 91.4%, 89.9%, and 89.9% amino acid identity, respectively. By reverse transcriptase-polymerase chain reaction, we found that the pmm/pgm gene was upregulated under cold stress condition. The PMM/PGM protein is known to catalyze the interconversion between mannose-1-phosphate and mannose-6-phosphate or glucose-1-phosphate and glucose-6-phosphate, which are important intermediates for lipopolysaccharide (LPS) biosynthesis. To confirm the role of PMM/PGM in the LPS biosynthetic pathway, we constructed a knock out mutant by homologous recombination. The respective LPSs were isolated from the V. anguillarum wild-type and mutant strains, and changes were compared by subjecting them to sodium dodecyl sulfate polyacrylamide gel electrophoresis. Based on the different patterns of the LPSs, we expect the pmm/pgm gene to have an important role in LPS biosynthesis. The pmm/pgm-deficient mutant of V. anguillarum will contribute to further studies about the role of LPS in V. anguillarum pathogenesis.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.57-64
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• 1999

Purpose : Paclitaxel is a chemotherapeutic agent with a potent microtubule stabilizing activity that arrests mitosis at G2-M phase of cell cycle which is the most radiosensitive period. Therefore paclitaxel is considered as a cell cycle-specific radiosensitizer. This study investigates the effect of paclitaxel on the radiation response of the normal large bowel mucosa of the rat. Materials and Methods: The rats were divided into the three groups i.e., single intraperitoneal infusion of paclitaxel (10 mg/kg), a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen, and a combination of irradiation (8 Gy, x-ray) given 24 hours after paclitaxel infusion. The histological changes as well as kinetics of mitotic arrest and apoptosis were evaluated on the large bowel mucosa at 6 hours, 1 day, 3 days and 5 days after treatment with paclitaxel alone, radiation alone and combination of paclitaxel and radiation. Results : The incidence of the mitotic arrest was not increased by paclitaxel infusion. The apoptosis appeared in 24 hours after paclitaxel infusion, and the histopathologic changes such as vesiculation, atypia and reduction of the goblet cell of the mucosa of the large bowel were demonstrated during the period from 6 hours to 3 days after, and returned to normal in 5 days after paclitaxel infusion. In irradiated group, the apoptosis was increased in 6 and 24 hours after irradiation, and the histopathologic changes of the mucosa were appeared in 24 hours and markedly increased in 3 days and returned to normal in 5 days. In combined group of irradiation and paclitaxel infusion, the apoptosis was appeared in 3 days and the histopathologic changes appeared during the period from 6 hours to 3 days after infusion. On the basis of the incidence of apoptosis and the degree of the histopathologic changes of the large bowel mucosa, there seemed to be additive effect by paclitaxel on radiation rather than sensitizing effect. Conclusions: The histopathological changes of large bowel mucosa in combined group compared to radiation alone group suggested an additive effect of paclitaxel on radiation response in the large bowel of rat.

• Journal of Soil and Groundwater Environment
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• v.10 no.2
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• pp.35-43
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• 2005

Bioslurping combines the three remedial approaches of bioventing, vacuum-enhanced free-product recovery, and soil vapor extraction. Bioslurping is less effective in tight (low-permeability) soils. The greatest limitation to air permeability is excessive soil moisture. Optimum soil moisture is very soil-specific. Too much moisture can reduce air permeability of the soil and decrease its oxygen transfer capability. Too little moisture will inhibit microbial activity. So Modified Fenton reaction as chemical treatment which can overcome the weakness of Bioslurping was experimented for simultaneous treatment. Although the diesel removal efficiency of SVE process increased in proportion to applied vacuum pressure, SVE process was difficulty to remediation quickly semi- or non-volatile compounds absorbed soil strongly. And SVE process had variation of efficiency with distance from the extraction well and depth a air flow form of hemisphere centering around the well. Below 0.1 % hydrogen peroxide shows the potential of using hydrogen peroxide as oxygen source but the co-oxidation of chemical and biological treatment was impossible because of the low efficiency of Modified Fenton reaction at 0.1 % (wt) hydrogen peroxide. NTA was more efficiency than EDTA as chelating agent and diesel removal efficiency of Modified Fenton reaction increased in proportion to hydrogen peroxide concentration. Hexadecane as typical aliphatic compound was removed less than Toluene as aromatic compound because of its structural stability in Modified Fenton reaction. What minimum 10% hydrogen peroxide concentration has good remediation efficiency of diesel contaminated groundwater may show the potential use of Modified Fenton reaction after bioslurping treatment.

• The Korean Journal of Gastroenterology
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• v.72 no.5
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• pp.271-273
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• 2018

내시경 시술 전 일시적으로 항응고제를 중단하는 것은 위장관 출혈의 위험과 혈전색전증의 위험 사이에 적절한 균형을 잡기 어렵기 때문에 논란의 여지가 많다. 와파린은 새로운 경구용 항응고제(direct oral anticoagulant agent, DOAC)보다 임상의에게 더 친숙하고, 효과를 쉽고 빠르게 전환시킬 수 있다는 장점이 있지만 복잡한 약역동학 특징과 좁은 치료적 범위 때문에 관리가 어렵다. 반면, DOAC는 약물의 모니터링 및 용량 조절 없이 정해진 용량으로 처방이 가능하며, 빠르게 작용하고, 반감기가 짧아 관리가 쉽지만 해독제가 없다는 단점이 있다. 이전 연구들에서 DOAC를 복용한 환자들은 와파린을 복용한 환자들보다 시술과 관련되지 않은 위장관 출혈의 위험이 높았다고 보고한 바 있다. 하지만 시술과 관련된 위장관 출혈 위험에 대하여는 알려진 바가 없는 실정이다. 미국이나 유럽 내시경 가이드라인들에서는 저위험 내시경 시술을 받는 환자들에서는 와파린과 DOAC를 유지하도록 권고하고 있으며, 고위험 시술의 경우에는 와파린를 사용하는 환자들에서 헤파린 교량 요법(heparin bridging)을 시행하도록 권고하고 있다. 임상적으로 DOAC를 사용하는 환자들 또한 혈전색전증을 예방하기 위하여 헤파린 교량 요법을 시행해볼 수 있는데, 와파린 및 DOAC의 헤파린 교량 요법과 관련된 출혈 및 혈전색전증 위험의 차이 또한 명확하지 않다. 따라서 저자들은 1) 와파린과 DOAC 치료를 받는 환자들에서의 출혈, 혈전색전증 및 사망의 위험을 비교하고자 하였으며, 2) 13종류의 고위험 내시경 시술 중에서 시술별 위험을 비교하고, 3) 헤파린 교량 요법이 합병증의 발생을 증가시키지 않는지 확인하고자 본 연구를 진행하였다. 일본 대규모 국가 입원 환자 데이터베이스를 이용하여 2014년 4월부터 2015년 5월까지 시술 전 와파린 또는 DOAC(rivaroxaban, apixaban, dabigatran, edoxaban)를 복용하고, 13종류의 고위험 내시경 시술을 시행받은 20세 이상의 성인 환자 총 16,977명을 확인하였다. 고위험 시술은 용종 절제술, 내시경 점막절제술, 내시경 점막하박리술, 협착 부위의 풍선확장술, 내시경 지혈술, 내시경 정맥결찰술, 내시경 주사 경화요법, 내시경 괄약근절개술, 내시경 초음파 유도하 미세침 흡인 검사, 경피적 위루술을 포함하였다. 일대일 성향 점수 매칭 분석(propensity score matching, 나이, 성별, 체질량 지수, 기저 질환, 병원의 규모, 시술의 종류, 약물의 종류를 매칭)을 시행하여 와파린군과 DOAC군에서 시술 위장관 출혈 및 혈전색전증, 사망의 발생을 비교하였다. 또한 경구항혈전제와 헤파린 교량 치료 시행 유무에 따라, DOAC 단독군, 와파린 단독군, DOAC와 헤파린 교량 요법군, 와파린과 헤파린 교량요법군으로 나누어, 하위군(subgroup) 분석을 시행하였다. 5,046쌍이 성향 점수 매칭 분석에 포함되었으며, 와파린군에서 DOAC군보다 통계적으로 의미 있게 위장관 출혈의 비율이 높았다(12.0% vs. 9.9% p=0.02). 혈전색전증 발생률(5.4% vs. 4.7%)과 입원중 사망률(5.4% vs. 4.7%)은 양 군에서 의미 있는 차이는 없었다. DOAC 종류별로 나누어 하위군 분석을 시행하였을 때, 와파린군은 rivaroxaban군에 비하여 위장관 출혈의 비율이 높았으며, rivaroxaban군, dabigatran군에 비하여 혈전색전증의 비율이 높았고, 입원 중 사망률에서는 의미 있는 차이는 없었다. 내시경 시술의 종류로 보정하였을 때 위장관 출혈 및 혈전색전증, 사망률은 DOAC 단독으로 치료한 환자에서보다 와파린과 헤파린 교량 요법(bridging) 또는 DOAC과 헤파린 교량 요법을 시행한 환자에서 높았다. 시술 종류 중에서는 위루관 삽입술에 비하여 내시경 점막하박리술, 내시경 점막절제술 및 내시경 정맥류결찰술, 내시경 주사경화요법을 시행한 환자에서 위장관 출혈의 위험이 가장 높았으며, 하부 내시경 점막절제술, 하부 용종 절제술, 내시경적 유두괄약근절제술 또는 내시경 초음파 유도하 미세침 흡인 검사는 중등도 위험을 보였다.