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$Site-Specific^{99m}$Tc-Labeling of Antibody Using Dihydrazinoph-thalazine (DHZ) Conjugation to Fc Region of Heavy Chain

  • Jeong, Jae-Min;Lee, Jae-Tae;Paik, Chang-Hum;Kim, Dae-Kee;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Archives of Pharmacal Research
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    • v.27 no.9
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    • pp.961-967
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    • 2004
  • The development of an antibody labeling method with $^{99m}$Tc is important for cancer imaging. Most bifunctional chelate methods for $^{99m}$Tc labeling of antibody incorporate a $^{99m}$Tc chelator through a linkage to lysine residue. In the present study, a novel site-specific $^{99m}$Tc labeling method at carbohydrate side chain in the Fc region of 2 antibodies (T101 and rabbit anti-human serum albumin antibody (RPAb)) using dihydrazinophthalazine (DHZ) which has 2 hydrazino groups was developed. The antibodies were oxidized with sodium periodate to pro-duce aldehyde on the Fc region. Then, one hydrazine group of DHZ was conjugated with an aldehyde group of antibody through the formation of a hydrazone. The other hydrazine group was used for labeling with $^{99m}$Tc. The number of conjugated DHZ was 1.7 per antibody. $^{99m}$Tc labeling efficiency was 46-85% for T101 and 67∼87% for RPAb. Indirect labeling with DHZ conjugated antibodies showed higher stability than direct labeling with reduced antibodies. High immunoreactivities were conserved for both indirectly and directly labeled antibodies. A biodistribution study found high blood activity related to directly labeled T1 01 at early time point as well as low liver activity due to indirectly labeled T101 at later time point. However, these findings do not affect practical use. No significantly different biodistribution was observed in the other organs. The research concluded that DHZ can be used as a site-specific bifunctional chelating agent for labeling antibody with $^{99m}$Tc. Moreover, $^{99m}$Tc labeled antibody via DHZ was found to have excellent chemical and biological properties for nuclear medicine imaging.edicine imaging.

Comparison of Physical & Histological Change of Alloplastic Implants after Implantation in Rat (흰쥐에 삽입된 인공성형삽입물의 생체내 물리, 조직학적 변화의 비교)

  • Kim, Sung Nam;Noh, Bok Kyun;Kim, Eui Sik;Hwang, Jae Ha;Kim, Kwang Seog;Lee, Sam Yong;Cho, Bek Hyun
    • Archives of Plastic Surgery
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    • v.33 no.2
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    • pp.219-224
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    • 2006
  • Augmentation rhinoplasty is one of the most popular aesthetic procedure in Asians. Numerous alloplastic implants have been used until now, but no accurate comparative analysis about the implant materials has been reported yet. This study in animal model was designed to determine the safety and effectiveness of various implant materials in augmentation rhinoplasty. The $15{\times}15{\times}2mm$ sized square shaped plate of $Gore-Tex^{(R)}$, silicone rubber, and $15{\times}15{\times}1.5mm$ sized $Medpor^{(R)}$ were implanted under panniculus carnosus of the abdomen wall of rat. And tissue specimens including the implant and surrounding soft tissue were obtained by en bloc excision in 6 months after implantation. The implants were estimated in weight and volume, and also the specimens were examined grossly and microscopically. The results revealed that increase of average weight 26.9%, decrease of average volume 55.4% in $Gore-Tex^{(R)}$ implant, increase of each average weight and volume 62.6%, 8.7% in $Medpor^{(R)}$ implant and very slight increase of both average weight and volume 4.7%, 1.1% in silicone rubber implant. Grossly, the $Gore-Tex^{(R)}$ was deformed, $Medpor^{(R)}$ was strongly adherent to surrounding soft tissue and the silicone rubber was well encapsulated and easily peeled off. Microscopically, silicone rubber showed foreign body reaction slightly and there were no inflammatory responses in all alloplastic implants. In our study, silicone rubber showed very proper alloplastic features for augmentation rhinoplasty due to causing no inflammatory response, no physical change, and no deformity.

Correction of Recurrent Ingrowing Toenail Using Partial Matricectomy and Paronychial Advancement Flap (부분기질절제술과 발톱주위전진피판을 이용한 재발성 내증식발톱의 교정)

  • Kim, Eui Sik;Kim, Sung Nam;Noh, Bok Kyun;Hwang, Jae Ha;Kim, Kwang Seog;Lee, Sam Yong
    • Archives of Plastic Surgery
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    • v.33 no.3
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    • pp.347-352
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    • 2006
  • Ingrowing toenail has been treated conventionally by various surgical treatment modlities. However, none of these procedures are perfect to achieve esthetic results with low cost, recurrence, and complication rates. Although mild cases can be treated conservatively, in severe recurrent cases, surgical treatment is preferred. The purpose of this study is to evaluate the effectiveness and safety of using partial matricectomy and paronychial advancement flap for correction of recurrent ingrowing toenail. Eight patients suffering from recurrent ingrowing toenail were operated using partial matricectomy and paronychial advancement flap in our department from August 2004 to August 2005. The number of recurrent episodes ranged from 2 to 5. With digital nerve block, the excision area was marked on nailplate and inflammed lateral nail fold. The horizontally designed paronychial flap considering defect size was effective for wide exposure of the neighboring germinal matrix, which is later to be completely excised or cauterized because remnant germinal matrix made postoperative spicule formation. The nailplate on the affected side was removed about 3-5 mm width longitudinally, being cautious not to damage the proximal dorsal nail fold. The same width of the sterile matrix including germinal matrix was excised longitudinally with inflammed granulation tissue and partial lateral nail fold on the affected side. The subcutaneously elevated paronychial flap was advanced to cover the defect and was anatomically sutured with 5-0 nylon sutures. We evaluated our procedure's effectiveness by examining some factors such as cosmetic results, recurrence, spicule formation, postoperative pain and duration of return to normal activities. In eight patients, no complication was observed such as recurrence, severe pain and spicule formation except for 1 case of infection. Postoperative discomfort was minimal. Average duration of return to normal activities was 12 days. Cosmetically the results were acceptable in all patients. The partial matricectomy and paronychial advancement flap for correction of recurrent ingrowing toenail were found to be technically simple, efficient procedure with a relative low recurrence rate and better cosmetic results.

KCl Mediates $K^+$ Channel-Activated Mitogen-Activated Protein Kinases Signaling in Wound Healing

  • Shim, Jung Hee;Lim, Jong Woo;Kim, Byeong Kyu;Park, Soo Jin;Kim, Suk Wha;Choi, Tae Hyun
    • Archives of Plastic Surgery
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    • v.42 no.1
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    • pp.11-19
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    • 2015
  • Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

In Vitro Pharmacodynamics of CKD-602 in HT-29 Cells

  • Park, In-Sook;Ahn, Mee-Ryung;Suh, Soo-Kyung;Choi, Hong-Serck;Sohn, Soo-Jung;Yang, Ji-Sun;Yoo, Tae-Moo;Kuh, Hyo-Jeong
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.718-723
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    • 2002
  • CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (>24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

Cultures of Ginkgo biloba, Effect of Nutritional and Hormonal Factors on the Growth of Cultured Cells Derived from Ginkgo biloba

  • Jeon, Mee-Hee;Sung, Sang-Hyun;Jeon, Soon-wha;Huh, Hoon;Kim, Jin-woong;Kim, Young-Choong
    • Archives of Pharmacal Research
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    • v.16 no.3
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    • pp.244-250
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    • 1993
  • Calli and suspension cultures were obtained following inoculation of the explant from leaves of Ginkgo biloba L on the supplemented MS basal medium. The obtained calli and suspension cultured cells were able to produce detectable amounts of ginkgolides which are known as natural specific PAF antagonists. The production of ginkgolides in the calli and suspension cultured celles were identified using GC/MS, GC and HPLC with authentic ocmpounds. Since the production of ginkgolides A and B the calli and suspension cultured cells had been confirmed, effects of types and concentration of plant growth regulators, media and illumination on the induction and growth of the callus were studied. The concentrations of growth regulators for optimal callus were studied. The concentrations of growth regulators for optimal callus induction were studied. The concentrations of growth regulators for optimal callus induction were 1.0 to 2.0 mg/L for NAA and o.1 mg/L for kinetin. The growth of the Callus seemed to be more simnultaed with the combination of NAA and kinetin than NAA and BA with illumination at all concentration ranges of 1.0 to 4.0 mg/l for NAA and o.1 to 1.0 mg/L for kinetin or BA studied. Amogn 8 different media used, the induction rate of callus on Anderson, Eriksson, and Shenk and Hildebrant at 4 weeks after the innoculation was almost the same as that of MS. However, callus was rarely induced on Heller or White medium. Suspension cultures were easily initiated with 3 g of callus (fresh weight) derived from ginkgo leaves on supplemented MS medium. A typical growth curve of suspension cultured cells could be obtained by measuring the fresh weight of the suspension cultured cells at every 3 days. To improve the growth of suspension cultured cells of ginkgo, effects of concentrations of NAA, sucrose, phosphate ions and molar ratio of $NH_{4}^+\;to\;NO_{3}^-$ ions in the culture medium were studied. The maximum growth of the cells was achieved when the culture medium contained 1.0 mg/L of NAA, 30 g/L sucrose, 1.75 mM phosphate ions and 1:5 molar ratio of $NH_{4}\;to\;NO_{3}^-$ ions.

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Effects of three-dimensionally printed polycaprolactone/β-tricalcium phosphate scaffold on osteogenic differentiation of adipose tissue- and bone marrow-derived stem cells

  • Park, Hannara;Kim, Jin Soo;Oh, Eun Jung;Kim, Tae Jung;Kim, Hyun Mi;Shim, Jin Hyung;Yoon, Won Soo;Huh, Jung Bo;Moon, Sung Hwan;Kang, Seong Soo;Chung, Ho Yun
    • Archives of Craniofacial Surgery
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    • v.19 no.3
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    • pp.181-189
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    • 2018
  • Background: Autogenous bone grafts have several limitations including donor-site problems and insufficient bone volume. To address these limitations, research on bone regeneration is being conducted actively. In this study, we investigate the effects of a three-dimensionally (3D) printed polycaprolactone (PCL)/tricalcium phosphate (TCP) scaffold on the osteogenic differentiation potential of adipose tissue-derived stem cells (ADSCs) and bone marrow-derived stem cells (BMSCs). Methods: We investigated the extent of osteogenic differentiation on the first and tenth day and fourth week after cell culture. Cytotoxicity of the 3D printed $PCL/{\beta}-TCP$ scaffold was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, prior to osteogenic differentiation analysis. ADSCs and BMSCs were divided into three groups: C, only cultured cells; M, cells cultured in the 3D printed $PCL/{\beta}-TCP$ scaffold; D, cells cultured in the 3D printed $PCL/{\beta}-TCP$ scaffold with a bone differentiation medium. Alkaline phosphatase (ALP) activity assay, von Kossa staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were performed for comparative analysis. Results: ALP assay and von Kossa staining revealed that group M had higher levels of osteogenic differentiation compared to group C. RT-PCR showed that gene expression was higher in group M than in group C, indicating that, compared to group C, osteogenic differentiation was more extensive in group M. Expression levels of proteins involved in ossification were higher in group M, as per the Western blotting results. Conclusion: Osteogenic differentiation was increased in mesenchymal stromal cells (MSCs) cultured in the 3D printed PCL/TCP scaffold compared to the control group. Osteogenic differentiation activity of MSCs cultured in the 3D printed PCL/TCP scaffold was lower than that of cells cultured on the scaffold in bone differentiation medium. Collectively, these results indicate that the 3D printed PCL/TCP scaffold promoted osteogenic differentiation of MSCs and may be widely used for bone tissue engineering.

Pedicled Deep Inferior Epigastric Perforator Flap for Treatment of Dystrophic Epidermolysis Bullosa-Associated Squamous Cell Carcinoma in the Groin - Case Report - (심부하복벽동맥 천공지 유경 피판을 이용한 이영양성 수포성 표피박리증에 합병된 서혜부 편평 세포 상피암의 치료 - 증례 보고 -)

  • Kim, Kyung-Pil;Kim, Ji-Hoon;Kim, Eui-Sik;Hwang, Jae-Ha;Kim, Kwang-Seog;Lee, Sam-Yong
    • Archives of Reconstructive Microsurgery
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    • v.19 no.2
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    • pp.97-100
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    • 2010
  • Purpose: Epidermolysis bullosa is a rare genetic disease, characterized by the presence of extremely fragile skin and formation of recurrent blister resulting from even a minor mechanical injury. Squamous cell carcinoma (SCC) is recognized as a complication of the chronic scarring associated with dystrophic epidermolysis bullosa (DEB). When a soft tissue defect happens in a patient with epidermolysis bullosa, it is difficult to cover it with a skin graft or a flap. We describe the successful use of a pedicled deep inferior epigastric perforator flap for the reconstruction of SCC associated with DEB in the groin. Methods: A 29-year-old man diagnosed with DEB at birth sustained an ulcer increasing in the right groin for the last 7 months. Under general anesthesia, the mass lesion and lymph nodes were removed and the resulting defect was covered with a pedicled deep inferior epigastric perforator flap. Results: The flap survived completely and his postoperative course was uneventful. Histopathological examination revealed a SCC in the right groin and malignant tumor cells in the removed lymph nodes as well. Additional positron emission tomogram showed a malignant lesion in the ileocecal area with regional lymph node metastasis. The patient was referred to an oncologist for chemotheraphy, but the patient refused to take it. During a 4-month follow-up period, there was no recurrence in the right groin. Conclusion: We suggest that perforator flaps can be considered as a reliable alternative for the reconstruction of soft tissue defects in a patient with DEB.

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Outcome of Suture Suspension Arthroplasty for Thumb Carpometacarpal Joint Arthritis (무지 수근중수 관절염에 대한 현수 봉합 관절성형술의 결과)

  • Kim, Sehun;Gong, Hyun Sik;Lee, Se Yeon;Lee, Minho;Kim, Jihyeung;Baek, Goo Hyun
    • Archives of Hand and Microsurgery
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    • v.23 no.4
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    • pp.223-229
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    • 2018
  • Purpose: A number of procedures were introduced to stabilize the 1st metacarpal bone after resection of the trapezium in the thumb carpometacarpal joint (CMCJ) arthroplasty. However, some surgical procedures may inevitably damage normal structures, such as harvesting tendons or drilling of a bone for tendon passage. Suture suspension arthroplasty is relatively less invasive and easier to perform than the previously described surgical methods. The purpose of this study was to report the therapeutic efficiency of the suture suspension arthroplasty. Methods: We retrospectively reviewed 12 patients who underwent suture suspension arthroplasty for the treatment of thumb CMCJ arthritis. Pain visual analogue scale (VAS), satisfaction about surgical outcomes, and the disabilities of the arm, shoulder and hand (DASH) scores were measured to evaluate the functional outcomes and the Trapezial Space Ratios were measured. Satisfaction was measured in the range of "very dissatisfied" (0) to "very satisfied" (10). Results: The mean follow-up period was 23 months. Pain VAS score improved significantly from 7.0 to 2.9 (p<0.05). And mean satisfaction scale was 6.9. However, there was no significant difference in DASH scores between before and after surgery (p=0.06). The mean trapezial space ratio was calculated to be 0.45 before surgery, 0.33 immediately after surgery, 0.23 at the last follow-up. Conclusion: Suture suspension arthroplasty is a satisfactory surgical procedure. And compared with other procedures, there is no significant difference in the reduction of the trapezial space. It may be useful in advanced thumb CMCJ arthritis.

A Study on the Legislation of 'The Records Management Innovation Road-map' (기록관리 '혁신' 로드맵의 법제화 연구)

  • Park, Mi-Ae
    • The Korean Journal of Archival Studies
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    • no.25
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    • pp.131-196
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    • 2010
  • The Records Management Act was established by the result of the National Archive reformism in 1999. However, it could not have brought high-quality changes of recording management since recording management innovation was not continuously achieved. On the other hand, in 2006 the Records Management Act was completely revised as a part of recording management innovation. The records management innovation road map is created as an agenda in order to accommodate difficulties we face in the process of the records management reformism and to establish a norm in accord with international standards, a redesign of records management process and a development of records management system so that it can react quickly to rapidly changing situations on records management paradigms. The organization of the Records Management Act was revised by compensating the defect and applying in international standards. This is due to the fact that it is the highest priority assignment to be able to help promote those sorts of innovation to provide an institutional strategy. 'The National Records Management Advancement Strategy' of National Archives in 2009 seems to be an extension of the recording management Innovation road map. Nonetheless, this strategy cannot be considered a strategy of the consecutive national records management reform since it reflects the basis of the existing policy without any assessment with respect to the records management innovation. Government-level talks on records management innovation should be regarded so as to establish a national policy on records management and to be consistent in carrying Out the policy. This research focuses on how the records management innovation road map is reflected in the Records Management Act in 2006 and how international standards are applied in the act in the national records management regime and current records management system. Furthermore, several challenges will be illustrated to overcome a limit of the Records Management Act in the process.