• 한국미생물·생명공학회지
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• 제37권2호
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• pp.140-146
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• 2009

Cyclosporin A 분자의 구성 아미노산 가운데 분지 아미노산인 valine, leucine, isoleucine, threonine 등에 대한 첨가 효과를 확인한 결과, L-valine 첨가구는 비첨가구보다 cyclosporin A 역가는 3.7배, cyclosporin A 구성비율은 약 40%로 가장 크게 증가하였다. 그리고 L-valine의 최적 농도는 0.75%로서 비첨가구에 비하여 cyclosporin A 역가는 3배, cyclosporin A 구성비율은 30% 증가하였다. 그러나 L-valine 1% 단독 첨가구보다 L-valine 0.5%, L-leucine 0.5% 혼합구가 cyclosporin A 역가에서는 약 16% 우수하였고, cyclosporin A 구성비율에서는 약 5% 증가하였다. 또한 다양한 유기질소원의 첨가 효과를 확인한 결과, meat peptone인 Bacto-peptone 첨가구는 유기질소원 비첨가구보다 cyclosporin A의 역가는 약 2배, cyclosporin A 구성비율은 약 13% 증가하였고, Bacto-peptone의 최적농도는 1%인 것으로 확인되었다. 그러나 Casiton, Tryptone, NZ-amine 등 우유 유래 유기질소원 첨가구의 경우, 비첨가구보다 cyclosporin A 역가가 오히려 약 10-20% 감소하는 현상을 보여 cyclosporin A 생합성을 억제하는 것으로 확인되었다. 본 연구에서 최적화된 배지 조건에서, 모균주인 T. inflatum ATCC 34921와 UV 조사로 얻어진 4종의 cyclosporin A 고생산 변이주 4종의 생산성을 비교한 결과, 변이주 YHC-004의 cyclosporin A 역가는 3,430 mg/L로 모균주인 ATCC 34921보다 약 7.1배로 증가하였지만, 모균주와 변이주 4종의 cyclosporin A 구성비율은 약 93-94% 범위에서 비슷한 값을 보였다.

• 미생물학회지
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• 제47권3호
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• pp.249-254
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• 2011

본 연구에서는 탄소원 및 질소원의 이용 패턴과 mycophenolic acid의 생성 패턴을 확인하기 위하여 먼저 5 L 발효조에서 mycophenolic acid 발효의 경시적 변화를 조사하였다. 그 다음에는 여러 가지 탄소원들이 세포 생장과 mycophenolic acid 생산에 미치는 효과를 조사하였다. 과당이 mycophenolic acid 발효에 가장 좋은 탄소원이었지만, 값이 고가인 단점이 있어서, 과당을 지니고 있는 설탕이 주성분인 당밀을 탄소원으로 사용한 결과 mycophenolic acid의 산업적 생산에 가장 좋은 것으로 확인되었다. 당밀을 첨가한 실험구는 포도당을 탄소원으로 사용한 대조구에 비하여 발효 생산성이 2배 이상 증가하였다. 양호한 세포 생장과 높은 mycophenolic acid 생산을 얻기 위하여 다양한 무기질소원과 유기질소원에 대한 실험을 실시하였다. 무기질소원들 가운데 요소는 암모늄 형태의 질소원을 천천히 공급함으로써 생장과 mycophenolic acid 생산을 저해하는 배양액의 급격한 pH 하락을 일으키지 않았다. 요소를 첨가한 실험구는 질산암모늄을 첨가한 대조구보다 발효 생산성이 3.6배 증가하였다. 카제인, 펩톤, casamino acid 같은 우유 단백질 유래 유기질소원들은 대조구에 비하여 mycophenolic acid 발효 생산성을 최고 3.4배까지 증진시켰다. 카제인의 가수분해물인 펩톤과 casamino acid는 mycophenolic acid 발효 생산성뿐만 아니라 세포 생장도 촉진하였다.

• Childhood Kidney Diseases
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• 제12권1호
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• pp.99-104
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• 2008

현미경적 다발성 동맥염은 폐출혈과 급속 진행성 사구체심염을 특징으로 하는 전신성 혈관염의 일종으로 소아에서는 매우 드문 질환이다. 저자들은 폐출혈과 급성 신부전을 동반한 7세 여아에서 신장조직검사와 p-ANCA 검사로 현미경적 다발성 동백염으로 진단 후 5년 뒤 2차 신장조직검사와 경구 ACE inhibitor, angiotensin II receptor blocker와 저용량의 cyclophosphamide를 투여 받은 환아를 7년간 추적관찰하였다. 발병당시에는 BUN 117 mg/dL, Cr 2.3 mg/dL이었으나, 퇴원시 BUN 20.8 mg/dL, Cr 1.6 mg/dL이었고, 최근 검사에서는 BUN 51.7 mg/dL, Cr 3.2 mg/dL으로 만성 신병증 소견을 보이고 있으며, 외래 추적 관찰 지속 중에 있다. 이에 문헌 고찰과 함께 증례 보고하는 바이다.

• Food Science and Biotechnology
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• 제17권3호
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• pp.598-602
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• 2008

Concentrated catfish Silurus asotus bile (SAB) containing high amounts of ursodeoxycholic acid (UDCA) and taurocholic acid may have immunosuppressive properties. To investigate the putative immunosuppressive properties of SAB, the anti-proliferation and suppression of early T cell activation markers, and the inhibition of cytokines induced by T cells in response to anti-CD3 mAb activation in mouse splenocytes were examined. The suppression of these activation repertoires are the main properties of calcineurin inhibitors. It was found that SAB effectively suppressed the activation of T cells, and cytokines from T cell activation, at levels similar to cyclosporine A, a calcineurin inhibitor. Although the mechanism in which suppression occurs is not clear, we speculate that SAB from Silurus asotus, which has been known to switch their intake habits to zoophagy during an early adult stage, may explain the suppressive effect of SAB as a result of high amounts of functional UDCA in bile. Our results suggest that the treatment or intake of SAB, either in therapy or as a food supplement, may act as an adjuvant therapy for the prevention of transplant rejection, although further investigation is required before this treatment can be applied clinically.

• Archives of Reconstructive Microsurgery
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• 제21권1호
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• pp.34-40
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• 2012

Prevention of acute rejection in composite tissue allotransplantation without continuous immunosuppression lacks reports in worldwide literature. Recently dendritic cells (DC) gained considerble attention as antigen presenting cells that are also capable of immunologic tolerance induction. This study assesses the effect of alloantigen-pulsed dendritic cells in induction of survival in a rat hindlimb allograft. We performed hindlimb allotransplantation between donor Sprague-Dawley and recipient Fischer344 rats. Recipient derived dendritic cells were harvested from rat whole blood and cultured with anti-inflammatory cytokine IL-10. Then donor-specific alloantigen pulsed dendritic cells were reinjected into subcutaneous tissue before limb transplantation. Groups: I) untreated (n=6), II) DC injected (n=6), III) Immunosuppressant (FK-506, 2 mg/Kg) injected (n=6), IV) DC and immunouppressant injected (n=6). Graft appearance challenges were assessed postoperatively. Observation of graft appearance, H-E staning, immunohistochemical (IHC) study, and confocal immunofluoreiscece were performed postoperatively. Donor antigen pulsed host dendritic cell combined with short-term immunosuppression showed minimal mononuclear cell infiltration, regulator T cell presence, and could prolong limb allograft survival.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권3호
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• pp.216-221
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• 2006

Cyclosporin A-induced gingival hyperplasia is frequently found in the patients who have been received an immunosuppressant for the organ transplantation. However, its exact mechanism is still unknown. The expression of FGF-5 and FGF-7 were studied in cyclosporine A-induced gingival hyperplasia (CGH) and inflammatory gingival hyperplasia (IGH). Immunohistochemistry and in situ hybridization were used for localization of protein and mRNA. The expression of FGF-5 and FGF-7 was different from CGH and IGH. FGF-5 and FGF-7 was strongly expressed in fibroblast in CGH (P<0.005 and P<0.05, respectively). FGF-5 mRNA was localized in the middle portion of connective tissue. FGF-7 mRNA was also identified in fibroblasts and mast cells. In conclusion, FGF-5 and FGF-7 were produced excessively by fibroblasts in CGH. Considering their known functions, their expression in CGH is important for production of collagen and proliferation of fibroblasts.

• Toxicological Research
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• 제26권3호
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• pp.163-170
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• 2010

Cyclosporine A (CsA) is a potent immunosuppressor that is widely used in transplant surgery and the treatment of several autoimmune diseases. However, major side effects of CsA such as nephrotoxicity, hepatotoxicity, neurotoxicity and cardiovascular diseases have substantially limited its usage. Although molecular mechanisms underlying these adverse effects are not clearly understood, there is some evidence that suggests involvement of reactive oxygen species (ROS). In parallel, protective effects of various antioxidants have been demonstrated by many research groups. Extensive studies of CsA-induced nephrotoxcity have confirmed that the antioxidants can restore the damaged function and structure of kidney. Subsequently, there have appeared numerous reports to demonstrate the positive antioxidant effects on liver and other organ damages by CsA. It may be timely to review the ideas to envisage the relationship between ROS and the CsA-induced toxicity. This review is comprised of a brief description of the immunosuppressive action and the secondary effects of CsA, and a synopsis of reports regarding the antioxidant treatments against the ROS-linked CsA toxicity. A plethora of recent reports suggest that antioxidants can help reduce many CsA's adverse effects and therefore might help develop more effective CsA treatment regimens.

• Archives of Plastic Surgery
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• 제32권4호
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• pp.441-446
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• 2005

Sole reconstruction should consider both functional and aesthetic aspects; durable weight bearing surface, adequate contour for normal footwear, protective sensation and solid anchoring to deep tissue to resist shearing. The anterolateral thigh perforator free flap has such favorable characteristics as long pedicle, reliable perforators and minimal donor site morbidity. This flap can be safely thinned to 3-4 mm. It can also be elevated with sufficient bulk with muscles like vastus lateralis for complex defect. Between June 2002 and December 2004, 48 cases of sole reconstruction were performed with anterolateral thigh perforator free flaps. Follow up period ranged from 4 to 34 months with a mean of 14.7 months and with exception of one case, all flaps survived. One case of total flap loss was noted due to infection in a patient who was administered lifetime immunosuppressant. Partial necroses developed in three cases but were treated conservatively. Satisfactory aesthetic and functional results were achieved and acceptable gait recovery was noted. Seventy-eight percent of the patients regained protective sensation by 6 months and earlier sensory recovery was noted in sensate flap group. The authors also present a standardized protocol for preoperative patient evaluation and postoperative management and rehabilitation.

• Journal of Microbiology and Biotechnology
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• 제29권12호
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• pp.1931-1937
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• 2019

The heterologous expression of the Streptomyces natural product (NP) biosynthetic gene cluster (BGC) has become an attractive strategy for the activation, titer improvement, and refactoring of valuable and cryptic NP BGCs. Previously, a Streptomyces artificial chromosomal vector system, pSBAC, was applied successfully to the precise cloning of large-sized polyketide BGCs, including immunosuppressant tautomycetin and antibiotic pikromycin, which led to stable and comparable production in several heterologous hosts. To further validate the pSBAC system as a generally applicable heterologous expression system, the daptomycin BGC of S. roseosporus was cloned and expressed heterologously in a model Streptomyces cell factory. A 65-kb daptomycin BGC, which belongs to a non-ribosomal polypeptide synthetase (NRPS) family, was cloned precisely into the pSBAC which resulted in 28.9 mg/l of daptomycin and its derivatives in S. coelicolor M511(a daptomycin non-producing heterologous host). These results suggest that a pSBAC-driven heterologous expression strategy is an ideal approach for producing low and inconsistent Streptomyces NRPS-family NPs, such as daptomycin, which are produced low and inconsistent in native host.

• Journal of Microbiology and Biotechnology
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• 제28권3호
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• pp.418-424
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• 2018

${\text\tiny{D}}-Allose$ is a potential medical sugar because it has anticancer, antihypertensive, antiinflammatory, antioxidative, and immunosuppressant activities. Allose production from fructose as a cheap substrate was performed by a one-pot reaction using Flavonifractor plautii ${\text\tiny{D}}-allulose$ 3-epimerase (FP-DAE) and Clostridium thermocellum ribose 5-phosphate isomerase (CT-RPI). The optimal reaction conditions for allose production were pH 7.5, $60^{\circ}C$, 0.1 g/l FP-DAE, 12 g/l CT-RPI, and 600 g/l fructose in the presence of 1 mM $Co^{2+}$. Under these optimized conditions, FP-DAE and CT-RPI produced 79 g/l allose for 2 h, with a conversion yield of 13%. This is the first biotransformation of fructose to allose by a two-enzyme system. The production of allose by a one-pot reaction using FP-DAE and CT-RPI was 1.3-fold higher than that by a two-step reaction using the two enzymes.