• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2003년도 제40회 국제학술심포지움
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• pp.163-164
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• 2003

• 한국식물학회:학술대회논문집
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• 한국식물학회 1996년도 제10회 식물생명공학심포지움 고등식물 발생생물학의 최근 진보
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• pp.61-74
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• 1996

Human and monogastric animals can not synthesize 10 out of the 20 amino asids and therefor need to obtain these from their diet. The plant seed is a major source of dietary protein. It is particular important in their study to increase nutritional quality of the seed storage proteins. The low contents of lysine, asparagine and threonenein various cereal seeds and of cystein and methionine. In legume seeds is due to the low proportions of these amino acids in the major storage proteins, we have tried to apply the three strategies; (1) mutagenesis and selection of specific amino acid analogue resistance, (2) cloning and expression study of lysine biosynthesis related gene, (3) transfomation of lysine rich soybean glycinin gene. The 5-methyltryptophan (5MT) resistant cell lines, SAR1, SAR2 and SAR3 were selected from anther derived callus of rice (Oryza sativa L. "Sasanishiki"). Among these selected cell lines, two (SAR1 and SAR3) were able to grow stably at 200 mg/L of 5MT. Analysis of the freed amino acids in callus shows that 5MT resistant cells (SAR3) accumulated free tryptophan at least up to 50 times higher than those that of the higher than of SAS. These results indicated that the 5MT resistant cell lines are useful in studies of amino acid biosynthesis. Tr75, a rice (Oryza sativa L., var. Sasanishiki) mutant resistant to 5MT was segregated from the progenies of its initial mutant line, TR1. The 5MT resistant of TR75 was inherited in the M8 generations as a single dominant nuclear gene. The content of free amino acids in the TR75 homozygous seeds increased approximately 1.5 to 2.0 fold compared to wild-type seeds. Especially, the contents of tryptophan, phenylalanine and aspartic acid were 5.0, 5.3 and 2.7 times higher than those of wild-type seeds, respectively. The content of lysine is significantly low in rice. The lysine is synthesized by a complex pathway that is predominantly regulated by feedback inhibition of several enzymes including asparginase, aspatate kinase, dihydrodipicolinat synthase, etc. For understanding the regulation mechanism of lysine synthesis in rice, we try to clone the lysine biosynthetic metabolism related gene, DHPS and asparaginase, from rice. We have isolated a rice DHPS genomic clone which contains an ORF of 1044 nucleotides (347 amino acids, Mr. 38, 381 daltons), an intron of 587 nucleotides and 5'and 3'-flanking regions by screening of rice genomic DNA library. Deduced amino acid sequence of mature peptide domain of GDHPS clone is highly conserved in monocot and dicot plants whereas that of transit peptide domain is extremely different depending on plant specie. Southern blot analysis indicated that GDHPS is located two copy gene in rice genome. The transcripts of a rice GDHPS were expressed in leaves and roots but not detected in callus tissues. The transcription level of GDHPS is much higher in leaves indicating enormous chloroplast development than roots. Genomic DNA clones for asparaginase genes were screened from the rice genomic library by using plaque hybridization technique. Twelve different genomic clones were isolated from first and second screening, and 8 of 12 clones were analyzed by restriction patterns and identified by Southern Blotting, Restriction enzyme digestion patterns and Southern blot analysis of 8 clones show the different pattern for asparaginase gene. Genomic Southern blot analysis from rice were done. It is estimated that rice has at least 2-3 copy of asparaginase gene. One of 8 positive clones was subcloned into the pBluescript SK(+) vector, and was constructed the physical map. For transformation of lysine rich storage protein into tobacco, soybean glycinin genes are transformed into tobacco. To examine whether glycinin could be stably accumulated in endosperm tissue, the glycinin cDNA was transcriptionally fused to an endosperm-specific promotor of the rice storage protein glutelin gene and then introduced into tobacco genomic via Agrobacterium-mediated transformation. Consequently the glycinin gene was expressed in a seed-and developmentally-specific manner in transgenic tobacco seeds. Glycinin were targeted to vacuole-derived protein bodies in the endosperm tissue and highly accumulated in the matrix region of many transgenic plant (1-4% of total seed proteins). Synthesized glycinin was processed into mature form, and assembled into a hexamer in a similar manner as the glycinin in soybean seed. Modified glycinin, in which 4 contiguous methionine residues were inserted at the variable regions corresponding to the C - teminal regions of the acidic and basic polypeptides, were also found to be accumulated similarly as in the normal glycinin. There was no apparent difference in the expression level, processing and targeting to protein bodies, or accumulation level between normal and modified glycinin. glycinin.

• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2003년도 식물바이오벤처 페스티발
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• pp.149-149
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• 2003

• 한국동물위생학회지
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• 제44권4호
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• pp.309-313
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• 2021

A 12-year-old, spayed female, Toy-poodle dog presented in progressive, pruritic carpal mass and mandibular papule. The skin lesions and enlarged superficial lymph nodes were surgically removed. According to histopathology and immunohistochemistry, the patient diagnosed as cutaneous epitheliotropic T-cell lymphoma with lymph node metastasis. Chemotherapy with L-asparaginase, lomustine and prednisolone was initiated. The patient deteriorated despite treatment and was admitted to the hospital. Blood tests revealed significant leukocytosis. Circulating large lymphocytes with convoluted and cerebriform nuclei seen in peripheral blood led to presumption of Sézary cells. Thus, considering skin, lymph nodes and blood involvement, Sézary syndrome was diagnosed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Journal of Biomedical and Translational Research
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• 제19권4호
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• pp.140-145
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• 2018

A one-year-old, intact female, Maltese dog was presented with a history of anorexia and regurgitation. Thoracic radiographs and ultrasonography scans suggested an abnormal mass in the cranial mediastinal region, and computed tomography confirmed the origin of this mass. Ultrasound-guided fine needle aspiration cytology showed the presence of intermediate to large lymphoid cells showing mitotic figures. B-cell lymphoma was confirmed by the result of a polymerase chain reaction assay for antigen receptor rearrangement, therefore the patient was diagnosed with primary mediastinal large B-cell lymphoma (PMBL). The patient underwent L-CHOP (L-asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy, and showed complete tumoral remission from the beginning of chemotherapy. Seventytwo weeks after the completion of chemotherapy, the patient is still alive without any evidence of metastasis or relapse. A standardized treatment protocol has yet to be established for primary mediastinal lymphoma in dogs. This case report describes the complete remission of PMBL by an L-CHOP-based chemotherapy protocol in a young Maltese. Clinicians should consider that L-CHOP based chemotherapy may be useful against PMBL in dogs.

• 한국임상수의학회지
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• 제35권4호
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• pp.150-154
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• 2018

A 9-month-old, castrated, male Labrador Retriever was referred for generalized progressing cutaneous reddish mass lesions with bleeding, scale, crust, and pruritus. On the basis of histopathological findings and the results of immunochemical staining, cutaneous nonepitheliotropic B-cell lymphoma was identified. A cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP)-based chemotherapy regimen was initiated, and the patient initially showed partial response to vincristine and $\text\tiny{L}$-asparaginase, but the cutaneous lesions progressed gradually. After the first cycle of the CHOP-based protocol, lomustine was administered instead. The cutaneous lesions showed partial response to lomustine, but the treatment did not stop the progression of cutaneous lymphoma. The patient was euthanized due to neurologic signs, including reduced consciousness and seizures, 53 days after initial presentation. The postmortem histopathological examination showed systemic metastasis involving the lymph nodes, skin, kidney, ureter, liver, brain, temporal muscle, diaphragmatic muscle, conjunctiva, and oral cavity.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2001년도 제2회 생물정보학 국제심포지엄
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• pp.129-137
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• 2001

We used cDNA microarrays to assess gene expression profiles in 60 human cancer used in a drug discovery screen by the National Cancer Institute. Using these data, we linked bioinformatics and chemoinformatics by correlating gene expression and drug activity pattens in the NCI60 lines. Clustering the cell lines on the basis of gene expression yielded relationships very different from those obtained by clustering the cell lines on the basis of their response to drugs. Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance. This is the first study to intergrate large databases on gene expression and molecular pharmacology.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제13권1호
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• pp.58-65
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• 2010

목 적: 소아에서 급성 췌장염은 췌장을 침범하는 가장 흔한 질환으로 최근 발생 빈도가 증가하고 있다. 이 질환에 대한 보고가 많지 않아 임상적 특징을 알아보고자 본 연구를 시행하였다. 방 법: 1996년 1월부터 2007년 6월까지 부산대학교병원 소아청소년과에서급성 췌장염을 진단받았던 41명을 대상으로 의무 기록을 후향적으로 분석하였다. 급성 췌장염의 진단은 임상 소견, 혈청 amylase 및 lipase치의 상승 및 방사선 소견이 합당한 경우로 하였으며, 이 질환의 원인, 임상 소견 및 경과, 중증도 판정, 치료등을 분석하였다. 결 과: 남자가 20명, 여자가 21명이었고, 진단 시 평균 나이는 8.7${\pm}$4.5세였다. 증상 발현에서 진단까지의 기간은 7.0${\pm}$7.4일이었고, 내원 당시 주증상은 복통 37예(90.2%), 구토 24예(58.5%), 발열과 경구 섭취 불량이 각각 6예(14.6%)였다. 췌장염의 원인으로는 원인불명 22예(53.7%), 총담관낭 9예(22.0%), 췌담관 합류 이상 3예(7.3%), Henoch-schonlein 자반병과 유행성 이하선염이 각각 2예(4.9%)였고 그 외 분할췌장, 용혈 요독 증후군, 외상, 바이러스성 간염, 약물(L-asparaginase)이 각각 1예였다. 간질성 췌장염이 36예(87.8%), 괴사성 췌장염이 5예(12.2%)였고 재발성 췌장염이 4예(9.8%)였다. 방사선학적 소견은 췌종대 18예(43.9%), 췌장 주위 액체저류 12예(29.3%), 복수 10예(24.4%), 췌장 주위 지방괴사 5예(12.2%)였다. 진단 당시 혈청 amylase치는 535.3${\pm}$553.2 U/L, lipase치는 766.2${\pm}$723.6 U/L였고, 혈청 amylase 및 lipase치가 1주 내에 정상으로 회복한 경우가 각각 22예(59.5%), 14예(42.4%)였고, lipase치가 4주 이후에 정상화된 경우가 11예(26.8%)였다. 중증도 판정기준인 APACHE II, Ranson 기준, Balthazar 점수에서 대부분 경증에 해당하였다. 금식과 총정맥 영양이 전례에서 시행되었고, 금식 기간은 평균 13.1${\pm}$17.0일, 총정맥 영양 기간은 평균 8.2${\pm}$13.7일이었다. Octreotide는 8명(19.5%), Gabexate mesilate는 4명(9.8%)에서 투여되었고, 4명에서 조임근절개술이 시행되었다. 합병증으로는 복수(32.3%), 패혈증(16.1%), 거짓낭(12.9%), 신장장애(12.9%), 흉수, 십이지장 궤양, 혈성복막(6.5%) 등이 있었다. 34명이 완전 회복되었고, 2명(4.9%)이 췌장염의 합병증으로 사망하였다. 결 론: 소아 급성 췌장염은 드문 질환이 아니며 성인과는 다른 원인, 증상 및 경과를 보였다. 대부분 환자들이 수 일 이내 완전 회복되지만 아직 사망률이 높으므로 조기 진단과 발병 초기에 중증도를 평가하여 적절한 치료 및 합병증 관리가 중요하다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제2권2호
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• pp.194-203
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• 1999

목 적: 급성췌장염의 원인이 성인의 경우와는 다르고 매우 다양하며 보고마다 많은 차이를 보여서 단일기관의 경험을 토대로 소아 췌장염의 원인을 알아보고자 하였고 췌장염의 중증도를 분석하기는 방법으로 쓰이는 Ranson 기준과 복부 단층촬영에 의한 조기 예후 판정기준(Balthazar의 CT기준)의 소아 췌장염에서 적용여부를 알고자 하였다. 대상 및 방법: 1992년 3월에서 1996년 8월까지 4년 6개월 동안 서울중앙병원 소아과에 내원하여 췌장염으로 진단 받은 30명을 대상으로 하였다. 이들의 병록지를 조사하여 췌장염을 일으키는 원인을 중심으로 임상양상, 합병증, 결과를 검토하였다. 또한 급성췌장염의 중증도를 조기에 객관적으로 판정할 수 있는 지표로서 널리 사용되고 있는 Ranson의 조기 예후 판정 기준과 복부 단층촬영에 의한 조기 예후 판정 기준(Balthazar 기준)을 산출하고 발생한 췌장염의 합병증의 수와 Ranson기준 및 CT 기준에 대하여 Spearman상관계수를 구하여서 이들 기준이 췌장염의 합병증의 발생과 연관성을 밝혀서 소아에서 췌장염의 중증도 평가의 적용여부를 밝히고자 하였다. 결 과: 1) 환아들의 발병당시의 평균연령은 7.3세(6개월에서 14.9세까지)이었고, 남아 14명, 여아 16명 이었고, 이중에 급성 췌장염이 28례, 만성 췌장염이 2례가 있었다. 2) 원인으로는 총수담관낭이 8례로 가장 많았으며, 약물복용 7례, 외상 4례, 감염 3례, 담석 췌장염 3례, 특별한 원인이 없는 경우가 2례, 용혈성 요독증후군 1례, 췌장두부 협착 1례, 역행성 담췌관조영술후 합병증에 의한 경우 1례였다. 약물복용은 L-asparaginase 5례, Erwinase 1례, Dexamethasone 1례가 있었고, 감염은 mumps 1례, Yersinia에 의한 감염 2례가 있었다. 3) 임상증상은 복통이 30례(100%)로 가장 많았고, 오심이 22례(73.3%), 구토가 20례(66.7%), 발열이 9례(30%), 복부팽만이 9례(30%), 설사가 5례(16.7%), 복부종물이 1례(3.3%)에서 있었다. 4) 국소적 합병증은 복수 5례, 가성낭 4례이었고, 전신적 합병증으로는 흉막삼출 3례, 폐혈증 1례, 저혈압 1례, 신부전 1례, 고혈당증 4례, 저칼슘혈증 3례, 고칼륨혈증 1례, 대사성 산증 1례가 있었다. 5) 모든 경우에서 금식등 대증요법이 치료의 근간을 이루었으나 6례에서 somatostatin을 투여하였다. 총수담관낭 8례는 모두 수술적 제거를 하였고, 가성낭 파열로 내부배액법을 1례에서 하였으며, 가성낭을 초음파에 의한 경피적 배액을 하였으나 췌루형성으로 지속적인 췌장액 배액이 있어서 내부배액법을 실시한 경우가 1례가 있었다. 6) 합병증의 수와 Ranson 및 CT 예후판정 기준사이에 상관성을 보기 위해 Spearman 상관 계수를 측정하였는데, Ranson의 중증도판정 기준과 합병증의 수 사이의 상관계수는 r=0.78 (P= 0.0016)이었고, CT기준과 합병증의 수 사이에도 r=0.65 (P=0.015)으로 유의한 상관성이 있었다. 결 론: 본 연구에서 췌장염의 원인으로는 총수담 관낭, 약물, 외상의 순으로 많았으며 기존 다른 저자들의 경험과는 다른 점으로는 급성췌장염의 원인으로 총수담관낭이 가장 많았다는 점으로 소아에서 췌장염의 증세를 발견시 적극적으로 총수담관의 기형유무를 찾아보아야 된다고 생각된다. 또한 Ranson에 의한 중증도판정 기준과 CT기준 모두가 일어난 합병증의 수와 의미있는 상관관계를 가지므로 Ranson기준과 CT기준 모두가 췌장염의 합병증과 밀접한 관계를 가지며 췌장염을 일으키는 병의 중증도를 예견하는 데에 있어서 소아에서도 유용할 것으로 사료된다.