항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

Dual color FISH karyotype of wild radish species

Yoon-Jung Hwang,Jeong-Hwan Mun,Hee-Ju Yu,Ki-Byung Lim 한국육종학회 2012 한국육종학회 심포지엄 Vol.2012 No.07

Radish, Raphanus sativus L., is an annual vegetable of the family Cruciferae. Radish has RR genome with 18 somatic chromosome numbers (2n=2x=18). Until now, detailed karyotypic analysis is not only constructed only by conventional staining techniques but also other method. Fluorescence in situ hybridization (FISH) is a powerful molecular cytogenetic technique using chromosomal markers that reveal the positions of specific genes, such as ribosomal DNAs, thereby making it easy to identify individual chromosomes. We have constructed detailed karyotypes of four different local and wild varieties of radish, based on the chromosome arm length and fluorescence in situ hybridization (FISH) with the 45S rDNA and 5S rDNA as probes. As for the karyotype of radish, 9 pairs of chromosomes were extremely small in size with about 1 to 3 um in length at mitotic metaphase having metacentrics or submetacentrics. Three pairs of 45S rDNA signals and two pairs of 5S rDNA signals were observed in four radish species. One pair of 45S rDNA signal was located on terminal region of short arm chromosome, while two pairs were in interstitial region. Two pairs of 5S rDNA signals were located on interstitial region of chromosome. In conclusion, it was feasible to identify the radish by karyotype and physical mapping analyzed using ribosomal DNA.

Auxin response factor gene family in <i>Brassica rapa</i> : genomic organization, divergence, expression, and evolution

Mun, Jeong-Hwan,Yu, Hee-Ju,Shin, Ja Young,Oh, Mijin,Hwang, Hyun-Ju,Chung, Hee Springer-Verlag 2012 Molecular genetics and genomics Vol.287 No.10

<P>Completion of the sequencing of the <I>Brassica rapa</I> genome enabled us to undertake a genome-wide identification and functional study of the gene families related to the morphological diversity and agronomic traits of <I>Brassica</I> crops. In this study, we identified the auxin response factor (<I>ARF</I>) gene family, which is one of the key regulators of auxin-mediated plant growth and development in the <I>B. rapa</I> genome. A total of 31 <I>ARF</I> genes were identified in the genome. Phylogenetic and evolutionary analyses suggest that <I>ARF</I> genes fell into four major classes and were amplified in the <I>B. rapa</I> genome as a result of a recent whole genome triplication after speciation from <I>Arabidopsis thaliana</I>. Despite its recent hexaploid ancestry, <I>B. rapa</I> includes a relatively small number of <I>ARF</I> genes compared with the 23 members in <I>A. thaliana</I>, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative genomic and mRNA sequencing analyses demonstrated that 27 of the 31 <I>BrARF</I> genes were transcriptionally active, and their expression was affected by either auxin treatment or floral development stage, although 4 genes were inactive, suggesting that the generation and pseudogenization of <I>ARF</I> members are likely to be an ongoing process. This study will provide a fundamental basis for the modification and evolution of the gene family after a polyploidy event, as well as a functional study of <I>ARF</I> genes in a polyploidy crop species.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00438-012-0718-4) contains supplementary material, which is available to authorized users.</P>

Genome-wide identification of NBS-encoding resistance genes in <i>Brassica rapa</i>

Mun, Jeong-Hwan,Yu, Hee-Ju,Park, Soomin,Park, Beom-Seok Springer-Verlag 2009 Molecular genetics and genomics Vol.282 No.6

<P>Nucleotide-binding site (NBS)-encoding resistance genes are key plant disease-resistance genes and are abundant in plant genomes, comprising up to 2% of all genes. The availability of genome sequences from several plant models enables the identification and cloning of NBS-encoding genes from closely related species based on a comparative genomics approach. In this study, we used the genome sequence of <I>Brassica rapa</I> to identify NBS-encoding genes in the <I>Brassica</I> genome. We identified 92 non-redundant NBS-encoding genes [30 CC-NBS-LRR (CNL) and 62 TIR-NBS-LRR (TNL) genes] in approximately 100 Mbp of <I>B. rapa</I> euchromatic genome sequence. Despite the fact that <I>B. rapa</I> has a significantly larger genome than <I>Arabidopsis thaliana</I> due to a recent whole genome triplication event after speciation, <I>B. rapa</I> contains relatively small number of NBS-encoding genes compared to <I>A. thaliana</I>, presumably because of deletion of redundant genes related to genome diploidization. Phylogenetic and evolutionary analyses suggest that relatively higher relaxation of selective constraints on the TNL group after the old duplication event resulted in greater accumulation of TNLs than CNLs in both <I>Arabidopsis</I> and <I>Brassica</I> genomes. Recent tandem duplication and ectopic deletion are likely to have played a role in the generation of novel <I>Brassica</I> lineage-specific resistance genes.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00438-009-0492-0) contains supplementary material, which is available to authorized users.</P>

Construction of a reference genetic map of Raphanus sativus based on genotyping by whole-genome resequencing

Mun, Jeong-Hwan,Chung, Hee,Chung, Won-Hyong,Oh, Mijin,Jeong, Young-Min,Kim, Namshin,Ahn, Byung Ohg,Park, Beom-Seok,Park, Suhyoung,Lim, Ki-Byung,Hwang, Yoon-Jung,Yu, Hee-Ju Springer-Verlag 2015 Theoretical and applied genetics Vol.128 No.2

Risk factors for neutropenic fever in non-Hodgkin’s lymphoma patients with primary granulocyte colony-stimulating factor prophylaxis

( Yu Ri Kim ),( Soo-jeong Kim ),( Yong Park ),( Sung Yong Oh ),( Hwan-jung Yun ),( Yeung-chul Mun ),( Jin Seok Kim ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.5

Background/Aims: Febrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin’s lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors. Methods: We evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis. Results: Data from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia. Conclusions: Elderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.

Basic : The change in age of hepatitis B virus e antigen seroconversion in Korean chronic hepatitis B patients: recent data (초)

( Mun Sun Choi ),( Jeong Hoon Lee ),( Jin Myung Park ),( Pyo Jun Kim ),( Han Ul Song ),( Ryun Oh ),( Su Jong Yu ),( Yoon Jun Kim ),( Jung Hwan Yoon ),( Chung Yong Kim ),( Hyo Suk Lee ) 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3(S)

Seven Yeast Strains Isolated from Freshwaters for the First Record in Korea

( Yu Jeong Jeon ),( Sangkyu Park ),( Hyejin Hwang ),( Yeong Hwan Park ),( Wonsu Cheon ),( Jaeduk Goh ),( Namil Chung ),( Hye Yeon Mun ) 한국균학회 2020 韓國菌學會誌 Vol.48 No.4

This study focused on the isolation and characterization of wild yeasts in Korea. The yeasts were identified by phylogenetically analyzing the D1/D2 domains of the 26S rDNA regions. Consequently, we identified seven strains, NNIBRFG856, NNIBRFG3732, NNIBRFG3734, NNIBRFG3738, NNIBRFG3739, NNIBRFG5497, and NNIBRFG6049, which were confirmed to be Kabatiella microsticta, Pichia membranifaciens, Candida vartiovaarae, Candida sake, Debaryomyces hansenii, Candida railenensis, and Schwanniomyces polymorphus, respectively, all of them being new in Korea. Morphological and cultural characteristics of these yeast species were investigated. None of the strains formed ascospores or pseudomycelia. Moreover, these yeasts grew in a pH range of 4-8. NNIBRFG3732, NNIBRFG3738, NNIBRFG3739, NNIBRFG5497, and NNIBRFG6049 were halotolerant or halophilic, and NNIBRFG3732, NNIBRFG3734, and NNIBRFG6049 grew in vitamin-free medium. NNIBRFG3732, NIBRFG3739, and NNIBRFG6049 grew at 35 °C, but not at 40 °C.

Genomic organization and evolution of NBS-encoding resistance genes in Brassica rapa

Jeong Hwan Mun,Hee Ju Yu,Soo Min Park,Beom Seok Park 한국육종학회 2009 한국육종학회 학술발표회 발표요지 Vol.41 No.1

신이식 환자의 폐에서 발생한 평활근종의

유선진 ( Yu Seon Jin ),정성진 ( Jeong Seong Jin ),김일 ( Kim Il ),박환철 ( Park Hwan Cheol ),윤여욱 ( Yun Yeo Ug ),이창화 ( Lee Chang Hwa ),강경원 ( Kang Gyeong Won ),강종명 ( Kang Jong Myeong ),박문향 ( Park Mun Hyang ) 대한신장학회 2003 Kidney Research and Clinical Practice Vol.22 No.6

The overall incidence of malignancy in a renal transplanted patient is 3 to 5 times higher compared with general population. We report a very rare case of multiple leiomyoma originated from lung after renal transplantation. 33-year-old male underwent renal transplantation in November, 1989. A 5 mm sized pulmonary nodule was found in the left lower lobe incidentally in March, 2001. The size of pulmonary nodule increased and same lesion was found on the opposite side of the lung on chest roentgenogram after one year, so we proceeded with computed tomography of the chest. Variable sized multiple nodules in the whole lung field were noted, which were thought be metastatic lesions, and for detection of the primary site of malignancy, further study including esophagogastroduodenoscope, colon study, abdominal ultrasound, abdominal CT, bone scan and tumor marker were checked, but there was no evidence of primary cancer. After open lung biopsy low malignant potential smooth muscle tumor was noted, and Epstein-barr virus (EBV) DNA was detected. The patient had been maintained on immunosuppressive therapy with cyclosporine and mycophenolate mofetil (MMF), and after the diagnosis of leiomyoma administration of MMF was stoped, and cyclosporine dosage was reduced. With the reduction of immunosuppressants, intravenous immunoglobulin trial was done for the first cycle, but the efficacy of treatment is not clear. (Korean J Nephrol 2003;22(6):767-772)