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주의력결핍과잉행동장애와 Alpha-1C-Adrenergic 수용체 유전자와의 연관성에 대한 연구
조수철,김재원,김붕년,황준원,박미라,김순애,조대연,유희정,정운선,손정우,박태원 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.1
Objectives : Neurobiological and pharmacological research has suggested that the dysregulation of the central noradrenergic systems might be involved in the pathophysiology of ADHD. The aim of this study was to examine the association of the alpha-1C-adrenergic receptor gene (ADRA1C) with ADHD in Korean subjects. Methods : In a case-control study, we assessed 186 DSM-IV ADHD probands and 150 normal controls. One hundred and eight trios were studied in a family-based association analysis. Psychiatric diagnoses were derived through structured diagnostic interviews. For the clinical evaluation of the ADHD subjects, the Child Behavior Checklist (CBCL), the ADHD Rating Scale-IV (ARS) and the Junior Temperament and Character Inventory (JTCI) were administered. A computerized continuous performance test (CPT) was used to measure the inattention and impulsivity of the ADHD children. Results : There were no significant differences in the genotype or allele frequencies of the ADRA1C PstI polymorphism between the ADHD and control group (p>0.05). The transmission disequilibrium test (TDT) analysis observed no evidence for biased transmission of any of the alleles of the PstI polymorphism. There were no significant differences in the CPT or JTCI profiles between those ADHD subjects with the CC genotype and those with the other (CT+TT) genotypes at the PstI polymorphism. Conclusion : The results of this study do not support the ADRA1C as a major genetic susceptibility factor in ADHD.
Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구
강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1
For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.
자궁내막에 발생한 점막 연관 림프조직 (MALT) 림프종 1예
전균호,조현진,박성균,김천복,김대연,김종혁,김용만,김영탁,목정은,남주현 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.4
Non-Hodgkin's 림프종의 약 40%는 결절외(extranodal) 림프종으로 대개 위장관에서 발생하며 이들 중 점막 연관 림프조직(mucosa-associated lymphoid tissue: MALT)에서 기원한 림프종은 MALT 림프종으로 분류된다. 위 외의 부위에서 원발성으로 발생하는 MALT 림프종은 매우 드물지만 실제 거의 모든 신체 장기에 발생하는 것으로 알려져 있는데, 가장 흔한 부위인 위 외에도 폐, 갑상선, 침샘, 눈물샘에 발생하고, 드물게 안구, 유방, 방광, 신장, 흉선 등에도 보고된 바 있다. MALT 림프종은 오랜 기간동안 원격 전이하지 않고 국소 병변으로 남아 있는 특징이 있어 치료 방향 또한 국소 병변의 치료에 집중되며, 예후도 림프절 기원의 림프종에 비해 양호한 것으로 알려져 있다. 본 저자 등은 자궁 내막에 원발성으로 발생한 MALT 림프종 1예를 경험하였기에 문헌 고찰과 함께 이를 보고하고자 한다. Mucosa associated lymphoid tissue (MALT) lymphoma can rarely develop primarily in extranodal sites other than stomach which is the most common site for it. Other rare primary sites are small intestine, colorectum, esophagus, lung, thyroid, salivary gland, lacrymal gland, breast and skin. MALT lymphoma represents a distinct clinicopathologic features: it is usually localized to their original site for a long time and shows much more favorable prognosis than lymphoma at other site, but some MALT lymphoma can arise simultaneously or successively in different organ or give rise to another MALT lymphoma of other organ and can be multifocally disseminated or recurred. We report a very rare case of high grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT) of the uterine endometrium, which was confirmed by immunohistochemical assay.
Brine Shrimp Bioassay를 이용한 해양생물의 세포독성검색
손병화,조용진,이대령,노연숙,이선미,최홍대 동의대학교 기초과학연구소 1994 基礎科學硏究論文集 Vol.4 No.1
As a part of chemical study on the bioactive metabolites from marine organisms, we have investigated cytotoxicity using brine shrimp bioassay for each solvent fractions of the marine algae(12 species), marine sponges(3 species), coelenterates(2 species), echinoderms(4 species), marine molluscs(17 species), and ascidians(2 species), respectively. As the results, chloroform extract of Stichopus japonicus (LC_50 : 274 ㎍/ml), ethyl acetate extract of Anthocidaris crassispina(LC_50 : 121 ㎍/ml), n-butanol extract of Undaria pinnatifida (LC_50 : 178 ㎍/ml), and water extract of Thais clavigera (LC_50 : 61 ㎍/ml), displayed the most significant cytotoxic activity against brine shrimp. Among the marine organisms tested, echinoderms and marine molluscs were thought to be the most active Phylums on screening of new bioactive compounds.
위암환자의 복강내에 투여한 Mitomycin C-Carbon Particle의 Mitomycin 용출에 관한 연구
노승무,조영훈,정경수,오정연,김진향,양준묵,강대영,송규상,조준식,최선웅,이진호,민병무,김용백,김창식,박근성,인현빈,정현용,김학용 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1
Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherpy seems a logical choice for cancer chemotherapy. The Mitomycin C(MMC) adsorbed by the activated charcoal particles(CH) is relatively released when the drug concentration surrounding the carbon particles becomes low in the peritoneum of the peritoneal cavity. For the intraperitoneal chemotherapy on the advanced gastric adenocarcnoma, mitomycin C adsorbed on activated carbon particles was administered in the peritoneal cavity just before abdominal wall closure. The closed drainage tubes were inserted in the peritoneal cavity and clamped for tuo hours after completion of operation. MMC concentrations were serially measured in peritoneal fluid, plasma and urine at 2hour, 48 hour, 72 hour and 168 hour following its administration in order to study the efficacy of the MMC-CH as a drug delivery system. There were minimal toxicities in born marrow, liver, and gastrointestinal system after intraperitoneal MMC-CH administration. The data of this study suggested that MMC-CH may have a somewhat more beneficial effect than surgery alone when administered in optimal dose and schedules, but the MMC concentration of the peritoneal fluid was not sufficient to eradicate remnant cancer cells, and effective duration of maintenance was only below 24 hours in the peritoneal fluid and plasma.
백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구
송규상,강대영,최정목,노승무,정경수,오정연,김진향,양준목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1
To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.
관상동맥 질환에서 CD14 유전자형에 따른 세균 및 Heat Shock Protein에 대한 반응의 차이
한주용,최수연,조현주,김화평,강현재,구본권,김남중,김효수,손대원,오병희,박영배,최윤식 대한감염학회 2007 감염과 화학요법 Vol.39 No.1
Background : CD14 is the receptor for lipopolysaccharides and heat shock protein (HSP), which has been suggested being associated with increased risk of coronary artery disease (CAD). We investigated whether the response to infectious agents or HSP is different according to CD14 polymorphism in Koreans. Materials and Methods : Antibody titers to Helicobacter pylori, Chlamydia pneumoniae, and human HSP60 (hHSP60) were measured in 48 patients with stable CAD and in 41 healthy controls by ELISA. CD14 genotype was determined by PCR and high-sensitivity C-reactive protein (hs-CRP) was measured. Results : Seropositivity to C. pneumoniae and H. pylori, and antibody titer to hHSP60 were not significantly associated with the presence of CAD. CD14 genotype distribution was 31 TT (35%), 43 CT (48%), and 15 CC (17%). To compare the response to the infectious organism and hHSP60, we divided study population into 3 groups; CAD patients with non-TT genotype (group I, n=30), CAD patients with TT genotype (group II, n=18), and normal controls (group III, n=41). Seropositivity to C. pneumoniae and H. pylori, and antibody titer to hHSP60 were not significantly different among 3 groups. Though hs-CRP level was significantly different among 3 groups, post-Hoc analysis showed that hs-CRP level was not significantly different between group I and group II (group I: 1.6[1.1-3.5] mg/L and group II: 0.35[0.1-2.0] mg/L). Conclusions : This study suggests that the inflammatory responses to infectious organisms and HSP do not differ according to the CD14 genotype in Koreans. 목적 : 만성적인 세균 감염이나 자가 면역 반응이 동맥경화와 연관되어 있다는 주장이 제기되어 왔다. CD14은 lipopolysaccharides (LPS)와 heat shock protein(HSP)의 수용체로 C(-260)→T 다형성이 관상동맥 질환의 위험과 관련되어 있다고 제안되어 왔다. 본 연구에서는 한국인에서 CD14 다형성에 따른 LPS와 HSP에 대한 반응성을 염증표지자를 측정하여 살펴보고자 하였다. 재료 및 방법 : 안정형 관상동맥 환자 48명과 정상 대조군 41명을 대상으로 Chlamydia pneumoniae, Helicobacter pylori 항체 및 인체 HSP60 (hHSP60) 항체 역가를 enzyme-linked immunosorbent assay (ELISA) 방법으로 측정하였다. CD14 유전자형은 중합효소연쇄반응을 이용하여 결정하였고 hs-CRP를 측정하였다. 결과 : C. pneumonias 및 H. pylori 항체 양성 여부 및 항체 역가, 그리고 hHSP60에 대한 항체 역가는 안정형 관상동맥 질환의 유무와 유의한 상관관계는 없었다. CD14 유전자형의 분포는 TT 30명(39%), CT 31명(40%), 그리고 CC 16명(21%)이었다. 관상동맥 질환 군에서 TT 유전자형은 38%, 대조군에서는 32%로 TT 유전자형과 관상동맥 질환의 유무와는 유의한 상관관계가 발견되지 않았다(P>0.05). CD14 유전자형에 따라 C. pneumonias와 H.pylori 감염 및 hHSP60에 따른 반응에 차이가 있는지 여 부를 알아보기 위해, 관상동맥 질환 군을 다시 TT 유전자형 군과 non-TT 유전자형 군으로 나누어, 전체적으로 세군에서 항체 양성률과 역가를 비교하였다(I군: CD14 TT 유전자형을 가진 안정형 관상동맥 환자, II군: CD14 TT 유전자형을 가진 안정형 관상동맥 환자, III군: 정상 대조군). 세 군에서 C. pneumonias와 H. pylori 항체 양성률 및 hHSP60 항체 역가에는 유의한 차이가 없었다. 세 군사이에 hs-CRP 값에 유의한 차이가 있었지만, post-Hoc분석에서 II군의 hs-CRP 값이 I군에 비해 유의하게 높지는 않았다(0.35 [0.1-2.0] mg/L in group II vs. 1.6 [1.1-3.5]mg/L in group I, P>0.05). 결론 : 본 연구는 한국인에서 CD14 유전자형에 따라 LPS나 HSP에 대한 반응이 유의하게 다르지 않음을 시사한다.
오승민,남혜윤,김준수,연제덕,신대희,이진영,박대규,조명행,정규혁 성균관대학교 약학연구소 1998 成均藥硏論文集 Vol.10 No.1
The acute and subacute toxicity of New Woohwangchungsimwon(NWCH) which was used l-muscone as substitutive material of musk were investigated in S.D. rats. In intraperitoneal acute toxicity test, rats(Sprague-Dawley, SPF) were injected intraperitoneally with dosages of 0, 540, 750, 1,070, 1,500 and 3,000 ㎎/㎏. Body weights were significantly decreased at 540 ㎎/㎏ dose group in both sexes and abnormal autopsy findings were founded in both sexes at all treated groups. Intraperitoneal LD_50 of NWCH was 812.3 ㎎/㎏ in male and 872.3 ㎎/㎏ in female rats. In the subacute toxicity study, NWCH was administrated orally to both sexes of rats for 4 weeks as several doses(0, 320, 800 and 2,000 ㎎/㎏). There were neither dead animals nor significant changes of body weights during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, urinalysis, hematology, serum biochemical analysis, and other findings. Above data strongly suggest that no observed adverse effect level of NWCH might be over 2,000 ㎎/㎏/day in this study.
Rat의 복강에 삽입한 Fluorouracil-Polyglycolic acid 제형의 Fluorouracil 용출에 관한 연구
노승무,정경수,오정연,김진향,양준묵,강대영,송규상,최정목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 忠南大學校 癌共同硏究所 1998 癌共同硏究所 硏究誌 Vol.2 No.1
A common form of relapse in adenocarcinoma of the stomach is intraperitoneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adcnocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.
김세주,김찬형,조대연,이홍식 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.1
Objectives : The definite cause of obsessive-compulsive disorder (OCD) is still unknown, Evidences from familial, twin and segregation studies support the role of a genetic factor. There also are growing evidences indicating that OCD has specific neurochemical and neuroanatomical basis. Derived from the effectiveness of serotonin reuptake inhibitors in OCD treatment, several candidate genes related to serotonin regulation have been hypothesized to play on important role in the development of OCD. One of them is the serotonin transporter gene. The aim of this study was to investigate the association between serotonin transporter gene and OCD. Methods : 124 OCD patients and 119 normal controls participated in this study. Genomic DNA was extracted from their blood. The genotypes and allele frequencies of the 5-HTTLPR polymorphism between OCD group and control group were compared.And we investigated the association between 4 factors derived from YBOCS checklists and 5-HTTLPR polymorphism. Results '. In this case-control study, we could not find any association between 5-HTRLPR polymorphism and development of OCD. In OCD group, patients with L (l/s+s/s) genotype had higher scores for the religious/somatic factor than those with S genotype. Conclusion : In this study, there was no difference in genotype distributions of 5-HTTLPR between OCD and control groups. But, L genotype of 5-HTTLPR polymorphism had negative effects on some factors of the obsessive-compulsive symptoms.