소아 악성 종양의 임상 통계적 관찰

구의본,이순용,서강석 인제대학교 1985 仁濟醫學 Vol.6 No.3

저자들은 1979년 7월부터 1984년 6월까지 만 5년간 부산백병원에 입원한 만 15세 이하의 소아 악성 종양 99예를 임상 통계적으로 관찰하고 그 결과를 보고하고자 한다. A clinical study was carried out on 99 cases of children with malignant tumors admitted to Pusan Paik Hospital during a period of 5 years, from July 1, 1979 to June 30, 1984, and the following results were obtianed. 1.The incidence of malignant tumors among total inpatients under 15 years of age was 0.62 percent. 2.The most common malignant tumor was leukemia(57.6%), and the next were brain tumor(8.1%), retinoblastoma (8.171), and neuroblastoma (7.1%)) in decreasing order of frequency. 3.The male to female ratio was 1.5:1. But the ratio of patients with malignant tumors to total inpatients was nearly equal in broth sexes. 4.A bout a half of the cases with malignant tumors in children (51.5%) were under 5 years of age. Most of the cases of neuroblastoma, Wilms tumor, and retinoblastoma were under 5 years of age. 5.A mong leukemia acute lymphoblastic leukemia was 59.6%, acute nonlymphblastic leukemia was 36.8% and chronic myelocytic leukemia was 3.5%. 6.Among brain turmors astrocytoma (37.5%) was the most common.

Higenamine Analog, YS 49, Inhibits Inducible Nitric Oxide Synthase Expression in RAW 264.7 Cell

Kang, Y. J.,Koo, E. B.,Lee, Y. S.,Yun, H. S.,Chang, K. C. 경상대학교 농업자원이용연구소 1998 심포지엄 자료집 Vol.1998 No.1

실험동물에 LPS 또는 cytokine 투여시 나타나는 패혈성 쇼크는 혈관 수축제에 대한 수축력의 저하와 여러 장기에 손상을 주게 되는데 이것은 nitric oxide (NO)라는 효소가 유도되기 때문이다. 한방에서 부자 추출물은 항류마티스에 쓰이는데 그 주된 성분은 higenamine이란 알칼로이드로 밝혀져있다. 본 연구에서는 LPS 및 interferon (IFN)-γ를 처리한 흰쥐 혈관세포 (RAVSMC) RAW 264.7세포에서 발현되는 iNOS효소에 대한 higenamine 유사체인 YS49의 억제 효과를 살펴보고자 하였다. YS 49는 RAVSMC와 RAW 264.7 세포에서 No를 농도-의존적으로 줄였으며 50%억제를 나타내는 농도는 각각 22 μM과 30 μM이었다. LPS에 의한 흰쥐 수축력 저하 작용은 YS 49의 전처리로 회복되었다. 또한 LPS는 혈관에서 iNOS mRNA를 발현 시켰으나 Ys 49투여시 발현이 줄어 들었고 특히 LPS 투여 혈관은 수축 시킨뒤 NOS의 기질인 L-arginine에 의해 혈관 이완이 일어났다. YS 49를 동시 투여한 혈관에서는 이완이 줄어 들었다. 이상의 결과는 YS 49가 RAVSMC와 RAW 264.7 세포에서 LPS나 cytokine에 의한 iNOS 발현을 억제하는 것을 시사하며 iNOS가 과다 발현되는 질병이나 패혈증상에 효과가 있을 것으로 생각된다. The inducible nitric oxide synthase (iNos) plays a key role in the development of vascular failure and multiple organ dysfunction in lipopolysaccharide (LPS)- and/or cytokine-induced endotoxic shock animal models. In the present study, we investigated the effect of a natural alkaloid YS 49, on the NO production and iNOS proteinexpression in cultured rat aortic vascular smooth muscle cells (RAVSMC) and RAW 264.7 cells by LPS with interferon (IFN)-γ. In addition, preventive effect of YS 49 not only on vascular hyporeactivity in vitro and ex vivo but also on survival rate (mice) and serum NOx (rat) levels was investigated in LPS-treated animals. YS 49, concentration-dependently, reduced NO production in RAVSMC and RAW 264.7 cells with IC_50 22 and 30 uM, respectively. Pre- or co-administration with YS 49 prevented the LPS-induced suppression of vascular contractility to vasoconstrictors (PE, U46619) in the rat thoracic aorta ex vivo and in vitro. Pretreatment with YS 49 reduced iNOS mRNA expression in rat aorta activated by LPS. NOS substrate, L-arginine, but not D-arginine, significantly reduced the relazation in YS 49 plus LPS-treated aortas. These data strongly suggest that YS 49 can suppress iNOS gene expression induced by LPS and/or cytokines in RAVSMC and RAW 264.7 cell at the transcriptional level, and may be beneficial in septic shock and other sideases associated with iNOS over-expression.

선천성 Cytomegalovirus 감염 1례

박강우,안호식,구의본,김성원,김길현 성분도병원 1990 성분도병원논문집 Vol.3 No.-

Lipopolysaccharide로 활성화시킨 흰쥐 혈관의 iNOS 발현에 대한 Higenamine의 효과

강영진,이균우,구의본,이회영,장기철,Kang Young-Jin,Lee Goun-Woo,Ku Eui-Bon,Lee Hoi-Young,Chang Ki-Churl 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

Higenamine was widely used as traditional remedy for the treatment of rhumatoid arthritis. Nitric oxide(NO) may be a critical mediator in this inflammatory disease. Synovial tissue from humans with inflammatory arthritis expresses NOS2(iNOS) mRNA and protein, and generates NO in vitro. We therefore, investigated the effect of higenamine on the induction of nitric oxide synthase(NOS) promoted by lipopolysaccharide(LPS). Prophylactic application of higenamine selectively prevented LPS-primed initiation of L-arginine-induced relaxation and restored rhenylephrine(PE)-induced contraction in rat aorta. LPS-stimulated nitrite production in the incubation medium was reduced by higenamine. Furthermore, RT-PCR and Northern analysis indicated that higenamine reduced iNOS expression primed by LPS in rat aorta. These results suggest that higenamine prevents LPS-promoted induction of NOS in vascular smooth muscle.

태변성 복막염 1례

유윤영,이현순,구의본,김성원,김길현 성분도병원 1990 성분도병원논문집 Vol.3 No.-

흰쥐 기관평활근에 대한 GS 386의 칼슘억제 및 포스포디에스테라제 억제 작용

장기철,이회영,강영진,구의본 大韓藥理學會 1996 대한약리학잡지 Vol.32 No.3

최근 본 연구실에서는 GS 386인 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline이 적출된 토끼의 심방세포에서 <TEX>$Ca^{++}$</TEX> 채널의 운동성 변화없이 <TEX>$Ca^{++}$</TEX> 채널이 열릴 가능성을 줄임으로써 <TEX>$Ca^{++}$</TEX> 전류의 증폭을 억제한다고 보고하였다. 이번 연구에서는 적출된 쥐의 기관지를 사용하여 GS 386의 작용기전에 대해 연구하였다. GS386은 carbachol <TEX>$(0.3{\mu}M)$</TEX>과 높은 농도의 <TEX>$K^+$</TEX> (65.4mM)에 의해 수축된 쥐의 기관지를 용량-의존적으로 이완시켰으며 이때 <TEX>$IC_{50}$</TEX>는 5.24와 <TEX>$5.67\;{\mu}M$</TEX>이었다. verapamil은 carbachol에 의한 수축시 보다 높은 농도의 <TEX>$K^+$</TEX>에 의해 수축된 조직에 더욱 효과적으로 억제하였다. <TEX>$Ca^{++}$</TEX>이 없는 상태에서 <TEX>$Ca^{++}$</TEX>에 의한 수축은 GS386에 의해 억제되었다. 더욱이 높은 농도의 GS386<TEX>$(100\;{\mu}M)$</TEX>은 verapamil과는 다르게 carbachol뿐만 아니라 caffeine에 의한 위상성 수축을 억제 시키므로 GS386은 세포질내로 들어가 sarcoplasmic retuculum과 같은 근육 내부에 2차적인 영향을 나타내었다. 더군다나GS386은 verapamil에 의해 영향을 받지않는 (verapamil-insensitive component)이완을 보였고 쥐 기관지의 평활근에서 cAMP의 양을 증가 시켰다. 이러한 결과는 GS386의 작용기전이 <TEX>$Ca^{++}$</TEX> 길항적인 작용 뿐만 아니라 posphodiesterase억제작용에 기인한다는 사실을 제시한다. Recently we reported that GS 386, 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline, inhibited amplitude of the <TEX>$Ca^{2+}$</TEX> current by reducing the probability of <TEX>$Ca^{2+}$</TEX> channel opening without changing channel kinetics in isolated rabbit atrial myocyte. In the present study, further investigation of the mechanism of action of GS 386 was performed using isolated rat trachealis. GS 386 concentration-dependently relaxed rat trachealis contracted by carbachol <TEX>$(0.3{\mu}M)$</TEX> and high <TEX>$K^+$</TEX>(65.4 mM) with <TEX>$IC_{50}$</TEX> 5.24 and 5.67 <TEX>${\mu}M$</TEX>, respectively. Verapamil inhibited more effectively the high <TEX>$K^+-contracted$</TEX> tissues than those with carbachol in the rat trachealis muscle. In <TEX>$Ca^{2+}-free$</TEX> media, <TEX>$Ca^{2+}-induced$</TEX> contraction was inhibited by GS 386. Furthermore, high concentration of GS 386 <TEX>$(100{\mu}M)$</TEX> but not verapamil, attenuated a phasic contraction induced not only by carbachol but also caffeine, indicating that GS386 can enter into the cytoplasm where it may exert secondary actions on internal sites of the muscle, such as sarcoplasmic reticulum. Moreover, GS 386 showed verapamil-resistant component of relaxation and increased cAMP levels in rat trachal smooth muscle. These results suggest that the mechanism of action of GS 386 attributes to not only <TEX>$Ca^{2+}$</TEX> antagonistic action but also weak phosphodiesterase inhibitory action.

Calcium Channel Blocking and Phosphodiesterase Inhibitory Action of GS386, a Dihydroisoquinoline Derivative, in Isolated Rat Trachea

장기철,이회영,강영진,구의본,Chang, Ki-Churl,Lee, Hoi-Young,Kang, Young-Jin,Koo, Eui-Bon The Korean Society of Pharmacology 1996 대한약리학잡지 Vol.32 No.3

최근 본 연구실에서는 GS 386인 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline이 적출된 토끼의 심방세포에서 $Ca^{++}$ 채널의 운동성 변화없이 $Ca^{++}$ 채널이 열릴 가능성을 줄임으로써 $Ca^{++}$ 전류의 증폭을 억제한다고 보고하였다. 이번 연구에서는 적출된 쥐의 기관지를 사용하여 GS 386의 작용기전에 대해 연구하였다. GS386은 carbachol $(0.3{\mu}M)$과 높은 농도의 $K^+$ (65.4mM)에 의해 수축된 쥐의 기관지를 용량-의존적으로 이완시켰으며 이때 $IC_{50}$는 5.24와 $5.67\;{\mu}M$이었다. verapamil은 carbachol에 의한 수축시 보다 높은 농도의 $K^+$에 의해 수축된 조직에 더욱 효과적으로 억제하였다. $Ca^{++}$이 없는 상태에서 $Ca^{++}$에 의한 수축은 GS386에 의해 억제되었다. 더욱이 높은 농도의 GS386$(100\;{\mu}M)$은 verapamil과는 다르게 carbachol뿐만 아니라 caffeine에 의한 위상성 수축을 억제 시키므로 GS386은 세포질내로 들어가 sarcoplasmic retuculum과 같은 근육 내부에 2차적인 영향을 나타내었다. 더군다나GS386은 verapamil에 의해 영향을 받지않는 (verapamil-insensitive component)이완을 보였고 쥐 기관지의 평활근에서 cAMP의 양을 증가 시켰다. 이러한 결과는 GS386의 작용기전이 $Ca^{++}$ 길항적인 작용 뿐만 아니라 posphodiesterase억제작용에 기인한다는 사실을 제시한다. Recently we reported that GS 386, 1-(4'-methoxybenzyl)-6,7-dimethoxy-3,4-dihydroisoquinoline, inhibited amplitude of the $Ca^{2+}$ current by reducing the probability of $Ca^{2+}$ channel opening without changing channel kinetics in isolated rabbit atrial myocyte. In the present study, further investigation of the mechanism of action of GS 386 was performed using isolated rat trachealis. GS 386 concentration-dependently relaxed rat trachealis contracted by carbachol $(0.3{\mu}M)$ and high $K^+$(65.4 mM) with $IC_{50}$ 5.24 and 5.67 ${\mu}M$, respectively. Verapamil inhibited more effectively the high $K^+-contracted$ tissues than those with carbachol in the rat trachealis muscle. In $Ca^{2+}-free$ media, $Ca^{2+}-induced$ contraction was inhibited by GS 386. Furthermore, high concentration of GS 386 $(100{\mu}M)$ but not verapamil, attenuated a phasic contraction induced not only by carbachol but also caffeine, indicating that GS386 can enter into the cytoplasm where it may exert secondary actions on internal sites of the muscle, such as sarcoplasmic reticulum. Moreover, GS 386 showed verapamil-resistant component of relaxation and increased cAMP levels in rat trachal smooth muscle. These results suggest that the mechanism of action of GS 386 attributes to not only $Ca^{2+}$ antagonistic action but also weak phosphodiesterase inhibitory action.

관상동맥이완과 혈소판응집에 대한 GS283 과 GS386 의 약리작용기전에 관한 연구

장기철(Ki Churl Chang),이회영(Hoi Young Lee),이균우(Goun Woo Lee),구의본(Eui Bon Koo),강영진(Young Jin Kang),이영수(Young Soo Lee) 한국응용약물학회 1997 Biomolecules & Therapeutics(구 응용약물학회지) Vol.5 No.3

Trimetoquinol (TMQ) and its analogs are known to have thromboxane A₂ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited Ca^(2+)-induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to α-adrenergic receptor. Taken together, we concluded that the mechamism of action of GS283 and GS386 is not related with in TXA₂ receptor but concerned with calcium antagonistic action and α-blocking action.