Genetic effect of <i>CCR3</i> and <i>IL5RA</i> gene polymorphisms on eosinophilia in asthmatic patients

Lee, June-Hyuk,Chang, Hun Soo,Kim, Ji Hyun,Park, Se-Min,Lee, Yong Mok,Uh, Soo Taek,Rhim, Taiyoun,Chung, Il Yup,Kim, Yong-Hoon,Park, Byung Lae,Park, Choon-Sik,Shin, Hyoung Doo Elsevier 2007 The journal of allergy and clinical immunology Vol.120 No.5

<P><B>Background</B></P><P>Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.</P><P><B>Objective</B></P><P>We investigated the association of polymorphisms in <I>CCR3</I> and <I>IL5RA</I> with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.</P><P><B>Methods</B></P><P>Polymorphisms in <I>CCR3</I> and <I>IL5RA</I> were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor α (IL-5Rα) protein expression on eosinophils was measured by means of flow cytometry.</P><P><B>Results</B></P><P>Although polymorphisms in <I>CCR3</I> were not associated with asthma susceptibility, the <I>CCR3</I> haplotype <I>ht2</I> showed a negative gene dose effect on the eosinophil count (<I>P</I> = .003–.009). <I>IL5RA c.−5091G>A</I> was weakly associated with eosinophil count. The effects of <I>ht2</I> were greater when paired with <I>IL5RA c.−5091A</I> (<I>P</I> = .001–.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without <I>ht2</I> than in those with <I>ht2</I>. Asthmatic patients with the <I>IL5RA c.−5091A</I> allele showed higher IL-5Rα expression than those who were homozygous for the G allele.</P><P><B>Conclusion</B></P><P>The genetic association between <I>CCR3</I> polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the <I>CCR3</I> polymorphisms were paired with polymorphisms in <I>IL5RA</I>. The protein expression levels of CCR3 and IL-5Rα on peripheral blood eosinophils are associated with the polymorphisms on their own genes.</P><P><B>Clinical implications</B></P><P>The identification of single nucleotide polymorphisms and haplotypes of <I>CCR3</I> and <I>IL5RA</I> might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.</P>

간장 ( 肝腸 ) 및 담도 ( 膽道 ) : B형 활동성 간염 환자에서 단기 Prednisolone과 ARA - AMP 겸용 치료의 경과에 따른 면역 지표의 변화에 관한 연구

민영일(Young Il Min),장린(Rin Chang),김병호(Byung Ho Kim),장영운(Young Woon Chang),이정일(Joung Il Lee),황이숙(Yi Sook Hwang),김정원(Jeong Won Kim),김효종(Hyo Jong Kim) 대한소화기학회 1990 대한소화기학회지 Vol.22 No.3

N/A Withdrawal of corticosteroids in patients with chronic type B hepatitis is frequently associated with enhanced cellular immune response to hepatitis B virus. This immunolgic rebound generally results in a transient reduction in levels of HBV-DNA and DNA polymerase, and seldom results in clearance of HBeAg. There was a pilot study that the combination of a short course of prednisone followed by ARA-AMP was potentially synergistic. The object of this study was to determine the effect of short term prednisolone followed by ARA-AMP on the immune system in patients with chronic active ltepatitis-B. Patients were started 40 mg of prednisolone daily for 4 weeks. After prednisolone therapy was discontinued, patients received no medication for 2 weeks. ARA-AMP was then given for 4 weeks at a dose of 500 mg daily. Immune parameters such as T cell subsets, IL, production, NK cell activeity, and LAK cell activity were tested before and during treatement period. The resullts were as follows. 1) Basal IL2 production in CAH-B (71.3 unit/ml) was lower than that of normal control (p<0.025). Basal NK activity, T4/T8 ratio and LAK activity of CAH-B were similar to those of normal control. 2) After prednisolone treatment, IL2 production, NK cell activity and LAK cell activity were significantly lower than those of basal value. 3) After induction of immune rebound, IL, production increased to 84.8 unit/ml (basal 71.3 unit/ml,

Ropivacaine 을 이용한 경막의 마취시 Clonidine 병용의 효과

김종일,조영훈,이상곤,민병우,이지향,반종석 대한마취과학회 2001 Korean Journal of Anesthesiology Vol.41 No.4

Effects of Clonidine Added to Ropivacaine in Epidural Anesthesia Young-Hoon Cho, M.D., Ji-Hyang Lee, M.D., Sang-Gon Lee, M.D., Jong-Il Kim, M.D.^*, Jong-Suk Ban, M.D., and Byung-Woo Min, M.D. Department of Anesthesiology, Daegu Fatima Hospital, Daegu, Korea ^*Kim Jong Il Pain clinic, Daegu, Korea Background: Clonidine has been regarded as an adequate supplementary anesthetic during epidural anesthesia and has been used with local anesthetics such as bupivacaine or lidocaine to support the effects of these anesthetics. The authors would examine whether clonidine is an adequate supplementary anesthetic when it is used with ropivacaine during epidural ane-sthesia. Methods: Thirty-two healthy patients undergoing a hip or lower limb surgery were diveded into two groups. In group 1, 0.5% ropivacaine 15 ml was administered. In group 2, 0.5% ropivacaine 15 ml combined with clonidine 150 ㎍ was administered. Onset, duration and maximal height of sensory block were assessed. Sedation score, blood pressure and heart rate were measured. Results: Duration of sensory block of group 2 was significantly longer than that of group 1. Sedation score of group 2 was significantly higher than that of group 1. Blood pressure of group 2 was sig-nificantly lower thatn that of group 1 at 50 min, 70 min and 90 min after epidural injection. No significant differences were observed in onset of sensory block and heart rate between the two groups. Conclusions: The addition of clonidine to ropivacaine during epidural anesthesia prolonged duration of sensory block and produced useful sedation. It caused relatively stable hemodynamic changes. These results suggest that clonidine is an adequate supplementary anesthetic when it is used with ropivacaine during epidural anesthesia. (Korean J Anesthesiol 2001; 41: 428~433)

화학적 요부 교감신경절 차단에서 한 분절 차단과 두 분절 차단의 비교

김종일,이규종,이상곤,민병우,반종석,문철준 대한마취과학회 2001 Korean Journal of Anesthesiology Vol.41 No.4

Chemical Lumbar Sympathetic Block: Comparison of One- Versus Two-needle Techniques Chul-Jun Mun, M.D., Kyu-Jong Lee, M.D., Sang-Gon Lee, M.D., Jong-Il Kim, M.D.^* Jong-Suk Ban, M.D., and Byung-Woo Min, M.D. Department of Anesthesiology, Fatima Hospital, Daegu, Korea ^*Kim Jong Il Pain Clinic, Daegu, Korea Background: It was frequently noticed in the course of performing a two-needle sympathectomy, that satisfactory spread of contrast solution could be produced by injection through only one of the needles. This led to a closer examination of the merits of single-needle technique. Methods: Forty patients were randomized into two groups. Patients in the single-needle group (n = 20) were injected at the second or third lumbar sympathetic ganglia, while patients in the two-needle group (n = 20) were injected at the second and thired lumbar sympathetic ganglia. Lumbar sympathetic blocks were performed using 3 ml of alcohol and the spread of injectate was verified with C-arm fluoroscopy. The indicators of a successful sympathetic block are increasing skin temperature, decreasing pain, and anhidrosis in the distal extremity. Results: The duration of anhidrosis was 12.2 ?? 2.6 months (mean ?? SD) in the single-needle group versus 13.6 ?? 3.6 months (mean << SD) in the two-needle group. Conclusions: As these results were not significantly different from those obtained in patients having considered to be effective for a neurolytic ;i,bar sympathectomy. (korean J Anesthesiol 2001; 41: 439~443)

捻轉法이 竝行된 鍼刺戟 및 電鍼刺戟이 鎭痛效果에 미치는 影響

金志勳,盧植,閔炳一,朴東錫 경희대학교 1998 慶熙醫學 Vol.14 No.3-4

Relieving effects of electroacupuncture on mechanical allodynia in neuropathic pain model of inferior caudal trunk injury in rat : mediation by spinal opioid receptors

Kim, Ji Hoon,Min, Byung-Il,Na, Heung Sik,Park, Dong Suk WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

The relieving effects of electroacupuncture (EA) on mechanical allodynia and its mechanism related to the spinal opioid system were investigated in a rat model of neuropathic pain. To produce neuropathic pain in the tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. Two weeks after the surgery, EA stimulation (2 or 100 Hz, 0.3 ms, 0.2~0.3 mA) was delivered to Zusanli (ST36) for 30 min. The degree of mechanical allodynia was evaluated quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. These rats were then subjected to an i.t. injection with one of the three specific opioid agonists in successive ways: the mu agonist (DAMGO 25, 50 and 100 pmol), the delta agonist (DADELT Ⅱ 0.5, 1 and 2 nmol), and the kappa agonist (U50488H 5, 10 and 20 nmol) separated by 10 min in cumulative doses. During 30 min of EA stimulation, specific opioid antagonists were subjected to i.t. injection: the mu antagonist (β-FNA 5, 10 and 20 nmol), the delta antagonist (naltrindole 5, 10 and 20 nmol), and the kappa antagonist (nor-BNI 3, 6 and 12 nmol) separated by 10 min in cumulative doses. As a result, EA reduced the behavioral signs of mechanical allodynia. Two Hz EA induced a robust and longer lasting effect than 100 Hz. All three opioid agonists also showed relieving effects on mechanical allodynia. However, nor-BNI could not block the EA effects on mechanical allodynia, whereas β-FNA or naltrindole significantly blocked EA effects. These results suggest that the mu and delta, but not kappa, opioid receptors in the spinal cord of the rat, play important roles in mediating relieving effects on mechanical allodynia induced by 2 Hz EA.

Relieving effects of electroacupuncture on mechanical allodynia in neuropathic pain model of inferior caudal trunk injury in rat : mediation by spinal opioid receptors

Kim, Ji Hoon,Min, Byung-Il,Na, Heung Sik,Park, Dong Suk WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

The relieving effects of electroacupuncture (EA) on mechanical allodynia and its mechanism related to the spinal opioid system were investigated in a rat inodel of neuropathic pain. To produce neuropathic pain in the tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. Two weeks after the surgery, EA stimulation (2 or 100 ㎐, 0.3ms 0.2 - 0.3 ㎃) was delivered to Zusanli (ST36) for 30 min. The degree of mechanical allodynia was evaluated quantitatively by touching the tail with von Frey hair (2.0g) at 10 min intervals. These rats were then subjected to an i.t. injection with one of the three specific opioid agonists in successive ways: the mu agonist (DAMGO 25, 50 and 100 pmol), the delta agonist (DADELT Ⅱ 0 5, 1 and 2 nmol), and the kappa agonist (U50488H 5, 10 and 20 nmol) separated by 10 min in cumulative doses. During 30 min of EA stimulation, specific opioid antagonists were subjected to i.t. injection: the mu antagonist (β-FNA 5, 10 and 20 nmol), the delta antagonist (naltrindole 5, 10 and 20 nmol), and the kappa antagonist (nor-BNI 3, 6 and 12 nmol) separated by 10 min in cumulative doses. As a result, EA reduced the behavioral signs of mechanical allodynia. Two ㎐ EA induced a robust and longer lasting effect than 100㎐. All three opioid agonists also showed relieving effects on mechanial allodynia. However, nor-BNI could not block the EA effects on mechanical allodynia, whereas β-FNA or naltrindole significantly blocked EA effects. These results suggest that the mu and delta, but not kappa opioid receptors in the spinal cord of the rat, play important roles in mediating relieving effects on mechanical allodynia induced by 2 ㎐ EA.

Signal transducer and activator of transcription 3‐mediated CD133 up‐regulation contributes to promotion of hepatocellular carcinoma

Won, Cheolhee,Kim, Byung‐,Hak,Yi, Eun Hee,Choi, Kyung‐,Ju,Kim, Eun‐,Kyung,Jeong, Jong‐,Min,Lee, Jae‐,Ho,Jang, Ja‐,June,Yoon, Jung‐,Hwan,Jeong, Won‐,Il,P John Wiley and Sons Inc. 2015 Hepatology Vol.62 No.4

<P>Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin‐6/signal transducer and activator of transcription 3 (IL‐6/STAT3) signaling up‐regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL‐6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL‐6, with a concomitant decrease of hypoxia‐inducible factor 1 alpha (HIF‐1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF‐κB) p65 subunit to positively regulate the transcription of HIF‐1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF‐1α and CD133 expression were not observed in Toll‐like receptor 4/IL‐6 double‐knockout mice. Long‐term silencing of CD133 by a lentiviral‐based approach inhibited cancer cell‐cycle progression and suppressed <I>in vivo</I> tumorigenicity by down‐regulating expression of cytokinesis‐related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF‐1α proteins. <I>Conclusion</I>: IL‐6/STAT3 signaling induces expression of CD133 through functional cooperation with NF‐κB and HIF‐1α during liver carcinogenesis. Targeting STAT3‐mediated CD133 up‐regulation may represent a novel, effective treatment by eradicating the liver tumor microenvironment. (H<SMALL>EPATOLOGY</SMALL> 2015;62:1160‐1173)</P>

염전법이 병행된 침자극 및 전침자극이 진통효과에 미치는 영향

朴東錫,閔炳一,盧植,金志勳 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 1998 東西醫學硏究所 論文集 Vol.1998 No.-

Twirling the needle (TN) is one of several needling methods frequently used for acupuncture in the oriental medicine. The present study was conducted to see if TN enhanced the antinociceptive effect produced by plainor electroacupuncture in the rat tail flick test. Rats (Sprague-Dawley, 200~300g) lightly anesthetized with thiopental sodium (40mg/kg, i.p.) were used in the tail-flick test. The basal reaction time for tail-flick was 2 sec. For "plain" acupuncture (PA), a needle was inserted for 20 min into a Chock-samni(ST36) acupuncture point which (is located at the anterior tibial muscle and about 10mm below the knee joint). For electroacupuncture (EA), train-pulses (3Hz, 0.3ms pulse width, 0.2!0.3mA) were applied to the inserted needle for the period of insertion. For combining TN with either PA or EA, TN was performed during the each acupuncture period. Two methods for TN were used; twirling 3 times for 1 second persisted for 1 min in every 5 mins (long-duration and long-interval; LDLI)and twirling 3 times for 1 second persisted for 10 sec in every 1 min (short-duration and short-interval; SDSI). PA and EA produced an increase in tail flick latency (TFL); peak increases were 21.3??5.1% and 42.1??17.3% of the pre-acupunture control, respectively, and occurred immediately after cessation of 20 min-acupuncture. Performing TN combined with PA increased TFL more than PA itself by showing a greater peak increase in TFL when performed with a SDSI-TN than with a LDLI-TN (60.6??12.5% and 42.7??22.7% of the pre-acupuncture control, respectively). Performing TN combined with EA also increased TFL more than EA itself and a greater peak increase in TFL was observed with a SDSI-TN as compared to a LDLI-TN (77.5??13.8% and 67.3??14.0% of the pre-acupuncture control, respectively). These results indicate that TN enhances both PA-and EA-produced antinociception where an enhanced antinociception than a LDLI-TN. It is suggested that performing a SDSI-TN combined with EA seems to be one of the most effective ways to produce analgesia.

Ginsenoside Rg1 enhances CD4^(+) T-cell activities and modulates Th1/Th2 differentiation

Lee, Eui-joon,Ko, Eunjung,Lee, Jinwoo,Rho, Samwoong,Ko, Seonggyu,Shin, Min-Kyu,Min, Byung-il,Hong, Moo-Chang,Kim, Si-young,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper(Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4 T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4^(+) T cells, but augmented CD4^(-) T-cell proliferation upon activation with anti-CD3/anti-CD28 autibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4^(-) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4^(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4^(+) T cells under Th2 skewed condition, while decreasing IFN-ysecretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naive CD4^(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4^(-) T-cell activity, as well as the correction of Th1-dominant pathological disorders.