• 한국수의병리학회지
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• 제1권1호
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• pp.7-12
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• 1997

Lethally irradited C3H/HeN mice were transplanted with syngeneic bone marrow. The B cell regeneration levels of spontaneous serum Ig, fecal igA and specific ig to diphtheria toxoid were determined at various time points. The number of B220+ cells reached normal range at 4 weeks after bone marrow transplantation(BMT) in spleen and lymph node. The B cell number of spleen returned to normal relatively soon than in the lymph node. Within 5 to 7 weeks after BMT, the transplanted mice contained nearly normal levels of spontaneous serum IgA, IgG2b and fecal IgA, but 2 fold lower levels of serum IgG2a, IgM and IgG3. Especially IgG3 levels were within low-normal range throughout the study. One to two weeks after immunization the predominant anti-diphtheria toxoid subtype was IgM. The levels of specific serum Ig were very low and after booster immunization at week 6, the short-lasting increase of Ig production was notd.

• IMMUNE NETWORK
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• 제3권2호
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

• The Korean Journal of Pain
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• 제23권4호
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• pp.230-235
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• 2010

Background: Bone cancer pain has a disruptive effect on the cancer patient's quality of life. Although ginsenosides have been used as traditional medicine in Eastern Medicine, the effect on bone cancer pain has not been throughly studied. The aim of this study was to determine whether ginsenosides may alter the bone cancer pain at the spinal level. Methods: NCTC 2472 tumor cells ($2.5{\times}10^5$) were injected into the femur of adult male C3H/HeJ mice to evoke bone tumor and bone cancer pain. To develop bone tumor, radiologic pictures were obtained. To assess pain, the withdrawal thereshold was measured by applying a von Frey filament to the tumor cells inoculation site. The effect of intrathecal ginsenosides was investigated. Effect of ginsenosides (150, 500, $1,000{\mu}g$) was examined at 15, 30, 60, 90, 120 min after intrathecal delivery. Results: The intrafemoral injection of NCTC 2472 tumor cells induced a radiological bone tumor. The withdrawal threshold with tumor development was significantly decreased compared to the sham animals. Intrathecal ginsenosides effectively increased the withdrawal threshold in the bone cancer site. Conclusions: NCTC 2472 tumor cells injection into the mice femur caused bone tumor and bone cancer pain. Intrathecal ginsenosides attenuated the bone cancer-related pain behavior. Therefore, spinal ginsenosides may be an alternative analgesic for treating bone cancer pain.

• Parasites, Hosts and Diseases
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• 제30권2호
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• pp.101-112
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• 1992

원발성 아메바성 수막뇌염을 일으키는 병원성이 강한 자유생환 아에바인 Acanthnmogbn culbertsoni이 영양형을 CSH/HeJ 마우스에 $1{\times}I0^4과{\;}1{\times}10^5$마리씩을 각각 감염시킨 후 12시 간, 1일, 2일, 5일, 10일 째에 감염 마우스를 희생하여 비장 세포의 부유액을 만들어 YAC-1 표적세포에 대한 세포독성을 $^{51}Cr$ 방출 검사법으로 측정하였고 단세포 독성 검사법으로 표적세포 결합능, 환성 자연살세포, 더 나아가 최대 자연살세포 살해능 및 최대 재순환능을 측정하였다. 감염 마우스의 사망률은 아메바 영양형 $1{\times}10^4$마리를 감염시켰을 때 34%이었으며 $1{\times}10^5$을 감염시켰을 때는 65%이었다. 또한 접종 후 20일까지 사망한 마우스의 평균 생존 기간은 각각 $16.40{\pm}3.50,{\;}13.20{\pm}4.09$ 일이었다. 자연살세포의 세포독성은 두 실험군 모두에서 아메바 접종 후 12시간 째에 대조군에 비하여 유의하게 증가하기 시작하여 접종 후 1일 째 가장 높았다. 2일 후에는 대조군과 비슷한 수준을 보였고 전종 후 10일 째에는 대조군에 비해 저하되었으며, 두 실험군 간에 차이는 발견할 수 없었다. 아메바 영양형 $1{\times}10^5$마리를 감염시킨 군에서 표적세포 결합능은 접종 후 12시간, 1일째에 유의하게 증가하였고 환성 연살세포도 비슷한 경향으로 증가하였으나 재순환능은 감염 겹과 시간 별로 대조군과 비교하여 차이를 발견할 수 없었다. 이상의 결과를 종합하면 A. culbertsoni 감염에 의해 비장세포의 자연살세포 독성이 증가하였는데, 이는 자연살세포의 표적세포 결합능과 활성 자연살세포수의 증가와 유의한 상관관계가 있고(p<0.05) 자연살세포의 재순환능과는 무관한 것으로 나타났다.

• 생명과학회지
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• 제17권11호
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• pp.1497-1504
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• 2007

사람의 혈소판조절인자 (TPO)의 분비와 기능을 분석하기 위하여 사람 간 cDNA로부터 TPO cDNA를 분리하여 동물세포에서 재조합체를 생산하였다. 또한, 당쇄의 기능분석을 위하여 6개의 당쇄첨가부위를 Ala으로 치환하여 각각의 돌연변이체 재조합체도 생산하여 이들의 생리활성분석을 위하여 피하주사하여 혈소판의 증가여부를 분석하였으며, 체내 약동학검사를 위하여 꼬리 정맥에 재조합체를 주사하여 24시간까지 혈액을 채취하였다. Wild-type TPO는 효과적으로 분비하였으나, 크로닝에서 분석되어 진 116개 아미노산이 삭제된 돌연변이체는 배양상층으로 분비되지 않았다. N-linked 당쇄첨가 부위는 3번과 4번을 제외하고는 거의 비슷한 발현양상을 나타내었다. 특히 4번당쇄부위는 TPO의 분비에 중요한 역할을 하는 것으로 나타났다. 재조합체 10ng을 피하주사에 의하여 체내 혈소판이 유의적으로 증가하였으며, 5ng을 이용한 약동학 분석결과 1시간에 최대로 증가하였으며 그 이후 급격하게 감소하여 10시간에는 거의 존재하지 않았다. 따라서, 이러한 연구는 고 활성을 가지는 유전자 재조합체 TPO의 생산을 가능하게 하고, 또한 새로운 분자의 TPO를 가능하게 할 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제27권6호
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• pp.541-553
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• 2023

Retinal prostheses have shown some clinical success in restoring vision in patients with retinitis pigmentosa. However, the post-implantation visual acuity does not exceed that of legal blindness. The reason for the poor visual acuity might be that (1) degenerate retinal ganglion cells (RGCs) are less responsive to electrical stimulation than normal RGCs, and (2) electrically-evoked RGC spikes show a more widespread not focal response. The single-biphasic pulse electrical stimulation, commonly used in artificial vision, has limitations in addressing these issues. In this study, we propose the benefit of multiple consecutive-biphasic pulse stimulation. We used C57BL/6J mice and C3H/HeJ (rd1) mice for the normal retina and retinal degeneration model. An 8 × 8 multi-electrode array was used to record electrically-evoked RGC spikes. We compared RGC responses when increasing the amplitude of a single biphasic pulse versus increasing the number of consecutive biphasic pulses at the same stimulus charge. Increasing the amplitude of a single biphasic pulse induced more RGC spike firing while the spatial resolution of RGC populations decreased. For multiple consecutive-biphasic pulse stimulation, RGC firing increased as the number of pulses increased, and the spatial resolution of RGC populations was well preserved even up to 5 pulses. Multiple consecutive-biphasic pulse stimulation using two or three pulses in degenerate retinas induced as much RGC spike firing as in normal retinas. These findings suggest that the newly proposed multiple consecutive-biphasic pulse stimulation can improve the visual acuity in prosthesis-implanted patients.

• 약학회지
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• 제35권3호
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• pp.154-164
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• 1991

These experiments were conducted to investigate the effects of Glycyrrhizae Radix extract(GR) on histamine synthesis, lymphocyte blastogenesis in C57BL/6J mice splenocytes, IL-1 production, $Ca^{2+}$ uptake by macrophage-like P388D$_{1}$ cells and plaque forming cell assay against SRBC. Histamine contents, lymphocyte blastogenesis, IL-1 activity, $Ca^{2+}$ uptake and plaque forming cell were determined by enzyme isotope method, [$^{3}$H]-thymidine incorporation, C3H/HeJ mouse thymocytes proliferation, the addition of 5 $\mu$Ci/ml $^{45}Ca^{2+}$ to P388D$_{1}$ cell suspension and assay to sheep red blood cell, respectively. Cytotoxicity, which was expressed as 50% mortality, was occurred by the addition of GR(10$^{-3}$g/ml). Histamine production in mouse spleen cell culture was significantly increased by 48 hour incubation added 0.25$\mu\textrm{g}$/ml of Con A. Con A-dependent T-lymphocyte proliferation was also enhanced by the addition of 0.25 $\mu\textrm{g}$/ml of Con A. GR depressed histamine contents at 10$^{-9}$~10$^{-4}$g/ml. and Con A (0.25 $\mu\textrm{g}$/ml) dependent T-lymphocyte proliferation at 10$^{-5}$~10$^{-4}$g/ml. IL-1 activity was significantly decreased by 10$^{-8}$~10$^{-4}$g/ml of GR. $Ca^{2+}$ uptake was not changed by GR, but antibody production markedly increased at 10.0~50.0 mg/kg of GR. From the above results, it is suggested that GR have immuno-regulatory action; GR decreased cell-mediated immune response and increased antibody production by B lymphocyte at high doses.

• IMMUNE NETWORK
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• 제5권3호
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• pp.163-171
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• 2005

Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.

• 대한미생물학회지
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• 제34권5호
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• pp.471-478
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• 1999

Spirochetes were isolated from the midgut of Ixodes persulcatus ticks captured at Chungju, Korea and identified as Borrelia afzelii strains by polymerase chain reaction. To determine the pathogenicity of the B. afzelii strains isolated in Korea, the microbiological and pathological features of Lyme disease were observed in C3H/He mice after intraperitoneal inoculation of the fresh isolate of B. afzelii strain. The results are summarized as follows 1) The Borrelia were detected in the tissues of heart, spleen, kidney, urinary bladder and knee joint within 7 days after inoculation of infection by dark field microscopic examination. The isolation rate from heart, urinary bladder and joint was significantly higher than the rate from spleen, kidney, and blood samples. 2) The Borrelia was detected in heart muscle by indirect immunofluorescent antibody test. 3) Antibody to the Borrelia was detected as early as one week after inoculation. 4) The marked tropism of the Borrelia was observed in myocardial, urinary tract and joint tissue. The main pathological features are inflammation in tissues of heart, kidney, joint and urinary bladder. From these results, the Borrelia afzelii strain isolated in Korea were determined as pathogenic strain.

• Journal of Ginseng Research
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• 제46권2호
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• pp.235-247
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• 2022

Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.