• Title/Summary/Keyword: GVL effect

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Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation

  • Lim, Ji-Young;Ryu, Da-Bin;Lee, Sung-Eun;Park, Gyeongsin;Choi, Eun Young;Min, Chang-Ki
    • Molecules and Cells
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    • v.38 no.11
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    • pp.966-974
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    • 2015
  • Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

Nonmyeloablative Stem Cell Transplantation (비골수제거성 조혈모세포이식)

  • Hyun, Myung-Soo
    • Journal of Yeungnam Medical Science
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    • v.19 no.1
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    • pp.11-27
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    • 2002
  • Allogenic hematopoietic stem cell transplantation is one of the effective therapy for several hematologic malignancies. Transplantation preparative regimen is designed to eradicate the patient's underlying disease and immunosuppress the patient adequately to prevent rejection of donor's hematopoietic stem cells. So, conventional myeloablative preparative regimens with high-dose chemotherapy or radiotherapy are related to high rate of morbidity and mortality. However, It has become clear that the high-dose therapy dose not eradicate the malignancy in some patients, and that the therapeutic benefit of allogenic transplantation is largely related to graft-versus-leukemia/graft-versus-tumor (GVL/GVT) effect. An new approach is to utilize less toxic, nonmyeloablative preparative regimens to achieve engraftment and allow GVL/GVT effects to develop. This strategy reduces the risk of treatment-related mortality and allows transplantation for elderly and those with comorbidities that preclude high-dose chemoradiotherapy.

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A Comparative Consideration of Treatment on Dementia in Oriental and Occidental Medicine (치매의 치료(治療)에 관(關)한 동서의학적(東西醫學的) 고찰(考察))

  • Lee, Dong-Weon;Shin, Gil-Jo;Lee, Won-Chul
    • The Journal of Dong Guk Oriental Medicine
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    • v.4
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    • pp.67-80
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    • 1995
  • This study was done in order to investigate the treatment of occidental and oriental medicine on dementia(mainly senile dementia and cerobrovascular dementia). The results were as follows ; 1. Dementia must treat a direct causes, but uncountable dementia(senile dementia) and cerobrovascular dementia can't treat at present. 2. Sciopsychological treatment in very important in dementia patient ; maintance of appropriate stimulation, psychological rest, physical examination, dietary cure and safety device is needed. On secondary mental disorder, antipsychotics, anxiolytics and antidepressants have to prescribe properly. 3. Treatments of Senile dementia(uncountable cerebral degenerative disease) proscribed hydergine which is peripheral vasodilator and physostigmine which increase cholinergic activity of brain, but this have slight effect on some patients. On treatments of cerobrovascular dementia, the medication that improved the cell metabolism and circulation of brain, this improved only a subjective symptom, but isn't foundamental treatment. 4. A tonic medicine is used basically, the methods are as follows. 1) Kenwihwadam(健胃火痰)-Sesimtang(洗心湯) 2) Bosiniksu(補腎益髓)-Hwansodan(還少丹) 3) Bosimiksin(補心益腎)-Gyuibitang(歸脾湯), Singyuo(神交湯) 4) Boheoansin(補虛安神)-Cilbokem(七福飮), sanggitang(生氣湯) 5) geoeohwalhyel(祛瘀活血)-tonggyuhwalhyeltang(通竅活血湯), 5. Acupuncture therapy on dementia used follow acupuncture point ; Yamen(啞門 GVl5), Laokung(勞宮 HC8), Tsusanli(足三里 ST36), Shenshu(腎兪 BL23), Tachui(大椎 GVl4), Chiuwei(鳩尾 CVl5), Sanyinchiao(三陰交 SP6), Yungchuan(涌泉 KI1), Shipsun(十宣), Shousanli(手三里 LI10), Taichong(太衝 LV3) In moxibustion therapy, Dachui(大椎 GVl4) point is used.

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A case report of the postpartum depression with Hominis Placenta Herbal acupuncture therapy (산후(産後) 우울증(憂鬱症)을 자하거(紫河車) 약침(藥鍼)을 활용하여 치료(治療)한 1례(例))

  • Lee, Cheol-Woong;Kim, Jin-Woo;Cho, Jin-Hyung;Lee, Soon-Yee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.19 no.2
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    • pp.282-294
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    • 2006
  • Purpose : The purpose of this study is to report the effect of oriental treatments to postpartum depression Methods : We treated the patient who had postpartum depression and visited Joong-hwa oriental hospital. The patient in this case, 36-years-old female, was admitted for 15days(161th/May/2005-30th/May/2005) due to postpartum depression which was measured by EPDS(Edinburgh Postnatal Depression Scale) and BDI(Beck's depression Inventory). The symptoms of patient are insomnia, anxiety, palpitation, chest discomfort and depression. This patient was treated with Hominis Placenta Herbal acupuncture at CV4(Kwanwon, Guanyuan), CV6(Kihae, Qihai), B23(Shinsu, shenshu), GVl5(Amun, Yamen), herb medication, acupuncture, auricular acupuncture, moxa treatment, and so forth. Results : As a result, symptoms are remarkably alleviated. Conclusions : Hominis Placenta Herbal acupuncture is expected to have an effect on postpartum depression. After this, further approach and study on postpartum depression might be needed.

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Decreasing Effect of Wet-Cupping at Daechu (대추, Dazhui:GVl4)-point on the Increase of Blood Pressure in Patients with Stroke (중풍환자의 혈압 상승에 대한 대추혈 사혈의 혈압 강하 효과)

  • 신정애;이영구
    • The Journal of Korean Medicine
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    • v.23 no.3
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    • pp.85-95
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    • 2002
  • Objectives : Daechu (Dazhui:GV14 (Governor Vessel 14))-point is located between the spinous process of the 7th cervical vertebra and that of the 1st thoracic vertebra. GV14 has been used to treat hypertension, high fever, neck pain, common cold, headache and so on. Hypertension often negatively affects the improvement of stroke patients. We investigated whether wet-cupping at GV14 had any effect of decreasing blood pressure (BP). Methods : In this study, 81 stroke patients were studied, from Oct. 2000 to Sept. 2001. They were composed of a Sample group (n=36) and Control group (n=45). The Sample group (n=36) was divided into Sample-Normal (n=9), Sample-Mild (n=7), Sample-Moderate (n=l1), and Sample-Severe group (n=9). The Control group (n=45) was divided into Control-Moderate (n=34) and Control-Severe group (n=ll). We checked blood pressure 5 times (just before treatment, then after 30,60, 90, and 120min. (2hrs.)) in each sample group and 3 times (baseline, after 30, and after 120min. (2hrs)) in the control group. Results : In a comparison of before-treatment BP and after-treatment BP in the sample group, SBP significantly decreased as time passed, while DBP slightly decreased but not significantly. In comparison of BP differences in each sample subgroup, BP slightly increased in the Sample-Normal group, but significantly decreased in the Sample-Mild, Sample-Moderate, and Sample-Severe groups. In comparison of BP differences between the sample and control groups, SBP and DBP of the sample group definitely decreased more than those of the control group, but not significantly. Conclusions : This study suggests that wet-cupping at GV14 has significant decreasing effectson blood pressure in stroke patients. Accordingly, we hope that this measure will be used more widely as an emergent treatment for increased blood pressure.

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Characterization of CTL Clones Specific for Single Antigen, H60 Minor Histocompatibility Antigen

  • Jeon, Ji-Yeong;Jung, Kyung-Min;Chang, Jun;Choi, Eun-Young
    • IMMUNE NETWORK
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    • v.11 no.2
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    • pp.100-106
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    • 2011
  • Background: Disparities of Minor H antigens can induce graft rejection after MHC-matched transplantation. H60 has been characterized as a dominant antigen expressed on hematopoietic cells and considered to be an ideal model antigen for study on graft-versus-leukemia effect. Methods: Splenocytes from C57BL/6 mice immunized with H60 congenic splenocytes were used for establishment of H60-specific CTL clones. Then the clones were characterized for proliferation capacity and cytotoxicity after stimulation with H60. Clone #14, #15, and #23 were tested for the TCR binding avidity to H60-peptide/$H-2K^b$ and analyzed for TCR sequences. Results: H60-specific CTL clones showed different levels of proliferation capacity and cytotoxic activity to H60-stimulation. Clones #14, #15, and #23 showed high proliferation activity, high cytotoxicity, and low activities on both aspects, respectively, and have TCRs with different binding avidities to H60-peptide/$H-2K^b$ with $t_{1/2}$ values of 4.87, 6.92, and 13.03 minutes, respectively. The TCR usages were $V{\alpha}12D-3-01+J{\alpha}11-01$ and $V{\beta}12-1-01+D{\beta}1-01+J2-7-01$ for clone #14, $V{\alpha}13D-1-02+J{\alpha}34-02$ and $V{\beta}13-1-02+D{\beta}2-01+J{\beta}2-7-01$ for clone #15, and $V{\alpha}16D+J{\alpha}45-01$ and $V{\beta}12-1-01+D{\beta}1-01+J{\beta}2-5-01$ for clone #23. Conclusion: The results will be useful for modeling GVL and generation TCR transgenic mouse.