• Title/Summary/Keyword: Hematopoietic damage

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Establishment of γ-irradiation-induced Hematopoietic Tissue Damage Model in ICR Mice (ICR 마우스에서 감마선 조사로 유도된 조혈조직 손상 모델 확립)

  • Kang, Jung Ae;Rho, Jong Kook;Jang, Beom-Su;Chung, Young-Jin;Park, Sang Hyun
    • Journal of Radiation Industry
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    • v.7 no.1
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    • pp.55-59
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    • 2013
  • Ionizing radiation causes the massive generation of reactive oxygen species, resulting in cellular and tissue damage. The present study was performed to evaluate ${\gamma}$-irradiation induced cellular damage in ICR mice. The mice were divided into four groups with ten mice in each group. Group 1 served as an unexposed control group. Groups 2, 3, and 4 were exposed to 3, 5, and 7 Gy of ${\gamma}$-radiation, respectively. Five mice per group were sacrificed 1 and 7 days after ${\gamma}$-radiation. Exposure to ${\gamma}$-irradiation resulted in hematopoietic damage in a dose-dependent manner when compared with the unexposed control group, which featured a significantly decreased spleen index. However, the exposed mice showed no significant differences in their serum AST, ALT and in the histopathological change of their liver. These results suggest that ${\gamma}$-irradiation is a good tool to prepare a hematopoietic damage model. This animal model can be employed to study the hematopoietic efficacy of biologically active compounds.

Acute Radiation Syndrome in an Irradiated Minipig Model for Patients with Radiation Exposure

  • Jang, Hyosun;Kim, Joong-sun;Shim, Sehwan;Jang, Won-seok;Lee, Sun-Joo;Myung, Jae Kyung;Lee, Seung-Sook;Park, Sunhoo
    • Journal of Radiation Protection and Research
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    • v.42 no.3
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    • pp.146-153
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    • 2017
  • Background: Acute radiation syndrome (ARS) primarily refers to damage to the hematopoietic system, myeloid system, and gastrointestinal (GI) system caused by radiation exposure. Such damage progresses to become life-threatening. In particular, as the syndrome develops very rapidly-within several hours from radiation exposure-prompt and accurate diagnosis and treatment are needed, as is further research into appropriate diagnostic and treatment modalities. Materials and Methods: Minipigs, which display human-like properties, underwent whole-body irradiation at 2 or 4 Gy (doses causing hematopoietic ARS) or at higher doses of 7 or 12 Gy. Changes in the blood cells and clinical symptoms were analyzed and we performed a necropsy when the animals succumbed to ARS. Results and Discussion: The minipig irradiated with 2 Gy showed a decrease in white blood cells, including neutrophils, lymphocytes, and platelets in the early stages. However, the blood cell counts gradually increased and returned to normal values. The minipig irradiated with 4 Gy succumbed due to hematopoietic ARS. In contrast, the minipigs irradiated with 7 or 12 Gy exhibited clinical symptoms of combined GI damage and hematopoietic syndrome. Moreover, a characteristic pattern of platelet changes was observed in the 7 and 12 Gy irradiated minipigs. Conclusion: The changes in the platelet count caused by radiation exposure observed in minipigs, which are hematologically and pathohistologically similar to humans, suggest that they can be used as a novel diagnostic criterion.

Newborn Screening for Lysosomal Storage Diseases in Taiwan

  • Lin, Hsiang-Yu;Chuang, Chih-Kuang;Lin, Shuan-Pei
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.3 no.1
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    • pp.14-19
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    • 2017
  • Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by the deficiency of specific lysosomal enzymes and subsequent accumulation of substrates. Enzyme deficiency leads to progressive intra-lysosomal accumulation of the incompletely degraded substances, which cause dysfunction and destruction of the cell and eventually multiple organ damage. Patients have a broad spectrum of clinical phenotypes which are generally not specific for some LSDs, leading to missed or delayed diagnosis. Due to the availability of treatment including enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation for some LSDs, early diagnosis is important. ERT products have been approved with optimal outcomes for some LSDs in the recent decades, including Gaucher, Fabry, mucopolysaccharidosis (MPS) I, Pompe, MPS VI, MPS II, and MPS IVA diseases. ERT can stabilize the clinical condition, prevent disease progression, and improve the long-term outcome of these diseases, especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods in the recent years, some LSDs, including Pompe, Fabry, Gaucher, MPS I, MPS II, and MPS VI diseases have been incorporated into nationwide newborn screening panels in Taiwan.

Radioprotective effect of fucoidan against hematopoietic and small intestinal stem cells of γ-ray irradiated mice (감마선을 조사한 마우스의 조혈 및 소장줄기세포에 대한 fucoidan의 방호효과)

  • Park, Eunjin;Jeon, Seong Mo;Joo, Hong-Gu;Hwang, Kyu-Kye;Jee, Youngheun
    • Korean Journal of Veterinary Research
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    • v.48 no.4
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    • pp.393-399
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    • 2008
  • We investigated the potential of fucoidan for its ability to provide protection from gamma rayinduced damage. In our results, the fucoidan significantly improved the counts of endogenous colony forming unit to $9.5 {\pm} 1.5$, from $5.5 {\pm} 2.5$ compared with un-treated irradiated control group at 10 day after 7 Gy whole body irradiation. After 2 Gy irradiation, fucoidan treatment attenuated the percent of tail DNA of splenocytes, parameters of DNA damage, from $30.17 {\pm} 1.7%$ to $13.67 {\pm} 2.81%$ 2.81% by comet assay and also accelerated the proliferation of splenocytes, compared with un-treated irradiated control group by 3Hthymidine incorporation assay. Furthermore, fucoidan decreased the number of apoptotic fragments per intestinal crypt by 31.8% at 1 days after 2 Gy irradiation. These results indicated that the fucoidan significantly improved the hematopoietic recovery, prevented the DNA damage in immune cells and enhanced their proliferation, which had been suppressed by ionizing radiation. in addition, fucoidan rescued intestinal cells from radiation-induced apoptosis. Thus, this study raises the possibility of using fucoidan as adjuvant therapeutic agent after radiotherapy.

The modulating activity of Ginsan on radiation-induced disturbance of antioxidant defense systems

  • Son, Soo-Jung;Kim, Chan-Wha;Yun, Yeon-Sook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.309.1-309.1
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    • 2002
  • Ginsan, a polysaccharide extracted from Panax ginseng. was earlier scrutinized for a biological-response modifier. We further studied the protective and restorative activity of Ginsan against sublethal dose irradiation owing to increase production of endogenous hematopoietic growth factors such as IL-1. TNF-${\alpha}$. IL-6, GM-CSF. Which induce strong redox-emzyme elevation. Exposing to radiation induces reactive oxygen species (ROS). which play an important causative role in radiation damage. (omitted)

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Plasminogen Activator Inhibitor-1 as a Radiation-Responsive Gene in Bone Marrow Stromal Cells (골수기질세포에서 방사선 반응 유전자로서의 Plasminogen Activator Inhibitor-1)

  • Song, Jee-Yeon;Kwon, Hyung-Joo;Park, Chan-Kyu;Jo, Deog-Yeon;Lee, Young-Hee
    • Development and Reproduction
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    • v.9 no.1
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    • pp.43-48
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    • 2005
  • Bone marrow stromal cells, a constituent of the niche for hematopoietic stem cells in bone marrow, provide various factors involved in the fate decision of the hematopoietic stem and progenitor cells. Radiation, a widely used anti-cancer therapy, provokes side effects including the damage of the blood cells. Therefore, it is necessary to recover the blood cells shortly after radiation via promoting the differentiation of hematopoietic cells. In this study, we screened genes modulated by radiation in human bone marrow stromal cells in order to understand the mechanism involved in hematopoiesis after radiation. We performed differential display method by using polymerase chain reaction(PCR) and agarose gel electrophoresis. We found plasminogen activator inhibitor-1(PAI-1) was consistently induced by radiation. The significance of the PAI-1 gene modulation is to be determined.

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SUGICAL TREATMENT OF MUCOSITIS AND FUNGAL INFECTION IN THE ACUTE LEUKEMIC PATIENTS (급성 백혈병 환자에서 점막 질환과 진균감염의 외과적 처치)

  • Ha, Won-Suk;Ye, Young-Geun;Park, Jae-Hong;Pyo, Sung-Un;Yun, Hyun-Jung;Lee, Sang-Hwa
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.2
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    • pp.172-177
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    • 2006
  • It is generally known that mucositis which often occur on hematopoietic disease patients, shows local necrosis of oral mucosa when the CBC is below the normal range. But sometimes, the lesions are occasionally infiltrate into adjacent tissue. When the pathologic destructive expansion is occurred, differential diagnosis with fungal infection, one of opportunistic infections, is needed. This means treatment and prognosis can be changed according to the diagnosis. So the diagnostic process is more important in this hematopoietic disease patients. In case of fungal infection, the range of tissue damage can expand broadly, and also proper antifungal agent and surgical extirpation should be done. After operation, continuous antifungal therapy and observations are needed. We made a comparative study of following 2 cases of fungal infection appeared on the acute lymphatic leukemia patients to discuss what the proper surgical treatment and medications are, and when the proper surgical intervention time is.

Development of A New Herbal Composition HemoHIM as An Immune-Improving Agent Using Irradiated Animal Models (방사선조사 동물모델 이용 면역기능개선-생약복합물 헤모힘(HemoHIM)개발)

  • Jo, Seong-Gi
    • Radioisotope journal
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    • v.21 no.4
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    • pp.38-45
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    • 2006
  • A new herbal composition. HemoHIM, was developed using irradiated animal models and was successfully applied as an immune-improving agent. In a view that the protection and recovery of immune, hematopoietic and self-renewal tissues are essential for radioprotective agents, HemoHIM was developed based on a novel combination of three edible herbs (Angelica Radix, Cnidii Rhizoma. Paeonin Radix) that meet all those requirements. HemoHIM significantly protected the immune and hematopoietic system and enhanced their recovery in y-irradiated mice. For the application of HemoHIM as a health functional food and a supplementary agent for the cancer patients, the efficacy of HemoHIM to improve the immune functions was further evaluated in immune-depressed animals and humans. Animal studies demonstrated that HemoHIM significantly improved the immune functions in cyclophosphamide-treated mice, aged mice, and dexamethasone-treated mice. In human studies, HemoHIM enhanced the immune activity and cytokine secretion in sub-healthy volunteers, and alleviated the severe leukocyre depression in cancer patients during radiation and chemotherapy. Based on these results, HemoHIM was approved by Korea FDA as a material of health functional food for immune function improvement and will be commercially available soon. This case of HemoHIM research and development suggested that irradiated animals can be good models for biological degenerations such as immune depression, self-renewal tissue damage, and aging for the development of biological modulators.

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Evaluation of apoptosis after ionizing radiation in feeding and starving rats

  • Lee, Jae-Hyun;Cho, Kyung-Ja;Hong, Seok-Il;Park, Min-Kyung
    • Korean Journal of Veterinary Pathology
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    • v.2 no.1
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    • pp.37-46
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    • 1998
  • It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.

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Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow

  • Lim, Ji-Young;Lee, Young-Kwan;Lee, Sung-Eun;Ju, Ji-Min;Park, Gyeongsin;Choi, Eun Young;Min, Chang-Ki
    • IMMUNE NETWORK
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    • v.15 no.3
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    • pp.125-134
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    • 2015
  • Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of $CD11b^+Gr-1^+$ myeloidderived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.