• BMB Reports
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• v.35 no.6
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• pp.537-546
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• 2002

NF-${\kappa}B$/Rel transcription factor family participates in diverse biological processes including embryo development, hematopoiesis, immune regulation, as well as neuronal functions. In this review, the NF-${\kappa}B$/Rel signal transduction pathways and their important roles in the regulation of immune system will be discussed. NF-${\kappa}B$/Rel members execute distinct functions in multiple immune cell types via the regulation of target genes essential for cell proliferation, survival, effector functions, cell trafficking and communication, as well as the formation of lymphoid architecture. Consequently, proper activation of NF-${\kappa}B$/Rel during immune responses to allergens, auto-antigens, allo-antigens, and pathogenic infection is crucial for the integrity of host innate and adaptive immunity.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.121-124
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• 2015

Now, it has been being accepted that reverse signaling through CD137 ligand (CD137L) plays an important role in vivo during hematopoiesis and in immune regulation. However, due to technical difficulty in dissecting both directional signaling events simultaneously in vivo, most biological activities caused by CD137-CD137L interactions are considered as results from signaling events of the CD137 receptor. To make the story more complex, $CD137^{-/-}$ and $CD137L^{-/-}$ mice have increased or decreased immune responses in a context-dependent manner. In this Mini review, I will try to provide a plausible explanation for how CD137L signaling is controlled during immune responses.

• Journal of Veterinary Clinics
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• v.15 no.2
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• pp.455-459
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• 1998

Ten sheeps from one farm had sudden onset of anorexia, jaundice and hemoglobinuria and died within 3 days after showing clinical signs during 3 months period. Postmortom examination was performed on one case and copper concentrations in the livers kidney and serum of the necmpsied minim were analysed. Grossly, the conjunctive, subcutaneous tissue and abdominal fat were generally icteric. The liver was enlarged with yellowish orange in color. The kidney was enlarged with dark red in color and the urinary bladder was filled with dark red urine. Histopathologically, centrilobular hepatocellular necrosis, neutrophilic infiltrations bile stasis and aggregation of fine granules-laden macrophages in the portal area were noted in the liver. Most of the Bowman's spaces and renal tubules were filled with homogenous eosinophilic fluid. Extramedullary hematopoiesis was noted in the submandibular lymph node. Copper concentrations in serum, liver and kidney of the necropsied animal were 25.0, 2732.8 and 471.3 ppm respectively. Based on the gross and histopathological findings and the high copper concentrations in the organs, this case was diagnosed as chronic copper toxicosis. Possible etiology on this outbreak is also discussed.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.323-329
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• 1996

A recombinant human erythropoietin (rHu-EPO), was administered intravenously to beagle dogs at doses of 100, 500 and 2, 500IU/kg/day for 30 days. There were no significant clinical signs such as body weight, food intake, physical and opthalmic examination, urine analysis, etc. Any toxic response was not observed except for enlarged spleen and extramedullary hematopoiesis. No observed adverse effect level (NOAEL) of rHu-EPO for 30 days was considered to be 100IU/kg/day in beagle dogs.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.317-327
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• 1998

The subchronic toxicity study of rHuEPO, a newly developed recombinant erythropoietin, was investigated for 13 weeks in Beagle dogs intravenously treated with doses of 100, 500 and 2,500 lU/kg/day. There were no significant changes in body weight, food intake, physical and opthalmic examination, urine analysis, etc. Any toxic response was not observed except for enlarged spleen and extramedullary hematopoiesis. These results indicate that the no-observed adverse effect level (NOAEL) of rHuEPO is 100 lU/kg in Beagle dogs.

• Kyungpook Mathematical Journal
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• v.48 no.4
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• pp.593-611
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• 2008

Global attractivity and oscillatory behavior of the following nonlinear impulsive parabolic differential equation which is a general form of many population models $$\array{\{{{\frac {{\partial}u(t,x)}{{\partial}t}=\Delta}u(t,x)-{\delta}u(t,x)+f(u(t-\tau,x)),\;t{\neq}t_k,\\u(t^+_k,x)-u(t_k,x)=g_k(u(t_k,x)),\;k{\in}I_\infty,}\;\;\;\;\;\;\;\;(*)$$ are considered. Some new sufficient conditions for global attractivity and oscillation of the solutions of (*) with Neumann boundary condition are established. These results no only are true but also improve and complement existing results for (*) without diffusion or impulses. Moreover, when these results are applied to the Nicholson's blowflies model and the model of Hematopoiesis, some new results are obtained.

• Molecules and Cells
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• v.43 no.2
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• pp.107-113
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• 2020

The Runt-related transcription factors (RUNX) transcription factors have been known for their critical roles in numerous developmental processes and diseases such as autoimmune disorders and cancer. Especially, RUNX proteins are best known for their roles in hematopoiesis, particularly during the development of T cells. As scientists discover more types of new immune cells, the functional diversity of RUNX proteins also has been increased over time. Furthermore, recent research has revealed complicated transcriptional networks involving RUNX proteins by the current technical advances. Databases established by next generation sequencing data analysis has identified ever increasing numbers of potential targets for RUNX proteins and other transcription factors. Here, we summarize diverse functions of RUNX proteins mainly on lymphoid lineage cells by incorporating recent discoveries.

• Toxicological Research
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• v.14 no.2
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• pp.129-141
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• 1998

Toxic effects of 2-bromopropane (2-BP) on the hematopoietic system and testis were investigated in male Srague-Dawley (SD) rats. 80 male SD rats, 5 weeks old, were treated with 2-BP in corn oil at levels of 0, 100, 330 and 1,000 mg/kg/day for 4 weeks orally. 10 animals from each group were maintained for additional 8 weeks following the treatment. In addition, 60 male SD rats were divided into 2 groups and administered 2-BP in corn oil at levels of 0 and 1,000 mg/kg/day orally and sacrificed after 1. 2 and 3 weeks of treatment. Clinical observation. body weight changes, food consumption, organ weight changes. hematology, serum chemistry and histopathology of the testis were performed in the study. No clinical sign and mortality were observed in the study. The body weights were significantly reduced with the treatment but gradually recovered. The relative organ weights of the testis and thymus significantly decreased in both of the groups treated with 1,000 mg/kg/day for 3 and 4 weeks. In the recovery groups, organ weights of the testis and epididymis were significantly reduced in both of the groups treated with 330 and 1,000 mg/kg/day. Platelets and reticulocytes were significantly reduced in both of the group treated with 1.000 mg/kg/day for 3 and 4 weeks. While red blood cells were de-creased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were increased in the recovery group. Significant increase of chloride was observed in all of the treatment groups except the recovery groups, and calcium was significantly increased in both of the groups treated with 1,000 mg/kg/ day for 3 and 4 weeks. On the other hand. there were significant decreases in alanine aminotransferase (ALT) and aspatate aminotransferase (AST) in most of groups treated with 1.000 mg/kg/day. In the testis. the spermatogonia in stages I-VI were mostly depleted and the spermatocytes in stages VII-VIII were de-generated or necrotized at week 1 after treatment of 2-BP. The degeneration of germ cells and the a-trophy of seminiferous tubules became more severe in time-dependent and dose-dependent manners. The damaged tubules showed regeneration in part. however. they did not appear to be completely recovered within 8 weeks of the recovery period. On the basis of the results. it is suggested that 2-BP would cause toxicities in hematopoiesis by possibly interfering the production of red blood cells and platelets and in spermatogenesis by the destruction oj spermatogonia in SD male rats.

• Development and Reproduction
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• v.9 no.2
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• pp.105-114
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• 2005

Embryonic stem(ES) cells have tremendous potential as a cell source for cell-based therapies. Realization of that potential will depend on our ability to understand and manipulate the factors that influence cell fate decision and to develop methods for getting enough cell numbers for clinical applications. Hematopoiesis has been widely studied, and hematopoietic differentiation from ES cells is a good model to study lineage commitment. In this study, we investigated stemness and compared the efficiency of hematopoietic differentiation using two different mouse embryonic stem cell lines TC-1 and B6-1. Although the two cell lines showed known stem cell properties with minor differences, the embryoid body formation efficiency in methylcellulose was much higher in TC-1 than B6-1. When measured potentials of hematopoietic differentiation using functional(colony-forming cell) and phenotypic(specific marker expression) assays, we found that TC-1 can differentiate into hematopoietic cells in methylcellulose culture but B6-1 cannot. These results imply that we can improve the efficiency of hematopoietic cell differentiation by selection of proper cell lines and this may be also applied in the differentiation of human embryonic stem cells.

• Toxicological Research
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• v.23 no.4
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• pp.391-403
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• 2007

The study was conducted to assess the repeated dose and reproduction and developmental toxicities of acetanilide, an intermediate for drug production, as a part of OECD Screening Information Data Set (SIDS) program. The test agent was administered by gavage at dose levels of 0, 22, 67, 200 and 600 mg/kg to Sprague-Dawley rats (12/group/sex) during pre-mating and mating period for males(up to 30 days) and females and pregnancy and early lactation period for females (up to 39-50 days). At 22 mg/kg, decreases in HGB, HCT (males) and MCHC (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow (both sexes) were observed. At 67 mg/kg, salivation (males), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC (males), increases in MCV (males) and spleen weight (males), hyperplasia of spleen red pulp and femur bone marrow (both sexes) were observed. At 200 mg/kg, decreases in locomotor activity and salivation (both sexes), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and increases in MCV, MCH, BUN, T-BIL (males), enlargement of spleen (both sexes), increased weight of spleen (males), hyperplasia of spleen red pulp and femur bone marrow and extramedullary hematopoiesis of liver (both sexes), atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. At 600 mg/kg, decreases in locomotor activity, cyanosis (both sexes), reddish tear, and salivation (males), mortality (4 out of 12 females), decreased body weight (females), reduced food consumption (both sexes), decreases in RBC, HGB, HCT and MCHC and increases in WBC, MCV, MCH, reticulocyte, neutrophil, lymphocyte, monocyte, AST, ALT, BUN, T-BIL, ALB, Ca and A/G ratio (males), enlargement of spleen, increased weights of spleen (both sexes), liver (males), kidney and ovary, decreased weights of thymus (females), hyperplasia of spleen red pulp, hyperplasia of femur bone marrow and extramedullary hematopoiesis of liver (both sexes), and atrophy of thymus and corpus luteum hyperplasia of ovary (females) were observed. Regarding the reproduction and development toxicities, there were no treatment-related changes in precoital time, mating index, fertility index and pregnancy index at all doses tested. At 22 and 67 mg/kg, there were no adverse effects on all the parameters observed. At 200 mg/ kg, decreased body weight of pups (day 4 p.p.) were observed. At 600 mg/kg, decreased body weight of pups (day 0 and 4 p.p.) and viability index (day 4 p.p.), increased incidence of newborns dead or with abnormal clinical signs were observed. The results suggest that the NOAELs for general toxicity are < 22 mg/kg, LOAELs are 22 mg/kg and the NOAELs for reproductive toxicity are 67 mg/kg.