• Clinical and Experimental Reproductive Medicine
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• v.20 no.2
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• pp.149-156
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• 1993

Human chorionic gonadotropin(hCG) and intravenous immunoglobulin(IVIG) treatment were attempted as a novel therapeutic approach for unexplained recurrent spontaneous abortion(RSA). Forty-four and 3 women with a history of RSA were treated with hCG and IVIG, respectively, during pregnancy. Of these patients, serum blocking factor assay was performed before and after each treatment, in 15 patients; 12 cases with hCG and 3 cases with IVIG. The results were as follows: 1. Of 44 women who receive hCG during pregnancy, 24 delivered healthy infants at term, 10 patients suffered repeat abortion, and 10 women are still pregnant under 28 weeks. Over all success rate of hCG treatment was 70.6% (24/34). Although there is no statistical significance, absolute serm blocking level was decreased after treatment(N=12). 2. Of 3 women who receive IVIG during pregnancy, all 3 women are still pregnant under 28 weeks. Serum blocking level was increased after treatment, however, this increment was not statistically significant. Although no conclusion could be extracted from the patients who received IVIG, the therapeutic effect of hCG is comparable to that of the other therapeutic regimens, such as allogeneic leukocytes. It was postulated that actual etiology of unknown RSA would be classified as hormonal origin although combined etiologies are common in Korean women.

• Reproductive and Developmental Biology
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• v.29 no.2
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• pp.69-73
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• 2005

The hematopoietic growth factor erythropoietin (EPO) is required for the maintenance, proliferation, and differentiation of the stem cells that produce erythrocytes. To analyse the biological activity of the recombinant human EPO (rec-hEPO), we have cloned the EPO cDNA and genomic DNA and produced rec-hEPO in the CHO cell lines. The growth and differentiation of EPO-dependent human leukemic cell line (F36E) were used to measure cytokine dependency and in vitro bioactivity of rec-hEPO. MIT assay values were increased by survival of F36E cells at 24h or 72h. The hematocrit and RBC values were increased by subcutaneous injection of 20 IU (in mice) and 100IU(in rats) rec-hEPO. Hematocrit values remarkably increased at $13.2\%$ (in mice) and $12.2\%$ (in rats). The pharmacokinetic behavior with injection of 6 IU of rec-hEPO remained detectable after 24 h in all mice tested. The highest peat appeared at 2h after injection. The long half-life of rec-hEPO is likely to confer clinical advantages by allowing less frequent dosing in patients treated for anemia. These data demonstratethat ree-hEPO produced in this study has a potent activity in vivo and in vitro. The results also suggest that biological activity of ree-hEPO could be remarkably enhanced by genetic engineering that affects the potential activity, including mutants with added oligosaccharide chain and designed to produce EPO-EPO fusion protein.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5037-5041
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• 2015

Background: An hCG regression curve has been used to predict the natural history and response to chemotherapy in gestational trophoblastic disease. We constructed hCG regression curves in high-risk gestational trophoblastic neoplasia (GTN) treated with EMA/CO and identified an optimal hCG level to detect EMA/CO resistance in GTN. Materials and Methods: Eighty-one women with GTN treated with EMA/CO were classified as primary high-risk GTN (n = 65) and single agent-resistance GTN (n = 16). The hCG levels prior to each course of chemotherapy were plotted in the 10th, 50th, and 90th percentiles to construct the hCG regression curves. Diagnostic performance was evaluated for an optimal cut-off value. Results: The median hCG levels were 264,482 mIU/mL mIU/mL and 495.5 mIU/mL mIU/mL for primary high-risk GTN and single agent-resistance GTN, respectively. The 50th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 4th and the 2nd course of chemotherapy, respectively. The 90th percentile of the hCG level in primary high-risk GTN and single agent-resistance turned to normal before the 9th and the 2nd course of chemotherapy, respectively. The hCG level of ${\geq}118.6mIU/mL$ mIU/mL at the 5thcourse of EMA/CO predicted the EMA/CO resistance in primary high-risk GTN patients with a sensitivity of 85.7% and a specificity of 100%. Conclusion: EMA/CO resistance in primary high-risk GTN can be predicted by using an hCG regression curve in combination with the cut-off value of 118.6 mIU/mL at the 5thcourse of chemotherapy.

• Korean Journal of Animal Reproduction
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• v.22 no.2
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• pp.137-143
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• 1998

The effects of continuous GH(hGH) secretion on the female reproduction was studies in adults female transgenic rats expressing the hGH gene with a mouse whey acid protein (mWAP) promotor. Two line of transgenic female rats carrying the mWAP/hGH gene were established and used in the study. One was characterized by relatively high levels of serum hGH (high line), and the other had relatively low levels (low line). 1. High line female rats had recurring, Pseudopregancy-like estrous cycles accompanied by increased serum progesterone level for 2 weeks after ovulation, and they were fertile. 2. In the rats, luteinization occurred spontaneously without cervical stimulation, probably due to high levels of serum hGH, which has prolactin (PRL)-like activity in the rat. 3. Low line female rats had recurring, regular 4-days estrous PRL surge following cervical stimulation were not, detected and PRL secretion was not induced by a dopamine antagonist. 4. The ovarian tissue in this line had a much higher number of corpora lutea and grew much heavier than in normal littermates, suggesting impairment of PRL induced structural luteolized. Su, pp.ession of PRL secretion in the low line rats was, at least in part, due to a marked decrease in the number of lactotrophs in the pituitary. The present study shows that the serum hGH level plays a crucial role in regulating luteal function in female transgenic rats expressing the hGH gene.

• Korean Journal of Agricultural Science
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• v.48 no.2
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• pp.353-365
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• 2021

Previously, we reported that tissue factor (Tf) was included in the list of differentially expressed genes as an upregulated gene in a rejected porcine heart after xenotransplantation into monkey. In this study, we analyzed that expression of Tf in aortic endothelial cells (pAEC) isolated from alpha 1,3-galactosyltransferase knockout pig in response to allogeneic porcine serum and xenogeneic human serum. The consequence was significant upregulation of Tf expression by responding to human serum compared with porcine serum. To analyze the function of Tf gene as a promoter, we constructed reporter vectors for expression of luciferase linked to 1,246 and 787 base pairs of porcine Tf (pTF1246 and pTF787), and 535 base pairs of human TF (hTF535) sequences including putative promoter regions and AP-1 biding site at the 5' end. The reporter vectors were transfected into pAEC including cytomegalovirus enhancer/chicken β-actin (CAG)-luciferase vector as a control. Luciferase assay showed that all of the promoters were insufficient to express luciferase compared with CAG promoter in basic culture conditions. Notably, pTF1246, pTF787, and hTF535 led to a significant increase of luciferase expression in response to human serum compared with porcine serum while no change of CAG. pTF1246 and pTF787 showed higher expression than hTF535. Taken together, our findings suggest that pTF1246 and pTF787 promoters could mediate target gene expression specifically at xenogeneic stress condition.

• Journal of Embryo Transfer
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• v.13 no.2
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• pp.97-106
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• 1998

The pronuclear injection of metallothionein-human growth hormone (MT-hGH) gene into rabbit zygotes was performed to establish in vitro developmental system and to detect the presence of the injected gene by nested PCR. Mature female New Zealand White rabbits were superovulated by eGG and hCG treatments. The rabbits were mated and the zygotes were collected from the oviducts 18-22 h after hCG injection by flushing with D-PBS. Two to three picoliters of MT-hGH gene was microinjected into male pronuclei. The foreign gene-injected zygotes were cultured in TCM-199 or RD mediurn containing 10% FCS with a monolayer of rabbit oviductal epithelial cefls in a 5% $CO_2$ incubator. The presence of injected DNA in rabbit embryos or blastomeres at different developmental stages .vas detected by a nested PCR analysis. The results are summarized as follows ; 1.The developmental rate of the MT-hGH gene-injected zygotes to blastocyst was significantly higher in TCM-199 medium (68.1%) than in RD medium (42.9%). 2.The gene injection into pronuclei at 18 or 22 hours post hCG treatment during pronuclear stage did not much affect on the in vitro development of the rabbit embryos. 3.The rate of gene-positive embryos detected by the nested PCR analysis was significantly decreased when they developed to blastocysts. The results indicate that the screening of transgene in rabbit embryos by nested PCR analysis could be a prornisible method for the preselection of transgenic embryos. Furthermore, the preselection of transgenic embryos would greatly reduce hoth the cost and effort of production of transgenic animals.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.69-69
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• 2003

Human CD99 is a ubiquitous 32-kDa transmembrane protein encoded by the mic2 gene. The major cellular functions of CD99 protein are related to homotypic cell adhension, apoptosis, vesicular protein transport, and differentiation of thymocytes or T cells. Recently it has been reported that expression of a splice variant of CD99 transmembrane protein (Type I and Type II) increases invasive ability of human breast cancer cells. To understand structural basis for cellular functions of CD99 (Type I), we have initiated studies on hCD99$^{TMcytoI}$ and hCD99$^{cytoI}$ using circular dichroism (CD) and multi-dimensional NMR spectroscopy. CD spectrum of hCD99$^{TMcytoI}$ in the presence of 200mM DPC and CHAPS displayed an existence $\alpha$-helical conformation. The solution structure of hCD99$^{cytoI}$ determined by NMR is composed of one N-terminal $\alpha$-helix, $\alpha$A, two C-terminal short $\alpha$-helix segments, $\alpha$B and $\alpha$C. While $\alpha$A and $\alpha$B are connected by the long flexible loop, $\alpha$B and $\alpha$C connected by type III$\beta$-turn. Although it has been rarely figured out the correlation between structure and functional mechanism of hCD99$^{TMcytoI}$ and hCD99$^{cytoI}$, there is possibility of dimerization or oligomerization. In addition, the feasible mechanism of hCD99$^{cytoI}$ is that it could have intramolecular interaction between the N- and C- terminal domain through large flexible AB loop.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.31-37
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• 2015

Chelating agents 1,4,7-triazacyclononanetriacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 30-amino-3,14,25-trihydroxy-3,9,14,20,25-penta-azatriacontane-2,10,13,21,24-pentaone (desferrioxamine, DFO) were labeled with $^{68}Ga$ and tested in vitro properties to check the feasibility of using DFO as a bifunctional chelating agent or renal imaging agent. The chelating agents of concentration $2{\mu}M$ were labeled with $^{68}Ga$ in 0.1 M HCl at pH 1.7-10.3 at room temperature and $80^{\circ}C$ and the optimal pH for labeling each chelating agent was found. And then, the chelating agents were labeled with $^{68}Ga$ in various concentration of chelating agents at optimal pH. The labeled chelating agents were subject to stability test in human serum and to binding studies to human red blood cell (RBC) and plasma protein. The optimal pH's of NOTA, DOTA and DFO for $^{68}Ga$-labeling were 4.4, 3.6 and 5.6, respectively. DFO ($10{\mu}M$) showed high labeling efficiency (>97%) at pH 5.6. All the labeled chelating agents showed high stability in human serum. $^{68}Ga$-DFO showed low RBC binding but significant amount was bound to plasma protein. The results demonstrated that $^{68}Ga$-DFO can be used as a bifunctional chelating agent but not as a renal imaging agent.

• Clinical and Experimental Reproductive Medicine
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• v.22 no.2
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• pp.183-189
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• 1995

In human IVF-ET, the development and morphology of the embryo have been known to affect implantation and pregnancy rates(PRs). Recently, pregnancy has been reported to related to the embryos with thick zona-pellucida, high levels of fragmentation, poor blastomere development and zona hardening. Although the mechanism of implantation is unclear, it is thought that the hatching process precedes implantation and that the hatching is related to implantation and PRs. This study was carried out to investigate the effect of assisted hatching(AHA) on the improvement of PRs in human IVF-ET. The results were as follows; 1. The PRs of the AHA group (40.8%) was significantly higher than that of control group(27.2%)(P<0.01). 2. According to the age of patients, the PRs of control and AHA groups were 33.9%(20/59), 44,4%(12/27) in <30 yrs, 26.1%(30/115), 38.3%(18/47) in 31-35 yrs, 22.4%(13/58), 41.4%(12/29) in >36 yrs, respectively. 3. According to the factors of infertility in AHA group, unexplained(immunologic factor) (40.0%) and male factors(41.9%) were higher than female(tubal obstruction, endometriosis, adhesion) factor (28.9%). As a result, it is suggested that AHA technique improve the PRs in poor prognosis patients. It is concluded that AHA method can be used to improve the PRs in human lVF-ET.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.51-58
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• 2021

Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2 treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2-treated cells; however, it recovered on G9a inhibition. H2O2-treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a. H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2-treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2-treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.