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Clinical significance of loss of p16 protein by immunohistochemical staining in acute lymphoblastic leukemia (급성림프구성백혈병에서 면역조직화학염색에 의한 p16 단백질 소실의 의의)

  • Jin, Hye Young;Kang, Kyoung In;Kim, Sun Young;Youn, You Sook;Kang, Joon Won;Jo, Deog Yeon;Kwon, Kye Chul;Park, Kyung Duk
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.73-77
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    • 2008
  • Purpose : p16 gene, mapped to the 9p21 chromosomal region, has emerged as a candidate tumor suppressor gene in human neoplasm. It is an inhibitor of cyclin-dependent kinase and inhibits Rb phosphorylation. In a variety of tumors including childhood acute lymphoblastic leukemia (ALL), deletion and/or mutation of the p16 gene has been found. Despite their high frequency, the prognostic importance of p16 alterations is still controversial in ALL and has been reported to be either unfavorable or similar to that of other patients. We studied the correlation between loss of p16 protein confirmed by immunohistochemical staining and clinical outcomes of patients diagnosed as ALL. Methods : We performed an immunohistochemical staining for p16 protein in 74 cases of bone marrow biopsy slide initially diagnosed as ALL between January 1998 and December 2006. We reviewed the clinical manifestations, laboratory findings, treatment outcomes retrospectively. Results : Of 74 slides, 12 were negative for p16 protein. Seven were males and 5 were females with a median age at diagnosis was 5.8 (1.3-18.8) years. Initial WBC were 17,225 $(500-403,300)/{\mu}L$. By immunologic surface marker analysis, 7 patients were early pre-B CALLA (+) and 5 patients were T-cell ALL. Two patients of intermediate risk group had relapsed and died. Three patients had family history of breast cancer. Four patients died and overall survival rates were $53.5{\pm}18.7%$. Conclusion : Loss of p16 protein is supposed to be an independent risk factor of childhood ALL associated with poor outcomes. In clinical setting, the clinician must take into account p16 status, not only at the genomic but also at the protein level. Further clinical experience on thoroughly investigated cases will help a better understanding between p16 status and clinical outcomes.

Rab Effector EHBP1L1 Associates with the Tetratricopeptide Repeat Domain of Kinesin Light Chain 1 (Kinesin Light Chain 1 (KLC1)의 Tetratricopeptide Repeat (TPR) 도메인과 Rab effector, EHBP1L1의 결합)

  • Jeong, Young Joo;Park, Sung Woo;Kim, Sang-Jin;Kim, Mooseong;Urm, Sang-Hwa;Lee, Jung Goo;Seog, Dae-Hyun
    • Journal of Life Science
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    • v.30 no.1
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    • pp.10-17
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    • 2020
  • Kinesin-1 is microtubule-dependent plus-end direct molecular motor protein essential for intracellular transport. It is a member of the kinesin superfamily proteins (KIFs) which transport cargo, including organelles, vesicles, neurotransmitter receptors, cell-signaling molecules, and protein complexes through interaction between its light chain subunit and the cargo. Kinesin light chain 1 (KLC1) is a non-motor subunit that associates with the kinesin heavy chain (KHC). Although KLC1 interacts with many different adaptor proteins and scaffolding proteins, its binding proteins have not yet been fully identified. We used the yeast two-hybrid assay to identify proteins that interact with the tetratricopeptide repeat (TPR) domain of KLC1, and found an interaction between KLC1 and EH domain-binding protein 1 like 1 (EHBP1L1). EHBP1L1 bound to the region containing all six TPR repeats of KLC1 and did not interact with KIF5B (a motor protein of kinesin 1) or KIF3A (a motor protein of kinesin 2) in the yeast two-hybrid assay. The carboxyl-terminus of the coiled-coil domain of EHBP1L1 is essential for interaction with KLC1. However, another EHBP1L1 isoform, EHBP1, did not interact with KLC1 in the yeast two-hybrid assay. KLC1 interacted with GST-EHBP1L1 and its coiled-coil domain but not with GST only. When co-expressed in HEK-293T cells, EHBP1L1 co-localized with KLC1 and co-immunoprecipitated with KLC1 and KIF5B but not KIF3A. These results suggest that kinesin 1 motor protein may transport EHBP1L1-associated cargo in cells.

The Effect of Weight Ratio of Carbon Source to Nitrogen Source on toe Growth and the Composition of Fatty Acid of Thraustochytrium aureum ATCC 34304 (탄소원과 질소원의 무게비가 Thraustochytrium aureum ATCC 34304의 성장 및 지방산 조성 특성에 미치는 영향)

  • Kim Won-Ho;Park Seung-Hye;Song Sang-Kyu;Bae Kyung-Dong;Hur Byung-Ki
    • KSBB Journal
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    • v.20 no.4
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    • pp.266-270
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    • 2005
  • The effect of the weight ratio of carbon source to nitrogen source on the growth and the composition change of fatty acids of Thraustochytrium aureum ATCC 34304 was investigated. The cell concentration of 5 days' culture increased and then decreased according to the increase of C/N, The ratioes for the maximum biomass were unique respectively and distributed between 1 and 4 with the initial sugar concentration in the range of 5 g/L to 25 g/L. The biomass yield, $Y_{x/s}$ decreased along with the increase of C/N, but maintained a constant value 0.35 between 10 and 20. The composition of myristic acid $(C_{14:0})$, one component of the lipid synthesized by T. aureum, was not affected with the change of C/N, but the composition of palmitic acid $(C_{16:0})$ was around $20\%$ below 4 of C/N and decreased to $15\%$ according to C/N about 4. The compositions of oleic acid $(C_{18:1})$ and linoleic acid $(C_{18:2})$ increased from 0 to $20\%\;and\;7\%$ respectively. The composition of $\gamma-linoleic$ acid $(C_{18:3})$, however, reduced from $5\%\;to\;2\%$. EPA $(C_{20:5})$ and DPA $(C_{22:5})$ showed a tendency of reduction in the weight composition according to the increase of C/N, but DHA $(C_{22:6})$ had a trend maintaining an approximately constant value, around $40\%$, irrespective of the change of C/N.

Apoptotic Effect of Proso Millet Grains on Human Breast Cancer MDA-MB-231Cells Is Exerted by Activation of BAK and BAX, and Mitochondrial Damage-mediated Caspase Cascade Activation (기장 종자 유래 추출물의 인간 유방암 MDA-MB-231 세포에 대한 세포독성에 관련된 미토콘드리아 손상-의존적 아폽토시스 유도 효과)

  • Do Youn Jun;Cho Rong Han;Young Ho Kim
    • Journal of Life Science
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    • v.33 no.1
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    • pp.15-24
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    • 2023
  • To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.

Bronchoalveolar Cellularity and IL-8 Levels in Patients with Post-measles Wheezing (홍역 후 천명환아의 기도내 세포양상 및 IL-8치)

  • Jung, Da Eun;Kim, Byeong Eui;Chung, Ju Young;Kim, Jeong Yeon;Ma, Sang Hyuk;Kim, Chang Keun
    • Clinical and Experimental Pediatrics
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    • v.46 no.8
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    • pp.763-768
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    • 2003
  • Purpose : This study was conducted to investigate the pulmonary cellular profiles and IL-8 levels in patients with post-measles wheezing. Methods : Twelve previously healthy infants with a minimum of three episodes of wheezing after measles pneumonia(Measles wheezing, median age, 1.3 years) were recruited by a retrospective examination of hospital records. They underwent bronchoalveolar lavage(BAL) with flexible bronchoscopy, and high-resolution computed tomography(HRCT) with a mean six(1-15) months interval. Comparisons were made with seven normal controls(Control, median age : 7.4 years). BAL cell counts and differentials were determined. IL-8 levels also were measured by ELISA. Results : The BAL cellular profiles were characterized by a significantly increased percentage of neutrophils in the Measles wheezing group(median 16.0%) compared to the control group(median 3.8 %)(P<0.01). IL-8 levels were markedly increased in the Measles wheezing group($mean{\pm}SD$, $512.7{\pm}324.0pg/mL$) compared to the control group($41.7{\pm}67.7pg/mL$)(P<0.01). Furthermore, IL-8 levels correlated significantly(r=0.816, P=0.001) with neutrophil percentages in BAL fluids in the Measles wheezing group. Abnormal HRCT findings were mosaic perfusion, bronchiectasis, bronchial wall thickening, and decreased vascularity. Conclusion : These results suggest that pulmonary neutrophils and IL-8 may play an important role in the pathogenesis of the post-measles wheezing.

Effect of Korean Red Ginseng on Blood Pressure and Aortic Vascular(endothelial) Histological Changes in Rats (홍삼이 정상 흰쥐의 혈압 및 대동맥 조직 소견 변화에 미치는 영향)

  • Joo, Il-Woo;Sung, Kyung-Hwa;Park, Jung-Min;Lew, Jae-Hwan;Oh, Han-Jin
    • Journal of Ginseng Research
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    • v.32 no.4
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    • pp.324-331
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    • 2008
  • Introduction : Korean red ginseng has been shown to have an preventive effect on atheroma formation and enhancing effect on nitric oxide synthesis in endothelial cell inducing vasodilatation. However, there are few studies showing the effect of Korean red ginseng on blood pressure and vascular(endothelial) pathologic changes together. We designed this study to show changes of blood pressure and vascular pathologic findings with Korean red ginseng administration compared with Chinese red ginseng and control for 3 months in rats. Materials and methods : We studied the in vitro hypotensive effect and effect on vascular pathologic changes of Korean red ginseng compared with Chinese red ginseng and control. Rats were randomly assigned to three groups(Korean red ginseng, Chinese red ginseng and control) and evaluated by blood pressure and aortic vascular(endothelial) pathologic changes monthly during 3-month administration. All results were analyzed by paired T-test, ANOVA and post-hoc. Results : Blood pressure lowering effect was noted on Korean red ginseng and Chinese red ginseng compared to control. Especially, in Korean red ginseng group, hypotensive effect was showed in first and second month, but, in Chinese red ginseng group, it was just noted in first month. In case of vascular(aortic endothelial) pathologic finding, endothelial wall thickening and elastic fiber tearing were noted in Chinese red ginseng group compared with Korean red ginseng group and control with statistical significance.(p<0.05) Discussion : These results suggested Korean red ginseng could have more hypotensive effect and maintenance rather than Chinese red ginseng. And the difference of hypotensive effect between Korean red ginseng and Chinese red ginseng might has some association with difference of vascular pathologic findings in each group. However, further evaluation and research of other mechanism will be needed to convince this hypothesis.

Marine Environment and the Distribution of Phytoplankton Community in the Southwestern Sea of Korea in Summer 2005 (여름 한국서남해역의 해양환경과 식물플랑크톤 군집분포)

  • Yoon, Yang-Ho;Park, Jong-Sick;Park, Yeong-Gyun;Noh, Il-Hyeon
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.10 no.3
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    • pp.155-166
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    • 2007
  • We carried out a study on the marine environment, such as water temperature, salinity, density and chlorophyll ${\alpha}$, and the distribution of phytoplankton community, such as species composition, dominant species and standing crops in the Southwestern Sea of Korea during early summer 2005. According to the analysis of a T-S diagram, three characteristics of water masses were identified. We classified them into Korean and Chinese coastal water, the cold water and the oceanic water. The first was characterized by high temperature and low salinity in the surface layer influenced by river run offs from China and Korea, the second by low temperature and salinity in bottom layer originated from the bottom cold water of the Yellow Sea, and the third by high temperature and high salinity influenced by Tsushima warm currents. The internal discontinuous layer among them was formed at the intermediate depth (about $10{\sim}20\;m$ layer). And the thermal front appeared in the central parts between Tsushima warm currents and Korean and Chinese coastal waters in the Southwestern Sea of Korea. Chlorophyll ${\alpha}$ concentration was high values in the Korean coastal waters and sub-surface layers. But It was low concentration in the Tsushima warm currents regions. The $Chl-{\alpha}$ maximum layers appeared in the sub-surface layer below thermocline. The phytoplankton community in the surface and stratified layers was composed of a total of 40 species belonging to 26 genera. Dominant species were 2 diatoms, Paralia sulcata, Skeletonema costatum and a dinoflagellate, Scripsiella trochoidea. Standing crops of phytoplankton in the surface layer were very low with cell density ranging from 5 to $3.8\;{\times}\;10^3\;cells/L$. Diatoms were controlled by the expanded low salinity coastal waters of the low salinity with high concentrations of nutrients. Otherwise phytoflagellates were dominant in the high temperature regions where the Tsushima warm currents approches the Southwestern Sea of Korea in early summer.

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The Developmental Effects of Radiation on ICR Mouse Embryos in Preimplantation Stage (착상전기(着床前期)에 있어서 ICR Mouse의 태아(胎兒)에 대한 방사선(放射線) 개체(個體) Level 영향(影響)의 연구(硏究))

  • Gu, Yeun-Hwa
    • Journal of Radiation Protection and Research
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    • v.21 no.4
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    • pp.273-284
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    • 1996
  • Embryos and fetuses are more sensitive to various environmental agents than are adults or children. The biological effects such as intrauterine death and malformation are closely connected with prenatal exposure very various agents. The sensitivity of these embryonic/fetal effects depends on the stage of pregnancy. From the viewpoint of fetal development, embryonic and fetal stages can be divided into three stages : Preimplantation, organogenetic and fetal. Each stage corresponds to 0 to 4.5days, 4.5 to 13.5days, and 13.5days of gestation in mice, respectively. Many studies on the biologcal effects of mice irradiated by ${\gamma}-rays$ at various stages during organogenesis and fetal period have been performed. Based on these results, the dose-effect and dose-response relationships in malformations, intrauterine death, or retardation of the physical growth have been practically modeled by the ICRP(International Commission on Radiological Protection) and other international bodies for radiation protection. Many experimental studies on mice have made it clear that mice embryos in the preimplantation period have a higher sensitivity to radiation for lethal effects than the embryos/fetuses on other prenatal periods. However, no eratogenic effects of radiation at preimplantation stages of mice have been described in many textbooks. It has been believed that 'all or none action results' for radiation of mice during the preimplantation period were applied. The teratogenic and lethal effects during the preimplantation stage are one of the most important problems from the viewpoint of radiological protection, since the preimplantation stage is the period when the pregnancy itself is not noticed by a pregnant woman. There are many physical or chemical agents which affect embryos/fetuses in the environment. It is assumed that each agents indirectly effects a human. Then, a safety criterion on each agent is determined independently. The pregnant ICR mice on 2, 48, 72 or 96 hours post-conception (hpc), at which are preimplantation stage of embryos, were irradiated whole body Cesium-gamma radiation at doses of 0.1, 0.25, 0.5, 1.5, and 2.5 Gy with dose rate of 0.2 Gy/min. In the embryos from the fetuses from the mice irradiated at various period in preimplantation, embryonic/fetal mortalities, incidence of external gross malformation, fetal body weight and sex ratio were observed at day 18 of gestation. The sensitivity of embryonic mortalities in the mice irradiated at the stage of preimplantation were higher than those in the mice irradiated at the stage of organogenesis. And the more sensitive periods of preimplantation stage for embryonic death were 2 and 48 hpc, at which embryos were one cell and 4 to 7 cell stage, respectively. Many types of the external gross malformations such as exencephaly, cleft palate and anophthalmia were observed in the fetuses from the mice irradiated at 2, 72 and 96 hpc. However, no malformations were observed in the mice irradiated at 48 hpc, at which stage the embryos were about 6 cell stage precompacted embryos. So far, it is believed that the embryos on preimplantation stage are not susceptible to teratogens such as radiation and chemical agents. In this study, the sensitivity for external malformations in the fetuses from the mice irradiated at preimplantation were higher than those in the fetuses on stage of organogenesis.

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Study of East Asia Climate Change for the Last Glacial Maximum Using Numerical Model (수치모델을 이용한 Last Glacial Maximum의 동아시아 기후변화 연구)

  • Kim, Seong-Joong;Park, Yoo-Min;Lee, Bang-Yong;Choi, Tae-Jin;Yoon, Young-Jun;Suk, Bong-Chool
    • The Korean Journal of Quaternary Research
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    • v.20 no.1 s.26
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    • pp.51-66
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    • 2006
  • The climate of the last glacial maximum (LGM) in northeast Asia is simulated with an atmospheric general circulation model of NCAR CCM3 at spectral truncation of T170, corresponding to a grid cell size of roughly 75 km. Modern climate is simulated by a prescribed sea surface temperature and sea ice provided from NCAR, and contemporary atmospheric CO2, topography, and orbital parameters, while LGM simulation was forced with the reconstructed CLIMAP sea surface temperatures, sea ice distribution, ice sheet topography, reduced $CO_2$, and orbital parameters. Under LGM conditions, surface temperature is markedly reduced in winter by more than $18^{\circ}C$ in the Korean west sea and continental margin of the Korean east sea, where the ocean exposed to land in the LGM, whereas in these areas surface temperature is warmer than present in summer by up to $2^{\circ}C$. This is due to the difference in heat capacity between ocean and land. Overall, in the LGM surface is cooled by $4{\sim}6^{\circ}C$ in northeast Asia land and by $7.1^{\circ}C$ in the entire area. An analysis of surface heat fluxes show that the surface cooling is due to the increase in outgoing longwave radiation associated with the reduced $CO_2$ concentration. The reduction in surface temperature leads to a weakening of the hydrological cycle. In winter, precipitation decreases largely in the southeastern part of Asia by about $1{\sim}4\;mm/day$, while in summer a larger reduction is found over China. Overall, annual-mean precipitation decreases by about 50% in the LGM. In northeast Asia, evaporation is also overall reduced in the LGM, but the reduction of precipitation is larger, eventually leading to a drier climate. The drier LGM climate simulated in this study is consistent with proxy evidence compiled in other areas. Overall, the high-resolution model captures the climate features reasonably well under global domain.

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Effects of Activation Treatments and Culture Condition on In Vitro Development of Caprine In Vivo and In Vitro Oocytes (재래산양의 체내 및 체외유래 난자의 활성화 처리방법 및 배양조건이 단위발생란의 체외발달에 미치는 영향)

  • Park H. S.;Kim T. S.;Lee Y. H.;Jung S. Y.;Lee M. Y.;Jin J. I.;Park J. K.;Lee J. S.;Kim C. H.
    • Reproductive and Developmental Biology
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    • v.28 no.3
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    • pp.181-185
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    • 2004
  • This study was conducted to examine whether activation treatments, source of oocytes and culture conditions affect in vitro developmental ability of caprine oocytes. Mature Korean native goats were pretreated with intravaginal CIDR for 10 days. The goats were then treated with a single intramuscular injection of 1,000 IU PMSG on Day 8 or twice daily injection of a total of 70 mg FSH for 3 days from Day 8 of CIDR insertion for superovulation. All the goats were injected with 10 mg PGF/sub 2a/ on Day 8 and 400 IU hCG on Day 10 of CIDR. Oocytes were surgically collected by oviduct flushing(in vivo maturation) or direct follicle aspiration(in vitro maturation) through mid-ventral incision at 35 h after hCG injection. Fifteen to twenty oocytes were placed in TCM-199 medium containing 25 mM Hepes and hormones under mineral oil at 39℃ in a humudified atmosphere of 5% CO₂ in air for 22 to 24 h. After maturation, the oocytes were activated by electric stimulation or ionomycin + 6-DMAP. The activated oocytes were then cultured in M16, TCM-199 and mSOF media supplemented with proteins at 39℃ for 6 to 7 days. Activation treatments did not affect cleavage of the oocytes. The cleavage rates were 64.1% (41/64) in oocytes activated by electric stimulation and 76.5% (218/285) in oocytes activated by ionomycin + 6-DMAP. The proportion of development to blastocyst was 15.6% (34/218) in oocytes activated by ionomycin + 6-DMAP, but activation by electric stimulation did not support embryos developed beyond morula stage. There were no differences in the cleavage rates of activated oocytes experiencing in vivo (86.8%, 66/76) and in vitro maturation (69.0%, 127/184). However, the development rate to blastocyst stage was significantly (P<0.05) higher for oocytes matured in vivo (50.0%, 33/66) compared to in vitro (0.8%, 1/127). Culture conditions did not affect the cleavage of -activated oocytes. The cleavage rates were 51.6% (49/95) in M16, 64.3% (18/28) in TCM-199 and 81.0% (145/179) in mSOF, respectively. By contrast, the development rate of activated oocytes to stage was greater (P<0.05) for oocytes cultured in mSOF medium (23.4%, 34/145) than in M16 or TCM-199 (0.0%). Our results suggest that source of oocytes and culture conditions are major factors affecting in vitro development of caprine parthenogenetic oocytes.