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Thymocyte Differentiation is Regulated by a Change in Estradiol Levels during the Estrous Cycle in Mouse

  • Lee, Hyojin;Kim, Heejung;Chung, Yiwa;Kim, Jinhee;Yang, Hyunwon
    • Development and Reproduction
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    • v.17 no.4
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    • pp.441-449
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    • 2013
  • Recent study showed that T cells in the immune organs and peripheral blood are influenced by estradiol, leading to a dysfunction of the immune system. However, little is known about the thymic-gonadal relationship during the estrous cycle in mouse. Therefore, the purpose of this study was to elucidate the mechanism by which a change in estradiol levels during the estrous cycle regulates the development of T cells in the mouse thymus. Six-week-old ICR mice were used and divided into four groups, including diestrous, proestrous, estrous, and metestrous. We first confirmed that ER-${\alpha}$ and - ${\beta}$ estrogen receptors were expressed in thymic epithelial cells, showing that their expression was not different during the estrous cycle. There was also no significant difference in thymic weight and total number of thymocytes during the estrous cycle. To determine the degree of thymocyte differentiation during the estrous cycle, we analyzed thymocytes by flow cytometry. As a result, the percentage of CD4+CD8+ double-positive (DP) T cells was significantly decreased in the proestrous phase compared to the diestrous phase. However, CD4+CD8- or CD4-CD8+ (SP) T cells were significantly increased in the proestrous phase compared to the diestrous phase. In addition, the percentage of CD44+CD25- (DN1) T cells was significantly decreased in the estrous phase compared to other phases, whereas the percentages of CD44+CD25+ (DN2), CD44-CD25+ (DN3), and CD44-CD25- (DN4) were not changed during the estrous cycle. These results indicate that the development of thymocytes may arrest in the DP to SP transition stage in the proestrous phase displaying the highest serum level of estradiol. This study suggests that a change in estradiol levels during the estrous cycle may be involved in the regulation of thymocyte differentiation in the mouse thymus.

Review on Quantitative Measures of Robustness for Building Structures Against Disproportionate Collapse

  • Jiang, Jian;Zhang, Qijie;Li, Liulian;Chen, Wei;Ye, Jihong;Li, Guo-Qiang
    • International Journal of High-Rise Buildings
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    • v.9 no.2
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    • pp.127-154
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    • 2020
  • Disproportionate collapse triggered by local structural failure may cause huge casualties and economic losses, being one of the most critical civil engineering incidents. It is generally recognized that ensuring robustness of a structure, defined as its insensitivity to local failure, is the most acceptable and effective method to arrest disproportionate collapse. To date, the concept of robustness in its definition and quantification is still an issue of controversy. This paper presents a detailed review on about 50 quantitative measures of robustness for building structures, being classified into structural attribute-based and structural performance-based measures (deterministic and probabilistic). The definition of robustness is first described and distinguished from that of collapse resistance, vulnerability and redundancy. The review shows that deterministic measures predominate in quantifying structural robustness by comparing the structural responses of an intact and damaged structure. The attribute-based measures based on structural topology and stiffness are only applicable to elastic state of simple structural forms while the probabilistic measures receive growing interest by accounting for uncertainties in abnormal events, local failure, structural system and failure-induced consequences, which can be used for decision-making tools. There is still a lack of generalized quantifications of robustness, which should be derived based on the definition and design objectives and on the response of a structure to local damage as well as the associated consequences of collapse. Critical issues and recommendations for future design and research on quantification of robustness are provided from the views of column removal scenarios, types of structures, regularity of structural layouts, collapse modes, numerical methods, multiple hazards, degrees of robustness, partial damage of components, acceptable design criteria.

Influence of Educational Experience and Attitude toward Performance Confidence of Cardiopulmonary Resuscitation in Care Helpers (요양보호사들의 심폐소생술 교육경험과 태도가 수행자신감에 미치는 영향)

  • Yoon, Susie;Seo, Hye-Jin
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.9
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    • pp.281-289
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    • 2017
  • This study was conducted to evaluate the influence of educational experience and attitude toward performance confidence of cardiopulmonary resuscitation amongcare helpers. This study was conducted using a descriptive survey design. Participants were 140 care helpers in C-province. Data were collected from February to April, 2017 using self-report questionnaires andthe collected data were analyzed using the SPSS WIN 20.0 program. Differences amongstudy variables by participants' characteristics were analyzed by a t-test, ANOVA, and Scheffe' test. Correlations between attitudes and confidence of CPR performance by Pearson's correlation coefficients. Factors influencing confidence in CPR were analyzed by Multiple regression. There were significant positive correlations between attitude and confidence in CPR(r=0.41, p<0.001). The result showed that the more than fourhours of education(${\beta}=0.28$) and a positive attitude toward CPR increased CPR performance confidence. Based on the present findings, CPR education should be included continuously in the workplace and developed to appropriately cope with cardiac arrest emergency situations in care facilitiesfor elderly people. Therefore, customized CPR education programs should be developed care helpers and included in job training and refresher education courses for care helpers.

Two Cases of MELAS Syndrome Manifesting Variable Clinical Cour (다양한 임상경과를 보인 멜라스(MELAS, mitochondrial encephalopathy, lactic acidosis, and stroke-like episode) 증후군 2례)

  • Choi, Seo Yeol;Lee, Seung-Ho;Myung, Na-Hye;Lee, Young-Seok;Yu, Jeesuk
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.2
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    • pp.102-108
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    • 2016
  • Mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome is one of mitochondrial encephalopathy. As the early clinical manifestations can be variable, it is important to suspect the disease, especially in patients with multiple organ dysfunctions. A boy was diagnosed with epilepsy when he was 9 years old. Two years later, severe headache and blurred vision developed suddenly. On examination, left homonymous hemianopsia was detected with corresponding cerebral parenchymal lesions in right temporo-occipito-parietal areas. MELAS syndrome was confirmed by genetic test, which showed m.3243 A>G mitochondrial DNA mutation. Multivitamins including coenzyme Q10 were added to anticonvulsant. He experienced 4 more events of stroke-like episodes over 5 years, but he is able to perform normal daily activities. A 13-year-old boy was brought to the hospital due to suddenly developed respiratory arrest and asystole associated with pneumonia. Past medical history revealed that he had multiple medical problems such as epilepsy, failure-to-thrive, optic atrophy, and deafness. He has been on valproic acid as an anticonvulsant which was prescribed from local clinic. He recovered after the resuscitation, but his cognition and motor function were severely damaged. He became bed-ridden. He was diagnosed with MELAS syndrome by brain MRI, muscle biopsy, and clinical features. Genetic test did not reveal any mitochondrial gene mutation. Four years later, he expired due to suddenly developed severe metabolic acidosis combined with hyperglycemic hyperosmolar nonketotic coma. The clinical features of MELAS syndrome are variable. Early diagnosis before the presentation to the grave clinical course may be important for the better clinical outcome.

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Clostridium difficile Toxin A Inhibits Wnt Signaling Pathway in Gut Epithelial Cells (대장상피세포 속 Wnt 신호 경로에 대한 C. difficile 톡신A의 영향)

  • Yoon, I Na;Kim, Ho
    • Journal of Life Science
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    • v.28 no.9
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    • pp.1016-1021
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    • 2018
  • Clostridium difficile toxin A causes pseudomembranous colitis. The pathogenesis of toxin A-induced colonic inflammation includes toxin A-dependent epithelial cell apoptosis, resulting in the loss of barrier function provided by epithelial cells against luminal pathogens. Toxin A-dependent epithelial cell apoptosis has been linked to toxin A-induced production of reaction oxygen species and subsequent p38MAPK activation; $p21^{CIP1/WAF1}$ upregulation-dependent cell cycle arrest; cytoskeletal disaggregation; and/or the induction of Fas ligand on epithelial cells. However, the molecular mechanisms underlying toxin A-induced apoptosis remain poorly understood. This study tested whether toxin A could block the Wnt signaling pathway, which is involved in gut epithelial cell proliferation, differentiation and antiapoptotic progression. Toxin A treatment of nontransformed human colonocytes (NCM460) rapidly reduced ${\beta}$-catenin protein, an essential component of the Wnt signaling pathway. Exposure of mouse ileum to toxin A also significantly reduced ${\beta}$-catenin protein levels. MG132 inhibition of proteasome-dependent protein degradation resulted in the recovery of toxin A-mediated reduction of ${\beta}$-catenin, indicating that toxin A may activate intracellular processes, such as $GSK3{\beta}$, to promote degradation of ${\beta}$-catenin. Immunoblot analysis showed that toxin A increased active phosphorylation of $GSK3{\beta}$. Because the Wnt signaling pathway is essential for gut epithelial cell proliferation and anti-apoptotic processes, our results suggest that toxin A-mediated inhibition of the Wnt signaling pathway may be required for maximal toxin A-induced apoptosis of gut epithelial cells.

Clinical Characteristics of Acute Dichlorvos Poisoning in Korea (국내 급성 dichlorvos 중독 현황과 임상상 분석)

  • Lee, Mi-Jin;Park, Joon-Seok;Kwon, Woon-Yong;Eo, Eun-Kyung;Oh, Bum-Jin;Lee, Sung-Woo;Suh, Joo-Hyun;Roh, Hyung-Keun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.6 no.1
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    • pp.9-15
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    • 2008
  • Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.

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Studies on the Suitability and Efficiency of Human Follicular Fluid as Protein Supplement in Assisted Reproductive Technology(ART);I. Effect of Human Follicular Fluid on Meiotic Maturation of Mouse Follicular Oocytes In Vitro (생식보조시술시 단백질원으로서 인간난포액의 적합성 및 효율성에 관한 연구;I. 인간난포액이 생쥐난포란의 체외성숙에 미치는 효과)

  • Chi, H.J.;Kim, D.H.;Kim, J.Y.;Koo, J.J.;Chang, S.S.;Chung, K.S.
    • Clinical and Experimental Reproductive Medicine
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    • v.23 no.1
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    • pp.87-94
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    • 1996
  • For evaluating the suitability of human follicular fluid(HFF) as protein supplement in ART, this preliminary study was performed to examine the maturation promoting activity of HFF on mouse follicular oocytes in vitro. Mouse follicular oocytes were collected from ovaries of 21-28 day old ICR mice by puncturing the antral follicles with fine needle at 48 hours after PMSG injection. The oocytes were rinsed and cultured in modified Whittingham's $T_6$ medium containing purines or dbcAMP to maintain meiotic arrest, and different concentrations of HFF were added into the culture medium to examine the effect of HFF on releasing the oocytes from the suppressive influence of the meiotic inhibitors. As a control for HFF, the maturation promoting activity of human fetal cord serum(HFCS) was investigated and compared with the activity of HFF. While HFF was separated, by molecular weight(M.W), into high M.W. fraction(M.W>30,000) and low M.W. fraction(M.W<30,000) and the effects of the fractions on meiotic resumption were investigated in the presence of the meiotic inhibitors. Also hormone analysis was performed to compare the content of hormones in HFF with that in HFCS. Same concentrations of HFF and HFCS induced similar germinal vesicle break down(GVBD) rates of the oocytes meiotic arrested by purines(4mM hypoxanthine+0.75mM adenosine), but the extrusion rate of 1st polar body(PB) of the oocytes cultured in HFF(65.0%, P<0.05) was significantly higher than that(51.6%) in HFCS. While, in the presence of 200 M dbcAMP, the maturation promoting activity of HFF (GVBD: 70.5%, $p<10^{-6}$; 1st PB extrusion: 67.1%, $p<10^{-3}$) was significantly greater than that of HFCS(GVBD: 35.2%; 1st PB extrusion: 41.1%). The oocytes cultured in the fraction of HFF containing high M.W. components showed higher meiotic maturation rates than the oocytes cultured in the low M.W. fraction of HFF. Gonadotropins and $E_2$ were known to improve the completion of maturation changes, and the levels of these hormones were higher in HFF than in HFCS. Therefore, HFF was more effective than HFCS to use for promoting meiotic resumption of mouse oocytes in vitro.

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Expression of p53 and Ki-67 in Salivary Gland Tumors (타액선 종양에서 p53과 Ki-67의 발현)

  • Min Hyun-Jung;Kim Kyung-Rae;Park Chul-Won;Lee Hyung-Seok;Paik Seung-Sam;Oh Young-Ha;Tae Kyung
    • Korean Journal of Head & Neck Oncology
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    • v.22 no.1
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    • pp.8-14
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    • 2006
  • Objectives: The p53 tumor suppressor gene has a key role in cellular control mechanisms involving apoptosis and DNA repair, leading to the G1 arrest following DNA damage. Its mutation is one of the most frequent alterations in human cancers. Ki-67 is identified in replicating cells of both benign and malignant lesions, so it can be the predictor of proliferative activity. The aim of this study is to evaluate the expression of p53 and Ki-67 in salivary gland tumors. Materials and Methods: Immunohistochemical analysis was used to detect expression of p53 and Ki-67 in paraffin-embedded samples from 31 benign and 27 malignant salivary gland tumors. Results were analyzed between benign and malignant tumors and compared with the clinical parameters such as stage and recurrence in malignant tumors. Results: p53 overexpression was detected in 19.6% of benign tumors and 40.7% of malignant tumors, but there was no statistical significance. p53 was significantly expressed in Warthin's tumor(45.5%) compared with pleomorphic adenoma(5.9%). Only 5.9% of pleomorphic adenoma were positive for p53, while 60% of carcinoma ex pleomorphic adenoma were positive for p53. Ki-67 was expressed in 3.2% of benign tumors and 51.9% of malignant tumors, which showed significant higher expression in malignant tumors. In malignant tumors, p53 and Ki-67 expressions bore no correlation to stage and recurrence. Conclusion: p53 overexpression is not associated with the progression of malignant tumors, and Ki-67 overexpression can be used as biologic indicator of malignant salivary gland tumors.

The Efficacy of Saururus chinensis on Cervical Cancer Cells : The Inhibitory Effect on the Function of E6 and E7 Oncogenes of HPV Type 16 (삼백초 추출물의 자궁경부암세포 억제 효능)

  • Chung, Yeon-Gu;Lee, Hae-Sook;Lee, Kyung-Ae;Joung, Ok;Oh, Won-Keun;Kim, Kwang-Dong;Lim, Jong-Seok;Moon, Ja-Young;Cho, Yong-Kweon;Park, Sue-Nie;Yoon, Do-Young
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.426-432
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    • 2002
  • Cervical cancer is one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papilloma viruses (HPV type 16 and 18) and cervical cancer has been well known. An extract of Saururus chinensis, named as PE-46, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. PE-46 inhibited the proliferation of human cervical cancer cell lines in a dose response manner. PE-46 also inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, PE-46 inhibited the in vitro binding of E7 and Rb which is essential tumor suppressor for the control of cell cycle. The levels of mRNA for E6 and E7 were also decreased by PE-46. SiHa cells treated with PE-46 induced G0/G1 arrest, resulting in inhibition of growth. Our study showed that the PE-46 can inhibit the cervical carcinomas via both inhibition of bindings between oncogenes and tumor suppressors, and inhibition of G1longrightarrowS transition. PE-46 inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus could be used as a putative modulating agent for the treatment of cervical carcinomas caused by HPV.

Modulacon of Cell Cycle Control by Histone Deacetylase Inhibitor Trichostatin A in A549 Human Non-small Cell Lung Cancer Cells (인체폐암세포 A549의 세포주기 조절인자에 미치는 histone deacetylase inhibitor trichostatin A의 영향)

  • Hwang Ji Won;Kim Young Min;Hong Su Hyun;Choi Byung Tae;Lee Won Ho;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.5 s.72
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    • pp.726-733
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    • 2005
  • Histone deacetylase (HDAC) inhibitors target key steps of tumor development. They inhibit proliferation, induce differentiation and/or apoptotic cell death, and exhibit potent antimetastatic and antiangiogenic properties in cancer cells in vitro and in vivo. Although they are emerging as a promising new treatment strategy in malignancy, how they exert their effect on human non-small cell lung cancer cells is as yet unclear. The present study was undertaken to investiate the underlying mechanism of a HDAC inhibitor trichostatin A (TSA)-induced growth arrest and its effect on the cell cycle control gene products in a human lung carcinoma cell line A549. TSA treaoent induced the growth inhibition and morphological changes in a concentration-dependent manner. Treatment of A549 cells with TSA resulted in a concentration-dependent increased G1 (under 100 ng/ml) and/or G2/M (200 ng/ml) cell population of the cell cycle as determined by flow cytometry Moreover, 200 ng/ml TSA treatment significantly induced the population of sub-G1 cells (23.0 fold of control). This anti-proliferative effect of TSA was accompanied by a marked inhibition of cyclins, positive regulators of cell cycle progression, and cyclin-dependent kinases (Cdks) expression and concomitant induction of tumor suppressor p53 and Cdk inhibitors such as p21 and p27 Although further studies are needed, these findings provide important insights into the possible molecular mechanisms of the anti-cancer activity of TSA in human lung carcinoma cells.