• Tuberculosis and Respiratory Diseases
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• v.70 no.2
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• pp.132-138
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• 2011

Background: Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily. A few studies have examined the role of maspin in tumor suppression of non-small cell lung cancer (NSCLC); however, its role in the development and progression of NSCLC still remains controversial. We evaluated the immunohistochemical expression of maspin in order to elucidate its clinical significance in NSCLC. Methods: We analyzed 145 patients with pathologically confirmed NSCLC, including 66 cases of squamous cell carcinomas (SCCs) and 79 cases of adenocarcinomas (ADCs). We performed a immuno-histochemical stain with maspin and PCNA (proliferating cell nuclear antigen) using tissue microarray blocks. Results: There were 108 men and 37 women in the study population. The mean age of patients in the study was 63.7 years (range, 40.0~82.0; median, 65.0). The proportion of maspin expression was significantly higher in SCCs (52/66, 78.8%; p<0.01) than in ADCs (17/79, 21.5%; p<0.01). Maspin expression was not associated with PCNA (p=0.828), lymph node involvement (p=0.483), or tumor stage (p=0.216), but showed correlation with well-to-moderate tumor differentiation (p=0.012). There was no observed correlation between maspin expression and survival with NSCLC (p=0.218). Conclusion: The present study suggests that maspin expression was significantly higher in SCCs than in ADCs and was associated with low histological grade. However, maspin expression was not an independent factor to predict a prognosis in NSCLC.

• Journal of Chest Surgery
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• v.32 no.8
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• pp.693-701
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• 1999

Recently non-invasive diagnostic imaging replaced the invasive catheter angiography in the diagnosis of vascular disease. Catheter methods are now almost confined to the purpose of intervention. Coronary artery or coronary artery bypass graft still needs catheter technique because of small diameter and the cardiac motion. The last challenge for radiologists in this domain is to obtain a non-invasive imaging. Electron beam tomography(EBT) for high temporal resolution is able to obtain a coronary arteriogram or coronary artery bypass graft (CABG), of which CABG imaging is quite useful for the evaluation of patency. In our experience as well as others, the accuracy of EBT angiogram in evaluating CABG patency revealed that the accuracy of patency of saphenous vein grafts(SVG) is high due to relatively wide lumen, short and straight course and less influence from cardiac motion. The sensitivity and specificity of patency of SVGs were 92%, 97% respectively in the prospective evaluat on and 100% each in the retrospective evaluation. A false positive and a false negative case are rudimentary errors in the initial learing period. In contrast the analysis of left internal mammary artery(LIMA) graft was difficult due to the inherent small size and the adjacent surgical clips provoking beam-hardening artifact; therefore, the method of combining 3 dimensional reconstruction and flow mode study was important in improving the accuracy of LIMA patency. The sensitivity and specificity of LIMA patency were 100% and 80% in both prospective and retrospective evaluation. Therefore, EBT angiography is an accurate non-invasive diagnostic modality for evaluating the patency of CABG, particularly in SVGs. The accuracy can be improved with the improvement of the EBT and the development of the image reconstruction software.

• The Korean Journal of Pharmacology
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• v.18 no.1
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• pp.65-72
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• 1982

It has been known that retinoids are intrinsically of critical importance for control of premalignant epithelial cell differentiation. In the absence of retinoids, normal cellular differentiation and growth does not occur in epithelia such as those of trachea and bronchi. Furthermore, it was also reported that retinoid deficiency enhanced susceptibility to chemical carcinogenesis in the respiratory system, in the bladder, and in the colon of the experimental animal. In 1974, Bollag examined the effects of synthetic retinoids in prevention of development of cancer and demonstrated synthetic retinoids to have more favorable therapeutic index than retinoic acid for causing regression of skin papilloma in mice. Therefore, it was assumed that this anticarcinogenic effect of vitamin A derivatives could be due to modification of the metabolism of the carcinogenic polycyclic hydrocarbon, which must first be activated to exert their effect. Hill and Shih reported that vitamin A compounds and analogs had inhibitory effect on drug metabolizing enzyme from liver and lung tissue of mouse and hamster. Lucy suggested that the chemoprevention effect of vitamin A derivatives is due to reaction with molecular oxygen, and it is possible that inhibition of hydroxybenzpyrene formation is a result of this property. On the other hand, butylated hydroxytoluene which is a potent antioxidant strongly inhibited the formation of mammary tumor induced by dimethylbenranthracene. Also, it was observed that this antioxidant inhibited cancer induction in rats by N-2-fluo-renylacetamide. The purpose of this experiment was to investigate the effect of vitamin A derivatives such as retinoic acid and retinoid on drug-metabolizing enzyme and to determine whether riboflavin tetrabutylate or vitamin E could prevent of modify any changes induced by vitamin A delivatives in the rats. The results obtained were as followings. 1) Body weight was significantly reduced by retinoic acid, but not by retinoid. 2) Retinoic acid markedly increased liver weight while retincid showed no effect on liver weight. Treatment of riboflavin tetrabutylate did not affect retinoic acid-induced change in both body weight and liver weight. 3) Both retinoic acid and retinoid remarkably decreased the activity of aminopyrine demethylase. Pretreatment of riboflavin tetrabutylate, however, prevented inhibitory effect of retinoic acid on the enzyme activity. 4) No significant effect of vitamin E on aminopyrine demethylase was observed in both groups treated with retinoic acid and retinoid.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.10
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• pp.1384-1389
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• 2006

Prolactin plays an important role in mammary gland development, milk section initiation and maintenance of lactation, so the bovine prolactin gene is considered as a potential quantitative trait locus affecting milk performance traits in dairy cattle. In this study, to determine the association between prolactin and milk performance traits, the genetic polymorphisms of a part of the prolactin gene were detected in a population of 649 cows of Chinese Holstein Dairy Cattle. Three SNPs in the promoter and one SNP in the intron1 of prolactin were identified, which was A/C (-767), G/T (-485), C/A (-247), and C/T (427), respectively. Statistical results indicated that one of SNP within promote, CHBP2, was significantly associated with milk yield (p<0.01), fat yield (p<0.05), protein yield (p<0.01), and protein percentage (p<0.05). The cows with genotype BB of CHBP2 had significantly higher milk yield (p<0.01), fat yield (p<0.05), and protein yield (p<0.01) than those of cows with genotype AA, while cows with genotype AA showed the highest protein percentage (p<0.05). In addition, based on the nine major haplotypes constructed from the four SNPs, the association analysis between diplotypes and milk performance trait was carried out. Results showed that the least square mean for fat yield of diplotype H2H8 was significantly higher than those of other eleven diplotypes (p<0.05). Our findings implied that CHBP2 and H2H8 of prolactin would be useful genetic markers in selection program on milk performance traits in Holstein Dairy Cattle.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.6
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• pp.788-794
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• 2013

Mastitis set apart as clinical and sub clinical is a disease complex of dairy cattle, with sub clinical being the most important economically. Of late, laboratories showed interest in developing biochemical markers to diagnose sub clinical mastitis (SCM) in herds. Many workers reported noteworthy alternation of acute phase proteins (APPs) and nitric oxide, (measured as nitrate+nitrite = NOx) in milk due to intra-mammary inflammation. But, the literature on validation of these parameters as indicators of SCM, particularly in riverine milch buffalo (Bubalus bubalis) milk is inadequate. Hence, the present study focused on comparing several APPs viz. ${\alpha}_1$-anti trypsin, ${\alpha}_1$-acid glycoprotein, fibrinogen and NOx as indicators of SCM in buffalo milk. These components in milk were estimated using standardized analytical protocols. Somatic cell count (SCC) was done microscopically. Microbial culture was done on 5% ovine blood agar. Of the 776 buffaloes (3,096 quarters) sampled, only 347 buffaloes comprising 496 quarters were found positive for SCM i.e. milk culture showed growth in blood agar with $SCC{\geq}2{\times}10^5$ cells/ml of milk. The cultural examination revealed Gram positive bacteria as the most prevalent etiological agent. It was observed that ${\alpha}_1$-anti trypsin and NOx had a highly significant (p<0.01) increase in SCM milk, whereas, the increase of ${\alpha}_1$-acid glycoprotein in infected milk was significant (p<0.05). Fibrinogen was below detection level in both healthy and SCM milk. The percent sensitivity, specificity and accuracy, predictive values and likelihood ratios were calculated taking bacterial culture examination and $SCC{\geq}2{\times}10^5$ cells/ml of milk as the benchmark. Udder profile correlation coefficient was also used. Allowing for statistical and epidemiological analysis, it was concluded that ${\alpha}_1$-anti trypsin indicates SCM irrespective of etiology, whereas ${\alpha}_1$-acid glycoprotein better diagnosed SCM caused by gram positive bacteria. NOx did not prove to be a good indicator of SCM. It is recommended measuring both ${\alpha}_1$-anti trypsin and ${\alpha}_1$-acid glycoprotein in milk to diagnose SCM in buffalo irrespective of etiology.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.10
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• pp.1379-1387
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• 2013

In a majority of mammals, male infants have heavier body mass and grow faster than female infants. Accordingly, male offspring nursing requires a much greater maternal energy contribution to lactation. It is possible that the maternal-fetal immunoendocrine dialog plays an important role in female preparation for lactation during pregnancy. Immune system genes are an integral part of gene regulatory networks in lactation and tumor necrosis factor alpha ($TNF{\alpha}$) is a proinflammatory cytokine that also plays an important role in normal mammary gland development. The aim of this study was to evaluate the influence of the sex of calf and/or the -824A/G polymorphism in the promoter region of $TNF{\alpha}$ gene on milk performance traits in Black Pied cattle over the course of lactation. We also studied the allele frequency differences of -824A/G variants across several cattle breeds, which were bred in different climatic conditions. The G allele frequency decreased gradually over the course of lactation events in the Black Pied dairy cattle because of a higher culling rate of cows with the G/G genotype (p<0.001). In contrast to the genotypes A/A and A/G, cows with G/G genotype showed significant variability of milk and milk fat yield subject to sex of delivered calf. Milk yield and milk fat yield were significantly higher in the case of birth of a bull calf than with a heifer calf (p<0.03). The G allele frequency varies from 48% to 58% in Grey Ukrainian and Black Pied cattle to 77% in aboriginal Yakut cattle. Our results suggest that the $TNF{\alpha}$-824A/G gene polymorphism may have an influence on the reproductive efforts of cows over the course of lactation events depending on the sex of progeny. Allocation of resources according to sex of the calf allows optimizing the energy cost of lactation. This may be a probable reason for high G allele frequency in Yakut cattle breeding in extreme environmental conditions. Similarly, the dramatic fall in milk production after birth of a heifer calf increases the probability of culling for the cows with the G/G genotype in animal husbandry.

• Reproductive and Developmental Biology
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• v.32 no.3
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• pp.205-209
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• 2008

This study was carried out to develop knock-in vector for EGFP (enhanced green fluorescent protein) expression in porcine $\beta$-casein locus. For construction of knock-in vector using porcine $\beta$-casein gene, we cloned the $\beta$-casein genome DNA from porcine fetal fibroblast cells, EGFP and SV40 polyA signal using PCR. The knock-in vectors consisted of a 5-kb fragment as the 5' recombination arm and a 2.7-kb fragment as the 3' recombination arm. We used the neomycin resistance gene ($neo^{r}$) as a positive selectable marker and the diphtheria toxin A (DT-A) gene as a negative selectable marker. To demonstrate EGFP expression from knock-in vector, we are transfected knock-in vector that has EGFP gene in murine mammary epithelial cell line HC11 cells with pSV2 neo plasmid. The EGFP expression was detected in HC11 cells transfected knock-in vector. This result demonstrates that this knock-in vector may be used for the development of knock-in transgenic pig.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.389-399
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• 2015

Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc ($Zn^{2+}$) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of $Zn^{2+}$ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular $Zn^{2+}$ levels are largely regulated by metallothioneins (MTs), $Zn^{2+}$ importers (ZIPs), and $Zn^{2+}$ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of $Zn^{2+}$. However, these regulatory actions of $Zn^{2+}$ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular $Zn^{2+}$ levels, $Zn^{2+}$-mediated signal transduction, impacts of $Zn^{2+}$ on ion channels and mitochondrial metabolism, and finally, the implications of $Zn^{2+}$ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of $Zn^{2+}$.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.

• Journal of Chest Surgery
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• v.38 no.5 s.250
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• pp.366-370
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• 2005

Background: In general, cardiac surgery has been performed via median sternotomy. During the past decade, improvements in endoscopic equipment and operative techniques have resulted in development of minimally invasive cardiac operation using small incisions. With the advent of a voice controlled camera-holding robotic arm (AESOP 3000, Automated Endoscope System for Optimal Positioning), cardiac surgery entered the robotic age. Material and Method: Between April 2004 and December 2004, a total of seventy eight patients underwent robotic cardiac surgery, of whom sixty four patients underwent robot-assisted minimally invasive cardiac surgery via 5cm right lateral minithoracotomy using voice controlled robotic arm, femoral vessels cannulation, percutaneous internal jugular cannulation, transthoracic aortic cross clamp. Other fourteen patients underwent MIDCAB via internal mammary artery harvesting using AESOP. Result: Robotic cardiac surgery were mitral valve repair in 37 cases, mitral valve replacement in 10 cases, aortic valve replacement in 1 case, MIDCAB in 14 cases, ASD operation in 9 cases, and isolated Maze procedure in 1 case. In mitral operation, mean CPB time was $165.3\pm43.1$ minutes and mean ACC time was $110.4\pm48.2$ minutes. Median length of hospital stay was 6 days (range 3 to 30) in mitral operation, 4 days (range 2 to 7) in MIDCAB, and 4 days (range 2 to 6) in ASD operation. For complications, 3 patients were required by reoperation for bleeding. There was no hospital mortality. Conclusion: Our experience of robot cardiac surgery suggests that many cardiovascular surgeons will be able to perform minimally invasive cardiac operations through small incisions with robot-assisted video-direction. Well-designed studies and close long-term follow-up will be required to analyze the benefits of robot-assisted operation.