• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.173-179
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• 2010

The antiestrogen tamoxifen is currently the most commonly used adjuvant treatment of breast cancer with antiestrogenic effect on mammary tissue. However, it is also associated with endometrial abnormalities, including hyperplasia, polyps, carcinoma, mostly interpreted as evidence of estrogenic effect on the endometrium. Previously, tamoxifen-associated polyp in breast cancer has been reported in the literature. Most studies had a long follow-up period and tamoxifen-associated polyp developed more than 1 year after tamoxifen treatment. In this case, we report an unusual case of rapid growing and multiple endometrial polyps that were developed only after 3 months' tamoxifen treatment in a postmenopausal breast cancer patient who received quadrant mastectomy with a brief review of literature.

• Journal of Veterinary Clinics
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• v.19 no.2
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• pp.228-235
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• 2002

Mastitis is the most costly disease results in lost milk production, decreased milk quality, milk discard, early culling of cows, drug costs and labor costs in dairy cow. Until now, a antibiotic administration at the end of lactation, dry cow therapy has been known the most effective and widely used mastitis control method. However, dry cow therapy do not control a new infection in the late dry and prepartum period because dry cow products have only persistent activity in the early dry period. Therefore, this study was conducted to evaluate clinical effect of sustained released biodegradable cephalexin microsphere using PLGA in bovine mastitis control during dry period. PLGA has been approved as controlled drug release system because of non-toxic, non-tissue reactive and bioerodible characteristics. This study revealed that cephalexin microsphere had a spherical shape with characteristic porous structure on the surface. Also, in vitro drug release studies are clearly observed that the release rate of cephalexin from PLGA microsphere decrease during the first 21 days after initial burst and then increase again between 3 and 4 weeks showing pulsatile releasing pattern. On the other hand, as tried in field the new infection rate, cure rate and mean SCC after parturition in cephalexin microsphere infused group were significantly differenced as compared to the control group. Accordingly, a sustained release of cephalexin from a biodegradable microsphere could make dry cow therapy more efficiently by preventing a new infection and decreasing the number of existing infection of mammary gland during dry period.

• Korean Journal of Agricultural Science
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• v.3 no.1
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• pp.85-94
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• 1976

Six cases of gangreous mastitis of goats infected spontaneously were observed clinically and pathologically in Daegu and Daejeon district. and with strain isolated purely from the infected goats, the artificial infection to the animal was examined, the sensitivity of strain to the antibiotics was tested and clinical treatment was carried out. The results obtained are summarized as follows: 1. In the six cases approximately same clinical findings were observed as the previously published literatures on gangrenous mastitis of cattle, sheep and goats. 2. The micrococcus pyogenes var aureus was highly virulent strain which was the causative organism for the gangrenous mastitis by inoculating in the udder. 3. The gangrenous mastis was probably occured by the formation of thrombosis in veins of udder. 4. In the sensitivity test, the micrococcus pyogenes var aureus resited for penicillin in 2 cases among the 6 strains, but sensitived for streptomycin, chloromycin, oxyteracycline, erythromycin, achromycin, neomycin and kanamycin in other 4 and in all case. 5. The treatment for gangrenous mastitis may be extirpated the gangrenous region surgically in the case of unilaterally or locally affected, treated by muscle injection or teat-operation in the case of severely or diffusely affected and infused antibiotics up to teat canal or treated by mammary tissue injection in the case of slightly affected.

• 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 $Zn^{2+}$.

• Radiation Oncology Journal
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• v.38 no.2
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• pp.109-118
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• 2020

Purpose: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. Methods: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at d_max and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). Results: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. Conclusion: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. NCT04175821).

• Radiation Oncology Journal
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• v.21 no.1
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• pp.82-93
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• 2003

Purpose : To reduce the Irradiation dose to the lungs and heart in the case of chest wail irradiation using an oppositional electron beam, we used an Individualized custom bolus, which was precisely designed to compensate for the differences In chest wall thickness. The benefits were evaluated by comparing the normal tissue complication probablilties (NTCPS) and dose statistics both with and without boluses. Materials and Methods : Boluses were made, and their effects evaluated in ten patients treated using the reverse hockey-stick technique. The electron beam energy was determined so as to administer 80% of the irradiation prescription dose to the deepest lung-chest wall border, which was usually located at the internal mammary lymph node chain. An individualized custom bolus was prepared to compensate for a chest wall thinner than the prescription depth by meticulously measuring the chest wall thickness at 1 emf intervals on the planning CT Images. A second planning CT was obtained overlying the individuailzed custom bolus for each patient's chest wall. 3-D treatment planning was peformed using ADAC-Pinnacle$^{3}$ for all patients with and without bolus. NTCPS based on 'the Lyman-Kutcher' model were analyzed and the mean, maximum, minimum doses, V$_{50}$ and V$_{95}$ for 4he heari and lungs were computed. Results .The average NTCPS in the ipsliateral lung showed a statistically significant reduction (p<0.01), from 80.2${\pm}$3.43% to 47.7${\pm}$4.61%, with the use of the individualized custom boluses. The mean lung irradiation dose to the ipsilateral iung was also significantly reduced by about 430 cGy, Trom 2757 cGy to 2,327 cGy (p<0.01). The V$_{50}$ and V$_{95}$ in the ipsilateral lung markedly decreased from the averages of 54.5 and 17.4% to 45.3 and 11.0%, respectively. The V$_{50}$ and V$_{95}$ In the heart also decreased from the averages of 16.8 and 6.1% to 9.8% and 2.2%, respectively. The NTCP In the contralateral lung and the heart were 0%, even for the cases with no bolus because of the small effective mean radiation volume values of 4.4 and 7.1%, respectively Conclusion : The use of an Individualized custom bolus in the radiotherapy of postrnastectorny chest wall reduced the NTCP of the ipsilateral lung by about 24.5 to 40.5%, which can improve the complication free cure probability of breast cancer patients.

• Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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• 2001.06a
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• pp.1031-1031
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• 2001

The mammary gland is made up of remarkably sensitive tissue, which has the capability of producing a large volume of secretion, milk, under normal or healthy conditions. When bacteria enter the gland and establish an infection (mastitis), inflammation is initiated accompanied by an influx of white cells from the blood stream, by altered secretory function, and changes in the volume and composition of secretion. Cell numbers in milk are closely associated with inflammation and udder health. These somatic cell counts (SCC) are accepted as the international standard measurement of milk quality in dairy and for mastitis diagnosis. NIR Spectra of unhomogenized composite milk samples from 14 cows (healthy and mastitic), 7days after parturition and during the next 30 days of lactation were measured. Different multivariate analysis techniques were used to diagnose the disease at very early stage and determine how the spectral properties of milk vary with its composition and animal health. PLS model for prediction of somatic cell count (SCC) based on NIR milk spectra was made. The best accuracy of determination for the 1100-2500nm range was found using smoothed absorbance data and 10 PLS factors. The standard error of prediction for independent validation set of samples was 0.382, correlation coefficient 0.854 and the variation coefficient 7.63%. It has been found that SCC determination by NIR milk spectra was indirect and based on the related changes in milk composition. From the spectral changes, we learned that when mastitis occurred, the most significant factors that simultaneously influenced milk spectra were alteration of milk proteins and changes in ionic concentration of milk. It was consistent with the results we obtained further when applied 2DCOS. Two-dimensional correlation analysis of NIR milk spectra was done to assess the changes in milk composition, which occur when somatic cell count (SCC) levels vary. The synchronous correlation map revealed that when SCC increases, protein levels increase while water and lactose levels decrease. Results from the analysis of the asynchronous plot indicated that changes in water and fat absorptions occur before other milk components. In addition, the technique was used to assess the changes in milk during a period when SCC levels do not vary appreciably. Results indicated that milk components are in equilibrium and no appreciable change in a given component was seen with respect to another. This was found in both healthy and mastitic animals. However, milk components were found to vary with SCC content regardless of the range considered. This important finding demonstrates that 2-D correlation analysis may be used to track even subtle changes in milk composition in individual cows. To find out the right threshold for SCC when used for mastitis diagnosis at cow level, classification of milk samples was performed using soft independent modeling of class analogy (SIMCA) and different spectral data pretreatment. Two levels of SCC - 200 000 cells/$m\ell$ and 300 000 cells/$m\ell$, respectively, were set up and compared as thresholds to discriminate between healthy and mastitic cows. The best detection accuracy was found with 200 000 cells/$m\ell$ as threshold for mastitis and smoothed absorbance data: - 98% of the milk samples in the calibration set and 87% of the samples in the independent test set were correctly classified. When the spectral information was studied it was found that the successful mastitis diagnosis was based on reviling the spectral changes related to the corresponding changes in milk composition. NIRS combined with different ways of spectral data ruining can provide faster and nondestructive alternative to current methods for mastitis diagnosis and a new inside into disease understanding at molecular level.

• Journal of Life Science
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• v.28 no.4
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• pp.389-397
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• 2018

The structure of glycan residues attached to glycoproteins can influence the biological activity, stability, and safety of pharmaceutical proteins delivered from transgenic pig milk. The production of therapeutic glycoprotein in transgenic livestock animals is limited, as the glycosylation of mammary gland cells and the production of glycoproteins with the desired homogeneous glycoform remain a challenge. The ${\beta}$-1,3-N-acetylglucosaminylatransferase1 (B3GNT1) gene is an important enzyme that attaches N-acetylglucosamine (GlcNAc) to galactose (Gal) residues for protein glycosylation; however, there is limited information about pig glycosyltransferases. Therefore, we cloned the pig B3GNT1 (pB3GNT1) and investigated its functional properties that could attach N-acetylglucosamine to galactose residue. Using several different primers, a partial pB3GNT1 mRNA sequence containing the full open reading frame (ORF) was isolated from liver tissue. The ORF of pB3GNT1 contained 1,248 nucleotides and encoded 415 amino acid residues. Organ-dependent expression of the pB3GNT1 gene was confirmed in various organs from adult and juvenile pigs. The pB3GNT1 mRNA expression level was high in the muscles of the heart and small intestine but was lower in the lungs. For functional characterization of pB3GNT1, we established a stable expression of the pB3GNT1 gene in the porcine kidney cell line (PK-15). As a result, it was suggested that the glycosylation pattern of pB3GNT1 expression in PK-15 cells did not affect the total sialic acid level but increased the poly N-acetyllactosamine level. The results of this study can be used to produce glycoproteins with improved properties and therapeutic potential for the generation of desired glycosylation using transgenic pigs as bioreactors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.3
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• pp.199-218
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• 2005

Purpose of Study: Peripheral nerve regeneration depends on neurotrophism of distal nerve stump, recovery potential of neuron, supporting cell like Schwann cell and neurotrophic factors such as BDNF. Peripheral nerve regeneration can be enhanced by the conduit which connects the both sides of transected nerve. The conduit maintains the effects of neurotrophism and BDNF produced by Schwann cells which can be made by gene therapy. In this study, we tried to enhance the peripheral nerve regeneration by using calcium phosphate coated porous conduit and BDNF-Adenovirus infected Schwann cells in sciatic nerve of rats. Materials and Methods: Microporous filter which permits the tissue fluid essential for nerve regeneration and does not permit infiltration of fibroblasts, was made into 2mm diameter and 17mm length conduit. Then it was coated with calcium phosphate to improve the Schwann cell adhesion and survival. The coated filter was evaluated by SEM examination and MTT assay. For effective allogenic Schwann cell culture, dorsal root ganglia of 1-day old rat were extracted and treated with enzyme and antimitotic Ara-C. Human BDNF cDNA was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into adenovirus shuttle vector pAACCMVpARS in which E1 was deleted. We infected the BDNF-Ad into 293 human mammary kidney cell-line and obtained the virus plaque 2 days later. RT-PCR was performed to evaluate the secretion of BDNF in infected Schwann cells. To determine the most optimal m.o.i of BDNF-Ad, we infected the Schwann cells with LacZ adenovirus in 1, 20, 50, 75, 100, 250 m.o.i for 2 hours and stained with ${\beta}$-galactosidase. Rats(n=24) weighing around 300g were used. Total 14mm sciatic nerve defect was made and connected with calcium phosphate coated conduits. Schwann cells$(1{\times}10^6)$ or BDNF-Ad infected Schwann cells$(1{\times}10^6)$ were injected in conduit and only media(MEM) was injected in control group. Twelve weeks after surgery, degree of nerve regeneration was evaluated with gait analysis, electrophysiologic measurements and histomorphometric analysis. Results: 1. Microporous Millipore filter was effective conduit which permitted the adhesion of Schwann cells and inhibited the adhesion of fibroblast. We could enhance the Schwann cell adhesion and survival by coating Millipore filter with calcium phosphate. 2. Schwann cell culture technique using repeated treatment of Ara-C and GDNF was established. The mean number of Schwann cells obtained 1 and 2 weeks after the culture were $1.54{\pm}4.0{\times}10^6$ and $9.66{\pm}9.6{\times}10^6$. 3. The mRNA of BDNF in BDNF-Ad infected Schwann cells was detected using RT-PCR. In Schwann cell $0.69\;{\mu}g/{\mu}l$ of DNA was detected and in BDNF-Adenovirus transfected Schwann cell $0.795\;{\mu}g/{\mu}l$ of DNA was detected. The most effective infection concentration was determined by LacZ Adenovirus and 75 m.o.i was found the most optimal. Conclusion: BDNF-Ad transfected Schwann cells successfully regenerated the 14mm nerve gap which was connected with calcium phosphate coated Millipore filter. The BDNF-Ad group showed better results compared with Schwann cells only group and control group in aspect to sciatic function index, electrophysiologic measurements and histomorphometric analysis.

• 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.