• Journal of Yeungnam Medical Science
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• v.23 no.1
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• pp.26-35
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• 2006

Background: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-${\kappa}B$ and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. Materials and Methods: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-${\kappa}B$ $cis$-elements. C57BL/6 NF-${\kappa}B^{EGFP}$ mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-${\kappa}B$ activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. Results: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-${\kappa}B$ activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. Conclusions: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.

• The Korean Journal of Malacology
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• v.22 no.1 s.35
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• pp.27-38
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• 2006

We investigated the reproductive cycle with gonad developmental phases of Solen grandis by histological observations. Seasonal changes in biochemical components of the adductor muscle, visceral mass, foot muscle and mantle were studied by biochemical analysis, from January to December, 2005. The reproductive cycle of this species can be classified into five successive stages: early active stage (December to January), late active stage (January to March), ripe stage (March to July), partially spawned stage (June to July) and spent/inactive stage (July to December). Total protein content was the highest in the foot muscle, the content was high in January (early active stage), the lowest in April (ripe stage), and was the highest in August (partially spawned stage). In the visceral mass, total protein content began to increase in February (late active stage) and reached a maximum in March (ripe stage). Thereafter, it gradually decreased between June and July (partially spawned stage). There was a strong negative correlation in total protein contents between visceral mass and mantle (r = -0.594, p = 0.042). Meanwhile there was a positive correlation between the adductor muscle and foot muscle, the correlation was not statistically significant (r = 0.507, p = 0.093). Total lipid content was the highest in the visceral mass; it was more than 2 to 5-fold higher than that in the adductor muscle, foot muscle, and mantle. Monthly changes in total lipid content were also most dynamic in the visceral mass. It was relatively higher between January and February, showed a maximum in March (the ripe stage), decreased rapidly from April to July (ripe and partially spawned stage), and gradually decreased from September to December (spent/inactive stage). There was a strong positive correlation in total lipid content between foot muscle and adductor muscle (r = 0.639, p = 0.025). Tthough a negative correlation was found between visceral mass and mantle (r = -0.392), the correlation was not statistically significant (p = 0.208). Glycogen contents changed within relatively narrow range and were similar among different tissues. There was no statistically significant correlation in glycogen contents among tissues.

• Journal of Life Science
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• v.33 no.4
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• pp.315-324
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• 2023

The underlying action of policosanol in lowering cholesterol level has not yet been clearly elucidated. Several recent studies have suggested that sterol regulatory element-binding proteins (SREBP)-1c play a role in the regulation of cholesterol synthesis via the fatty acid synthesis pathway. To date, no study has evaluated the effects of policosanol on SREBP-1c-mediated fatty acid synthesis. Therefore, this study aimed to investigate whether the SREBP-1c-mediated fatty acid biosynthetic pathway is associated with the cholesterol-lowering effects of policosanol. Seven-week-old C57BL/6 male mice were randomly divided into 7 groups (n=7 per group) and treated for 8 weeks as follows: 1) normal diet (normal control), 2) high-fat diet (HFD), 3) HFD+ethanol (Pol-0), 4) HFD+policosanol 1 mg/kg (Pol-1), 5) HFD+policosanol 2 mg/kg (Pol-2), 6) HFD+policosanol 4 mg/kg (Pol-4), and 7) HFD+simvastatin 50 ㎍/kg (positive control). Policosanol and simvastatin were administered at the same time every day while maintaining the HFD. Body weight and food intake were measured weekly for 8 weeks. After 8 weeks, serum cholesterol levels were measured, histological analysis was carried out, and the expressions of SREBP-1c and fatty acid synthase (FAS) in the liver tissues were examined. Policosanol reduced body weight and the amount of food intake in a dose-dependent manner. Serum cholesterol levels were significantly lowered in the Pol-1 and Pol-4 groups. The expression of SREBP-1c and FAS was also significantly decreased in the Pol-4 group. These results suggest that the cholesterol-lowering effects of policosanol can occur due to the inhibition of the expression of SREBP-1c and FAS.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.139-146
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• 2002

Purpose : This study evaluated the treatment outcomes, patterns of failure, and treatment related complications of primary lymphoma patients who received definitive radiation therapy. Materials and Methods : A retrospective analysis was undertaken for 31 patients with primary orbital lymphoma at the Asan Medical Center between February 1991 and April 2001. There were 18 males and 13 females with ages ranging from 3 to 73 years (median, 44 years). The involved sites were 9 conjunctivae, 12 eyelids and 10 other orbits. The histological types were 28 MALT lymphomas (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type), 1 diffuse large B-cell lymphoma, 1 anaplastic large cell lymphoma and 1 lymphoblastic lymphoma. The Ann Arbor stages were all IE $(100\%)$. Ann Arbor stage III or IV patients were excluded from this study, Bilateral orbital involvement occurred in 6 cases. Radiation therapy was given with one anterior port of high energy electrons $(6\~16\;MeV)$ for the lesions located at the anterior structures like the conjunctivae or eyelids. Lesions with a posterior extension or other orbital lesions were treated with 4 or 6 MeV photons with appropriately arranged portals. In particular, lens blocks composed of lead alloy were used in conjunctival or eyelid lesions. Twelve patients received chemotherapy. The median follow-up period was 53 months. Results : The 5-year overall, cause-specific, and disease-free survival was $91\%,\;96\%,\;and\;80\%$, respectively. The complete response rate 6 months after radiation therapy was $100\%$. Local recurrences were observed in 2 patients at 16 and 18 months after completion of radiation treatment. They were salvaged with additional radiation therapy. Two patients developed distant metastases. A MALT lymphoma patient with a lung relapse was successfully salvaged with radiotherapy, but the other lymphoblastic lymphoma patient with bone marrow relapse expired. There were no severe complications but 5 patients developed radiation-induced cataracts and 2 patients developed dry eye. Conclusion : Most primary orbital lymphomas consisted of MALT lymphomas. Radiation therapy was a successful treatment modality for orbital lymphoma without any severe complications. In cases of local relapses, radiation therapy is also a very successful salvage treatment modality.

• Radiation Oncology Journal
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• v.26 no.1
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• pp.65-73
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• 2008

Purpose: Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Materials and Methods: Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor(ER), progesterone receptor(PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. Results: There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history(4/14) and bilateral breast cancers(3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2-associated cancers demonstrated more expression of ER-negative(19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors(negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was not a prognostic factor. Conclusion: Breast cancer that occurs in women with a germline BRCA1 or BRCA2 mutations have recognizable immunohistochemical features, which may be useful in identifying individuals that are more likely to carry germline mutations. Although the BRCA1/2 mutation status was not a prognostic factor in Korean women with early-onset breast cancer, more cases with a longer follow-up period are needed for further study.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.45-55
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• 1998

Purpose: To make objective standards of small intestinal mucosal changes in cow's milk-sensitive enteropathy (CMSE) we analyzed histological changes of endoscopic duodenal mucosa biopsy specimens from normal children and patients of CMSE. Methods: We review the medical records of patients who had been admitted and diagnosed as CMSE by means of gastrofiberscopic duodenal mucosal biopsy following cow's milk challenge and withdrawal. Thirteen babies with CMSE, ranging from 14 days to 56 days of age, were studied. Five non-CMSE patients were used as control, ranging from 22 days to 72 days of age. The morphometric parameters under study were villous height, crypt zone depth, ratio of villous height to crypt zone depth, total mucosal thickness and length of surface epithelium by using H & E stained specimens under the drawing apparatus attached microscope. In addition, the numbers of lymphocytes in the epithelium and eosinophil cells in the lamina propria and epithelium were measured. Results: In the duodenal mucosal biopsy specimens in CMSE we found partial and subtotal villous atrophy with an increased number of interepithelial lymphocytes. The mean villous height($135{\pm}59\;{\mu}m$), ratio of villous height to crypt zone depth ($0.46{\pm}0.28$), total mucosal thickness ($499{\pm}56\;{\mu}m$), length of surface epithelium of small intestinal mucosa ($889{\pm}231\;{\mu}m$) in CMSE was significantly decreased compared with the control (p<0.05). The mean crypt zone depth ($311{\pm}65\;{\mu}m$) was significantly greater than the control ($188{\pm}24\;{\mu}m$)(p<0.05). Infiltration of interepithelial lymphocytes ($34.1{\pm}10.5$) were significantly greater than the control ($13.6{\pm}3.6$)(p<0.05). The number of eosinophil cells in both lamina propria and epithelium was no significant differences between groups (p>0.05). The small intestinal mucosa in treated CMSE showed much improved enteropathy of villous height, crypt zone depth, interepithelial lymphocytes compared with the control as well as untreated CMSE. Conclusion: Quantitation of mucosal dimensions confirmed the presence of CMSE. It seems to be a limitation in the capacity of crypt cells to compensate for the loss of villous epithelium in CMSE. Specimens obtained by gastrofiberscopic duodenal mucosal biopsy were suitable for morphometric diagnosis of CMSE. Improvement of CMSE also can be confirmed histologically after the therapy of protein hydrolysate.

• Journal of Acupuncture Research
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• v.22 no.3
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• pp.227-241
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• 2005

Objective & Methods : The purpose of this study is to observe the effects of Asari Herba Cum Radice herbal-acupuncture solution(AHCR-HAS) on arthritis of mice induced by Collagen II at Joksamni(ST36). The author performed several experimental items. First, it is the cell survival rate of mice lung fibroblasts and expression of TNF-${\alpha}$ in synovial cells. Second, it is the incidence rate of arthritis and the weight of spleen. Third, it is the levels of IL-6, TNF-${\alpha}$, INF-${\gamma}$, IgG, IgM and anti-collagen II in serum Fourth, it is histological analysis of the mice joint. Fifth, it is expression ratio of CD3e+ to CDl9+ cell, CD4+ to CD8+ cell, CD69+/CD3e+ cells, CD11+/CD19+ cells and CD11b+/Gr-1+ cells. Result : 1. The highest survival rate of mice lung fibroblasts were measured in the 1% AHCR-HAS, and the expression of TNF-${\alpha}$ in synovial cells were significantly decreased in the 1% AHCR-HAS. 2. In the AHCR-HA I & AHCR-HAII groups, the incidence of arthritis and the weight of spleen were significantly decreased. 3. In AHCR-HAI & AHCR-HAII groups, the levels of IL-6, INF-${\gamma}$, TNF-${\alpha}$, IgG, IgM and anti-collagen II in serum of CIA mice were significantly decreased. 4. In histology, the cartilage destruction and synovial cell proliferation were decreased in the AHCR-HA I & AHCR-HAII groups, and the collagen fiber expressions in the AHCR-HA I & AHCR-HAII groups were similar with that of the Normal group. 5. In the AHCR-HA I & AHCR-HA II groups, the expression ratio of CD3e+ to CD19+ cell and CD4+ to CD8+ cell were similarly maintained as Normal group in lymph nodes, and CD69+/CD3e+ cells and CD11a+/CD19+ cells were decreased in Iymph nodes, and CD11b+/Gr-1+ cells were decreased in synovium. Conclusion : Taking all these observations into account, AHCR-HA is considered to be effective in prophylaxis and treatment of rheumatoid arthritis, and then more effective in prophylaxis than treatment, so put to practical use in future rheumatoid arthritis clinic.

• The Korean Journal of Malacology
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• v.22 no.2
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• pp.125-134
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• 2006

We investigated the reproductive cycle of the hard clam, Meretrix petechialis with its gonadal development by histological observations. The seasonal changes in biochemical component of the adductor muscle, visceral mass, foot muscle and mantle of the clam were studied by biochemical analysis, from January to December, 2002. The reproductive cycle of this species can be divided into five successive stages: early stage (January to March), late active stage (February to May), ripe stage (April to August), partially spawned stage (July to August) and spent/inactive stage (September to January). Total protein content in the visceral mass was over two times higher than that in the adductor muscle. Monthly changes of total protein content in the adductor muscle were not statistically significant (ANOVA, p = 0.071), while the changes in the visceral mass were significant (p < 0.001). Total protein content in visceral mass was higher during the early active, late active, and ripe stages (from January to May), while the lowest in July. Glycogen content in the adductor muscle was higher than that in the visceral mass. Monthly changes in glycogen contents were statistically significant in both adductor muscle (F = 237.2, p < 0.001) and the visceral mass (F = 64.04, p < 0.001). Glycogen content in the adductor muscle was the highest in the ripe stage (April). Its content was lower in the partially spawned and the spent/inactive stages (June-September). Glycogen contents in the visceral mass were relatively lower until the early active stage, while the highest in the late active stage. RNA content was higher in visceral mass than that in the adductor muscle. Monthly changes in RNA contents were significant in both adductor muscle (F = 195.2, p < 0.001) and visceral mass (F = 78.85, p < 0.001). RNA content in the adductor muscle was high in the early active stage (January-February), and then it decreased rapidly in the late active stage (March-April), thereafter, slightly increased during the partially spawned stage (June-July). RNA content in the visceral mass reached a maximum during the ripe stage (May), and then it decreased rapidly during the partially-spawned stage (June-July). There was significant positive correlation in total protein contents between adductor muscle and visceral mass (r = 0.715, p = 0.020). However, there was no correlation between adductor muscle and visceral mass in glycogen (p = 0.550), while a negative correlation was found between the adductor muscle and visceral mass in RNA (p = 0.518) contents. Especially, changes in RNA content showed a negative correlation between the adductor muscle tissue and visceral mass. Therefore, these results suggest that the nutrient content of the adductor muscle, visceral muscle and foot muscle changed in response to gonadal energy needs.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.