• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4263-4266
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• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Journal of Microbiology and Biotechnology
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• v.28 no.12
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• pp.2133-2140
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• 2018

Norovirus is the most common cause of acute gastroenteritis. Its pathogenesis is poorly understood owing to the difficulty of establishing viral infection in animal models. Here, post-weaning gnotobiotic pigs were infected with human norovirus genogroup II genotype 4 (HuNoV GII.4) to investigate the pathogenesis and replication of the virus. Three groups of four pigs were infected with $1{\times}10^5$, $1{\times}10^6$, or $1{\times}10^7$ genomic equivalent (GE) copies of HuNoV GII.4. Four pigs were used as negative controls. Blood and rectal swab samples were collected after viral infection, and gross legions were examined after necropsy. Diarrhea was induced in 25% and 75% of pigs infected with $1{\times}10^6$ and $1{\times}10^7$ GE copies, respectively. Viral shedding was detected in 50%, 75%, and 50% of pigs infected with $1{\times}10^5$, $1{\times}10^6$, and $1{\times}10^7$ GE copies, respectively. Viremia was detected in 25% of pigs infected with either $1{\times}10^6$ or $1{\times}10^7$ GE copies. When gross lesions of gastroenteritis were investigated, the ileum walls of the infected pigs were thinner than those of the controls. Villi atrophy and inflammatory cell infiltration were identified in the ileum of each infected pig. Viral capsid was identified in the jejunum, ileum, colon, spleen, and mesenteric lymph node. Virus replication was newly verified in the spleen and mesenteric lymph nodes by detection of negative-sense viral RNA. In conclusion, HuNoV GII.4 could induce acute gastroenteritis and replicate in the extra-intestinal lymphoid tissues in post-weaning gnotobiotic pigs. Therefore, such pigs would be a suitable animal model for studying the pathogenesis and replication of HuNoV.

• Journal of Gastric Cancer
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• v.6 no.3
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• pp.154-160
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• 2006

Purpose: According to the 2nd English Edition of the Japanese Gastric Cancer Association (JGCA) in 1998, in case of distal gastric cancer, the 14v (superior mesenteric vein) lymph node (LN) is included in the N2 group. However, in Korea, a modified radical gastrectomy is performed, and a 14v LN dissection is not done as a routine procedure. Thus, we investigated the rate of metastatic 14v LNs, evaluated the necessity of dissection of the 14v LN, and searched for indications of 14v LN dissection. Materials and Methods: From April 2004 to August 2005, we enrolled the patients who were diagnosed as having advanced gastric cancer in the distal third portion of the stomach. We peformed a distal gastrectomy with D2 lymph node dissection as defined in the 2nd English edition of the JGCA classification. We calculated the positive rate of metastatic LNs of each station and analyzed the relationship between the positive rates of No.6 LNs and 14v LNs. We also compared the positive 14v LN group with the negative 14v LN group. Results: The total number of patients was 50, the mean age was 56 (range $30{\sim}80$) years, and sex ratio (Male/Female) was 1.63 : 1. In 47 (94%) cases, distal a gastrectomy with gastroduodenostomy was done, and in the remaining 3 (6%) cases, a distal gastrectomy with gastrojejunostomy was done. The most frequently metastatic LNs were nos. 3 and 6 (54%). The metastatic rate of the f4v LN was 10%, which was similar to that of LN no. 9. In the comparison of the 14v positive group with the 14v negative group, there were significant differences in the numbers of metastatic LNs (mean 25.4 vs 4.91, P<0.001) and the numbers of metastatic no. 6 LNs, (mean 6.8 vs 1.42, P<0.001), and if no. 6 LNs were metastatic, the possibility of metastasis to the 14v LN was 19.2%. In the 14v positive group, all cases were more than stage 3 by the UICC 6th edition. Conclusion: In cases of advanced cancer with metastasis to the no. 6 IN, there was a good chance of metastasis to the 14v LN. Thus, in the operative field, if the tumor is advanced to more than stage 3 by the UICC classification and the no. 6 LN is metastatic, a 14v LN dissection is necessary. However, the usefulness of a 14v LN dissection should be evaluated prospectively through an analysis of tumor recurrence and long-term survival.

• Korean Journal of Veterinary Research
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• v.47 no.3
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• pp.315-319
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• 2007

Fibrinopurulent peritonitis and abdominal abscesses associated with Streptococcus (S.) equi subsp. zooepidemicus is reported in a 1-year-old female thoroughbred horse. The horse died after showing 5-day history of the cold, severe abdominal distention, abdominal breathing, hyperthermia, anorexia, and loss of intestinal sound. At necropsy, several liters of turbid yellowish green fluid were seen in the abdominal cavity. Yellowish creamy and fibrinous or bloody materials were presented on the serosa of various abdominal organs that were intensively adhered with each other. Spleen and mesenteric lymph node were remarkably enlarged. Affected lobes of the lung showed severe congestion, hemorrhage and doughy consistency. Histologically, the lung showed hemorrhagic pneumonia with diffuse congestion and edema. Severe diffuse fibrinopurulent peritonitis with Gram-positive bacterial cocci and adjacent fibrosis were showed in the serosa of various abdominal organs such as liver, spleen, stomach, and intestine. And multifocal abscess pouches were presented in the granulation tissue of abdominal viscera. S. equi subsp. zooepidemicus was isolated from the peritoneal swab, abdominal organs, and lung. Hematogenous dissemination of bacteria from hemorrhagic pneumonia is proposed as the route of infection in this case.

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1267-1274
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• 2004

Colostrum contains various kinds of cytokines including TGF-$\beta$ that has potent regulatory effects on cells of the immune system. We compared the levels of TGF-$\beta$1 and TGF-$\beta$2 in bovine and human colostrum. Based on the isoform-specific ELISA, bovine colostrum collected on day 1 post-delivery retained $53.71{\pm}29.55\;ng/ml$ of TGF-$\beta$1 and $40.41{\pm}21.78\;{\mu}g/ml$ of TGF-$\beta$2 (n=4), while in human, $381.45{\pm}158.24\;ng/ml$ of TGF-$\beta$1 and $41.47{\pm}9.63\;ng/ml$ of TGF-$\beta$2 (n=5). Thus, dominant TGF-$\beta$ isoforms were completely opposite between human and bovine colostrum samples. The concentrations of both isoforms declined as lactation proceeded. Biological activities of the colostrum samples were determined using an MV1LU cell line. Consistent with the result from the immunoassay, TGF-$\beta$1 in human and TGF-$\beta$2 in bovine colostrum were responsible for the anti proliferative activity against MV1LU cells. Furthermore, bovine colostrum increased IgA secretion by LPS-stimulated mesenteric lymph node (MLN) cells, and this effect was abrogated by either anti­TGF-$\beta$2 antibody or combined anti-TGF-$\beta$1/$\beta$2 antibody, but not by anti- TGF-$\beta$1 antibody alone. Similarly, TGF-$\beta$2 in bovine colostrum enhanced the Ig germ line (GL) promoter activity, which is the earliest event toward IgA isotype switching. Taken together, these results suggest that TGF-$\beta$ isoforms, differentially expressed in human and bovine colostrum, may promote IgA isotype production in the neonatal intestine.

• Korean Journal of Medicinal Crop Science
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• v.15 no.2
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• pp.132-137
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• 2007

Inhibitory effect of Scutellaria baicalensis ethanol extracts (SR) on chemical mediator release and immunoglobulin (Ig) production from Sprague-Dawley rats originated cells as type I allergic reaction was examined. SR showed concentration-dependent inhibition on basal and concanavalin A (ConA)-stimulated Ig production. In the mesenteric lymph node lymphocytes, the inhibitory effect of SR on the IgE production in the presence of Con A was stronger than these on IgA and IgG production. Moreover, tumor necrosis factor-alpha $(TNF-{\alpha})$ production-inhibiting effect of SR in the presence ConA was observed. However, SR did not affect the production of $interferon-{\gamma}$. SR also inhibited histamine release from the peritoneal exudate cells stimulated with a calcium ionophore A23187. In the case of leukotriene B4, SR markedly inhibited it at the concentration of 100 mg/ml. From these results, ethanol extracts obtained from Scutellaria baicalensis may have an anti-allergic effect on the intestinal system of rats.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.8
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• pp.1182-1187
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• 2003

Two experiments involving 92 crossbred, 21 day old weaned pigs were used to evaluate the effect of glutamine supplement in a dietary or culture medium on lymphocyte proliferation. In Exp. 1, 88 pigs were fed diets supplemented with 0, 0.5, 1.0, or 1.5% glutamine for 28 days. Lymphocytes were prepared from peripheral blood mononuclear cells (PBMC), ileal Peyer's patches (PP), the mesenteric lymph node (MLN), and the spleen in each dietary supplement group on days 7, 14, or 28 postweaning. Lymphocytes were cultured at $37^{\circ}C$ for 72 h in a RPMI-1640 medium with or without mitogen-stimulated, and pulsed with 3Hthymidine for an additional 18 h. The stimulation index of PBMC proliferation in 1.0% dietary glutamine supplement group and both of the MLN and splenocytes proliferation in 1.5% dietary glutamine supplement group was significantly (p<0.05) increased at 14 days postweaning. In Exp. 2, four weaned pigs were fed a basal diet for 14 days. The 3H-thymidine incorporation of PBMC, PP, and MLN cells, incubated with 0.125 to 0.25 mM glutamine in culture medium were markedly enhanced with Con A-stimulated, however, the splenocyte proliferation was not affected in the addition of glutamine medium. These observations suggest that dietary glutamine supplement might enhance the lymphocyte proliferation of weaned pigs.

• Parasites, Hosts and Diseases
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• v.45 no.2 s.142
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• pp.95-102
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• 2007

The mRNA expression of several cytokines was evaluated in splenocytes and mesenteric lymph node (MLN) cells of rats infected with Capillaria hepatica by reverse-transcription (RT)-PCR until week 12 after infection. IgG1 and IgG2a, which are associated with Th1 and Th2 response, respectively, were also assessed by ELISA. The results indicated that the majority of cytokines, including the Th1 (IL-2 and $IFN-{\gamma}$ and Th2 cytokines (IL-4, IL-5 and IL-10) were expressed at maximal levels during the early stage of infection (after week 1-2), and the ELISA data also evidenced a similar pattern of changes in IgG1 arid IgG2a. Th1 and Th2 cytokines responded in a similar fashion in this rat model. The expression of cytokines in splenocytes was significantly higher than that in MLN cells, thereby indicating that cytokine production is controlled more by spleen than by MLN. In addition, the observation that $IFN-{\gamma}$ expression increased unexpectedly at the time of maximal egg production (6 weeks after infection) indicated that $IFN-{\gamma}$ is a cytokine reacting against egg production. However, increased IL-5 expression occurring in tandem with worm activity indicated that the activity of C. hepatica might be controlled by IL-5 expression.