• Laboraroty Animal Research
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• 제34권4호
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• pp.166-175
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• 2018

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

• 대한수의학회지
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• 제36권4호
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• pp.1013-1016
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• 1996

Since 1993, sudden and massive death has occurred among penaeid shrimp, Penaeus orientalis cultured in Korea. We investigated the pathological characterizations on the spontaneously and experimentally infected penaeid shrimp. The major gross findings of the spontaneous cases were 2-6mm sized-white spots on the inside of the carapace and reddish discolorization. Histopathologically, massive necrosis of lymphoid organ, degeneration and necrosis of epithelia of epidermis and foregut were observed in both spontaneous and experimental cases. Amphophilic to basophilic intranuclear inclusion bodies were readly observed epithelia of epidermis, foregut and gills. Electron microscopy revealed enveloped, non-occuluded ellipsoid to rod shaped virus particles, within the nucleus, in the lymphoid organs and interstitial cells of hepatopancreas of both spontaneously and experimentally infected shrimps. The size of the virion was $375{\times}167nm$, and the nucleocapsid was $290{\times}75nm$. The causative agent causing massive death in penaeid shrimps in Korea resembles baculovirus associated with white spot syndrome (WSBV) occurred in Taiwan in virus morphology and gross and histological changes of the shrimps.

• International Journal of Stem Cells
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• 제16권1호
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• pp.108-116
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• 2023

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

• Biomolecules & Therapeutics
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• 제15권4호
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• pp.245-251
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• 2007

The object of this study was to evaluate the single dose toxicity of Kong-Jin-Dan (KJD), a polyherbal formula in male and female mice. KJD was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for increases of lymphoid organ weights in KJD-dosing groups. These increases of lymphoid organ weights considered that related to the immune modulate effect of KJD not toxicological signs. In addition, no KJD-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the KJD does not cause any toxicological signs. The $LD_{50}$ and approximate LD of KJD extracts in both female and male mice were considered as over 2000 mg/kg.

• 대한수의학회지
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• 제31권4호
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• pp.471-477
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• 1991

Attempts to isolate chicken anemia agent (CAA) were made by inoculating tissue homogenates into MDCC-MSBl or LSCC-1104B1 cell lines and passaging the cells serially. CAA was isolated from the liver and thymus of 11 weeks old layer chickens and from the liver of 10 weeks old broiler breeder chickens. The layer flock experienced approximately 45% mortality during 9 to 14 week of age from gangrenous dermatitis and lymphoid organs of affected chickens were severely atrophied. The broiler breeder flock experienced approximately 7% mortality during 7 to 9 weeks of age and affected birds showed lesions of colibacillosis, staphylococcal arthritis, and coccidiosis together with atrophied lymphoid organs. The isolated viruses were identified as CAA by the indirect fluorescent antibody test and virus neutralization test using CAA immune sera including one to Gifu-1 strain of CAA. The CAA isolate 89-69, when inoculated into susceptible 1 day old SPF chicks, induced anemia 14 to 16 days after inoculation. It did not induce any cytopathic effects in chicken embryo liver and chicken embryo fibroblast cell cultures. Infectivity of the isolate was not affected by the treatment of chloroform or heat ($70^{\circ}C$ for 15 minutes).

• Asian-Australasian Journal of Animal Sciences
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• 제30권5호
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• pp.690-699
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• 2017

Objective: This study aimed to examine the effect of sodium butyrate (SB) on growth performance, immune status, organs weights, and microarchitecture of lymphoid organs and small intestine. Methods: A total of 120, 1-d-old broiler chicks were distributed into the following four treatment groups: corn-soy based basal diet (BD) without supplement (control), or the same BD supplemented with 0.1 g/kg zinc bacitracin (ZnB), 0.5 g/kg SB (SB-0.5), or 1.0 g/kg SB (SB-1), respectively. Six birds/group were killed on d-21 and d-35, and samples were collected. Results: Cell-mediated immune response at 48 h post-Phytohemagglutinin-P injection, and antibody titer against Newcastle disease vaccine and sheep red blood cells on d-35 was noted higher (p<0.05) in SB-1 compared to ZnB and control. Lower (p<0.05) feed conversion ratio (FCR) was attained by the supplemented groups. Thymus and spleen weighed more (p<0.05) in SB-1, and bursa registered more (p<0.05) weight in both SB groups compared to control. On d-21, areas of thymus medulla and spleen germinal centers were noted higher (p<0.05) in SB-1 group. The villus height and villus surface area increased (p<0.05) in duodenum and jejunum in both SB groups on d-21, and in SB-1 on d-35, respectively compared to ZnB and control. On d-21, number of goblet cells containing mucins of acidic nature increased (p<0.05) in all the segments of small intestines in SB-1 group compared to control, and on d-35 in ileum compared to other groups. Conclusion: In conclusion, SB improved growth performance and immunity as well as modulated morphology of lymphoid organs and gut mucosa in broiler chickens.

• 대한수의학회지
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• 제42권3호
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• pp.335-349
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• 2002

The immune response against Salmonella gallinarum infection was investigated in immunosuppresed chickens. Newly hatched chickens were treated with cyclophosphamide at the first and second day after birth and were challenged intraperitoneally with S gallinarum ($1{\times}10^7CFU/m{\ell}$) on day 6. Group 1, Immunosuppresed and Challenged group, was treated with cyclophaiphamide and challenged with S gallinarum; group 2, Immunosuppressed group, was only treated with cyclophsphamide; group 3, Challenged group, was only challenged with S gallinarum; group 4, Control group. In each group, the localization of lymphocytes of the lymphoid organs and intestine was immunohistochemically compared using a variety of monoclonal antiboies ($CD4^+$, $CD8^+$, and B lymphocyte). Also, S gallinarum were assessed by Maccallum-Goodpasture stain and immunohistochemical analysis in the paraffin-embedded intestinal tissues. In S gallinarum challenged chickens, $CD4^+$ and $CD8^+$ lymphocytes of the intestinal organs such as duodenum, jejunum, ileum and colon were increased. However, in cyclophophamide treated chickens, $CD4^+$ and $CD8^+$ lymphocytes and especially B lymphocytes of the lymphoid organs such as thymus, spleen, and bursa of Fabricius were dramatically decreased. These results suggest that cyclophsophamide is an immunosuppressive agent that especially causes depletion of B lymphocytes, suppress humoral immunity and eventually suppresses avian immune responses. Its protection against S gallinarum infection is mainly dependent on both cell-mediated mechanism and the humoral immune response.

• 한국동물위생학회지
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• 제27권1호
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• pp.63-73
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• 2004

The present experiment was carried out to study the pathogenesis of Newcastle disease(ND), ND virus (NDV) antigens and genes in various organs from NDV inoculated chickens were detected by immunohistochemistry and RT-PCR. Immunohistochemically, NDV antigens were detected in the spleen, thymus, cecal tonsil, proventriculus, trachea and lungs at 12 hour post-inoculation (hpi). Viral antigens were localized mainly in the cytoplasm of lymphocytes and macrophages. After 48 hpi, clinical findings of the affected chickens were open-mouth breathing, conjunctivitis, watery diarrhea and edema around the eye and neck. After 72 hpi, chickens showed muscular tremor, paralysis of the legs and wings, and coma. Histopathological results consist of multi-focal necrosis with hemorrhages in lymphoid aggregates of the intestinal tracts, necrosis of the lymphoid tissues, neuronal degeneration and necrosis, and perivascular cuffing. Using RT-PCR, virus genes were detected in the spleen and proventriculus at 48 hpi, and in the brain at 60 hpi.

• 대한두경부종양학회지
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• 제40권1호
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• pp.23-26
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• 2024

Mucosa-associated lymphoid tissue (MALT) lymphomas comprise 7.6% of non-Hodgkin's lymphomas (NHLs) and they are recently recognized B-cell subset of NHLs. They are originated from gastrointestinal tract most frequently but may also occur in other organs including head and neck, lung, skin, thyroid and breast. Primary thyroid lymphomas (PTLs) constitute up to 5% of all thyroid malignancies. Diffuse large B-cell lymphoma is most common type of PTLs and MALT lymphoma is relatively rare subtype of PTLs. Thyroid MALToma arises in chronic inflammatory conditions with autoimmune or infectious etiologies. The optimal treatment regimen still remains controversial. However, It is reported that localized thyroid MALT lymphoma has excellent survival rate after surgical resection alone. We report a case of 48-years-old woman with primary thyroid MALToma.

• Toxicological Research
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• 제11권1호
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• pp.9-14
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• 1995

The immune system is partially under the control of the sympathetic and parasymphathetic nervous systems through the regulatory feedback loop. Methamphetamine (MA) is a neurotoxic chemical which affects the neurotransmitter system. The objective of this study was to investigate the immunotoxic effect of MA on the major immune target organ and lymphocyte proliferation to the various mitogens. Female Balb/C mice, 15 to 20 g, were injected subcutaneously with 0, 0.5, or 5 mg MA/kg for 14 consecutive days. In MA treated mice, the body weight gain and relative spleen and thymus weight were decreased in doserelated manner. Histopathologically, there was a paucity of lymphold follicles and germinal centers in the spleen, and thymic cortical atrophy with lymphophagocytosis was prominent. Apoptosis also occurred in germinal centers of spleen and thymic cortex. The threshold and peak of lymphocyte proliferation at various concentration of mitogens showed similar patterns. However, the response to lipopolysaccaride (LPS) and pokeweed mitogen (PWM) in the 5 mg MA/kg treated group showed threshold and peak proliferation at high concentration of mitogens (25${\mu}g$ LPS/ml for MA vs 15${\mu}g$ LPS/ml for control; 60${\mu}g$ PWM/ml for MA vs 45${\mu}g$ PWM/ml for control), which suggest that MA impairs T cell dependent-B cell function. This preliminary study indicated that MA affected the lymphold organs and immune function.