• Laboraroty Animal Research
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• v.34 no.4
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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.

• The Journal of Korean Medicine
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• v.24 no.1
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• pp.41-53
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• 2003

The effect of Banhasasim-tang extracts on the hepatic, splenic and cardiac toxicity induced by doxorubicin administration (three injection protocol) were monitored using male ICR mice. Changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. The results were as follows: 1. Decrease of body weight after doxorubicin treatment was dose-dependently inhibited by Banhasasim-tang extracts. 2. The degrees of anorexia, ataxia and dehydration that were observed in doxombicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. 3. Increase of absolute and relative liver weight observed in the doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of the doxorubicin-only treatment group. It is also demonstrated that elevated serum GOT and GPT levels in the doxorubicin treatment group were significantly decreased in the Banhasasim-rang extracts dosing group. 4. Decrease of absolute and relative spleen weight observed in doxorubicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of doxorubicin-only treatment group. 5. Increase of absolute and relative heart weight observed in doxorubicin treatment groups were dose-dependently inhibited by Banhasasim-rang extracts. In addition, the degrees of heart congestion and enlargement were significantly and dose-dependently decreased in the Banhasasim-rang extracts dosing group compared to that of the doxorubicin-only treatment group. In conclusion, the toxicity of doxorubicin treatment (decrease of body weight, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhasasim-rang extracts. According to these results, it is considered that Banhasasim-rang has some preventive effect against the toxicity induced by doxorubicin.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.8 no.1
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• pp.9-21
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• 2002

Object The effect of Banhasasim-tang extracts on the hepatic, splenic toxicity and induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Method The changes of body weigh, organ weights of liver and spleen were observed with blood GOT and GPT level. Results 1. Increase of absolute and relative liver weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of liver congestion and necrotic spot were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in Doxorubicin treatment group were significantly decreased in Banhasasim-tang extracts dosing groups. 2. Decrease of absolute and relative spleen weight observed in Doxorubicin treatment group were dose dependently inhibited by Banhasasim-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group.

• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.190-202
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• 2003

Object : The effect of Banhabakchulchunma-tang extracts on the hepatic, splenic and cardiac toxicity induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Methods : The changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. Results : 1. Decrease of body weight and The degrees of anorexia, ataxia and dehydration after Doxorubicin treatment were dose-dependently inhibited by Banhabakchulchunma-tang extracts. 2. Increase of absolute and relative liver and heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of liver congestion necrotic spot and the degrees of heart congestion enlargement were dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in doxorubicin treatment group were significantly decreased in Banhabakchulchunma-tang extracts dosing groups. 3. Decrease of absolute and relative spleen weight observed in doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. Conclusion : the toxicity of doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhabakchulchunma-tang extracts. According to these results, it is considered that Banhabakchulchunma-tang has some preventive effect against to doxorubicin induced toxicity.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.110-116
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• 1997

The present study was designed to evaluate the effects of a recombinant human granulocyte-colony stimulating factor (G-CSF) on leukopenia and tumor growth in mice treated with DA-125, an adri-amycin (ADM) derivative. In normal mice, single intravenous injection of DA-125 produced transient leukopenia accompanied with weight loss and splenic atrophy in a dose-related manner. However, subcutane-ous administration of G-CSF (5$\mu$g/head) for 5 consecutive days after DA-125 resulted in a significantly elevated nadir of leukocyte counts and facilitation of recovery from the leukopenia. To investigate the effect of G-CSF on antitumor effects of DA-125, ADM (12 mg/kg) or DA-125 (40 mg/kg) was administered to Colon-26 murine adenocarcinoma-bearing Balb/c mice with G-CSF. Regardless of treatment with G-CSF, DA-125 and ADM markedly retarded the growth of implanted tumor, though they failed to increase mean survival time of tumor-bearing mice. These results suggest that G-CSF is able to not only ameliorate, but reconstitute DA-125-induced myelosuppression without affecting its antitumor potential.

• Journal of Chest Surgery
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• v.6 no.2
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• pp.243-248
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• 1973

Eventration of the diaphragm is, by definition, abnormally high or elevated position of diaphragm as a result of paralysis, aplasia or atrophy of varing degrees of muscle fibers, and the cause of which may be congenital or acquired. The unbroken continuity of the diaphragm differentiates it from diaphragmatic hernia. The clinical manifestations of the condition, if present, are usually due to the interference of the ventilatory function of the lung and digesive dysfunction due to gastrointestinal distorsion. Treatment consists of surgical repair of the relaxed diaphragm to it`s normal position. A ease of left sided eventuration of the diaphragm, 31 year old officer, was found by chance after traffic accident with chief complaints of hemoptysis and multiple superficial contusions. Routine chest roentgenogram and barium study of the colon revealed moderately elevated left hemidiaphragm with displacement of the splenic flexure of the colon into the left chest. Past history revealed frequent attack of upper respiratory infection and some abnormal condition on his left chest announced by screen cheek of chest X-ray at the time of entrance for his army service 3 years before. Plication of the relaxed diaphragm through left thoracotomy was done and result was excellent as seen on Fig. 5. Cause of eventration of the left hemidiaphragm was due to paralysis of the left phrenic nerve which was tested during thoracotomy.

• Korean Journal of Veterinary Pathology
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• v.1 no.2
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• pp.125-134
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• 1997

Porcine Reproductive and Respiratory Syndrome Virus infection (PRRSV) was confirmed by serology histopathology immunohistochemistry and bacteriologic examination in young pigs. Four suckling and six weaned piglets submitted from three different farms showed coughing sneezing labored rapid abdominal respiration lethargy and anorexia. Grossly apical and cardiac lung lobes appeared mottled with pale to dark tan discoloration. Submandibular and bronchial lymph nodes were tan and enlarged. All piglets were seropositive for PRRSV antibodies by the indirect immunofluorescent antibody(IFA) test. Microscopically lung lesions were characterized by hyperplasia and hypertrophy of type 2 pneumocytes infiltration of mononuclear cells in alveolar intersitium accumulation of necrotic debris in alveolar spaces accompanied by proliferation of alveolar multinucleated syncytial cells. Using immunohistochemical technique PRRSV antigens were demonstrated in alveolar macrophages and type 2 pneumocytes in histologic lung tissue sections. Also PRRSV antigens were detected in brain lymph nodes spleen and heart. Additionally piglets showed nonsuppurative meningoencephalitis mandibular necrotic lymphadenopathy splenic atrophy and myocardial necrosis.