Sample records for mice receiving spleen

  1. Human spleen microanatomy: why mice do not suffice.

    Steiniger, Birte S


    The microanatomical structure of the spleen has been primarily described in mice and rats. This leads to terminological problems with respect to humans and their species-specific splenic microstructure. In mice, rats and humans the spleen consists of the white pulp embedded in the red pulp. In the white pulp, T and B lymphocytes form accumulations, the periarteriolar lymphatic sheaths and the follicles, located around intermediate-sized arterial vessels, the central arteries. The red pulp is a reticular connective tissue containing all types of blood cells. The spleen of mice and rats exhibits an additional well-delineated B-cell compartment, the marginal zone, between white and red pulp. This area is, however, absent in human spleen. Human splenic secondary follicles comprise three zones: a germinal centre, a mantle zone and a superficial zone. In humans, arterioles and sheathed capillaries in the red pulp are surrounded by lymphocytes, especially by B cells. Human sheathed capillaries are related to the splenic ellipsoids of most other vertebrates. Such vessels are lacking in rats or mice, which form an evolutionary exception. Capillary sheaths are composed of endothelial cells, pericytes, special stromal sheath cells, macrophages and B lymphocytes. Human spleens most probably host a totally open circulation system, as connections from capillaries to sinuses were not found in the red pulp. Three stromal cell types of different phenotype and location occur in the human white pulp. Splenic white and red pulp structure is reviewed in rats, mice and humans to encourage further investigations on lymphocyte recirculation through the spleen.

  2. Effect of Spleen Lymphocytes on the Splenomegaly in Hepatocellular Carcinoma-bearing Mice

    FANG Jing Jing; ZHU Zhen Yuan; DONG Hui; ZHENG Guo Qiang; TENG An Guo; LIU An Jun


    Objective To study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model. Methods Cell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of IL-2 were measured, and two-dimensional gel electrophoresis (2-DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice. Results Compared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3+ T lymphocytes and CD8+ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility. Conclusion It is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.

  3. Expression of NALP3 in the Spleen of Mice with Portal Hypertension

    夏泽锋; 王国斌; 万赤丹; 刘涛; 王帅; 王博; 程锐


    This study examined the mRNA expression of NALP3 in the spleen of the mice with hypersplenism due to portal hypertension(PH).The mouse hypersplenism models were established by oral administration of tetrachloromethane(2 mL/kg/week for 12 weeks by oral gavage).All the mice were randomly divided into a control group and an experimental group.The blood routine test was conducted,spleen index was calculated and spleen was histologically examined.Portal vein sera were taken for detection of the level of uric aci...

  4. Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ(null) mice generates humanized mice that improve functional B cell development.

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Park, Jae Berm; Chang, Jun; Kim, Sung Joo


    We previously generated humanized TB34N mice that received human fetal thymus (T), bone tissue (B) and fetal liver-derived (FL)-CD34(+) cells (34) in immunodeficient, NOD/SCID IL2Rγ(null) (N) mice. Although humanized TB34N mice had excellent hematopoiesis, here, we sought to further improve this model by additional transplantation of human spleen tissue (S) as a secondary hematopoietic tissue (TBS34N). The human spleen grafts were enlarged and differentiated into a similar morphology of adult humans, including follicular lymphoid structures with T- and B-cells. The TBS34N mice mimicked mature human immune system (HIS): mature T- and B-cells and follicular dendritic cells; activated germinal center B-cells expressing CD71, BR3(+) cells, memory B-cells and activation-induced cytidine deaminase(+) B-cells; CD138(+) plasma cells were enriched in the mouse spleen. HBsAg-specific hIgG antibodies were secreted into the sera of all TBS34N mice upon immunization with HBsAg. Taken together, the humanized TBS34N mice improved mature HIS and achieved adaptive antibody responses.

  5. Effects of Aging and Advanced Glycation on Gene Expression in Cerebrum and Spleen of Mice



    Objective To analyze the effects of aging or advanced glycation on gene expression in the cerebrum and spleen of female C57BL/6J mice. Methods The gene expression profile was determined by using cDNA expression arrays containing 588 cDNA. Results Aging and advanced glycation resulted in differential gene expression patterns of cerebrum and spleen compared with young mice. Among the 80 genes detected in cerebrum, 43 exhibited a change in mRNA ratios with aging or treatment. Thirty-four changes (79%) were common in aged and D-galactose treated mice,whereas the cerebrum from aged and AGE-lysine treated mice showed common changes in expression of 38 genes(88%). Of the 86 genes detected in spleen, 29 (34%) displayed an age-related decrease in expression, whereas 3 (3%) displayed an increase in expression levels with aging. Eighteen genes from the detectable genes exhibited expression changes in both cerebrum and spleen of mice.Conclusions The gene expression profiles of D-galactose and AGE-lysine treated mice resemble those of aged mice. Use of cDNA hybridization arrays may provide a promising tool to explore the mechanism of aging at a molecular level.

  6. Age-related changes in the bone marrow and spleen of SAS/4 mice.

    Coggle, J E; Gordon, M Y; Proukakis, C; Bogg, C E


    The total number of nucleated cells in the bone marrow of SAS/4 mice increase some twofold between 1 and 24 months of age but when related to body weight remains essentially constant over a wide range of ages. The concentration of CFU-S in femoral marrow is also constant with age and since other bones containing marrow appear, at least in young mice, to have the same CFU-S concentration as the femur it is concluded that the CFU-S compartment size of the whole bone marrow is independent of age when expressed on a body weight basis, In contrast, both the absolute number and the concentration of exogenous CFU-S in the spleen decline markedly in old mice. Smilary there is a decline in the number of endogenous colony-forming cells and the spleens of 24-month-old mice seem virtually devoid of such colonies. Not only were older mice less capable of supporting the growth of endogenous colonies, but their spleens also appear to provide a poorer environment for exogenous colony growth when compared with growth in younger recipient spleens.

  7. The toxic effects of melamine on spleen lymphocytes with or without cyanuric acid in mice.

    Yin, Rong H; Liu, Jiao; Li, Hua S; Bai, Wen L; Yin, Rong L; Wang, Xin; Wang, Wen C; Liu, Bao S; Han, Xiao H; Han, Jie; He, Jian B; Han, Xiao R


    Melamine is an organic nitrogenous compound whose acute toxicity was generally thought to be low in animals. In the present work, we investigated the potential cytotoxic effects of melamine on spleen lymphocytes in mice. In the treated group, morphological changes were observed in cultured lymphocytes in vitro. The co-administration of melamine and cyanuric acid caused a declining tendency in stimulation index of spleen lymphocyte. All treated groups had lower ratios of CD4+/CD8+. Both early apoptotic and late apoptotic/necrotic rates of lymphocyte were significantly higher in the co-administration high groups of melamine and cyanuric acid. Melamine-related toxicity promoted the expression of Bax mRNA, and suppressed the expression of Bcl-2 mRNA in spleen of the treated mice. These results provided useful information for assessing the toxicity of melamine on immune system of mammals, and contributed to the existing toxic profile of melamine.

  8. Histopathology effects of nickel nanoparticles on lungs, liver, and spleen tissues in male mice

    Ajdari, Marziyeh; Ziaee Ghahnavieh, Marziyeh


    Because of the classification of the nickel compounds as carcinogenic substances, there is a need for in vivo tests to nickel nanoparticles (NiNPs) for observing their effects on health experimentally. Spherical NiNPs with 10 nm in diameter and 75 ppm concentration were applied for investigating their toxicities within male albino mice as an in vivo model. We randomly made sham group, control group, and 75 ppm group (with five animals in each group). Then, the nanoparticles were injected into mice intraperitonealy for 7 days and after that their lungs, liver, and spleen were removed for histopathological observations. At the end of the test, section microscopic observations of liver, spleen, and lung in sham and control groups showed normal tissues but these tissues underwent significant abnormal effects in 75 ppm group. NiNPs can cause undesirable effects in lungs, liver, and spleen tissues with same condition of this study.

  9. Spleen content of selected polyphenols, splenocytes morphology and function in mice fed Rhodiola kirilowii extracts during pregnancy and lactation.

    Lewicki, S; Stankiewicz, W; Skopińska-Różewska, E; Wilczak, J; Leśniak, M; Suska, M; Siwicki, A K; Skopiński, P; Zdanowski, R


    The genus Rhodiola (Crassulaceae) consists of many species, growing mainly in Asia and traditionally used as adaptogens and anti-inflammatory drugs. In order to elaborate herbal immunostimulator which could be safely given to pregnant women, we performed a study on immunotropic effects of feeding pregnant and lactating mice Rhodiola kirilowii extracts. This paper presents the results of the first part of our study - spleen content of selected polyphenols, spleen cellularity, splenocytes phenotype and their response to mitogens. Experiments were performed on adult inbred females of Balb/c strain, mated with adult males. Females, since copulatory plug was noted, up to the 28-th day after delivery were fed daily with 20 mg/kg b.m. water (RKW) or hydro-alcoholic (RKW-A) extracts of Rhodiola kirilowii. 1. Significantly lower proportion of pregnant mice in experimental groups than in the control. 2. Cellularity of spleen and flavonol quercetin spleen concentration were significantly lower in experimental groups in comparison to the controls. 3. Flavanols ((+)-catechin and epicatechin) levels were significantly higher in the spleens of experimental mice than in the controls. 4. Positive correlation between spleen cellularity and quercetin, and negative correlation between spleen cellularity and epicatechin content were observed. 5. Spleen mass and spleen lymphocytes phenotype and proliferation in RKW and RKW-A fed mice did not differ from the control. These results, together with suspicion of some embryo-toxicity, are worrying and eliminate the possibility of use Rhodiola kirilowii extracts for long-term treatment in pregnant females.

  10. Effects of Sleep Deprivation on Mice Bone Marrow and Spleen B Lymphopoiesis.

    Lungato, Lisandro; Nogueira-Pedro, Amanda; Carvalho Dias, Carolina; Paredes-Gamero, Edgar Julian; Tufik, Sergio; D'Almeida, Vânia


    B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response. Sleep is an essential event for the maintenance and integrity of all systems, including the immune system (IS). Thus, sleep deprivation (SD) causes problems in metabolism and homeostasis in many cell systems, including the IS. In this study, our goal was to determine changes in B lymphocytes from the bone marrow (BM) and spleen after SD. Three-month-old male Swiss mice were used. These mice were sleep deprived through the modified multiple platform method for different periods (24, 48, and 72 h), whereas another group was allowed to sleep for 24 h after 72 h of SD (rebound group) and a third group was allowed to sleep normally during the entire experiment. After this, the spleen and BM were collected, and cell analyses were performed. The numbers of B lymphocytes in the BM and spleen were reduced by SD. Additionally, reductions in the percentage of lymphocyte progenitors and their ability to form colonies were observed. Moreover, an increase in the death of B lymphocytes from the BM and spleen was associated with an increase in oxidative stress indicators, such as DCFH-DA, CAT, and mitochondrial SOD. Rebound was not able to reverse most of the alterations elicited by SD. The reduction in B lymphocytes and their progenitors by cell death, with a concomitant increase in oxidative stress, showed that SD promoted a failure in B lymphopoiesis.

  11. Radiation-induced apoptosis in SCID mice spleen after low dose irradiation

    Takahashi, A.; Kondo, N.; Inaba, H.; Uotani, K.; Kiyohara, Y.; Ohnishi, K.; Ohnishi, T.

    To assess the radioadaptive response of the whole body system in mice, we examined the temporal effect of low dose priming as an indicator of challenging irradiation-induced apoptosis through a p53 tumor suppressor protein- mediated signal transduction pathway. The p53 protein also plays an important role both in cell cycle control and DNA repair through cellular signal transduction. Using severe combined immunodeficiency mice defective in DNA-dependent protein kinase catalytic subunit, we examined the role of DNA-dependent protein kinase activity in radioadaptation induced by low dose irradiation. Specific pathogen free 5-week-old female severe combined immunodeficiency mice and the parental mice (CB-17 Icr +/ + were irradiated with X-ray at 3.0 C3y at 1, 2, 3 or 4 weeks after the conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after the challenging irradiation. The p53-dependent apoptosis related Bax proteins on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method The apoptosis incidence in the sections was measured by hematoxylin-eosin staining. The frequency of Bax- and apoptosis-positive cells increased up to 12 h after the challenging irradiation in the spleen of both mice. However, these cells were not observed after a low dose irradiation at 0.15-0.60 Gy When pre-irradiation at 0.45 Gy 2 weeks before the challenging irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by challenging irradiation were depressed in the spleens of CB-17 Icr +/ + mice, but not in severe combined immunodeficiency mice. These data suggest that DNA-dependent protein kinase might play a major role in radioadaptation induced by pre-irradiation with a low dose in mice spleen. We expect that the present findings will provide useful information in the health care of space crews.

  12. Fusarenon-X-induced apoptosis in the liver, kidney, and spleen of mice

    Sutjarit, Samak; Poapolathep, Amnart


    Fusarenon-X is a non-macrocyclic type B trichothecene mycotoxin. It occurs naturally in agricultural commodities, such as wheat and barley. We investigated fusarenon-X-induced apoptosis in the liver, kidney, and spleen of male and female mice after a single exposure. Thus, mice were orally administered fusarenon-X (4 mg/kg body weight) and were assessed at 0, 3, 9, 18, 24, and 48 hours after treatment. Apoptosis in the liver, kidney, and spleen was determined using hematoxylin and eosin staining, the terminal deoxynucleotidyl transferase dUTP nick end labeling method, immunohistochemistry for proliferating cell nuclear antigen, and electron microscopy. Fusarenon-X-induced apoptosis at 9 hours after treatment, particularly hepatocytes around the central lobular zone of the liver, in proximal tubular cells of the kidney, and in hematopoietic cells in the red pulp area of the spleen in both male and female mice. The results of this study should be very useful with regard to the toxicity of fusarenon-X in both humans and domestic animals, which has been attributed to the intake of food contaminated with mycotoxins, especially fusarenon-X. PMID:27559248

  13. The relative efficacy of different strain combinations of lactic acid bacteria in the reduction of populations of Salmonella enterica Typhimurium in the livers and spleens of mice.

    Tsai, Cheng-Chih; Liang, Hsin-Wen; Yu, Bi; Hsieh, Chang-Chi; Hwang, Chin-Fa; Chen, Ming-Hui; Tsen, Hau-Yang


    Multispecies probiotics have been reported to be more effective than monostrain probiotics in health promoting for the host. In this study, 12 lactic acid bacteria (LAB) strains were selected based on the level of induction of tumor necrosis factor (TNF)-α in RAW 264.7 macrophage cells. Their adherence to Caco-2 cells and inhibitory effects on Salmonella invasion of Caco-2 cells were compared. Strains with different probiotic properties were then combined and BALB/c mice were fed with LAB strains for 63 days; then the mice were challenged with Salmonella on day 64. For Salmonella-unchallenged mice that received a multistrain combination of LAB strains that have greater TNF-α production in macrophages, greater adherence and inhibit Salmonella invasion of Caco-2 cells to a greater extent, their peritoneal macrophages had greater phagocytic activity. For Salmonella-challenged mice, a significant reduction of Salmonella cells in the livers and spleens of the mice was observed 8 days post challenge. The addition of 12% skim milk powder together with LAB strain combinations significantly enhanced the reduction of Salmonella cells in the mice livers and spleens. In conclusion, we have shown that LAB strain combinations with particular probiotic properties when fed to mice can inhibit Salmonella invasion of the liver and spleen.

  14. Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice.

    Pantic, Igor; Paunovic, Jovana; Basta-Jovanovic, Gordana; Perovic, Milan; Pantic, Senka; Milosevic, Nebojsa T


    The effects of aging on structural complexity in hematopoietic tissue are unknown. In this work, in a mouse experimental model, we report the age-related reduction of spleen hematopoietic tissue (SHT) complexity. Spleen tissue was obtained from the total of 64 male Swiss albino mice divided into 8 age groups: newborns (0 days old), 10 days, 20 days, 30 days, 120 days, 210 days, 300 and 390 days old. SHT was stained using conventional hematoxylin/eosin, and DNA-binding toluidine blue dyes. Fractal dimension as an indicator of cellular complexity, and lacunarity as indicator of tissue heterogeneity were determined based on the binarized SHT micrographs. Results indicate that fractal dimension of mice spleen hematopoietic tissue decreases with age, while lacunarity increases. These changes/trends have been detected in SHT stained both with toluidine blue and conventional hematoxylin/eosin. Fractal dimension was negatively correlated with lacunarity. The detected reduction in complexity suggests that age-related structural changes are present in mouse SHT both in general tissue architecture and progenitor cell DNA. © 2013.

  15. Immunomodulatory effects in the spleen-injured mice following exposure to titanium dioxide nanoparticles.

    Sang, Xuezi; Fei, Min; Sheng, Lei; Zhao, Xiaoyang; Yu, Xiaohong; Hong, Jie; Ze, Yuguan; Gui, Suxin; Sun, Qingqing; Ze, Xiao; Wang, Ling; Hong, Fashui


    Immune injuries following the exposure of titanium dioxide nanoparticles (TiO₂ NPs) have been greatly concerned along with the TiO₂ NPs are widely used in pharmacology and daily life. However, very little is known about the immunomodulatory mechanisms in the spleen-injured mice due to TiO₂ NPs exposure. In this study, mice were continuously exposed to 2.5, 5, or 10 TiO₂ NPs mg kg(-1) body weight for 90 days with intragastric administration to investigate the immunomodulatory mechanisms in the spleen. The findings showed that TiO₂ NPs exposure resulted in significant increases in spleen and thymus indices, and titanium accumulation, in turn led to histopathological changes and splenocyte apoptosis. Furthermore, the exposure of TiO₂ NPs could significantly increase the levels of macrophage inflammatory protein (MIP)-1α, MIP-2, Eotaxin, monocyte chemotactic protein-1, interferon-γ, vascular cell adhesion molecule-1, interleukin-13, interferon-γ-inducible protein-10, migration inhibitory factor, CD69, major histocompatibility complex, protein tyrosine phosphatase, protein tyrosine kinase 1, basic fibroblast growth factor, Fasl, and GzmB expression, whereas markedly decrease the levels of NKG2D, NKp46, 2B4 expression involved in immune responses, lymphocyte healing and apoptosis. These findings would better understand toxicological effects induced by TiO₂ NPs exposure.

  16. Radiosensitivity of mice and its modifiers based on the endogeneous spleen colony formation

    Kobayashi, Jindo; Wagatuma, Kaoru


    In irradiated mouse hematopoietic tissue, there is a group of cells which can proliferate and form macroscopic colonies. In the spleen, the colonies formed in this manner are discrete and easy to count. In order to look into a difference of radiosensitivity between male and female and the mechanisms of the modification, such as protective agent and hormones on radiosensitivity, the spleen colony forming (SCF) is used as an indicator of reactions in the x-rays irradiated mice. A linear decrease was found in SCF depended on x-rays dose. From the colony forming after irradiation the male was more radiosensitive than female. AET protected from the injury depended on the radiation dose in male mice, but in female mice, protection effects were not observed. Gonatropin showed protective effects for radiation injury on high dose irradiation both in male and female mice. Adrenaline showed similar effects as Gonatropin. Insuline showed a negative effects of protection on 400 R irradiation, while on 600 R irradiation, protective effects were observed.

  17. Clonogenic colony-forming ability of hepatic stem cells in the spleens of mice


    To confirm the existence of hepatic stem cells (HSCs), fetal liver cells isolated from mice on embryonic day 13 (ED13) were long-term cultured in vitro. Growth of the cells was observed intensively and characteristics were identified by immunocytochemistry. The results showed that some of the cells grew as colonies, in which some cells expressed AFP, CD34 and Albumin. Then the cells were transplanted intravenously into irradiated syngeneic mice. At day 12 a number of small hyperplasia nodules were seen in the apparently enlarged spleens of recipient mice. Moreover, some nodules were positive for AFP and CD34 and consisted of various types of cells, suggesting the very existence of hepatic stem cells in the mouse fetal liver.

  18. 3,5,6,7,8,3',4'-Heptamethoxyflavone reduces interleukin-4 production in the spleen cells of mice.

    Nakajima, Mitsunari; Ogawa, Minetaro; Amakura, Yoshiaki; Yoshimura, Morio; Okuyama, Satoshi; Furukawa, Yoshiko


    In our previous studies, we reported anti-inflammatory functions of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), which is a polymethoxyflavone rich in various citrus fruits. Here, we investigated the immunomodulatory function of HMF in mice. HMF administration (50 mg/kg, i.p., 2 times/week) tended to reduce the production of antigen-specific IgE induced by ovalbumin in combination with aluminum hydroxide gel. Fluorescence-activated cell sorting analysis revealed the reduction of interleukin-4(+)CD4(+) spleen cells and sustained presence of interferon-γ(+)CD4(+) spleen cells in mice administered HMF, whereas the ratio of CD4(+)CD8(-) versus CD4(-)CD8(+) spleen cells was not affected. Interleukin-4 release from CD3/CD28-stimulated spleen cells of mice administered HMF was reduced, whereas interferon-γ release was not affected. These results suggest that HMF has an immunomodulatory function via reduced interleukin-4 expression.

  19. Experimental infection with cytopathic bovine viral diarrhea virus in mice induces megakaryopoiesis in the spleen and bone marrow.

    Seong, Giyong; Lee, Jin-Sol; Lee, Kyung-Hyun; Choi, Kyoung-Seong


    Here, we infected mice with cytopathic bovine viral diarrhea virus 1 (cp BVDV1) by oral inoculation and investigated the effects of infection by histopathological, immunohistochemical (IHC), hematological methods. Twelve mice were infected, and samples were obtained at day 2, 5, and 9 postinfection (pi). Most of the infected mice exhibited clinical signs of illness such as reduced movement, crouching, loose feces, loss of appetite, and reduced water intake. Blood samples from six mice were positive for BVDV based on reverse transcription polymerase chain reaction (RT-PCR). Blood analysis also revealed thrombocytopenia and lymphopenia. Viral antigens were detected in the spleen (12/12), bone marrow (12/12), and/or mesenteric lymph nodes (4/12) of all infected mice by IHC analysis. The spleens showed significant histopathological changes including (i) substantially increased numbers of megakaryocytes, (ii) lymphocyte depletion, and (iii) hemorrhages. The bone marrow also had an increased number of megakaryocytes, although this increase was not as strong as it was in the spleen. Severe lymphoid depletion was observed in the mesenteric lymph nodes. Viral infections were present in the lymphocytes but not detected in megakaryocytes of the spleen, bone marrow, or mesenteric lymph nodes. These results suggest that the increased numbers of megakaryocytes may be a direct result of BVDV infection. BVDV infection in mice following oral inoculation of cp BVDV1 leads to megakaryopoiesis in the spleen and bone marrow to replenish the platelets.

  20. The Role of Apoptosis in the Cellular Response of Liver and Spleen of BALB/c Mice in Cutaneous Leishmaniasis

    Mahvash Jafari


    Full Text Available Background: Cutaneous leishmaniasis is a common parasitic disease in Iran being mainly caused by Leishmania (L. major. The aim of this study was to investigate the occurrence of apoptosis in the spleen and liver of female mice infected with L. major. Methods: BALB/c mice were randomly assigned into the control and experimental groups (ten mice per group. The experimental groups were subcutaneously inoculated with promastigotes of L. major at stationary phase. The animals were sacrificed after 20, 40, 60, 90, and 120 days of injection. The liver and spleen were analyzed for various parameters of apoptosis. Results: Activities of superoxide dismutase and caspase-3, levels of superoxide anion production and malondialdehyde, and the percent of DNA fragmentation were increased in the liver and spleen of the infected mice. Catalase activity in the liver was increased, while glutathione level in both tissues was decreased after 90 and 120 days of infection. The numbers of apoptotic nuclei in the spleen were higher than the liver at 90 and 120 days post-infection using the TUNEL method. Conclusion: L. major infection induces a time-dependent increase in apoptosis in the liver and spleen as evidenced by the production of ROS, increasing activation of caspase-3, elevated DNA fragmentation, and increasing lipid peroxidation. Induction of oxidative stress was observed in the liver and spleen after 90 and 120 days of initiation of the infection. However, the spleen tissue appears to be more sensitive to the infection to L. major on oxidative stress and apoptosis induction compared with the liver tissue.

  1. The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

    Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.


    The capacity of spleen and peritoneal cells from iron deficient mice, ad libitum fed control mice, and pair-fed mice to kill allogenic tumor cells (mastocytoma tumor P815) has been investigated. In the first study, mice were sensitized in vivo with 10(7) viable tumor cells 51 and 56 days after weaning. The capacity of splenic cells and peritoneal cells from sensitized and nonsensitized mice to kill tumor cells was evaluated 5 days after the second dose of tumor cells. At ratios of 2.5:1 to 100:1 of attacker to target cells, the percentage /sup 51/Cr release after 4 h of incubation was significantly less in iron-deficient mice than control and/or pair-fed mice (p less than 0.05). Protein-energy undernutrition in pair-fed mice had no significant effect. In the second study, spleen cells and enriched T cell fractions were incubated in vitro for 5 days with uv irradiated Balb/C spleen cells in a 2:1 ratio. The cytotoxic capacity against the same allogenic tumor cells was again evaluated. The percentage chromium release at different attacker to target cells was less than 30% in the iron-deficient group compared to either control or pair-fed supporting the results of in vivo sensitized cells. The possible mode of impairment of the cytotoxic capacity is discussed.

  2. Relationship between HMGB1 content and MHC-Ⅱ expression in circulating monocytes and spleen of mice challenged with zymosan

    L(U) Yi; LU Jiang-yang; ZHAO Min; LI Zhi-hong; YANG Yi


    Objective: To observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-Ⅱ-I-Ab expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes. Methods: One hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-Ab positive monocytes. Results: In normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-Ab positive monocytes in circulating blood and spleen decreased at 1-2 days (t=9.589, 4.432, P<0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zyrnosan challenge, I-Ab expression on circulating monocytes was downregulated (t=5.977, P<0.01), while that in spleen upregulated (t=4.814, P<0.01). Conclusion: In mice with MODS, up-regulated HMGB1 expression can regulate I-Ab expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.

  3. Experimental infection with non-cytopathic bovine viral diarrhea virus 1 in mice induces inflammatory cell infiltration in the spleen.

    Han, Yu-Jung; Kwon, Young-Je; Lee, Kyung-Hyun; Choi, Eun-Jin; Choi, Kyoung-Seong


    Previously, our study showed that oral inoculation of mice with cytopathic (cp) bovine viral diarrhea virus (BVDV) led to lymphocyte depletion and increased numbers of megakaryocytes in the spleen as well as thrombocytopenia and lymphopenia. In the present study, to investigate the possible differences in the detection of viral antigen, histopathological lesions, and hematologic changes between non-cytopathic (ncp) BVDV1 and cp BVDV1, mice were orally administered low and high doses of ncp BVDV1 and were necropsied at days 0, 2, 5, and 9 postinfection (pi). None of the ncp BVDV1-infected mice exhibited clinical signs of illness, unlike those infected with cp BVDV1. Statistically significant thrombocytopenia was observed during ncp BVDV1 infection, and lymphopenia was found only in mice infected with a high dose at day 9 pi. Interestingly, ncp BVDV1 infection increased the numbers of basophils, eosinophils, neutrophils, and monocytes in some infected mice. Viral antigen was detected in the lymphocytes of the spleen, mesenteric lymph nodes, Peyer's patches, and bone marrow by immunohistochemistry. Lymphoid depletion was evident in the mesenteric lymph nodes of mice infected with a high dose and also found in the Peyer's patches of some infected mice. Infiltration of inflammatory cells, including neutrophils and monocytes, and an increased number of megakaryocytes were seen in the spleen. These results suggest that the distribution of viral antigens is not associated with the presence of histopathological lesions. Inflammatory cell infiltration was observed in the spleens as a result of viral replication and may be attributable to the host reaction to ncp BVDV1 infection. Together, these findings support the possibility that mice can be used as an animal model for BVDV infection.

  4. Protective effects of desferrioxamine and deferiprone on the spleen tissue of aluminum intoxicated mice: A Fourier transform infrared spectroscopy study.

    Sivakumar, S; Khatiwada, Chandra Prasad; Sivasubramanian, J


    The present study was designed to examine the protective effects of the chelating agents desferrioxamine (DFO) and deferiprone (DFP) in aluminum intoxicated spleen tissue of mice by Fourier transform infrared (FTIR) spectroscopy. The finding revealed the alterations on the major biochemical constituents, such as lipids, proteins, phosphodiester and nucleic acids of the spleen tissue of mice at molecular level. The significant decreased in the peak areas of asymmetric and symmetric mode of the phosphodiester groups from control to aluminum intoxicated, but improved it by DFP and DFO+DFP treatments respectively for nearer control value. The bands ratio at I1081/I1232 significantly decreased from control to aluminum, but enhanced it by DFP and DFO+DFP respectively. This result suggests that DFO and DFP are the phosphodiesterase inhibitor, recovered from chronic growth of diseases in the spleen. Amide I and amide II peak area values decreased from control to aluminum intoxicated spleen tissue, but treated with DFP and DFO+DFP significantly improved. This result suggests an alteration in the protein profile. The absence of Olefinic=CH stretching in aluminum intoxicated spleen suggests an altered lipid levels. Concentrations of trace elements were found by ICP-OES. Histopathological findings confirmed the biochemical observations of this study. The results of the FTIR study were found to be in agreement with biochemical studies and demonstrated that FTIR can be used successfully applied to toxicological studies at molecular level.

  5. Antimalarial and antioxidant activities of Indigofera oblongifolia on Plasmodium chabaudi-induced spleen tissue injury in mice.

    Lubbad, Mahmoud Y; Al-Quraishy, Saleh; Dkhil, Mohamed A


    Malaria is still one of the most common infectious diseases and leads to various public health problems worldwide. Medicinal plants are promising sources for identifying novel agents with potential antimalarial activity. This study aimed to investigate the antimalarial and the antioxidant activities of Indigofera oblongifolia on Plasmodium chabaudi-induced spleen tissue injury in mice. Mice were divided into five groups. The first group served as a vehicle control; the second, third, fourth, and fifth groups were infected with 1 × 10(6) P. chabaudi-parasitized erythrocytes. Mice of the last three groups were gavaged with 100 μl of I. oblongifolia leave extract (IOLE) at a dose of 100, 200, and 300 mg IOLE/kg, respectively, once daily for 7 days. IOLE was significantly able to lower the percentage of parasitemia. The most effective dose was the 100 mg IOLE/kg, which could reduce the parasitemia from about 38 to 12 %. The infection induced spleen injury. This was evidenced by disorganization of spleen white and red pulps, appearance of hemozoin granules and parasitized erythrocytes. These changes in spleen led to the increased histological score. Also, the infection increased the spleen oxidative damage where the levels of nitrite/nitrate, malondialdehyde, and catalase were significantly altered. All these infection-induced parameters were significantly improved during IOLE treatment. In addition, the mRNA expression of inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha were upregulated after infection with P. chabaudi, whereas IOLE significantly reduced the expression of these genes. Our results indicate that I. oblongifolia leaves extract exhibits a significant antimalarial and antioxidant effects, and protects host spleen tissue from injuries induced by P. chabaudi.

  6. A Taenia crassiceps factor induces apoptosis of spleen CD4+T cells and TFG-β and Foxp3 gene expression in mice.

    Zepeda, N; Tirado, R; Copitin, N; Solano, S; Fernández, A M; Tato, P; Molinari, J L


    This study was undertaken to determine whether a parasite substance produces structural pathology in the mouse spleen. A low-molecular-weight Taenia crassiceps metacestode factor (MF) isolated from the peritoneal fluid of female mice infected with T. crassiceps metacestodes induced pathological and immunological changes in mouse spleen cells in vivo. Electron microscopy and confocal microscopy revealed severe changes in the spleen histoarchitecture of T. crassiceps-infected and MF-treated mice. Apoptotic degenerated spleen cells were observed in the white and red pulps and were more conspicuous in the white pulp of the spleen from the T. crassiceps-infected mice than in that of the MF-treated mice. Flow cytometry analysis revealed that the numbers of spleen CD4+T cells were significantly lower in both experimental groups than in control mice. The ex vivo expression of transforming growth factor (TGF)-β and factor Foxp3 were significantly higher in splenocytes of the experimental mice than the basal expression observed in the control cells. These findings may have potential applications for a better understanding of the host-parasite relationship in human neurocysticercosis.

  7. Stress downregulates lipopolysaccharide-induced expression of proinflammatory cytokines in the spleen, pituitary, and brain of mice.

    Goujon, E; Parnet, P; Laye, S; Combe, C; Kelley, K W; Dantzer, R


    Mice injected with LPS (10 mu g/mouse, sc) or saline were submitted to a 15-min restraint stress and sacrificed 1 or 2 h later to assess the effect of stress on the induction of interleukin-1beta (IL-1beta) and other proinflammatory cytokines (IL-1alpha, IL-1ra, IL-6, and tumor necrosis factor-alpha) in the spleen, pituitary, hypothalamus, hippocampus, and striatum. LPS-induced cytokine gene expression, as determined by comparative RT-PCR, was lower in stressed than in nonstressed mice. LPS increased plasma and tissue levels of IL-1beta, as determined by ELISA, but this effect was less marked in stressed than in nonstressed mice. These results are discussed in relation to the modulatory effects of glucocorticoids on cytokine production.

  8. Effects of Astragalus polysaccharide on bone marrow and spleen progenitor cells in mitomycin—induced myelosuppresive mice

    XiaX; CuiYJ


    Astragalus polysaccharide(APS) is an extract of Astragalus membranaceus Var.mongolicus.The effects of APS on bone marrow and spleen progenitor cells in mitomycin (MMS)-induced myelosuppressive micr was observed.MMC7 mg·kg-1 was injected ip on day 0,APS 100mg·kg-1·d-1 was given ac in 3 reginens (1)on day 0-4,(2)on day 0-11,(3)12 doses in 3 weeks.APS increased the number of bone marrow progeniter cells(CFU-C) of MMC treated micr 3-fold,from 1870±40 per femur to 6240±110 per femur on day3.APS treatment resulted in a higher level of bone marrow CFU-C at all time points from day 3 to day 18,in comparison with the control group.APS also significantly stimulated the proliferation of spleen pregenitor cells on day 14 (3-fold higher) and day 18(4-fold higher) after MMC treatment,although APS had no effect on spleen progenitor cells before day 14.These results demonstrate that APS enhances the proliferation and maturation of the progenitors of peripheral blood cells in MMC treated mice.




    Full Text Available Accessory spleen is a small nodule of splenic tissue found apart from main body of spleen. Other name for accessory spleen is supernumerary spleen, splenule or splenunculus. It is usually congenital failure of fusion of splenunculus found close to hilum of spleen, greater omentum, tail of pancreas. Accessory spleen is found approximately in 10% population. MATERIALS AND METHODS The present study 100 cadaveric spleens obtained from routine dissection, specimens present in Department of Anatomy, Andhra Medical College, Vishakhapatnam in 3 years span, out of which 25 are foetal spleens, 75 are adult spleens. RESULTS We got 4 accessory spleens in adult and 1 in foetal spleen. CONCLUSION The knowledge of accessory spleen is medically significant. That they may result in interpretation errors in diagnostic imaging and symptoms may be continued after splenectomy.

  10. Toxicological mechanisms of nanosized titanium dioxide-induced spleen injury in mice after repeated peroral application.

    Sang, Xuezi; Li, Bing; Ze, Yuguan; Hong, Jie; Ze, Xiao; Gui, Suxin; Sun, Qingqing; Liu, Huiting; Zhao, Xiaoyang; Sheng, Lei; Liu, Dong; Yu, Xiaohong; Wang, Ling; Hong, Fashui


    Due to an increase in surface area per particle weight, nanosized titanium dioxide (nano-TiO2) has greatly increased its function as a catalyst and is used for whitening and brightening foods. However, concerns over the safety of nano-TiO2 have been raised. The purpose of this study was to determine whether the protein kinase MAPKs/PI3-K/Akt signaling pathways and transcription factors are activated prior to or concurrent with COX-2 up-regulation in mouse spleen following exposure to 10 mg/kg BW of pure anatase nano-TiO2 by the intragastric route for 15-90 days. The study clearly showed that nano-TiO2 was deposited in the spleen and resulted in reactive oxygen species production, time-dependent splenic inflammation, and necrosis, coupled with a 12.64-64.06% increase in COX-2 and prostaglandin E2 expression, respectively. Furthermore, nano-TiO2 elevated the expressions of ERK, AP-1, CRE, Akt, JNK2, MAPKs, PI3-K, c-Jun, and c-Fos in the spleen by 1.08-6-fold with increased exposure duration, respectively. These findings suggested that nano-TiO2-induced COX-2 expression may be mediated predominantly through the induction of AP-1 and CRE and that AP-1/CRE induction occurred via the MAPKs/PI3-K/Akt signaling pathways in the spleen. Therefore, the findings suggest the need for caution when using nanomaterials as food additives.

  11. Cellular Composition of the Spleen and Changes in Splenic Lysosomes in the Dynamics of Dyslipidemia in Mice Caused by Repeated Administration of Poloxamer 407.

    Goncharova, N V; Shurlygina, A V; Mel'nikova, E V; Karmatskikh, O L; Avrorov, P A; Loktev, K V; Korolenko, T A


    We studied the effect of dyslipidemia induced by poloxamer 407 (300 mg/kg twice a week for 30 days) on cellular composition of the spleen and splenocyte lysosomes in mice. Changes in blood lipid profile included elevated concentrations of total cholesterol, aterogenic LDL, and triglycerides most pronounced in 24 h after the last poloxamer 407 injection; gradual normalization of lipid profile was observed in 4 days (except triglycerides) and 10 days. The most pronounced changes in the spleen (increase in organ weight and number of cells, inhibition in apoptosis, and reduced accumulation of vital dye acridine orange in lysosomes) were detected on day 4; on day 10, the indices returned to normal. Cathepsin D activity in the spleen also increased at these terms. The relationship between changes in the cellular composition of the spleen and dynamics of serum lipid profile in mice in dyslipidemia caused by repeated administrations of relatively low doses of poloxamer 407 is discussed.

  12. Immunotoxicity of skin acid secretion produced by the sea slug Berthellina citrina in mice spleen: Histological and Immunohistochemical study.

    Awaad, Aziz; Moustafa, Alaa Y


    Acid secretion containing sulfuric and hydrochloric acids is a fascinating defensive phenomenon within many groups of marine organisms. This study aimed to investigate the mice spleen histology and immunotoxicity using skin acid secretion (SAS) of the sea slug Berthellina citrina after oral administration. The spleen showed atrophy in the white pulp, decrease in the splenocytes density, megakaryocytes cytoplasmic degeneration as well as inflammatory cells infiltrations. The white and red pulp splenocytes number decreased time-dependently in the treated spleens. Additionally, the size of the megakaryocytes increased as compared with the control. The administration with SAS increased the number of the IgA(+) cells aggregation in the splenic red pulp. Furthermore, after 7days of the administration, large number of dispersed IgA(+) cells were distributed in splenic parenchyma. The IgA(+) cells numbers increased time-dependently as compared with those in the control. The aggregation sizes and number of the F4/80(+) cell in the splenic red pulp were increased. Furthermore the F4/80(+) cells numbers increased time-dependently as compared with those in the control. The UEAI(+) cells were found as free cells but not in aggregations in the control splenic red pulp. Contradictory to the number of IgA(+) cells and F4/80(+) cells the number of the UEAI(+) cells decreased time-dependently after administration with SAS. Hematologically, abnormal numbers of WBCs different cells were observed after administration with SAS. This study provides new insight about the toxicity of a marine extract may be used in natural products industry or medical applications.

  13. Gene expression patterns of spleen, lung and brain with different radiosensitivity in C57BL6 mice

    Majumder, Zahidur Rahman; Lee, Woo Jung; Bae, Sang Woo; Lee, Yun Sil [Laboratory of Radiation Effect, Seoul (Korea, Republic of); Lee, Su Jae [Laboratory of Radiation Experimental Therapeutics, Seoul (Korea, Republic of)


    Although little information is available on the underlying mechanisms, various genetic factors have been associated with tissue-specific responses to radiation. In the present study, we explored the possibility whether organ specific gene expression is associated with radiosensitivity using samples from brain, lung and spleen. We examined intrinsic expression pattern of 23 genes in the organs by semi-quantitative RT-PCR method using both male and female C57BL/6 mice. Expression of p53 and p21, well known factors for governing sensitivity to radiation or chemotherapeutic agents, was not different among the organ types. Both higher expression of sialyltransferase, delta7-sterol reductase, leptin receptor splice variant form 12.1, and Cu/Zn SuperOxide Dismutase (SOD) and lower expression of alphaB crystalline were specific for spleen tissue. Expression level of glutathione peroxidase and APO-1 cell surface antigen gene in lung tissue was high, while that of Na, K-ATPase alpha-subunit, Cu/ZnSOD, and cyclin G was low. Brain, radioresistant organ, showed higher expression of Na, K-ATPase-subunit, cyclin G, and nucleolar protein hNop56 and lower expression of delta7-sterol reductase. The result revealed a potential correlation between gene expression patterns and organ sensitivity, and identified genes which might be responsible for organ sensitivity.

  14. Global inhibition of DC priming capacity in the spleen of self-antigen vaccinated mice requires IL-10

    Douglas Matthew Marvel


    Full Text Available DC in the spleen are highly activated following intravenous vaccination with a foreign antigen, promoting expansion of effector T cells, but remain phenotypically and functionally immature after vaccination with a self-antigen. Up-regulation or suppression of expression of a cohort of pancreatic enzymes 24-72 hours post-vaccination can be used as a biomarker of stimulatory versus toleragenic DC, respectively. Here we show, using MUC1 transgenic mice (MUC1.Tg and a vaccine based on the MUC1 peptide which these mice perceive as a self-antigen, that the difference in enzyme expression that predicts whether DC will promote immune response or immune tolerance, is seen as early as 4-8 hours following vaccination. We also identify early production of IL-10 as a predominant factor that both correlates with this early time point and controls DC function. Pre-treating mice with an antibody against the IL-10 receptor (IL-10R prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses. This study suggests that transient inhibition of IL-10 prior to vaccination could improve responses to cancer vaccines that utilize self-tumor antigens.

  15. Expression of pro-inflammatory genes in lesions, spleens and blood neutrophils after burn injuries in mice treated with silver sulfodiazine.

    Akhzari, Soheyla; Rezvan, Hossein; Zolhavarieh, Seyed Masoud


    It is now supposed that cytokines released during the burn injuries have a great impact on the immunological and pathological responses after the burn. The main objective of this study was to investigate the expression of some pro-inflammatory genes in the wound, spleen and blood neutrophils during the healing process of burn wounds in a murine model. The expression of ten pro-inflammatory genes were examined in wounds, spleens and blood neutrophils of mice with burn injuries treated with either silver sulfodiazine or phosphate-buffered saline (PBS) using RT-PCR at the end of the first and second weeks after injuries. None of the pro-inflammatory genes were expressed in the skin, spleen and blood neutrophils of healthy mice. In the group control, IL-12P35, IL-12P40, CCR5, IL-1β and IFN-γ were expressed in the spleen and blood neutrophils in the first week. Instead, CCL5, CCR5, IL-1β and IFN-γ were expressed in the wound, but in the second week, the expression of the genes became similar. In the test group, in the first week, TNF-α, IL-12P35, IL-12P40 and IL-1β were expressed in the lesions, CCL4, IL-1α, IL-12P35, IL-12P40, CCR5 and IFN-γ were expressed in the spleen and no pro-inflammatory gene expression was detected in blood neutrophils. IL-1β and IFN-γ are expressed in wound, spleen and neutrophils of untreated mice, but not in silver sulfodiazine treated mice. Hence, treatment with silver sulfodiazine suppressed the expression of pro-inflammatory genes in some stages of healing.

  16. Expression of pro-inflammatory genes in lesions, spleens and blood neutrophils after burn injuries in mice treated with silver sulfodiazine

    Soheyla Akhzari


    Full Text Available Objective(s: It is now supposed that cytokines released during the burn injuries have a great impact on the immunological and pathological responses after the burn. The main objective of this study was to investigate the expression of some pro-inflammatory genes in the wound, spleen and blood neutrophils during the healing process of burn wounds in a murine model. Materials and Methods: The expression of ten pro-inflammatory genes were examined in wounds, spleens and blood neutrophils of mice with burn injuries treated with either silver sulfodiazine or phosphate-buffered saline (PBS using RT-PCR at the end of the first and second weeks after injuries. Results: None of the pro-inflammatory genes were expressed in the skin, spleen and blood neutrophils of healthy mice. In the group control, IL-12P35, IL-12P40, CCR5, IL-1β and IFN- γ were expressed in the spleen and blood neutrophils in the first week. Instead, CCL5, CCR5, IL-1β and IFN- γ were expressed in the wound, but in the second week, the expression of the genes became similar. In the test group, in the first week, TNF-α, IL-12P35, IL-12P40 and IL-1β were expressed in the lesions, CCL4, IL-1α, IL-12P35, IL-12P40, CCR5 and IFN- γ were expressed in the spleen and no pro-inflammatory gene expression was detected in blood neutrophils.  Conclusion: IL-1β and IFN- γ are expressed in wound, spleen and neutrophils of untreated mice, but not in silver sulfodiazine treated mice. Hence, treatment with silver sulfodiazine suppressed the expression of pro-inflammatory genes in some stages of healing.

  17. Podophyllotoxin and Rutin Modulates Ionizing Radiation-Induced Oxidative Stress and Apoptotic Cell Death in Mice Bone Marrow and Spleen

    Singh, Abhinav; Yashavarddhan, M. H.; Kalita, Bhargab; Ranjan, Rajiv; Bajaj, Sania; Prakash, Hridayesh; Gupta, Manju Lata


    The present study is aimed to investigate the radioprotective efficacy of G-003M (combination of podophyllotoxin and rutin) against gamma radiation-induced oxidative stress and subsequent cell death in mice bone marrow and spleen. Prophylactic administration of G-003M (−1 h) rendered more than 85% survival in mice exposed to 9 Gy (lethal dose) with dose reduction factor of 1.26. G-003M pretreated mice demonstrated significantly reduced level of reactive oxygen species, membrane lipid peroxidation, and retained glutathione level. In the same group, we obtained increased expression of master redox regulator, nuclear factor erythroid-derived like-2 factor (Nrf-2), and its downstream targets (heme oxygenase-1, Nqo-1, glutathione S-transferase, and thioredoxin reductase-1). In addition, G-003M preadministration has also shown a significant reduction in Keap-1 level (Nrf-2 inhibitor). Radiation-induced lethality was significantly amended in combination-treated (G-003M) mice as demonstrated by reduced 8-OHdG, annexin V FITC+ cells, and restored mitochondrial membrane potential. Expression of antiapoptotic protein Bcl-2 and Bcl-xL was restored in G-003M pretreated group. However, proapoptotic proteins (Puma, Bax, Bak, Caspase-3, and Caspase-7) were significantly declined in this group. Further analysis of immune cells revealed G-003M-mediated restoration of CD3 and CD19 receptor, which was found decreased to significant level following irradiation. Similarly, Gr-1, a marker of granulocytes, was also retained by G-003M administration prior to radiation. Modulatory potential of this formulation (G-003M) can be exploited as a safe and effective countermeasure against radiation-induced lymphohemopoietic injury. PMID:28289414

  18. Effects of Fluoride on the Expression of p38MAPK Signaling Pathway-Related Genes and Proteins in Spleen Lymphocytes of Mice.

    Shi, Zeyu; Zhan, Yaqi; Zhao, Junxing; Wang, Jinming; Ma, Haili


    This study investigated the effects of sodium fluoride on the expression of p38MAPK signaling pathway-related genes and proteins in the spleen lymphocytes of mice, revealing the mechanism of the toxicity of fluoride to the immune system. The spleen lymphocytes, isolated from mice consuming different NaF doses (0, 50, 100, and 150 mg/L) for 60 days, were cultured in medium with bacteria lipopolysaccharide, and the cells' proliferation ability was analyzed through MTT; real-time PCR detected the change of MLK3/MKK6/p38MAPK/MSK1/ATF1 on mRNA, and the difference of protein expression of MKK6/p38MAPK were detected through the Western blotting. The results suggested that the proliferation ability of spleen lymphocytes isolated from mice consuming different NaF doses is lower, and the expression of genes and proteins of MKK6/p38MAPK showed a decreasing trend. These results demonstrate that fluoride can suppress the activation of p38MAPK pathway in mice spleen lymphocytes and further influences the function of the immune system.

  19. Life span, testis damage and immune cell populations of spleen in C57BL mice with neutron irradiation by lying flat pose

    Chun, Ki Jung; kim, Myung Sup; Kyung, Yoo Bo [KAERI, Taejon (Korea)


    This study deals with the biological effects of black mouse (C57BL) irradiated with neutron irradiation by using Boron Neutron Capture Therapy facility in HANARO reactor. These include mortality, body wt., hair color, testis volume, sperm count and immune cell populations in mouse spleen after 80 days later by thermal neutron irradiation. Six week old C57BL male mice were irradiated with neutron irradiation for 1 hr or 2 hrs (flux : 1.036739E +09). These irradiat ion doses estimated 15Gy and 30Gy, respectively. Survival days and hair color in mice was checked. On day 80 after irradiation, testis were taken for volume and sperm count. Also spleen was taken for FACS and spleen cells were isolatd and discarded RBC by treating with lysising solution. These cells were placed on ice and immunofluorescence staining was performed. Phycoerythrin (PE )-anti-CD3e, fluorescein isothiocyanate (FITC)-anti-CD4, and FITC-anti-CD8 were added, then the immunostaining cells were incubated on ice for 40 min. The resulting cells were washed with a PBS buffer 3 times and analyzed using a Flow cytometer. All experimental animals survived over 90 days but in case of 30 Gy neutron irradiation, black mice hair were changed white color on the center of the back. Neutron irradiation of black mice show similar in damage of spleen immune cells by subpopulation of T helper and T cytotoxic cells compared to the control non - irradiated group. These results show that treatment of neutron irradiation without boron compounds for 2 hrs in mice can survive over 90 days with hair color change from black to white. Damaged spleen cells recover after long time by irradiation but testis volume and no. of sperm are not recover compared to the normal group in response to neutron irradiation.

  20. T-cell populations and cytokine expression are impaired in thymus and spleen of protein malnourished BALB/c mice infected with Leishmania infantum.

    Sergio Cuervo-Escobar

    Full Text Available Visceral leishmaniasis (VL is a parasitic infectious disease that causes significant morbidity and mortality in the tropical and subtropical regions of the world. Although infections with visceralizing Leishmania may be asymptomatic, factors such as undernutrition increase the likelihood of progressing to clinical disease. Protein malnutrition, the most deleterious cause of malnutrition in developing countries, has been considered as a primary risk factor for the development of clinical VL. However, data regarding the immunological basis of this association are scarce. With the aim to analyze the effects of protein malnutrition on Leishmania infantum infection, we used BALB/c mice subjected to control or low protein isocaloric diets. Each animal group was divided into two subgroups and one was infected with L. infantum resulting in four study groups: animals fed 14% protein diet (CP, animals fed 4% protein diet (LP, animals fed 14% protein diet and infected (CPi, and animals fed 4% protein diet and infected (LPi.The susceptibility to L. infantum infection and immune responses were assessed in terms of body and lymphoid organ weight, parasite load, lymphocyte subpopulations, and cytokine expression. LPi mice had a significant reduction of body and lymphoid organ weight and exhibited a severe decrease of lymphoid follicles in the spleen. Moreover, LPi animals showed a significant decrease in CD4+CD8+ T cells in the thymus, whereas there was an increase of CD4+ and CD8+ T cells percentages in the spleen. Notably, the cytokine mRNA levels in the thymus and spleen of protein malnourished-infected animals were altered compared to the CP mice. Protein malnutrition results in a drastic dysregulation of T cells and cytokine expression in the thymus and spleen of L. infantum-infected BALB/c mice, which may lead to defective regulation of the thymocyte population and an impaired splenic immune response, accelerating the events of a normal course of

  1. Identification of schistosoma mansoni antigens recognised by spleen cells of C57B1/6 mice immunized with ultraviolet-irradiated cercariae

    Osman, A.; El Ridi, R. (Cairo Univ. (Egypt)); Guirguis, N. (VACSERA, El Agouza Cairo (Egypt). Biomedical Research Dept.); Dean, D.A. (U.S. Naval Medical Research Unit No. 3, Cairo (Egypt))


    Spleen cells of C57B1/6 mice immunized twice with Schistosoma mansoni cercariae attenuated by ultraviolet irradiation proliferated and produced interleukin-(I1)-2 and/or I1-4 in response to both soluble schistosomular and adult worm antigens of 72-68, 60-62, 50, 45, 29.5 and 28 kDa. All of these bands, except the 45 kDa, were also recognized by serum antibodies in Western blotting. (author).

  2. Action of the schistosomotic spleen in male mices on the regulation of thyroid hormones; Possivel influencia do baco esquistossomotico em camundongos machos na modulacao dos hormonios tireotroficos

    Neves, S.R.S.; Silva, I.M.S.; Pereira, S.S.L.; Lima Filho, G.L.; Catanho, M.T.J.A. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Biofisica e Radiobiologia; Neves, E.S.; Silveira, M.F.G. [Pernambuco Univ., Recife, PE (Brazil). Dept. de Anatomia


    For the purpose to study the action of the schistosomotic spleen on the regulation of TSH, T4 and albumin levels in serum, spleens from adults mice infected by Schistosoma mansoni were homogeneized, centrifuged and cromatographed in a column of Sephadex G-100, resulting in two proteans fractions (I and II). The biologic activity was determinated through the administration of the fractions by intraperitoneal way (IP), in male mice aged 27-30 days, in a period of three following days. Five days after the last administration, the animals were sacrified and their blood was collected for obtainment of serum and determination of TSH, T4 and albumin levels. Obtained results showed that the albumin levels no change when compared to control and that fraction I infected change the TSH and T4 levels, but the fraction II infected no change this levels. These results suggest that spleens from mice infected by S. mansoni have a factor that modifies the hormonal regulation in level hypophysial and the synthesis of thyroid hormones (T4), changing the basal metabolism. The seric levels of TSH and T4 were determined by radioimmunoassay using I-125. (author). 12 refs., 1 tab.

  3. Flow cytometric gating for spleen monocyte and DC subsets: differences in autoimmune NOD mice and with acute inflammation.

    Dong, Matthew B; Rahman, M Jubayer; Tarbell, Kristin V


    The role of antigen presenting cells (APCs) in the pathogenesis of autoimmune and other inflammatory diseases is now better understood due to advances in multicolor flow cytometry, gene expression analysis of APC populations, and functional correlation of mouse to human APC populations. A simple but informative nomenclature of conventional and plasmacytoid dendritic cell subsets (cDC1, cDC2, pDC) and monocyte-derived populations incorporates these advances, but accurate subset identification is critical. Ambiguous gating schemes and alterations of cell surface markers in inflammatory condition can make comparing results between studies difficult. Both acute inflammation, such as TLR-ligand stimulation, and chronic inflammation as found in mouse models of autoimmunity can alter DC subset gating. Here, we address these issues using in vivo CpG stimulation as an example of acute inflammation and the non-obese diabetic (NOD) mouse as a model of chronic inflammation.We provide a flow cytometric antibody panel and gating scheme that differentiate 2 monocytic and 3DC subsets in the spleen both at steady state and after CpG stimulation. Using this method, we observed differences in the composition of NOD DCs that have been previously reported, and newly identified increases in the number of NOD monocyte-derived DCs. Finally, we established a protocol for DC phosphoflow to measure the phosphorylation state of intracellular proteins, and use it to confirm functional differences in the identified subsets. Therefore, we present optimized methods for distinguishing monocytic and DC populations with and without inflammation and/or autoimmunity associated with NOD mice.


    王美琴; 白春学; 钮善福; 方晓惠; 陈常庆; 陈波


    To explore the effect of antisense oligonucleotide on the production of IL-5 by mouse spleen T lymphocytes.Methods Based on the IL-5 cDNA sequence of mouse, a segment of antisense oligonucleotide was designed and synthesized. 5’-labeling of antisense oligonucleotide was signed by T4 PNK in order that the efficiency of stearylamine liposome in transfecting antisense oligonucleotide can be evaluated. Asthma model was duplicated with ovalbumin(OVA) absorbed to aluminum hydroxide. T lymphocytes of mice were separated by nylon fiber method, then T lymphocytes transfected with different concentration of antisense oligonucleotide with cation stearylamine liposme were incubated respectively in order to observe the effect of antisense oligonucleotide on Il-5 production by T lymphocytes. IL-5 levels in the supernatants of T lymphocyte cultures were determined by ELISA.Results Stearylamine liposome could markedly increase the efficiency of antisense oligonucleotide transfection. The transfection efficiency of antisense oligouncleotide increased approximately 12 times at a ratio of 1: 15m/m (antisense oligonucleotide to SA liposome). In healthy and asthma Balb/c mice, IL-5 was not detectable in the supernatants of T lymphocyte cultures without stimulated with OVA; however, IL-5 was increased markedly in the supernatants of T lymphocyte cultures stimulated with OVA. After transfection with different concentrations of antisense oligonucleotide, IL-5 levels in the supernatants of T lymphocyte cultures were significantly lower than those in control cultured without antisense oligonucleotide transfection. IL-5 levels decreased from 44.60±6.23 pg/ml to 30.70±7.362 pg/ml, 17.20±6.181 pg/ml and 8.16±2.34 pg/ml respectively. And IL-5 synthesis was inhibited by 31.17%, 61.43% and 81.7% respectively.Conclusion IL-5 synthesis could be obviously inhibited by antisense oligonucleotide and showed a markedly correlation between dose and effectiveness. It suggests the production

  5. Wandering spleen

    Qazi Shabir


    Full Text Available Wandering spleen is a rare clinical entity, characterized by splenic hypermobility that results from elongation or maldevelopment of its suspensary ligaments. The wandering spleen is in constant danger of torsion and infarction. This condition poses a great diagnostic challenge due to lack of awareness and paucity of symptoms. Among adults, it usually occurs in females of childbearing age, the children below ten years of age are other sufferers. The clinical presentation may be acute or chronic; such as asymptomatic abdominal mass, an acute abdomen, or, most commonly, a mass associated with vague abdominal symptoms. Computed tomography and duplex ultrasonography are best diagnostic modalities. The traditional conservative approach carries high risk of infarction leading to splenectomy and postsplenectomy sepsis. Splenopexy is the treatment of choice for all noninfarcted wandering spleens. Splenectomy should only be performed when there is no evidence of splenic blood flow after detorsion of the spleen. The present study, reviews the presentation, course, diagnostic modalities and management options of wandering spleen

  6. Cytokine production by spleen cells from mice with ovalbumin-specific, IgE-selective unresponsiveness induced by ovalbumin-liposome conjugate

    Atsuko Horino


    Full Text Available Ovalbumin coupled with liposomes (OVA–liposome induced selective unresponsiveness of anti-OVA IgE antibody production in BALB/c mice, whereas OVA adsorbed with aluminum hydroxide (OVA–alum induced a substantial amount of anti-OVA IgE antibody production. Ovalbumin–liposome and OVA–alum predominantly induced IgG2a and IgG1 anti-OVA production, respectively. These results suggest that OVA–liposome and OVA–alum induce type 1 and type 2 T helper (Th immune responses, respectively. To further investigate this issue, we examined the cytokine production induced by these two distinct adjuvants. Spleen cells taken from mice immunized with either OVA–liposome or OVA–alum were cultured in vitro with OVA and the cytokine production from each culture was analyzed. It was demonstrated that spleen cells from mice immunized with OVA–liposome produced more interferon (IFN-γ than those immunized with OVA–alum and, furthermore, interleukin (IL-4 was produced only by spleen cells from mice immunized with OVA–alum. These results favor the notion that OVA–liposome and OVA–alum induce Th1 and Th2 cytokines, respectively. Interestingly, the production of IL-2, a Th1 cytokine, was higher in the OVA–alum-immunized group and the production of IL-10, a Th2 cytokine, remained at low levels in both groups after primary immunization; levels of IL-10 increased in the OVA–liposome-immunized group after secondary immunization. These results do not agree with the above notion and, thus, suggest that it may be important to consider the balance between IFN-γ-producing cells and IL-4-producing cells rather than that between Th1 and Th2 cells for the regulation of IgE antibody production.

  7. Suppressive effects of Chelidonium majus methanol extract in knee joint, regional lymph nodes, and spleen on collagen-induced arthritis in mice.

    Lee, Young-Cheol; Kim, Seung-Hyung; Roh, Seong-Soo; Choi, Ho-Young; Seo, Young-Bae


    Chelidonium majus L. has multiple applications in Korean traditional medicine because of its anti-tumoral, cytotoxic, anti-inflammatory and anti-microbial activities and has long been known to have anti-inflammatory effects. However, no study on the anti-arthritic activity of Chelidonium majus has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN), and spleen, using ELISA and competitive RT-PCR. DBA/1J mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CME orally at 400, 40mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Administration of CME significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-6 in spleen and lymph node. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CME. In conclusion, our results demonstrates that CME significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-alpha, IL-6, IFN-gamma, B cells, gammadelta T cells (in spleen) and increased proportion of CD4+CD25+ regulatory T cells in vivo. In the serum of CME-treated mice, the levels of IgG and IgM RA factor were decreased.

  8. Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

    Wen, Shu Wen; Everitt, Sarah J; Bedő, Justin; Chabrot, Marine; Ball, David L; Solomon, Benjamin; MacManus, Michael; Hicks, Rodney J; Möller, Andreas; Leimgruber, Antoine


    There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60 Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (pspleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.

  9. Bacteriophage Administration Reduces the Concentration of Listeria monocytogenes in the Gastrointestinal Tract and Its Translocation to Spleen and Liver in Experimentally Infected Mice

    Volker Mai


    Full Text Available To investigate the efficacy of phage supplementation in reducing pathogen numbers, mice were treated via oral gavage with a Listeria monocytogenes phage preparation (designated ListShield before being orally infected with L. monocytogenes. The concentrations of L. monocytogenes in the liver, spleen, and intestines were significantly lower (P<.05 in the phage-treated than in the control mice. Phage and antibiotic treatments were similarly effective in reducing the levels of L. monocytogenes in the internal organs of the infected mice. However, the significant weight loss detected in the control and antibiotic-treated groups was not observed in the infected, ListShield-treated mice. Long-term (90 days, biweekly treatment of uninfected mice with ListShield did not elicit detectable changes in the microbiota of their large intestines or deleterious changes in their health. Our data support the potential feasibility of using bacteriophages to control proliferation of L. monocytogenes in mice without affecting commensal microbiota composition.

  10. [The evaluation of ketoconazole in mice inoculated with Paracoccidioides brasiliensis by liver and spleen histopathology and by the intradermal paracoccidioidin reaction].

    Silva, M R; de Paiva e Rosália, L F; Jesuino, S A


    Male albino mice were inoculated intravenously with 0.5 x 10(7) viable yeast forms of P. brasiliensis (strain 2052). These animals were treated with two doses of ketoconazole (50 and 100 mg/kg) during fifty days and the sacrificed. We studied the presence of P. brasiliensis, the inflammatory granulomatous response of liver and spleen and the anti P. brasiliensis delayed hypersensitivity response measured by the footpad test after 48 hours. It was observed that: 1. animals infected and treated with ketoconazole showed reduction in the number of fungi in the organs studied; 2. there was no difference in the number of granulomas among animals treated and non-treated; 3. the cutaneous delayed tests intensity was similar in all animals.

  11. Dihydroartemisinin inhibits activation of the Toll-like receptor 4 signaling pathway and production of type I interferon in spleen cells from lupus-prone MRL/lpr mice.

    Huang, Xueqin; Xie, Zhijun; Liu, Fenfen; Han, Chunwen; Zhang, Dongyu; Wang, Dawei; Bao, Xi; Sun, Jing; Wen, Chengping; Fan, Yongsheng


    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various immunological abnormalities. Dihydroartemisinin (DHA), a metabolite of artemisinin, has been recently reported to exhibit immunosuppressive properties. The present study aims to determine the effects of DHA on spleen cell activation triggered by lipopolysaccharide (LPS) and investigate the effects of DHA on LPS-induced activation of the Toll-like receptor 4 (TLR4)/interferon regulatory factor (IRF) signaling pathway. Spleen cells from lupus-prone MRL/lpr mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with DHA, and spleen cell proliferation was analyzed using MTS assay. Protein expressions of TLR4, IRF3, and IRF7 were analyzed by Western blot. IRF3 phosphorylation was also determined. Gene expression levels of IFN-α and IFN-β were measured using real-time PCR, and protein levels in cells' supernatants were determined by ELISA. DHA was found to inhibit LPS-induced spleen cell proliferation, decrease LPS-induced protein expression of TLR4, and inhibit IRF3 phosphorylation. Furthermore, LPS significantly induced IRF3 expression and slightly increased IRF7 expression in the nucleus of spleen cells, which was accompanied by enhanced IFN-α and IFN-β production. DHA inhibited the effects of LPS in spleen cells of MRL/lpr mice. Taken together, the data obtained reveal that DHA inhibits LPS-induced cell activation possibly by suppressing the TLR4/IRF/IFN pathway in spleen cells of MRL/lpr mice. These data suggest that DHA has the potential therapeutic utility for the treatment of SLE.

  12. Neutrophils and neutrophil serine proteases are increased in the spleens of estrogen-treated C57BL/6 mice and several strains of spontaneous lupus-prone mice

    Dai, Rujuan; Cowan, Catharine; Heid, Bettina; Khan, Deena; Liang, Zhihong; Pham, Christine T. N.; Ahmed, S. Ansar


    Estrogen, a natural immunomodulator, regulates the development and function of diverse immune cell types. There is now renewed attention on neutrophils and neutrophil serine proteases (NSPs) such as neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CG) in inflammation and autoimmunity. In this study, we found that although estrogen treatment significantly reduced total splenocytes number, it markedly increased the splenic neutrophil absolute numbers in estrogen-treated C57BL/6 (B6) mice when compared to placebo controls. Concomitantly, the levels of NSPs and myeloperoxidase (MPO) were highly upregulated in the splenocytes from estrogen-treated mice. Despite the critical role of NSPs in the regulation of non-infectious inflammation, by employing NE-/-/PR3-/-/CG-/- triple knock out mice, we demonstrated that the absence of NSPs affected neither estrogen’s ability to increase splenic neutrophils nor the induction of inflammatory mediators (IFNγ, IL-1β, IL-6, TNFα, MCP-1, and NO) from ex vivo activated splenocytes. Depletion of neutrophils in vitro in splenocytes with anti-Ly6G antibody also had no obvious effect on NSP expression or LPS-induced IFNγ and MCP-1. These data suggest that estrogen augments NSPs, which appears to be independent of enhancing ex vivo inflammatory responses. Since estrogen has been implicated in regulating several experimental autoimmune diseases, we extended our observations in estrogen-treated B6 mice to spontaneous autoimmune-prone female MRL-lpr, B6-lpr and NZB/WF1 mice. There was a remarkable commonality with regards to the increase of neutrophils and concomitant increase of NSPs and MPO in the splenic cells of different strains of autoimmune-prone mice and estrogen-treated B6 mice. Collectively, since NSPs and neutrophils are involved in diverse pro-inflammatory activities, these data suggest a potential pathologic implication of increased neutrophils and NSPs that merits further investigation. PMID:28192517

  13. Differential expression of migration inhibitory and migration stimulatory factors in two lines of mice genetically selected for high or low responsiveness to phytohemagglutinin. 1. Migration stimulatory factor(s) from T and B cells of immune spleen.

    Gauthier-Rahman, S; el-Gharbi, N; Siddiqui, M U; Couderc, J; Decreusefond, C; Stiffel, C


    Expression of the lymphokine migration inhibition factor in two lines of mice genetically selected for the high (Hi/PHA) or low (Lo/PHA) response of their lymph node cells to phytohemagglutinin was found to be modulated by concomitant expression of migration stimulation factor(s) [MStF(s)]. The expression of both lymphokines was dependent on genetic character and the immunizing dose of antigen. In mice immunized 5 days earlier with 50 micrograms ovalbumin in Freund's complete adjuvant (Ova in FCA immune), migration inhibition factor, assessed with a sensitive photoelectric method, was well expressed by male spleen or lymph node 24-hour culture supernatants of Lo/PHA but Hi/PHA, especially female, expressed marked MStF(s) instead. Immunization with 500 micrograms Ova in FCA markedly enhanced expression of MStF(s) in Lo/PHA but inhibited it in Hi/PHA. MStF(s) of Ova in FCA immune spleens of the two lines were found to derive from both T and B cells, B cell activity being greater. Lo/PHA were by far better expressors of both T- and B-cell-derived MStF(s) as compared to Hi/PHA (p less than 0.01). Spleen cells of mice immunized with FCA alone also expressed MStF(s) but to lesser extent than Ova in FCA immune spleens, expression by Lo/PHA B cells being significantly higher than in Hi/PHA (p less than 0.05). The MStF(s) of Ova in FCA immune spleens was found to be non-immunoglobulin in nature.

  14. B lymphocyte differentiation in lethally irradiated and reconstituted mice. I. The effect of strontium-89 induced bone marrow aplasia on the recovery of the B cell compartment in the spleen

    Rozing, J.; Buurman, W.A.; Benner, R.


    The influence of /sup 89/Sr-treatment on the recovery of the B cell compartment in lethally irradiated, fetal liver reconstituted mice was studied by means of membrane fluorescence, /sup 89/Sr is a bone-seeking radio-isotope which causes in a dose of 3 /sup 89/Sr/g body weight a depletion of all nucleated cells, including immunoglobulin-bearing (B) cells, of the bone marrow. Treatment of irradiated and fetal liver reconstituted mice with 3 /sup 89/Sr/g body weight immediately and at 17 days after irradiation and reconstitution prevented recovery of the nucleated cell population, including B cells, in the bone marrow. In the spleen of such mice both nucleated cells and B cells reappeared at day 7 and 14 respectively. The B cell population in the spleen did not recover up to normal values during the experimental period of 45 days. It is concluded that B cell differentiation in lethally irradiated, fetal liver reconstituted mice can take place outside the bone marrow. The efficiency of this extra-medullary differentiation is discussed. The conclusion was drawn that mice with a /sup 89/Sr-induced bone marrow aplasia are able to generate B lymphocytes. Consequently the bone marrow microenvironment seems not to be obligate to the differentiation of B lymphocytes. The peripheral lymphoid organs of such mice were found to be unable to compensate completely for the absence of B lymphocyte production in the bone marrow.

  15. Rapid, sequential activation of mitogen-activated protein kinases and transcription factors precedes proinflammatory cytokine mRNA expression in spleens of mice exposed to the trichothecene vomitoxin.

    Zhou, Hui-Ren; Islam, Zahidul; Pestka, James J


    Since proinflammatory cytokine mRNA expression is induced within lymphoid tissue in vivo by the trichothecene vomitoxin (VT) in a rapid (1-2 h) and transient (4-8 h) fashion, it was hypothesized that mitogen-activated protein kinases (MAPKs) and transcription factors associated upstream with gene transcription of these cytokines are activated prior to or within these time windows. To test this hypothesis, mice were first treated with a single oral dose of VT and then analyzed for MAPK phosphorylation in the spleen. As little as 1 mg/kg of VT induced JNK 1/2, ERK 1/2, and p38 phosphorylation with maximal effects being observed at 5 to 100 mg/kg of VT. VT transiently induced JNK and p38 phosphorylation over a 60-min time period with peak effects being observed at 15 and 30 min, respectively. In contrast, ERK remained phosphorylated from 15 to 120 min. Next, the binding of activating protein 1 (AP-1), CCAAT enhancer-binding protein (C/EBP), CRE-binding protein (CREB), and nuclear factor-kappaB (NF-kappaB) was measured by electrophoretic mobility shift assay (EMSA) using four different consensus transcriptional control motifs at 0, 0.5, 1.5, 4, and 8 h after oral exposure to 25 mg/kg of VT. AP-1 binding activity was differentially elevated from 0.5 h to 8 h, whereas C/EBP binding was elevated only at 0.5 h. CREB binding decreased slightly at 0.5 h but gradually increased, reaching a maximum at 4 h. NF-kappaB binding was increased only slightly at 4 and 8 h. The specificities of AP-1, C/EBP, CREB, and NF-kappaB for relevant DNA motifs were verified by competition assays, using an excess of unlabeled consensus and mutant oligonucleotides. Supershift EMSAs and Western blot analysis identified specific VT-inducible DNA binding proteins for AP-1 (cJun, phospho c-jun, JunB, and JunD), C/EBP (C/EBPbeta), CREB (CREB-1 and ATF-2), and NF-kappaB (p50 and cRel). Finally, when the effects of oral VT exposure on proinflammatory gene expression were assessed at 3, 6, and 9 h

  16. Hypoglossal motoneurons in newborn mice receive respiratory drive from both sides of the medulla

    Tarras-Wahlberg, S; Rekling, J C


    Respiratory motor output in bilateral cranial nerves is synchronized, but the underlying synchronizing mechanisms are not clear. We used an in vitro slice preparation from newborn mice to investigate the effect of systematic transsections on respiratory activity in bilateral XII nerves. Complete...... correlations, where large-amplitude XII-bursts on one side was synchronized with small-amplitude XII-burst on the contralateral side. These characteristic amplitude correlations suggest that hypoglossal motoneurons receive respiratory drive from bilateral sources. Retrograde labeling confirmed that commissural...... in bilateral XII nerves. Hypoglossal motoneurons receive respiratory drive from both sides of the medulla, possibly mediated by contralaterally projecting dendrites....

  17. Genetics of host response to Leishmania tropica in mice - different control of skin pathology, chemokine reaction, and invasion into spleen and liver.

    Tetyana Kobets

    Full Text Available BACKGROUND: Leishmaniasis is a disease caused by protozoan parasites of genus Leishmania. The frequent involvement of Leishmania tropica in human leishmaniasis has been recognized only recently. Similarly as L. major, L. tropica causes cutaneous leishmaniasis in humans, but can also visceralize and cause systemic illness. The relationship between the host genotype and disease manifestations is poorly understood because there were no suitable animal models. METHODS: We studied susceptibility to L. tropica, using BALB/c-c-STS/A (CcS/Dem recombinant congenic (RC strains, which differ greatly in susceptibility to L. major. Mice were infected with L. tropica and skin lesions, cytokine and chemokine levels in serum, and parasite numbers in organs were measured. PRINCIPAL FINDINGS: Females of BALB/c and several RC strains developed skin lesions. In some strains parasites visceralized and were detected in spleen and liver. Importantly, the strain distribution pattern of symptoms caused by L. tropica was different from that observed after L. major infection. Moreover, sex differently influenced infection with L. tropica and L. major. L. major-infected males exhibited either higher or similar skin pathology as females, whereas L. tropica-infected females were more susceptible than males. The majority of L. tropica-infected strains exhibited increased levels of chemokines CCL2, CCL3 and CCL5. CcS-16 females, which developed the largest lesions, exhibited a unique systemic chemokine reaction, characterized by additional transient early peaks of CCL3 and CCL5, which were not present in CcS-16 males nor in any other strain. CONCLUSION: Comparison of L. tropica and L. major infections indicates that the strain patterns of response are species-specific, with different sex effects and largely different host susceptibility genes.

  18. Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection.

    Hei-Jen Huang

    Full Text Available BACKGROUND: Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer's disease (AD. However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4 against hyperglycemia/lipopolysaccharides (LPS damage were also evaluated in this study. METHODOLOGY/PRINCIPAL FINDINGS: Ten days after streptozotocin (STZ or vehicle (sodium citrate treatment in mice, EX-4 treatment (10 µg/kg/day was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. CONCLUSIONS/SIGNIFICANCE: These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the

  19. Aged mice receiving caffeine since adulthood show distinct patterns of anxiety-related behavior.

    Botton, Paulo Henrique S; Pochmann, Daniela; Rocha, Andreia S; Nunes, Fernanda; Almeida, Amanda S; Marques, Daniela M; Porciúncula, Lisiane O


    Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of caffeine have been described in adult animals with controversial findings about its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging are still poorly known. In this study, adult mice (6months old) started to receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM) testing were used to determine the effects of caffeine on anxiety-related behavior in adult and aged mice (18-20months old). Because aging alters synaptic proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an astrocyte marker) and adenosine A1 and A2A receptors levels in the cortex. According to the OF analysis, caffeine did not change both hypolocomotion and anxiety with aging. However, aged mice showed less anxiety behavior in the EPM, but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as adult mice. While SNAP-25 and adenosine A2A receptors increased with aging, both GFAP and adenosine A1 receptors were not affected. Caffeine at moderate dose prevented the age-related increase of the SNAP-25, with no effect on adenosine A2A receptors. The absence of effect for the highest dose suggests that tolerance to caffeine may have developed over time. Aged mice showed high responsiveness to the OF, being difficult to achieve any effect of caffeine. On the other hand this substance sustained the adult anxious behavior over time in a less stressful paradigm, and this effect was coincident with changes in the SNAP-25, suggesting the involvement of this synaptic protein in the ability of caffeine to preserve changes related to emotionality with aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Study of Sijunzi Tang on the Pathogenicity due to Candia Infection in the Mice of Spleen Deficiency%四君子汤对脾虚小鼠感染念珠菌的致病性研究

    吴艳梅; 邓虎; 马贤德; 韩晓伟; 孙宏伟; 谭健; 关洪全


    Objective To study the changes of body immunity after the lavage of sijunzi tang in the mice after candida infection at the condition of spleen deficiency. Methods Fifty mice were randomized into a control group(A group),a spleen - deficiency model group(B group),a spleen deficiency + candida group (C group),a spleen deficiency + candida + fluconazole(D group)and a spleen deficiency + candida + sijunzi tang group(E group),10 mice in each one. Except the A group,the compound factors were adopted to pre-pare spleen deficiency mice models in the rest groups. After candida infection,the viable bacterial count in the kidney and stool was determined and the morphologic changes of intestinal mucosa were observed under light microscope. Results As compared with the A group,the viable bacterial count in stool was increased apparently in the B group(P < 0. 05)and the structural changes in some villus and organelle of the small in-testine epithelium were more apparent. In comparison between the C and E groups,the viable bacterial count in the kidney and stool was reduced apparently(P < 0. 01),the structure of villus of small intestine epitheli-um was recovered,the enteraden was well arranged,submucous structure was complete basically and the con-gestion and edema were not found. Conclusion The immunity is reduced after candida infection in the mice of spleen deficiency. Sijunzi tang benefits qi,strengthens the spleen and improves the body immunity so that to treat the disease.%目的:研究脾虚时经口感染白念珠菌后经四君子汤灌胃治疗后机体免疫力的变化情况。方法将50只小鼠随机分为对照组(A 组)、脾虚模型组(B 组)、脾虚+白念珠菌组(C 组)、脾虚+白念珠菌+氟康唑组(D 组)、脾虚+白念珠菌+四君子汤组(E 组),每组10只。除 A 组外,其余组别采取复合因素制造脾虚小鼠模型,经口感染白念珠菌,测定小鼠肾脏内和粪便中活菌菌数,观察脾虚小

  1. 三种癌裸鼠移植瘤肝脾转移的比较研究%A Comparative Study on the Liver and Spleen Metastasis of Three Transplanted Carcinomas in Nude Mice

    褚芳; 余华; 方铝; 周艳艳; 郑国安; 范其坤; 丁琦


    Objective To observe and compare the liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice. Method The human ovarian cancer, gastric cancer and colon cancer were transplanted to the nude mice. The growth rate of the solid tumors, the survival time, and the pathological changes in the liver and spleen metastasis of three transplanted carcinomas were observed. Results The rates of tumor formation and the liver metastasis of xenografted human ovarian cancer, gastric cancer and colon cancer in nude mice were 100% . The spleen metastasis rate of human ovarian cancer was 100% , that of gastric cancer was 62. 5% , and that of colon cancer was 75% . The tumor growth rate of solid tumor of human ovarian cancer in nude mice was higher than that of solid tumor of gastric cancer and colon cancer, and spleen metastasis of human ovarian cancer was rapider with a short survival time. There were differences in the pathological changes in the liver and spleen metastasis of three transplanted carcinomas. Conclusion The models of liver and spleen metastasis of transplanted human ovarian cancer, gastric cancer and colon cancer in nude mice can reproduce clinical processes of the liver and spleen metastasis of three transplanted carcinomas, which makes for the studies on biological mechanism of liver and spleen metastasis of human ovarian cancer, gastric cancer and colon cancer and anti-metastasis.%目的 利用人卵巢癌、胃癌、结肠癌裸鼠移植瘤动物模型观察比较肝脾转移情况.方法 分别将人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,在建立人卵巢癌、胃癌、结肠癌裸鼠实体瘤模型的基础上,观察裸鼠实体瘤生长速度、存活时间及肝脾转移病理形态学变化.结果 人卵巢癌、胃癌、结肠癌实体瘤移植到裸鼠皮下,移植成瘤率、肝转移率皆为100%;卵巢癌脾转移100%;胃癌脾转移62.5%;结肠癌脾转移75%.人

  2. Paradoxical effects of Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates on hCD45(+) cells in the bone marrow and spleen of leukemia-engrafted NOD/SCID or NRG mice.

    Bergstrom, Dane; Leyton, Jeffrey V; Zereshkian, Arman; Chan, Conrad; Cai, Zhongli; Reilly, Raymond M


    (111)In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the overexpression of the interleukin-3 receptor α-subchain (CD123) relative to the β-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with (111)In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency (NOD/SCID) mice or NOD-Rag1(null)IL2rγ(null) (NRG) mice engrafted with CD123(+) human AML-5 cells. The toxicity of three doses of (111)In-DTPA-NLS-CSL360 (3.3-4.8MBq; 11-15μg each) injected i.v. every two weeks was studied in non-engrafted NOD/SCID or NRG mice pre-treated with 200cGy of γ-radiation required for AML engraftment. Engraftment efficiency of (1-5)×10(6) cells AML-5 cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric analysis for human CD45(+) (hCD45(+)) cells in the bone marrow (BM) and spleen. AML-5 engrafted mice were treated with two or three doses (3.7MBq; 10μg each) every two weeks of (111)In-DTPA-NLS-CSL360, non-specific (111)In-DTPA-NLS-hIgG, unlabeled CSL360 (10μg) or normal saline. The percentage of hCD45(+) cells in the BM and spleen were measured at one week after completion of treatment. (111)In-DTPA-NLS-CSL360 in combination with 200cGy of γ-radiation caused an initial transient decrease in body weight in NOD/SCID but not in NRG mice. There were no hematological, liver or kidney toxicities. The spleen exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice inoculated with 1×10(6) cells but both organs were highly (>85%) engrafted in NRG mice. Unexpectedly, (111)In-DTPA-NLS-CSL360 or non-specific (111)In-DTPA-NLS-hIgG caused a paradoxical 1.5-fold increase (PDTPA-NLS-CSL360 reduced hCD45(+) cells in the spleen by 3.0-fold compared to (111)In-DTPA-NLS-hIgG (P=0.0015) but the proportion of hCD45(+) cells was not significantly different than in normal saline treated mice. Unlabeled CSL360 decreased the percentage of hCD45

  3. 脾虚小鼠伴口腔白念珠菌感染唾液中sIgA含量改变%sIga Level Changes In Saliva of Mice With Spleen Deficiency Infected With Candida Albicans

    任平; 马贤德; 关洪全


    Objective:To determine saliva slgA content changes in saliva of mice with spleen deficiency infected with oral Candida albicans and the relationship between spleen deficiency and Candida albicans susceptibility. Methods: The animal model of spleen deficiency was prepared by irregular-feeding and overstrain, using a local method of inoculation to establish oral Candida albicans infection model. The number of living Candida albicans in saliva was tested, enzyme-linked immunosorbent assay (ELISA) was used to measure levels of slgA in saliva in each groups. Results: There were increased number of living Candida albicans in saliva of mice with spleen deficiency infected with oral Candida albicans. slgA in saliva was significantly lower than other groups (P<0.01). Conclusion: The mice with spleen deficiency has high susceptibility of oral Candida albicans.%目的:通过测定脾虚小鼠伴口腔白念珠茵感染后唾液中sIgA的含量变化,探讨脾虚小鼠与白念珠菌易感性的关系.方法:采用饮食失节加劳倦过度的复合因素制备脾虚小鼠模型,采用局部接种的方法于正常对照组以及脾虚小鼠建立口腔黏膜白念珠菌感染模型,检测小鼠唾液中活白念珠菌数,应用酶联免疫吸附法(ELISA)测定各组小鼠唾液中sIgA的含量.结果:脾虚伴口腔白念珠菌感染组小鼠的唾液中活白念珠菌数增高,唾液中sIgA含量明显低于其他各组(P<0.01).结论:小鼠在脾虚状态下对口腔白念珠菌的易感性增强.

  4. CD25 signaling regulates the function and stability of peripheral Foxp3+ regulatory T cells derived from the spleen and lymph nodes of mice.

    Wang, Kunpeng; Gu, Jian; Ni, Xuhao; Ding, Zheng; Wang, Qi; Zhou, Haoming; Zheng, SongGuo; Li, Bin; Lu, Ling


    Regulatory T cells (Tregs) play a critical role in sustaining immune tolerance and maintaining immune balance to alloantigen after transplatation. However, the functions of peripheral Tregs in different organs have not been fully characterized. Here, we showed that spleen-derived Tregs exhibited higher expression of Foxp3, greater suppressive capacity, and lower levels of IL-17A secretion than lymph node-derived Tregs in vitro in the presence or absence of inflammatory cytokines, such as IL-6. We found a higher percentage of CD25(bright) Tregs among spleen-derived Tregs than among lymph node-derived Tregs. Additionally, in vivo experiments demonstrated that adoptive transfer of spleen-derived Tregs, but not lymph node-derived Tregs, alleviated ischemia-reperfusion injury. These results reveal novel functions of Tregs derived from peripheral organs. In particular, spleen-derived Tregs, primarily consisting of CD25(bright) cells, may provide a more significant contribution to the suppression of immune-mediated autoimmune and inflammatory disease.

  5. A rare case of hemangiomatosis of the spleen and intrapancreatic accessory spleen.

    Makino, Isamu; Tajima, Hidehiro; Kitagawa, Hirohisa; Nakagawara, Hisatoshi; Ohta, Tetsuo


    We presented a very rare case of hemangiomatosis of the spleen and intrapancreatic accessory spleen in the tail of the pancreas. A previously healthy 45-year-old woman felt left back pain and received CT scan. Multiple splenic masses and a pancreatic mass in the tail were detected. Both the lesions presented gradual and weak enhancement and pooling of the contrast medium until very late phase on dynamic MRI. Since the lesions in the spleen and the pancreas presented the same characteristics on dynamic CT/MRI, ultrasonography, and positron emission tomography using fluorine-18-fluorodeoxyglucose, we suspected these lesions as hemangiomatosis of the spleen and intrapancreatic accessory spleen. We performed distal pancreatectomy with splenectomy, and pathological diagnosis was hemangiomatosis of the spleen and intrapancreatic accessory spleen. We should consider the possibility of splenic tumors arising from the spleen and intrapancreatic accessory spleen when we find similar lesions in the spleen and the tail of the pancreas. Gradual and weak enhancement and pooling of the contrast medium until very late phase may be important findings for diagnosing splenic hemangiomatosis.

  6. Protective Effects of Changyikang Decoction on Intestinal Function in Mice with Spleen Deficiency Induced Diarrhea%肠益康汤对脾虚泄泻小鼠肠道功能的保护作用

    李华; 龙亚秋; 彭娟; 魏蕾初; 邓虹珠; 姚锐; 焦河玲


    Objective To investigate regulative actions of Changyikang Decoction, a traditional Chinese medicine prescription, against the imbalance of intestinal flora and gastrointestinal dysfunctions in mice with spleen deficiency . Methods The mouse mode of spleen deficiency induced diarrhea was induced by intragastric injection of thubarb decoction. The mice with spleen deficiency were continuously given Changyikang Decoction via intragastric injection for 14 days. The intestinal flora was detected by using microscopy.The propulsion rate of ink in the intestine was observed by ink imprinting method. The histomorphological changes of intestinal mucosa were observed using transmission electron microscope. Results Compared with those in the model group, the amount of bifidobacterium and lactobacillus significantly increased in high-, middle- and low-dose Changyikang Decoction treated groups ( P<0. 05 ) , and the propulsion rate of ink in the intestine significantly decreased in high- and middle-dose Changyikang Decoction treated groups ( P<0. 05 ) , and the pathological changes of mouse intestinal mocosa were significantly alleviated in high-, middle- and low-dose Changyikang Decoction treated groups. Conclusion Changyikang Decoction can adjust the imbalance of intestinal flora,inhibit the propulsion movement of the intestine, and alleviate pathological changes of intestinal mucosa in mice with thubarb induced spleen deficiency.%目的 观察肠益康汤对脾虚动物肠道菌群失调及胃肠功能异常的调整作用.方法 用大黄诱导脾虚泄泻小鼠模型,连续灌胃给予肠益康汤14 d,采用镜检法测定肠道菌群水平,墨汁印迹法检测小肠推进率,电镜观察小肠黏膜.结果 与模型组比较,肠益康汤高、中、低剂量组小鼠双歧杆菌和乳酸杆菌数量显著增加(P<0.05),肠益康高、中剂量组小鼠小肠碳末推进率显著降低(P<0.05),肠益康汤高、中、低剂量组小鼠小肠黏膜病理改变

  7. 奥美拉唑对小鼠胸腺、脾脏免疫功能的影响%Effects of omeprazole on thymus and spleen immunity in mice

    齐东江; 徐阿曼


    Objective To investigate if long-term use omeprazole( OME) will inhibit lysosomal in vivo in mice and its effect on the im-mune organs of mice.Methods Mice were divided into 3 group:control group,low dose OME group,high dose OME group,10 mice in each group.After 24 wk mice were sacrificed to collect samples and calculate the spleen index,ELISA was employed to assay the serum concentration of acid phosphatase(ACP)and N-acetyl -β-D-glucosaminidase(NAG).Results OME group compare with the control group,spleen weight index,thymus index decreased significantly,serum lysosomal enzyme levels also decreased significantly,the differences was satatically significant(P<0.05).Conclusion OME can inhibit the lysosomal hydrolase activity in mice,resulting in systemic immune function is impaired,thereby reducing immune function in mice.%目的:研究长期使用奥美拉唑( omeprazole,OME)是否会抑制小鼠体内溶酶体及其对小鼠免疫器官的影响。方法实验分为单纯对照组、OME低剂量组(6 mg· kg-1)、OME高剂量组(30 mg· kg-1),每组10只小鼠。饲养24周后处死小鼠, ELISA法检测小鼠血清及脾脏中酸性磷酸酶( acid phosphatase,ACP)、N-乙酰-β-D-氨基葡萄糖苷酶( N-acetyL-β-D-glucosamini-dase,NAG)含量,采集小鼠胸腺、脾脏并称重计算小鼠脾脏、胸腺重量指数。结果 OME组与对照组相比血清中溶酶体酶活性下降,两者差异具有统计学意义(P<0.05),同时小鼠脾脏及胸腺重量指数明显下降。结论 OME可以抑制小鼠体内溶酶体及其水解酶的活性,导致系统性免疫功能受损,从而降低小鼠免疫功能。

  8. Telocytes in the Spleen.

    Yuqiao Chang

    Full Text Available Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM. The primary culture of telocytes was performed after combined enzymatic digestion. The characteristic morphology was analyzed by a scanning electron microscopy (SEM. It was shown that telocytes displayed a piriform/spindle/triangular shape with long and slender telopods and extremely long prolongation contracting with surrounding cells in the spleen. Their dynamic profiles of cytoplasmic separation were recorded by the Live Cell Imaging System. The length of telopods was mostly distributing in 20-30 μm, in accordance with normal distribution. Most telocytes had three or two telopods (28.71% and 22.58% respectively. Immunostaining indicated that these cells were positive for vimentin, CD34, nanog and sca-1, but negative for c-kit. These data prove the existence of telocytes in the spleen, which may serve as the experimental base for exploring their roles in the spleen.

  9. Telocytes in the Spleen.

    Chang, Yuqiao; Li, Cixia; Gan, Li; Li, He; Guo, Zhikun


    Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM). The primary culture of telocytes was performed after combined enzymatic digestion. The characteristic morphology was analyzed by a scanning electron microscopy (SEM). It was shown that telocytes displayed a piriform/spindle/triangular shape with long and slender telopods and extremely long prolongation contracting with surrounding cells in the spleen. Their dynamic profiles of cytoplasmic separation were recorded by the Live Cell Imaging System. The length of telopods was mostly distributing in 20-30 μm, in accordance with normal distribution. Most telocytes had three or two telopods (28.71% and 22.58% respectively). Immunostaining indicated that these cells were positive for vimentin, CD34, nanog and sca-1, but negative for c-kit. These data prove the existence of telocytes in the spleen, which may serve as the experimental base for exploring their roles in the spleen.

  10. In vivo redox effects of Aspidosperma quebracho-blanco Schltdl., Lantana grisebachii Stuck and Ilex paraguariensis A. St.-Hil. on blood, thymus and spleen of mice.

    Canalis, A M; Cittadini, M C; Albrecht, C; Soria, E A


    Argentinian native plants Aspidosperma quebracho-blanco, Lantana grisebachii and Ilex paraguariensis are known to have antiinflammatory and antioxidant properties. We demonstrated it in vivo by the redox changes in murine hemolymphatic tissues after infusive extract intake of these plants as revealed in organic trophism, tissue phenolics, hydroperoxides, superoxide, nitrites and gamma-glutamyltranspeptidase in thymus, blood and spleen. A. quebracho-blanco reduced hydroperoxidation in blood and spleen of both sexes, with gamma-glutamyltranspeptidase negativization in lymphatic organs and thymic nitrosative up-regulation. Males have shown increased phenolic content in blood after treatment. L. grisebachii and I. paraguariensis treatment exhibited incomplete antioxidation and oxidative induction in the studied tissues. Different results according to sex were found in redox response to phenolics and their kinetics, with males showing antioxidant effects, whereas females showed oxidative susceptibility. A. quebracho-blanco exhibited protection of murine tissues against oxidation in both sexes and modulation of their trophism, supporting its therapeutic uses in inflammatory diseases. Also, gender had significant influence in phenolic biodistribution and redox response.

  11. Caspase-3 mediates the pathogenic effect of Yersinia pestis YopM in liver of C57BL/6 mice and contributes to YopM's function in spleen.

    Zhan Ye

    Full Text Available The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found associated with myeloid cells in foci of inflammation and in liver sinusoids. A new in-vivo phenotype of YopM was revealed: death of inflammatory cells, evidenced by TUNEL staining beginning at d 1 of infection. Based on distributions of Ly6G(+, F4/80(+, and iNOS(+ cells within foci, the cells that were killed could have included both PMNs and macrophages. By 2 d post-infection, YopM had no effect on distribution of these cells, but by 3 d cellular decomposition had outstripped acute inflammation in foci due to parent Y. pestis, while foci due to the ΔyopM-1 strain still contained many inflammatory cells. The destruction depended on the presence of both PMNs in the mice and YopM in the bacteria. In mice that lacked the apoptosis mediator caspase-3 the infection dynamics were novel: the parent Y. pestis was limited in growth comparably to the ΔyopM-1 strain in liver, and in spleen a partial growth limitation for parent Y. pestis was seen. This result identified caspase-3 as a co-factor or effector in YopM's action and supports the hypothesis that in liver YopM's main pathogenic effect is mediated by caspase-3 to cause apoptosis of PMNs.

  12. 破布木果提取物对小鼠脾淋巴细胞的增殖作用%Proliferative effects of extracts from Cordia dichotoma seeds on spleen lymphocytes in mice

    朱明; 欧亮苗; 何巧丽; 哈木拉提·吾甫尔; 田树革


    Objective To investigate the proliferative effects of extracts from Cordia dichotoma seeds on spleen lymphocytes of mice.Methods Detect the effects of the extracts with different concentrations from Cordia dichotoma seeds on mouse spleen lymphocytes by concanavalin A (ConA)and lipopolysaccharide (LPS)in vitro treatment;Detect the proliferation ability of lymphocyte by MTT assay.Results The ex-tracts of Cordia dichotoma seeds in the range of 2.69-86 mg/mL had a synergistic effect in vitro on the mouse spleen lymphocytes proliferation induced by ConA and LPS;polysaccharides of Cordia dichotoma seeds in the range of 21.50-86 mg/mL had synergistic effects in vitro on the spleen lymphocyte prolifera-tion induced by ConA;polysaccharides in the range of 10.75-86 mg/mL had synergistic effects in vitro on the spleen lymphocyte proliferation induced by LPS;rosmarinic acid standard,used as the positive control drug,had a synergistic effect in vitro on the mouse spleen lymphocytes proliferation induced by ConA and LPS.Conclusion This primary study showed that the extracts from Cordia dichotoma seeds,polysaccha-rides of Cordia dichotoma seeds and rosmarinic acid standards had some immunomodulatory effects.%目的:研究破布木果提取物对小鼠脾淋巴细胞的增殖作用。方法不同浓度的破布木果提取物对刀豆蛋白 A(concanavalin A,ConA)、脂多糖试剂(LPS)体外处理的小鼠脾淋巴细胞的作用;采用 MTT法测定淋巴细胞的增殖能力。结果破布木果提取液在2.69~86 mg/mL范围内,均与 ConA、LPS诱导的小鼠脾淋巴细胞的增殖在体外具有协同作用;破布木果多糖在21.50~86 mg/mL范围内,与 ConA诱导的小鼠脾淋巴细胞的增殖在体外具有协同作用;在10.75~86 mg/mL范围内,与 LPS诱导的小鼠脾淋巴细胞的增殖在体外具有协同作用;迷迭香酸标准品作为药物的阳性对照,均与 ConA、LPS诱导的小鼠脾淋巴细胞的增殖

  13. The Challenge of Stability in High-Throughput Gene Expression Analysis: Comprehensive Selection and Evaluation of Reference Genes for BALB/c Mice Spleen Samples in the Leishmania infantum Infection Model

    Gonzalez-García, Ana C.; Quispe-Ricalde, M. Antonieta; Larraga, Vicente; Valladares, Basilio; Carmelo, Emma


    The interaction of Leishmania with BALB/c mice induces dramatic changes in transcriptome patterns in the parasite, but also in the target organs (spleen, liver…) due to its response against infection. Real-time quantitative PCR (qPCR) is an interesting approach to analyze these changes and understand the immunological pathways that lead to protection or progression of disease. However, qPCR results need to be normalized against one or more reference genes (RG) to correct for non-specific experimental variation. The development of technical platforms for high-throughput qPCR analysis, and powerful software for analysis of qPCR data, have acknowledged the problem that some reference genes widely used due to their known or suspected “housekeeping” roles, should be avoided due to high expression variability across different tissues or experimental conditions. In this paper we evaluated the stability of 112 genes using three different algorithms: geNorm, NormFinder and RefFinder in spleen samples from BALB/c mice under different experimental conditions (control and Leishmania infantum-infected mice). Despite minor discrepancies in the stability ranking shown by the three methods, most genes show very similar performance as RG (either good or poor) across this massive data set. Our results show that some of the genes traditionally used as RG in this model (i.e. B2m, Polr2a and Tbp) are clearly outperformed by others. In particular, the combination of Il2rg + Itgb2 was identified among the best scoring candidate RG for every group of mice and every algorithm used in this experimental model. Finally, we have demonstrated that using “traditional” vs rationally-selected RG for normalization of gene expression data may lead to loss of statistical significance of gene expression changes when using large-scale platforms, and therefore misinterpretation of results. Taken together, our results highlight the need for a comprehensive, high-throughput search for the most

  14. In vivo immunotoxicity of perfluorooctane sulfonate in BALB/c mice: Identification of T-cell receptor and calcium-mediated signaling pathway disruption through gene expression profiling of the spleen.

    Lv, Qi-Yan; Wan, Bin; Guo, Liang-Hong; Yang, Yu; Ren, Xiao-Min; Zhang, Hui


    Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that is used worldwide and is continuously being detected in biota and the environment, thus presenting potential threats to the ecosystem and human health. Although PFOS is highly immunotoxic, its underlying molecular mechanisms remain largely unknown. The present study examined PFOS-induced immunotoxicity in the mouse spleen and explored its underlying mechanisms by gene expression profiling. Oral exposure of male BALB/c mice for three weeks followed by one-week recovery showed that a 10 mg/kg/day PFOS exposure damaged the splenic architecture, inhibited T-cell proliferation in response to mitogen, and increased the percentages of T helper (CD3(+)CD4(+)) and cytotoxic T (CD3(+)CD8(+)) cells, despite the decrease in the absolute number of these cells. A delayed type of PFOS immunotoxicity was observed, which mainly occurred during the recovery period. Global gene expression profiling of mouse spleens and QRT-PCR analyses suggest that PFOS inhibited the expression of genes involved in cell cycle regulation and NRF2-mediated oxidative stress response, and upregulated those in TCR signaling, calcium signaling, and p38/MAPK signaling pathways. Western blot analysis confirmed that the expressions of CAMK4, THEMIS, and CD3G, which were involved in the upregulated pathways, were induced upon PFOS exposure. Acute PFOS exposure modulated calcium homoeostasis in splenocytes. These results indicate that PFOS exposure can activate TCR signaling and calcium ion influx, which provides a clue for the potential mechanism of PFOS immunotoxicity. The altered signaling pathways by PFOS treatment as revealed in the present study might facilitate in better understanding PFOS immunotoxicity and explain the association between immune disease and PFOS exposure.

  15. Spleen removal - open - adults - discharge

    Splenectomy - adult - discharge; Spleen removal - adult - discharge ... You had surgery to remove your spleen. This operation is called splenectomy . The surgeon made a cut (incision) in the middle of your belly or on the left side ...

  16. Hemangiopericytoma of the spleen.

    Illuminati, Giulio; Pizzardi, Giulia; Calio, Francesco; Pacilè, Maria A; Carboni, Fabio; Palumbo, Piergaspare; Vietri, Francesco


    Hemangiopericytoma of the spleen is a very rare tumor, with 14 isolated reports. It was our aim to review our experience and compare it with all the reported cases in an attempt to standardize surgical treatment, adjuvant treatment and follow-up protocol of this infrequent condition. A consecutive case series study, with a mean follow-up of 44 months. Five patients (mean age, 49 years) underwent simple splenectomy for hemangiopericytoma limited to the spleen followed by adriamycin-based chemotherapy in one patient. All the patients are alive and free from disease. For tumors confined to the spleen, simple splenectomy can be considered curative, without any need for further adjuvant treatment. On review of the medical literature, cure can still be achieved with complete resection of recurrences, when feasible, with adjuvant chemotherapy being also indicated. The slow-growing pattern of the tumor suggests a 10-year follow-up. Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  17. Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice.

    Al-Quraishy, Saleh; Dkhil, Mohamed A; Abdel-Baki, Abdel Azeem S; Delic, Denis; Santourlidis, Simeon; Wunderlich, Frank


    Epigenetic reprogramming of host genes via DNA methylation is increasingly recognized as critical for the outcome of diverse infectious diseases, but information for malaria is not yet available. Here, we investigate the effect of blood-stage malaria of Plasmodium chabaudi on the DNA methylation status of host gene promoters on a genome-wide scale using methylated DNA immunoprecipitation and Nimblegen microarrays containing 2,000 bp oligonucleotide features that were split into -1,500 to -500 bp Ups promoters and -500 to +500 bp Cor promoters, relative to the transcription site, for evaluation of differential DNA methylation. Gene expression was analyzed by Agilent and Affymetrix microarray technology. Challenging of female C57BL/6 mice with 10(6) P. chabaudi-infected erythrocytes resulted in a self-healing outcome of infections with peak parasitemia on day 8 p.i. These infections induced organ-specific modifications of DNA methylation of gene promoters. Among the 17,354 features on Nimblegen arrays, only seven gene promoters were identified to be hypermethylated in the spleen, whereas the liver exhibited 109 hyper- and 67 hypomethylated promoters at peak parasitemia in comparison with non-infected mice. Among the identified genes with differentially methylated Cor-promoters, only the 7 genes Pigr, Ncf1, Klkb1, Emr1, Ndufb11, and Tlr6 in the liver and Apol6 in the spleen were detected to have significantly changed their expression. Remarkably, the Cor promoter of the toll-like receptor Tlr6 became hypomethylated and Tlr6 expression increased by 3.4-fold during infection. Concomitantly, the Ups promoter of the Tlr1 was hypermethylated, but Tlr1 expression also increased by 11.3-fold. TLR6 and TLR1 are known as auxillary receptors to form heterodimers with TLR2 in plasma membranes of macrophages, which recognize different pathogen-associated molecular patterns (PAMPs), as, e.g., intact 3-acyl and sn-2-lyso-acyl glycosylphosphatidylinositols of P. falciparum

  18. sCD200 present in mice receiving cardiac and skin allografts causes immunosuppression in vitro and induces Tregs.

    Gorczynski, Reginald; Chen, Zhiqi; Khatri, Ismat; Yu, Kai


    CD200 overexpression in transgenic mice increases skin, cardiac, and renal allograft survival. Elevated levels of soluble CD200 (sCD200) are found in the serum of cancer individuals. We investigated whether sCD200 levels increase in mice with prolonged graft survival. Control or CD200 BL/6 recipients of BALB/c cardiac or skin grafts received low-dose rapamycin (0.5 mg/kg) at 36-hr intervals, a dose shown previously not to augment the survival of control grafts or alter the host antigraft immunity or graft gene expression profiles. Separate groups received high-dose rapamycin (1.5 mg/kg). Serum was obtained at 8, 15, and 80 days after grafting and assayed for sCD200 (enzyme-linked immunosorbent assay), for the suppression of immunity in mixed leukocyte cultures (MLCs), for the induction of regulatory T cells able to suppress cytotoxic T lymphocyte induction in MLCs, and for the ability to transfer graft survival to naïve recipients. Both CD200 and conventional mice with early enhanced graft survival had increased levels of sCD200 in serum, which induced Tr1 able to suppress MLCs. Suppression was abolished after passage of serum over a CD200 immunoadsorbent column. Dendritic cells maturing in the presence of sCD200 serum could induce populations of Foxp3 regulatory T cells able to suppress MLCs in vitro. In CD200 mice with long-term surviving cardiac (skin) allografts in the absence of continued transgene induction (>80 days [>35 days]), sCD200 levels returned to baseline, with no loss of grafts, but sera were unable to suppress MLCs in vitro. sCD200 serum adoptively transferred increased graft survival to naïve mice. We conclude that monitoring sCD200 at early times after engraftment may predict allograft survival.

  19. Histopathological Study of the Lungs of Mice Receiving Human Secretory IgA and Challenged with Mycobacterium tuberculosis.

    Alvarez, Nadine; Infante, Juan Francisco; Borrero, Reinier; Mata, Dulce; Payan, Jorge Barrios-; Hossain, Md Murad; Mohd Nor, Norazmi; Sarmiento, María Elena; Hernandez-Pando, Rogelio; Acosta, Armando


    Humoral and cellular immune responses are associated with protection against extracellular and intracellular pathogens, respectively. In the present study, we evaluated the effect of receiving human secretory immunoglobulin A (hsIgA) on the histopathology of the lungs of mice challenged with virulent Mycobacterium tuberculosis. The hsIgA was purified from human colostrum and administered to Balb/c mice by the intranasal route prior to infection with M. tuberculosis or in a pre-incubated formulation with mycobacteria, with the principal aim to study its effect on qualitative pulmonary histopathology. The intranasal administration of hsIgA and the pre-incubation of mycobacteria with this preparation was associated with the presence of organised granulomas with signs of immune activation and histological features related to efficient disease control. This effect was highly evident during the late stage of infection (60 days), as demonstrated by numerous organised granulomas with numerous activated macrophages in the lungs of treated mice. The administration of hsIgA to mice before intratracheal infection with M. tuberculosis or the pre-incubation of the bacteria with the antibody formulation induced the formation of well-organised granulomas and inflammatory lesions in lungs compared with non-treated animals which correlates with the protective effect already demonstrated by these antibody formulations.

  20. Isolation of myeloid-derived suppressor cells subsets from spleens of orthotopic liver cancer-bearing mice by fluorescent-activated and magnetic-activated cell sorting: similarities and differences.

    Xu, Yaping; Zhao, Wenxiu; Wu, Duan; Xu, Jianfeng; Lin, Suqiong; Tang, Kai; Yin, Zhenyu; Wang, Xiaomin


    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that commonly expand during tumor development and that play a critical role in suppression of immune responses. MDSCs can be classified into two groups: Mo-MDSCs and G-MDSCs. These cells differ in their morphology, phenotype, differentiation ability, and immunosuppressive activity, and inhibit immune responses via different mechanisms. Therefore, identifying an effective method for isolating viable Mo-MDSCs and G-MDSCs is important. Here, we demonstrated the differences and similarities between fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) in sorting G-MDSCs and Mo-MDSCs. Both MACS and FACS could obtain G-MDSCs and Mo-MDSCs with high viability and purity. A high yield and purity of G-MDSCs could be obtained both by using FACS and MACS, because G-MDSCs are highly expressed in the spleen of tumor-bearing mice. However, Mo-MDSCs, which comprise a small population among leukocytes, when sorted by MACS, could be obtained at much greater cell number, although with a slightly lower purity, than when sorted by FACS. In conclusion, we recommended using both FACS and MACS for isolating G-MDSCs, and using MACS for isolation of Mo-MDSCs.

  1. Morphological changes of blood spleen barrier in portal hypertensive spleen

    LI Zong-fang; ZHANG Shu; HUANG Ying; XIA Xian-ming; LI Ai-min; PAN Dun; ZHANG Wei; WANG Juan


    Background The pathogenesis of hypersplenism and the immune function of the spleen in patients with portal hypertension(PH)remain obscure.This study aimed to evaluate the morphological changes of blood spleen barrier in spleen with hypersplenism due to PH and provide evidence for an in-depth investigation of the immune function of the spleen with hypersplenism and the mechanism of hypersplenism.Methods Spleen samples from 12 portal hypertensive patients and 4 patients with traumatic ruptures of spleen were examined.The samples of spleen were made into pathological sections,stained with Masson trichrome stain,Gomori stain,and CD68,CD34 immunohistochemistry,and were examined microscopically for the changes in the distribution of collagen fibers,reticular fibers,macrophages,and vascular endothelial cells.The changes in ultrastructure of macrophages and endothelial cells in marginal zone were also evaluated by transmission electron microscopy.Results As compared to the normal spleen,the density of macrophage in the PH spleen was decreased,but the macrophages were mainly located in the marginal zone and distributed around the splenic corpuscle,with many villi and pseudopodium-like protrusion on the cell surface.The accrementition of collagen fibers was obvious around the splenic corpuscle and central artery.The increased reticulate fibers encircled the splenic corpuscle with more connection between the fibers.The vascular endothelial cells were in diffused distribution,without any regionality in PH spleen,but the vessel with enlarged lumina increased in red pulp.Conclusions The morphological changes of the blood spleen barrier can be one of the pathological fundaments for the abnormality of the immune function and the increased destruction of blood cells located in the spleens of patients with PH.However,this still entails clarification.

  2. Locally vascularized pelvic accessory spleen.

    Iorio, F; Frantellizzi, V; Drudi, Francesco M; Maghella, F; Liberatore, M


    Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

  3. Role of spleen in acute rejection of mice undergoing allogeneic liver transplantation%脾脏在小鼠同种肝移植排斥反应中的作用

    万赤丹; 黄韬; 勾善淼; 周静; 刘涛; 王春友


    目的 观察脾切除在小鼠同种肝移植急性排斥反应过程中的作用.方法 双袖套法建立小鼠原位肝移植模型,随机分为3组,即建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组,各组于移植术后14 d处死,ELESA法测定血清IgM水平;肝功能检测采用速率法;流式细胞仪检测CD4与CD8T细胞亚群;并同时行肝脏及脾脏的病理形态观察.结果 建模保留脾脏组、建模3 d后切除脾脏与建模同时切除脾脏组血清IgM水平分别为3.0181±0.4627、3.0936±0.4559、3.1953±0.4449,各组间差异无统计学意义(P>0.05);ALT水平分别为108.6875±20.3657、83.0000±22.7799、76.8000±19.5784,差异有统计学意义(P<0.05);AST水平分别为:105.3750±29.0583、93.0000±22.7799、93.2000±33.4220,各组间差异无统计学意义(P>0.05);CD46+/CD8+T细胞分别为:1.9162±0.2778、1.5654±0.4750、1.4616±0.2762,差异有统计学意义(P>0.05);3组肝脏间质及汇管区淋巴细胞浸润程度依次减弱,供肝灶状坏死程度逐渐减轻,在保留脾脏组中建模后第14天脾脏边缘区及淋巴鞘较建模同时切除的脾脏增宽.结论 在小鼠同种异体肝移植排斥反应中细胞免疫起主要作用,脾切除可部分抑制同种异体肝移植急性排斥反应,保护供体肝脏.%Objective To study the role of spleen in acute rejection of mice undergoing aUogeneie liver transplantation.Methods Orthotopic liver transplantation was performed from C57BL mice to KM mice by using a two-cuff teehinique.C57BL mice as receptors were divided into 3 groups by simple random method:Group A ( n = 18 ),transplantion without splenectomy; Group B ( n = 18),transplantion and splenectomy were done simultaneously; Group C ( n = 18 ) ,spleneetomy was done 3 days after liver transplantation.All mice were killed 14 days after liver transplantation.ALT,AST,IgM,subgroups of T cells,pathological changes of lvier and kidney were analyzed.Results There was

  4. Natural suppressor cells in spleens of irradiated, bone marrow-reconstituted mice and normal bone marrow: Lack of Sca-1 expression and enrichment by depletion of Mac1-positive cells

    Sykes, M.; Sharabi, Y.; Sachs, D.H. (National Cancer Institute, Bethesda, MD (USA))


    We have recently reported the development of natural suppressor (NS) cells in lethally irradiated, bone marrow-reconstituted mice during the early weeks after bone marrow transplantation (BMT). These cells were shown to be derived primarily from the syngeneic marrow component in recipients of mixed allogeneic plus syngeneic (host type) marrow, and it was speculated that they might be responsible for the anti-GVHD effect previously described for T-cell-depleted syngeneic marrow. It was therefore of interest to look for such suppressive activity in normal adult bone marrow, which might serve as an obtainable source of such cells if they were to be isolated and used clinically. Such activity has indeed been found in normal adult bone marrow and its characteristics compared to that in spleens of early BMT recipients. Suppressive cells from both sources were similar in their specificity patterns and radiosensitivity, and were of the null (i.e., non-T, non-B, nonmacrophage) cell phenotype. Suppression from either source can be enriched by removal of Mac1-positive cells, providing a possible approach to obtaining NS-enriched populations for in vitro expansion and adoptive transfer studies. Such depletion of Mac1-positive cells was associated with a threefold enrichment of Thy1-positive cells, of which one half were CD4- and CD8-negative, similar to the reported phenotype of cultured NS cell lines. Even when enriched in this manner, the contribution of Thy1-positive cell populations did not reach statistical significance. A recent report has suggested that NS cells might actually be pluripotent hematopoietic stem cells. In contrast, we report here that depletion of Sca1-positive pluripotent hematopoietic stem cells with monoclonal antibody plus immunomagnetic beads does not remove NS activity.

  5. Neonatal microbial colonization in mice promotes prolonged dominance of CD11b+Gr-1+cells and accelerated establishment of the CD4+T cell population in the spleen

    Kristensen, Matilde Bylov; Metzdorff, Stine Broeng; Bergström, Anders;


    To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b+Gr-1+ splenocytes present perinatally was sustained for a longer period in conventionally...... event, which we suggest impacts the subsequent development of the T cell population in the murine spleen....

  6. Study on the Immune Protective Effect of Sophora japonical Water Extract on the Spleen Cells of 60Co-γ Ray Irradiated Injured Mice%槐白皮水提物对60Co-γ射线损伤小鼠脾细胞的免疫保护作用研究

    张跃进; 董海艳; 张婵; 李安乐; 陈向敏


    目的:研究槐白皮水提物对50Co-γ射线损伤小鼠脾细胞的免疫保护作用.方法:实验分为5组,即正常(等容生理盐水)、照射对照(等容生理盐水)和槐白皮水提物高、中、低剂量(0.8、0.4、0.2 mL·kg-1)组.除正常组外其余各组给予60Co-γ射线一次性照射,照射后立即给药,每天1次,连续10d.测定小鼠脾细胞培养上清液中一氧化氮(NO)水平及脾指数.结果:槐白皮水提物中剂量组NO含量显著低于照射对照组(P<0.05);槐白皮水提物中、低剂量组脾指数显著高于照射对照组(P<0.01或P<0.05).结论:槐白皮水提物能降低射线对脾细胞的损伤,具有免疫保护作用.%OBJECTIVE: To evaluate the immune protective effect of Sophora japonical water extract on the spleen cells of 6cCo-y ray irradiated injured mice. METHODS: Mice were randomly divided into 5 groups: normal group (constant volume normal saline), irradiation control group (constant volume normal saline) ,S. Japonical water extract high-dose, medium-dose and low-dose groups(0.8, 0.4, and 0.2 mL?kg"'). All the mice were irradiated with Mco-y ray except normal group, and then S. Japonical water extract was given once a day for 10 days. And then nitric oxide (NO) level and spleen index was detected in spleen cell of mice. RESULTS: NO level of S. Japonical water extract medium-dose group was significantly lower than irradiation control group(P< 0.01), and the spleen index of S. Japonical water extract medium-doce group and low-dose groups was significantly higher than irradiation control group(f <0.01 or P<0.05). CONCLUSIONS: S. Japonical water extract can reduce the damage of the irradiated spleen cells, and have the immune protective function.

  7. Torsion of a wandering spleen

    of peri-umbilical pain progressing to generalised abdominal pain ... surgical intervention. A midline ... No improvement was noted on detorsion of the vascular pedicle, and a ... Surgical treatment of patients with wandering spleen: Report of six.

  8. Anatomical variation of arterial supply to the rabbit spleen.

    Ikegami, Reona; Tanimoto, Yoshimasa; Kishimoto, Miori; Shibata, Hideshi


    The rabbit, which is widely used as an experimental animal and is also popular as a companion animal, has a flat and elongated spleen with the longitudinal hilus running along its visceral surface. The spleen receives via the hilus an arterial supply that is essential for splenic nutrition and normal functioning. However, the distribution and variation of the arteries to the spleen have not been studied in detail. This study investigated anatomical variations of splenic arterial supply in 33 New Zealand White rabbits with a colored latex injection into arteries. We also examined whether the length of the spleen correlated with the number of the splenic branches of the splenic artery. The splenic artery always arose as the first independent branch of the celiac artery and ran along the splenic hilus to usually provide 6 (range, 3 to 10) splenic branches to the spleen. There was a moderate correlation (R=0.6) between the number of splenic branches and the longitudinal length of the spleen. The splenic branches often arose as a trunk or trunks in common with short gastric arteries. The number of common trunk(s) was usually 1 (range, 0 to 4). The data showed that the pattern and number of arterial branches to the spleen varied according to the individual animal, suggesting that such variations should be considered when performing experimental and veterinary surgical treatments in rabbits.

  9. Neonatal microbial colonization in mice promotes prolonged dominance of CD11b+Gr-1+cells and accelerated establishment of the CD4+T cell population in the spleen

    Kristensen, Matilde Bylov; Metzdorff, Stine Broeng; Bergström, Anders;


    To assess the microbial influence on postnatal hematopoiesis, we examined the role of early life microbial colonization on the composition of leukocyte subsets in the neonatal spleen. A high number of CD11b+Gr-1+ splenocytes present perinatally was sustained for a longer period in conventionally...

  10. Pathological rupture of malarial spleen.

    Mokashi A


    Full Text Available Two cases of spontaneous rupture of malarial spleen are reported here. One of them was a male who was on chloroquine for an acute attack of malaria. While on therapy, he complained of pain in left hypochondrium followed by palpitations. The other patient was a female who was admitted for continuous dull aching pain and fever. In both the patients, exploratory laparotomy revealed an enlarged spleen with tear. Splenectomy was performed. Histopathological examination revealed dilated congested sinusoid with follicular atrophy, and RBCs with malarial parasites. The post-operative course was smooth in both patients.

  11. Following EAU recovery there is an associated MC5r-dependent APC induction of regulatory immunity in the spleen.

    Lee, Darren J; Taylor, Andrew W


    IRBPp-specific regulatory immunity is found in the spleens of mice recovered from experimental autoimmune uveoretinitis (EAU). Induction of this regulatory immunity is dependent on the expression of the melanocortin 5 receptor (MC5r). Therefore, the authors investigated whether dependence on the expression of MC5r was with the T cells or with the APCs mediating protective regulatory immunity in the EAU-recovered mouse spleen. Wild-type and MC5r-/- mice were immunized to induce EAU. The IRBPp-stimulated T-cell response in spleens of wild-type and MC5r-/- mice were compared for surface markers and cytokine production. Spleen APC were isolated and used to stimulate cytokine production and regulatory activity in IRBP-specific T cells from wild-type or MC5r-/- mice assayed in culture by ELISA, by flow cytometry, and in vivo by adoptive transfer into EAU mice. IRBPp-specific CD25+CD4+ T cells from spleens of EAU-recovered wild-type mice express a Treg cell phenotype of FoxP3 and TGF-β compared with the effector T-cell phenotype of IFN-γ and IL-17 production in EAU-recovered MC5r-/- mice. APCs from the spleens of wild-type mice recovering from EAU promoted regulatory T-cell activation in IRBP-specific effector T cells from the spleens of EAU-recovering MC5r-/- mice. Spleen APCs from EAU-recovering wild-type, but not MC5r-/-, mice induced TGF-β expression by primed IRBP-specific effector T cells. Dependence on MC5r expression is with an APC that promotes or selectively activates IRBP-specific FoxP3+ TGF-β+ CD25+CD4+ Treg cells in the spleens of EAU-recovered mice.

  12. Spleen-specific isoforms of Pax5 and Ataxin-7 as potential proteomic markers of lymphoma-affected spleen.

    Bharti, Brij; Mishra, Rajnikant


    The splenomegaly, enlargement of spleen, has been observed in several diseases. It has been intended to evaluate histochemical alterations, spleen-specific enzymatic and proteomic markers during splenomegaly, and lympho-proliferative disorders from spleen of mice bearing Dalton's lymphoma. The higher expression of c-fos, c-jun, and MAPK testifies proliferation of lymphocytes. The lower expression of Pax5, higher expression of CD3, and the presence of additional form of Zap-70 suggest hypertrophy of follicles and splenomegaly influenced by weak B-cell receptor-mediated signaling, but activated T-cell receptor-mediated signaling. Simultaneously, lower levels of SOD, NDR2, and MIB2 and higher expression levels of Ataxin-7 and LDH also suggest impact of stress either as a cause or effect of cell proliferation. Spleen-specific isoform of Pax5, NDR2, MIB2, and Ataxin-7 can be considered as spleen-specific unique molecular markers for the evaluation of splenomegaly and lympho-proliferative disorders.

  13. Evidences of Protective Potentials of Microdoses of Ultra-High Diluted Arsenic Trioxide in Mice Receiving Repeated Injections of Arsenic Trioxide

    Pathikrit Banerjee


    Full Text Available The present study was undertaken to examine if microdoses of ultra-high diluted arsenic trioxide (a potentized homeopathic remedy, Arsenicum Album 200C, diluted 10-400 times have hepatoprotective potentials in mice subjected to repeated injections of arsenic trioxide. Arsenic intoxicated mice were divided into: (i those receiving Arsenicum Album-200C daily, (ii those receiving the same dose of diluted succussed alcohol (Alc 200C and (iii another group receiving neither drug nor succussed alcohol. Two other control groups were also maintained: one fed normal diet only and the other receiving normal diet and Alc-200C. Toxicity biomarkers like aspartate and alanine aminotransferases, glutathione reductase, catalase, succinate dehydrogenase, superoxide dismutase and reduced glutathione contents were periodically assayed keeping the observer “blinded”. Additionally, electron microscopic studies and gelatin zymography for matrix metalloproteinases of liver tissues were made at day 90 and 120. Blood glucose, hemoglobin, estradiol and testosterone contents were also studied. Compared to controls, Arsenicum Album-200C fed mice showed positive modulations of all parameters studied, thereby providing evidence of protective potentials of the homeopathic drug against chronic arsenic poisoning.

  14. The Effect of Flavonoids from Paulownia tomentosa Flowers on the Ultrastructure and Immune Function of Spleen and Thymus in Mice%毛泡桐花黄酮对小鼠脾和胸腺超微结构及疫功能的影响

    王占彬; 王亚锴; 赵德明; 张自强


    To explore the effect of flavonoids from flowers of Paulownia tomentosa on the ultrastructure of spleen and thymus in mice,120 Kunming mice were randomly divided into four groups (n =30,half male and half female).Using daily intragastric administration of flavonoids from Paulownia tomentosa flower according to the weight to establish the experimental animal model:Mice in flavonoid group Ⅰ,flavonoid group Ⅱ and flavonoid group Ⅲ were drenched (once daily for 28 days) with 40,120 and 360 mg · (kg · d)-1 flavonoid,respectively.Mice in control group were gavaged with equal volume PBS containing 0.5 % CMC-Na.On the 28th day of the treatment,spleens and thymuses were collected and organ index was calculated.Proliferation and transformation of spleen lymphocytes induced by ConA were determined by MTT method.Phagocytosis of peritoneal macrophages was tested by neutral red test.The ultrastructure of spleen and thymuses were observed through scanning electron microscope.The results showed that different doses of flavonoids from Paulownia tomentosa flowers can significantly improve the thymus and spleen index and lymphocyte proliferation response (P<0.05) in a dose-dependent manner.Compared with the control group,the number of mature lymphocytes in mice spleen and thymus increased significantly in the three flavonoid-treated groups,especially in high dose group.The results suggest that flavonoids from Paulownia tomentosa flowers affect the ultrastructure of spleen and thymus by increasing immune organ quality,immune organs mature lymphocyte number.In addition,lymphocyte proliferation response,flavonoids from Paulownia tomentosa flowers has a certain regulation effect on the immune function in mice by reinforcing the T lymphocyte proliferation response of spleen and thymus to the cellular immune function.%为研究毛泡桐花黄酮对小鼠脾和胸腺超微结构的影响,将120只昆明种小白鼠随机分为4组:对照组(灌服0.3mL·d-1含0.5

  15. The tissue distribution of diazinon and the inhibition of blood cholinesterase activities in rats and mice receiving a single intraperitoneal dose of diazinon.

    Tomokuni, K; Hasegawa, T; Hirai, Y; Koga, N


    The tissue distribution of diazinon and the inhibition of cholinesterase (ChE) activities in plasma, erythrocyte and brain were investigated using male rats and mice which received a single intraperitoneal (i.p.) dose of diazinon (20 or 100 mg/kg body wt) in olive oil. The blood diazinon level was estimated to reach a maximum at 1-2 h after the i.p. administration. It was demonstrated that the diazinon residue levels are the highest in the kidney, when comparing the distribution of diazinon among liver, kidney and brain in the animals after dosing. It was indicated that the ChE inhibition by diazinon exposure is greater in the plasma than in the erythrocytes for male mice, while its inhibition is greater in the erythrocytes for male rats. Brain ChE activity was also inhibited markedly in the mice after dosing.

  16. Lipid peroxidation induced by joint exposure to gaseous formaldehyde and trichloroethylene in spleen of mice%气态甲醛与三氯乙烯联合暴露染毒对小鼠脾脏的脂质过氧化作用

    周隽隽; 原福胜; 张淑云; 梁瑞峰; 赵五红


    Objective To investigate the lipid peroxidation induced by joint exposure to gaseous formaldehyde and trichloroethylene in spleen of mice, and the type of the joint effect. Methods A total of 108 healthy and clean Kunming mice were included and randomly divided into 9 groups by means of the 3 ×3 factorial design, including formaldehyde (0, 1, 5 mg/m3) group and trichloroethylene (0, 1 000, 5 000 mg/m3) group, and the combined group of both exposures. The mice were exposed by static inhalation for 14 days, 2 hours per day. The activities of total super-oxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the content of malondialdehyde (MDA) in the spleen of the mice were determined after the exposure. Results The activities of SOD and GSH-PX in the spleen of the mice were significantly decreased and the content of MDA was significantly increased along with the increased con-tents of formaldehyde and trichloroethylene, and there were statistically significant differences ( P<0.05). Conclusion Inhaling gaseous formaldehyde and trichloroethylene can induce oxidative damage in spleen of mice, and the joint exposure may have interaction effect.%目的:探讨气态甲醛、三氯乙烯联合暴露染毒对小鼠脾脏的脂质过氧化作用及二者联合作用的类型。方法选择健康清洁级昆明种小鼠108只,按3×3析因设计随机分为9组,设甲醛(0、1、5 mg/m3)和三氯乙烯(0、1000、5000 mg/m3)单独以及二者联合染毒组,采用静式吸入染毒法染毒,每天2 h,连续14 d。染毒结束后测定小鼠脾脏的总超氧化物歧化酶(SOD)活力、谷胱甘肽过氧化物酶(GSH-PX)活力和丙二醛(MDA)含量。结果小鼠脾脏SOD和GSH-PX活力随甲醛、三氯乙烯染毒剂量的升高而明显下降,MDA含量则明显升高,差异均有统计学意义(P<0.05)。结论气态甲醛、三氯乙烯吸入染毒对小鼠脾脏具有氧化损伤作用,两者联合可能存在一定的交互作用。

  17. Heparin inhibits burn-induced spleen cell apoptosis by suppressing interleukin-1 expression

    Zhao Songfeng; Zhang Xiao; Zhang Xiaojian; Shi Xiuqin; Yu Zujiang; Kan Quancheng


    Background Epidermal burn injury may trigger significant apoptosis of the spleen cells,which might be caused by a burninduced systemic inflammatory reaction.Heparin has been shown to possess anti-inflammatory properties.Interleukin 1 (IL-1) is centrally important among pro-inflammatory cytokines.We hypothesized that heparin might inhibit burn-induced apoptosis in the spleen via suppression of the IL-1 pathway.Methods Burn injury was performed on IL-1 R+/+ (IL-1 receptor wild-type mouse) and IL-1 R-/-(IL-1 receptor knockout mouse) mice,and they were then treated with heparin,saline or IL-1 receptor antagonist IL-Ra.Apoptosis,IL-1α and IL-1β expression were assessed in the spleens and serum.Survival curve analysis was further applied to elucidate the mechanism of heparin's protective properties.Results Burn induced significant apoptosis (sham:3.6%±2.1% vs.burn:28.8%±5.9%; P <0.001)and remarkable expression o IL-1α and IL-1β in the mouse spleens and serum.Heparin reduced the burn-induced apoptosis in the spleens (heparin treated:8.6%±3.4%,P <0.005),which could be blocked by IL-1Ra.Heparin markedly decreased both IL-1α and IL-1β expression in the spleens and serum of burned mica.IL-1 R-/-mice demonstrated considerably less apoptosis in the spleens and had a higher survival rate after burns.Heparin did not significantly decrease apoptosis in the spleen and the mortality rate in IL-1 R-/-mice after burns.Conclusion Heparin inhibits burn-induced apoptosis of the spleen cells by suppressing IL-1 expression in mice.

  18. Toxoplasma gondii vs ionizing radiation: cell and humoral immunity in spleen and gut of isogenic mice immunized with {sup 60}Co irradiated tachyzoites; Toxoplasma gondii vs radiacao ionizante: imunidade humoral e celular em baco e intestino de camundongos isogenicos imunizados com taquizoitos irradiados por cobalto 60

    Galisteo Junior, Andres Jimenez


    We are developing a vaccine for toxoplasmosis, using ionizing radiation as a tool. Here we analyzed the production of systemic and intestinal immunity, with protection studies, in several strains of inbred mice, by oral or parenteral route, using 255 Gy irradiated tachyzoites of T. gondii RH strain, with challenge with cysts of ME- 49 strain. C57Bl/6j, BALB/c and C57Bl/6j IFN-{gamma}{sup -/-} mice were immunized with 10{sup 7} irradiated tachyzoites, be parenteral or oral route. Those preparations, both by parenteral or oral routes, induced the production of specific IgG, mainly of the lgG2b subclass, and IgA immunoglobulins in serum, , as determined by ELISA. IgM production was negligible. Parenteral immunized mice showed higher IgG avidity maturation, as compared to oral immunized mice. Fecal excretion of IgG, IgA and IgM was detected in stools of immunized animals, more intense in oral immunized mice. In cellular immunity studies, induced by antigen, with detection of cytokine production by quantitative real-time PCR, there are a great production of IFN-y by spleen cells, with lower levels in Peyer patches cells, where there are a greater IL-2 production. Challenge studies in immunized mice demonstrated protection to infection in all used schedules, greater in BALB/c mice. C57Bl/6j IFN-{gamma} -{sup /-} mice, when immunized, showed no signs of disease and produced similar or greater levels of antibodies than wild type mice. They also excreted S-lgA and S-IgM in stools, but with low numbers of brain cysts in parenteral immunized mice, despite similar mortality. Our data points to a fair possibility of use of those irradiated parasites as an oral vaccine, devised to use for veterinary or wild felines vaccination, reducing the production of oocysts by those hosts and interrupting the chain transmission of human toxoplasmosis. (author)

  19. Infusion of donor spleen cells and rejection in liver transplant recipients.

    Scornik, J C; Lauwers, G Y; Reed, A I; Howard, R J; Dickson, R C; Rosen, C B


    Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo-controlled trial to determine whether heat-treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat-treated (45 degrees C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One-yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p spleen cell group versus 1.3 + 1.7 for the placebo group (p = 0.034). It is concluded that heat-treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7-d protocol liver biopsies.

  20. Effects of 17β-estrodiol on the expression of estrogen receptor in spleen dendritic cells of lupus model-NZB/wF1 mice%雌二醇对NZB/wF1狼疮鼠脾脏树突状细胞雌激素受体表达的影响

    姜波; 杨希; 孙凌云; 侯亚义


    目的 通过检测系统性红斑狼疮(SLE)模型鼠脾脏树突状细胞(DC)中雌激素受体(ER)的表达及对体外雌激素的反应性是否异常,探索雌激素调控DC参与SEE发病的机制.方法 红细胞裂解法收集SLE模型鼠—NZB/wF1雌鼠及BALB/c雌鼠的脾脏单个核细胞,抗小鼠CD11c单抗标记磁珠纯化DC,以无酚红RPMI-1640及葡聚糖-活性炭处理的新生牛血清体外培养DC,加入不同浓度10-8 mol/L,10-7 mol/L,10-6 mol/L的雌二醇(E2)体外处理24h,RT-PCR检测DC胞内ER的mRNA水平.结果 两种小鼠脾DC均表达ERα,但不表达ERβ;NZB/wF1雌鼠脾DC的ERα基础表达显著高于同周龄的BALB/c雌鼠(0 mol/L组P<0.05);低浓度10-8 mol/L E2显著增加两种鼠脾DC的ERα表达(NZB/wF1鼠P<0.05,BALB/c鼠P<0.05),中浓度10-7 mol/L(NZB/wF1鼠P<0.05,BALB/c鼠P<0.05)和高浓度10-6 mol/L(NZB/wF1鼠P<0.05,BALB/c鼠P<0.05)E2显著降低两种鼠脾DC的ERα表达.结论 ER表达在狼疮鼠中存在明显异常,不同剂量雌激素对其受体调控作用不同,提示雌激素可能通过调控DC的ER参与SEE发病.%Objective To research the mechanism how estrogen abnormally modulates dendritic cells(DC) to involve in systemic lupus erythematosus(SLE) by investigating the expression of estrogen receptor(ER) in spleen DCs of SLE model mice and the reaction of ER to estrogen in vitro.Methods Harvest the spleen mononuclear cells of female NZB/wF1 and BALB/c mice by lysing erythrocytes.Monoclonal anti-mouse CD11c antibody-labeled bead was used to purify DCs from mononuclear cells.DC were cultured in phenol red-free RPMI1640 with 10% charcoaldextran treated fetal bovine serum and different concentration:10-8 mol/L,10-7 mol/L,10-6 mol/L of 17β-estrodiol (E2) for 24 hours.RT-PCR was used to detect the mRNA level of ER in E2-stimulated lymphocytes.Results The spleen DC of female NZB/wF1 and BALB/c mice both express the mRNA of ERα,but not ERβ.The expression of ERαin NZB/wF1 spleen DC

  1. Effect of LA on the Growth and Development of the Main Organs in Female Mice.

    He, Xiuyuan; Lin, Feng; Li, Yongtao; Chen, Yuxia; Li, Jing; Guo, Linlin; Han, Xuelei; Song, Huan


    Effects of lead acetate (LA) on the growth and development of major organs in female mice were studied. Female mice were divided randomly into four treatment groups and one control group. In treatment groups, mice were injected with different concentrations of LA solution every 2 days; whereas control-group mice received equal volumes of sterile normal saline. Body weight (BW) and symptoms were recorded every 2 days. After LA exposure, mice were executed by cervical dislocation and main organs (heart, liver, spleen, lung, kidney) collected for evaluation of morphologic and histologic changes. LA could greatly affect increases in BW, and BW decreased with increasing dose and time of exposure to LA. Compared with the control group, organ coefficients in treatment groups were of the order kidney and spleen > liver and lung > heart and demonstrated obvious dose-time effects. LA exposure could damage the heart, liver, spleen, lung, and kidney. Damage to the kidney and spleen was the most severe, followed by that to the liver, heart, and lung. Damage was aggravated with increasing doses and exposure time to LA in an obvious dose-time relationship; when LA dose was ≥20 mg/kg, the growth and development of mice were obviously inhibited. These results suggest that long-term exposure to low-dose LA can result in universal pathologic damage to mouse organs and that severity is dependent on the dose and duration of LA exposure.

  2. FoxO3a基因缺失致小鼠脾脏进行性慢性炎性反应的观察%Progressive chronic inflammatory reaction in spleens of FoxO3a gene knockout mice

    邱红; 陈晨; 王若立; 罗红; 赵宝霞


    目的 观察FoxO3a基因缺失致小鼠脾脏进行性慢性炎性反应.方法 分别于16周、24周和12个月称取FoxO3a基因敲除小鼠和对照小鼠体重;于16、24和38周处死各组小鼠,取脾脏,肉眼观察脾脏变化,并制备脾细胞悬液,进行细胞计数,同时取各组小鼠卵巢、肺及皮下等组织,观察其炎性变化.流式细胞术检测24周的FoxO3a基因敲除小鼠和对照小鼠脾细胞中T、B淋巴细胞和Mac-1+细胞数量及百分率;Real-time PCR检测脾细胞中炎性细胞因子S100A8和S100A9基因mRNA的表达水平.结果 与对照小鼠相比,FoxO3a基因敲除小鼠脾脏明显肥大,且随年龄增加更加显著,卵巢、肺及皮下等组织内可见大量炎性细胞浸润,脾细胞数明显升高;基因敲除组老年小鼠的体重明显低于对照小鼠;FoxO3a基因敲除小鼠的脾细胞中T、B淋巴细胞数增加明显,但所占脾细胞的百分率无明显增加,Mac-1+细胞数和百分率均明显增加;S100A8和S100A9基因mRNA的表达水平明显高于对照小鼠.结论 FoxO3a基因缺失致小鼠脾脏进行性慢性炎性反应.%Objective To observe the progressive chronic inflammatory reaction induced by Fox03a gene knockout in mice. Methods The bodyweights of Fox03a gene knockout and normal control mice were weighed at ages of 16 weeks, 24 weeks and 12 months separately. Partial mice in the two groups were killed at ages of 16, 24 and 38 weeks respectively, of which the spleens were collected, observed visually, prepared into splenocytes and counted. Meanwhile, the inflammatory reactions in various tissues including ovary, lung and subcutaneous tissues were observed. The counts and percentages of T and B lymphocytes and Mac-1+ cells in spleens of FoxO3a gene knockout and control mice at age of 24 weeks were determined by flow cytometry, while the expression levels of S100A8 and S100A9 mRNAs in splenocytes by real-time PCR. Results Compared with those of control mice, the


    Siva Chidambaram


    Full Text Available The Spleen is a large lymphoid organ situated in the left hypochondrial region having an important role in immunological and hematological functions of the human body. The aim of this study was to find the morphological variations of the spleen with respect to it’s a Shape, b Number of notches on its borders and c Presence of anomalous fissure on its surface. The Study was done on 60 formalin fixed cadaveric spleen from the Department of Anatomy, Narayana Medical College, Nellore, Andhra Pradesh. Out of 60 spleens we examined, the various shapes of the spleen were noted suc h as wedge shape (73.33%, triangular (13.33%, tetrahedral (6.67% and oval shape(6.67%.The number of spleen showing notches on its superior border was 38(63.33% and in inferior border it was 6(10%. Absence of splenic notch was observed in 10(16.67% s pleens and the remaining 6 spleens (10% shows notches on its both the borders. The anomalous splenic fissure was found in 4(6.67% spleens on its diaphragmatic surface. The knowledge of variations in the morphology of spleen are essential for physician, s urgeon, radiologist and forensic surgeon to differentiate it from the splenic pathology and splenic injury. In addition to this, it is also important for anatomist during routine classroom dissection and discussion.

  4. Dietary phytoestrogens present in soy dramatically increase cardiotoxicity in male mice receiving a chemotherapeutic tyrosine kinase inhibitor.

    Harvey, Pamela Ann; Leinwand, Leslie Anne


    Use of soy supplements to inhibit cancer cell growth is increasing among patients due to the perception that phytoestrogens in soy inhibit carcinogenesis via induction of apoptosis. Genistein, the most prevalent phytoestrogen in soy, is a potent endocrine disruptor and tyrosine kinase inhibitor (TKI) that causes apoptosis in many cells types. Chemotherapeutic TKIs limit cancer cell growth via the same mechanisms. However, TKIs such as Sunitinib cause cardiotoxicity in a significant number of patients. Molecular interactions between Sunitinib and dietary TKIs like genistein have not been examined in cardiomyocytes. Significant lethality occurred in mice treated with Sunitinib and fed a phytoestrogen-supplemented diet. Isolated cardiomyocytes co-treated with genistein and Sunitinib exhibited additive inhibition of signaling molecules important for normal cardiac function and increased apoptosis compared with Sunitinib alone. Thus, dietary soy supplementation should be avoided during administration of Sunitinib due to exacerbated cardiotoxicity, despite evidence for positive effects in cancer.

  5. Clinical application of laparoscopic spleen-preserving operation in traumatic spleen rupture

    SHEN Han-bin; LU Xiao-ming; ZHENG Qi-chang; CAI Xiao-tang; ZHOU Hong; FEI Ke-li


    Objective: To evaluate the effect of laparoscopic spleen-preserving operation for traumatic spleen rupture. Methods: From 1997 to 2003, 15 cases of traumatic spleen rupture were treated with laparoscopic spleen-preserving operation in our hospital. Nine cases had operation history in the middle and lower abdomen. ZT binding, electrocoagulation, fibrin and gelfoam tamping and suture repairing were used in patients with spleen rupture of grade I and grade II. Combined hemostasis was used for spleen rupture of grade III.Results: All patients did not need laparotomy during operation and no postoperative bleeding occurred. They were all cured and followed up for 3-12 months. Determination of immunoglobulinis after operation showed normal, and spleen ultrasonic examination, CT and body state evaluations were all satisfactory.Conclusions: Laparoscopy in the management of spleen trauma can be used in confirmed diagnosis and in determining the degree of spleen injury. For patients with stable vital signs laparoscopic spleen-preserving operation can be used. The laparoscopic spleen-preserving operation is safe in the treatment of traumatic spleen rupture.

  6. Liposomal Nanoparticles of a Spleen Tyrosine Kinase P-Site Inhibitor Amplify the Potency of Low Dose Total Body Irradiation Against Aggressive B-Precursor Leukemia and Yield Superior Survival Outcomes in Mice.

    Uckun, Fatih M; Myers, Dorothea E; Cheng, Jianjun; Qazi, Sanjive


    This study was designed to improve the efficacy of radiation therapy against radiation-resistant leukemia. We report that the potency of low dose radiation therapy against B-precursor acute lymphoblastic leukemia (BPL) can be markedly enhanced by combining radiation with a liposomal nanoparticle (LNP) formulation of the SYK-P-site inhibitor C61 ("C61-LNP"). C61-LNP plus low dose total body irradiation (TBI) was substantially more effective than TBI alone or C61-LNP alone in improving the event-free survival outcome NOD/SCID mice challenged with an otherwise invariably fatal dose of human ALL xenograft cells derived from relapsed BPL patients. C61-LNP plus low dose TBI also yielded progression-free survival, tumor-free survival and overall survival outcomes in CD22ΔE12 × BCR-ABL double transgenic mice with advanced stage, radiation-resistant BPL with lymphomatous features that were significantly superior to those of mice treated with TBI alone or C61-LNP alone.

  7. Human spleen and red blood cells

    Pivkin, Igor; Peng, Zhangli; Karniadakis, George; Buffet, Pierre; Dao, Ming


    Spleen plays multiple roles in the human body. Among them is removal of old and altered red blood cells (RBCs), which is done by filtering cells through the endothelial slits, small micron-sized openings. There is currently no experimental technique available that allows us to observe RBC passage through the slits. It was previously noticed that people without a spleen have less deformable red blood cells, indicating that the spleen may play a role in defining the size and shape of red blood cells. We used detailed RBC model implemented within the Dissipative Particle Dynamics (DPD) simulation framework to study the filter function of the spleen. Our results demonstrate that spleen indeed plays major role in defining the size and shape of the healthy human red blood cells.

  8. Protective effect of humus extract against Trypanosoma brucei infection in mice.

    Kodama, Hiroshi; Denso; Okazaki, Fumi; Ishida, Saeko


    Humic substances are formed during the decomposition of organic matter in humus, and are found in many natural environments in which organic materials and microorganisms are present. Oral administration of humus extract to mice successfully induced effective protection against experimental challenge by the two subspecies, Trypanosoma brucei brucei and T. brucei gambiense. Mortality was most reduced among mice who received a 3% humus extract for 21 days in drinking water ad libitum. Spleen cells from humus-administered mice exhibited significant non-specific cytotoxic activity against L1210 mouse leukemia target cells. Also, spleen cells produced significantly higher amounts of Interferon-gamma when stimulated in vitro with Concanavalin A than cells from normal controls. These results clearly show that administration to mice of humus extract induced effective resistance against Trypanosoma infection. Enhancement of the innate immune system may be involved in host defense against trypanosomiasis.

  9. Iron oxides in human spleen.

    Kopáni, Martin; Miglierini, Marcel; Lančok, Adriana; Dekan, Július; Čaplovicová, Mária; Jakubovský, Ján; Boča, Roman; Mrazova, Hedviga


    Iron is an essential element for fundamental cell functions and a catalyst for chemical reactions. Three samples extracted from the human spleen were investigated by scanning (SEM) and transmission electron microscopy (TEM), Mössbauer spectrometry (MS), and SQUID magnetometry. The sample with diagnosis of hemosiderosis (H) differs from that referring to hereditary spherocytosis and the reference sample. SEM reveals iron-rich micrometer-sized aggregate of various structures-tiny fibrils in hereditary spherocytosis sample and no fibrils in hemochromatosis. Hematite and magnetite particles from 2 to 6 μm in TEM with diffraction in all samples were shown. The SQUID magnetometry shows different amount of diamagnetic, paramagnetic and ferrimagnetic structures in the tissues. The MS results indicate contribution of ferromagnetically split sextets for all investigated samples. Their occurrence indicates that at least part of the sample is magnetically ordered below the critical temperature. The iron accumulation process is different in hereditary spherocytosis and hemosiderosis. This fact may be the reason of different iron crystallization.

  10. Automated segmentation of the injured spleen.

    Dandin, Ozgür; Teomete, Uygar; Osman, Onur; Tulum, Gökalp; Ergin, Tuncer; Sabuncuoglu, Mehmet Zafer


    To develop a novel automated method for segmentation of the injured spleen using morphological properties following abdominal trauma. Average attenuation of a normal spleen in computed tomography (CT) does not vary significantly between subjects. However, in the case of solid organ injury, the shape and attenuation of the spleen on CT may vary depending on the time and severity of the injury. Timely assessment of the severity and extent of the injury is of vital importance in the setting of trauma. We developed an automated computer-aided method for segmenting the injured spleen from CT scans of patients who had splenectomy due to abdominal trauma. We used ten subjects to train our computer-aided diagnosis (CAD) method. To validate the CAD method, we used twenty subjects in our testing group. Probabilistic atlases of the spleens were created using manually segmented data from ten CT scans. The organ location was modeled based on the position of the spleen with respect to the left side of the spine followed by the extraction of shape features. We performed the spleen segmentation in three steps. First, we created a mask of the spleen, and then we used this mask to segment the spleen. The third and final step was the estimation of the spleen edges in the presence of an injury such as laceration or hematoma. The traumatized spleens were segmented with a high degree of agreement with the radiologist-drawn contours. The spleen quantification led to [Formula: see text] volume overlap, [Formula: see text] Dice similarity index, [Formula: see text] precision/sensitivity, [Formula: see text] volume estimation error rate, [Formula: see text] average surface distance/root-mean-squared error. Our CAD method robustly segments the spleen in the presence of morphological changes such as laceration, contusion, pseudoaneurysm, active bleeding, periorgan and parenchymal hematoma, including subcapsular hematoma due to abdominal trauma. CAD of the splenic injury due to abdominal

  11. [The influence of some retarding agents NOS of dihydrothiazine-thiazoline rank on postradiational of recovery endogenous CFU-S-8 of mice].

    Konopliannikov, A G; Proskuriakov, S Ia; Konopliannikov, O A; Trishkina, A I; Shteĭn, L V; Verkhovskiĭ, Iu G; Kolesnikova, A I; Trofimova, T P; Mandrugin, A A; Fedoseev, V M; Bachurin, S O; Proshin, A N; Skvortsov, V G


    In this work the attempt to estimate a nitric oxide (NO*) role in regulation of the number of pool haemopoietic stem cells at the irradiated mice was made. With this purpose the number of new compounds from dihydrothiazine-thiazoline line was synthesized, their NO-inhibiting activity was investigated in vivo by the method of ESR-spectroscopy of spin trap and their influence on an output endogenous spleen colonies (CFU-S-8) after the total sublethal y-irradiation of mice in a doze of 6 Gy was also investigated. Was shown, that the tested compounds reduced the contents of NO* in a liver tissue of mice which have received an injection of nitric oxide synthesis inductor - lipopolysaccharide, and also increased an output CFU-S-8 forming endogenous colonies in the spleen of the irradiated mice. Received data testify to perceptivity of search radioprotective agents among NO* synthesis inhibitors.

  12. 五指毛桃药物血清对老龄小鼠脾淋巴细胞氧化损伤的影响%Effects of Drug-containing Serum of Ficus Hirta on Oxidative Damage of Spleen Lymphocyte in Aged Mice

    杨杰; 卫东锋; 王文潇; 程卫东


    Objective To study the effects of drug-containing serum of Ficus Hirta on oxidative damage of spleen lymphocyte due to aging in aged mice; To discuss its mechanism of action.Methods Forty aged mice were randomly divided into control group and high-, medium- and low-dose Ficus Hirta groups. Control group was given 0.9% sodium chloride solution for gavage, while high-, medium- and low-dose Ficus Hirta groups were given 6.6, 4.4, and 2.2 g/kg aqueous extract of Ficus Hirta for gavage. The spleen index was observed for optimum dose in aged mice. The optimum time and dilution of drug-containing serum of Ficus Hirta were confirmed by MTT method in lymphocyte proliferation test. The positive rate of senescent cells, the activity of T-SOD and the contents of MDA and ROS were determined in cellular antioxidant experiment after treated by optimal drug-containing serum for 48 h. Results Compared with the control group, the spleen index was significantly improved in high-, medium- and low-dose Ficus Hirta groups (P<0.05,P<0.01). 20% drug-containing serum of Ficus Hirta cultivated for 48 h had the best effects on lymphocyte proliferation in aged mice. 20% drug-containing serum of Ficus Hirta could significantly decrease the positive rate of senescent cells (P<0.01), improve T-SOD activity and decrease the contents of MDA and ROS (P<0.05,P<0.01).Conclusion The drug-containing serum of Ficus Hirta can improve the proliferative activity of spleen lymphocyte in aged mice and the mechanism of action may be involved in decreasing the positive rate of senescent cells and increasing antioxidant ability of lymphocyte.%目的:观察五指毛桃药物血清对老龄小鼠衰老所致脾淋巴细胞氧化损伤的影响,探讨其作用机制。方法将40只老龄小鼠随机分为空白对照组和五指毛桃高、中、低剂量组,分别给予0.9%氯化钠溶液和6.6、4.4、2.2 g/kg五指毛桃水提物灌胃,测定脾脏指数,确定五指毛桃水提物的最佳剂量,

  13. A wandering spleen: A common presentation of an uncommon ...

    Wandering spleen is a rare entity with less than 500 cases reported in literature so far. Method: This case report ... spleen.7 The noninvasiveness of ultrasonography makes ... Abell I. Wandering spleen with torsion of the pedicle. Ann Surg ...

  14. Effects of BCG Vaccination on Specific Antibodies in Serum and Ex-pression of Immunity-related Cytokines in Spleen from Mice%BCG免疫对小鼠血清特异性抗体与脾脏免疫相关细胞因子表达的影响∗

    武月章; 安潇潇; 张文慧; 张林波


    为深入了解卡介苗诱导机体产生免疫效应的分子机制,对卡介苗( Bacillus calmettee⁃guerin,BCG)免疫后小鼠血清特异性抗体与脾脏免疫相关细胞因子表达变化及相关性进行了研究。利用BCG免疫C57BL/6小鼠,采集不同时间点的外周血和脾脏样本。应用间接ELISA方法检测血清中特异性抗体效价,实时荧光定量PCR方法检测脾脏中免疫相关细胞因子表达水平。结果表明:在BCG接种的后期,血清中抗体效价呈极显著的上升趋势( P<0�01);脾脏中Th1型细胞因子白细胞介素⁃2( Interleukin⁃2,IL⁃2)、γ干扰素( Interferon⁃γ, IFN⁃γ)的表达水平与对照组相比呈显著性上升( P<0�05),但Th2型细胞因子白细胞介素⁃4( Interleukin⁃4,IL⁃4)的表达水平则明显下降( P<0�05)。这说明BCG免疫后,机体会同时产生细胞免疫应答和体液免疫应答,但免疫后期Th1型细胞因子与体液免疫效应呈正相关,某些Th2型细胞因子则与体液免疫效应呈负相关性。%In order to understand immune mechanism induced by Bacillus Calmettee⁃Guerin( BCG) in vivo, experiments were carried out to study effects of BCG vaccination on specific antibodies in serum and expression of immunity⁃related cytokines in spleen from mice. Peripheral blood and spleen from C57BL/6 mice vaccinated with BCG were collected at different time points. Then specific anti⁃bodies in serum were detected by indirect ELISA, and expression of immunity⁃related cytokines in spleen were detected by real⁃time quantitative PCR. The results showed that value of specific anti⁃bodies was in a significant increase trend in the late stage of vaccination (P<0�01). In addition, expression of Th1 type cytokine interleukin⁃2(IL⁃2), interferon⁃γ(IFN⁃γ) was increased, and difference was significant( P<0�05) . However, expression of Th2 type cytokine interleukin⁃4

  15. Insulin-producing cells from embryonic stem cells rescues hyperglycemia via intra-spleen migration.

    Ren, Meng; Shang, Changzhen; Zhong, Xiaomei; Guo, Ruomi; Lao, Guojuan; Wang, Xiaoyi; Cheng, Hua; Min, Jun; Yan, Li; Shen, Jun


    Implantation of embryonic stem cells (ESC)-derived insulin-producing cells has been extensively investigated for treatment of diabetes in animal models. However, the in vivo behavior and migration of transplanted cells in diabetic models remains unclear. Here we investigated the location and migration of insulin-producing cells labeled with superparamagnetic iron oxide (SPIO) using a dynamic MRI tracking method. SPIO labeled cells showed hypointense signal under the kidney subcapsules of diabetic mice on MRI, and faded gradually over the visiting time. However, new hypointense signal appeared in the spleen 1 week after transplantation, and became obvious with the time prolongation. Further histological examination proved the immigrated cells were insulin and C-peptide positive cells which were evenly distributed throughout the spleen. These intra-spleen insulin-producing cells maintained their protective effects against hyperglycemia in vivo, and these effects were reversed upon spleen removal. Transplantation of insulin-producing cells through spleen acquired an earlier blood glucose control as compared with that through kidney subcapsules. In summary, our data demonstrate that insulin-producing cells transplanted through kidney subcapsules were not located in situ but migrated into spleen, and rescues hyperglycemia in diabetic models. MRI may provide a novel tracking method for preclinical cell transplantation therapy of diabetes continuously and non-invasively.

  16. Auxiliary liver organ formation by implantation of spleen-encapsulated hepatocytes.

    Nishio, Reiji; Nakayama, Miyuki; Ikekita, Masahiko; Watanabe, Yoshifumi


    Hepatocyte transplantation is an attractive alternative to orthotopic liver transplantation. However, its application has been limited because of its short-term success only. Here we report a new approach to hepatocyte transplantation resulting in the generation of an auxiliary liver in vivo. Isolated primary hepatocytes were encapsulated in isolated spleens and then transplanted by attaching the spleens to the livers of recipient animals (mice or rats) using biodegradable adhesive. A vascular network was rapidly established, and protein molecules circulated freely between the transplanted spleen and the liver, to which they adhered. In contrast, the spleen, which did not adhere to the liver or adhered elsewhere (adipose tissue or peritoneum), did not become vascularized but shrank and died. Encapsulation of hepatocytes in an isolated spleen enhanced their survival significantly, and co-encapsulation of Engelbreth- Holm-Swarm gel together with the hepatocytes further enhanced it. The encapsulated hepatocytes expressed liver-specific differentiation genes for more than 3 weeks. Plasma albumin concentrations in Nagase analbuminemic rats began to increase 3 days after transplantation. The transplanted hepatic cells migrated into the liver parenchyma, whereas the spleen was absorbed. Thus, we have developed a novel, simple approach for the rapid and efficient formation of functional auxiliary liver using a modified hepatocyte transplantation method.

  17. Liver and spleen elastography in patients with diffuse liver diseases

    Alexey Borsukov


    Full Text Available The purpose of the research was to estimate the clinical-diagnostic and predictive value of non-invasive ultrasonic elastography in dynamic monitoring in patients with diffuse liver disease. A number of 114 patients with diffuse liver disease were examined, specifically 68 (59.6% men and 46 (40.4% women. The patients were divided into three groups: 40 patients with steatosis; 38 with hepatitis; 36 with cirrhosis. The research included clinical and bio-chemical analysis, ultrasound examination of liver and spleen with doppler v. portae and v. lienalis, elastography of liver and spleen. The study found a high correlation of elastography data as regards the liver and spleen in patients with alcoholic cirrhosis (r=0.96, average correlation (r=0.69 in patients with steatosis and hepatitis of alcoholic etiology. On the basis of the statistical program receiver operating characteristic (ROC-analysis it was ascertained that the spleen is in perfect condition (AUC 0.9-1.0, and the liver is in a very good condition (0.8-0.9. The research revealed therapeutically significant factor ΔF/ΔL for dynamic monitoring: the ΔF/ΔL 1 can predict a more favorable course of the disease. Noninvasive ultrasound elastography helps to forecast the process of the disease and correct the therapeutic approach. The research contributes to the search for additional and reliable techniques of identifying the stage of disease of patients with hepatic fibrosis, the dynamics of the disease as well as forecasting further complications.

  18. Essential role of TNF-alpha in development of spleen fibroblastic reticular cells.

    Zhao, Lintao; Chen, Junying; Liu, Lina; Gao, Jianbao; Guo, Bo; Zhu, Bo


    TNF-alpha plays an important role in the development of secondary lymphoid tissues. Earlier studies showed that fibroblastic reticular cells express TNF-alpha receptor, suggesting that TNF-alpha may affect the development of FRCs. To test this, we analyzed the development and function of FRCs in wild-type or TNF-alpha knockout mice. We found that GP38 expression was down-regulated in the spleen of TNF-alpha knockout mice. Chemokines, mainly secreted by GP38(+) FRCs, were also down-regulated. Additionally, we found that absence of TNF-alpha decreased the homing ability to direct T cells to the spleen. However, absence of TNF-alpha did not affect the development of lymph nodes FRCs. These data reveal that TNF-alpha plays an important role in the development of spleen FRCs. Absence of TNF-alpha could cause abnormality of spleen FRCs, thereby weakening the homing ability of T cells to localize to the spleen T cell zone.

  19. Localized SCF and IGF-1 secretion enhances erythropoiesis in the spleen of murine embryos

    Keai Sinn Tan


    Full Text Available Fetal spleen is a major hematopoietic site prior to initiation of bone marrow hematopoiesis. Morphologic analysis suggested erythropoietic activity in fetal spleen, but it remained unclear how erythropoiesis was regulated. To address this question, we performed flow cytometric analysis and observed that the number of spleen erythroid cells increased 18.6-fold from 16.5 to 19.5 days post-coitum (dpc. Among erythropoietic cytokines, SCF and IGF-1 were primarily expressed in hematopoietic, endothelial and mesenchymal-like fetal spleen cells. Cultures treated with SCF and/or IGF-1R inhibitors showed significantly decreased CD45−c-Kit−CD71+/−Ter119+ erythroid cells and downregulated Gata1, Klf1 and β-major globin expression. Administration of these inhibitors to pregnant mice significantly decreased the number of CD45−c-Kit−CD71+/−Ter119+ cells and downregulated β-major globin gene expression in embryos derived from these mice. We conclude that fetal spleen is a major erythropoietic site where endothelial and mesenchymal-like cells primarily accelerate erythropoietic activity through SCF and IGF-1 secretion.

  20. Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development

    Lenti, Elisa; Farinello, Diego; Penkov, Dmitry; Castagnaro, Laura; Lavorgna, Giovanni; Wuputra, Kenly; Tjaden, Naomi E. Butler; Bernassola, Francesca; Caridi, Nicoletta; Wagner, Michael; Kozinc, Katja; Niederreither, Karen; Blasi, Francesco; Pasini, Diego; Trainor, Paul A.


    The molecular mechanisms that underlie spleen development and congenital asplenia, a condition linked to increased risk of overwhelming infections, remain largely unknown. The transcription factor TLX1 controls cell fate specification and organ expansion during spleen development, and Tlx1 deletion causes asplenia in mice. Deregulation of TLX1 expression has recently been proposed in the pathogenesis of congenital asplenia in patients carrying mutations of the gene-encoding transcription factor SF-1. Herein, we have shown that TLX1-dependent regulation of retinoic acid (RA) metabolism is critical for spleen organogenesis. In a murine model, loss of Tlx1 during formation of the splenic anlage increased RA signaling by regulating several genes involved in RA metabolism. Uncontrolled RA activity resulted in premature differentiation of mesenchymal cells and reduced vasculogenesis of the splenic primordium. Pharmacological inhibition of RA signaling in Tlx1-deficient animals partially rescued the spleen defect. Finally, spleen growth was impaired in mice lacking either cytochrome P450 26B1 (Cyp26b1), which results in excess RA, or retinol dehydrogenase 10 (Rdh10), which results in RA deficiency. Together, these findings establish TLX1 as a critical regulator of RA metabolism and provide mechanistic insights into the molecular determinants of human congenital asplenia. PMID:27214556

  1. Sonographic evaluation of spleen size and prevalence of accessory spleen in a healthy male Turkish population

    Selim Serter


    Full Text Available Objective: It is known that the measurement of splenic length in routine clinical practice is a very good indicator of actual splenic size. Knowledge of the normal range of spleen size in the population being examined is a prerequisite. Racial differences in splenic length could result in incorrect interpretation of splenic measurements. The purpose of this study was to establish the range of spleen length in a young male Turkish population.Material and Methods: A total of 2179 volunteers, healthy men aged 17-42 years, from the annual Army Reserve Officer Training Corps training camp at Manisa were included in the study. Sonographic measurements of spleen length were performed on 2179 military personnel. Presence of accessory spleen was also determined. In addition, the height, weight, and age of each volunteer were recorded. Using linear regression analysis, the relation of spleen length and body height, weight and body mass index (BMI was evaluated. Additionally, the prevalence of accessory spleen detected on ultrasound was calculated.Results: The mean±SD height was 173,1±6,5 cm, mean weight 69,1±9,7 kg, and mean BMI 22,62±2,87. Mean spleen length was 10,76±1,8 cm. The length of the spleen was below 12,80 cm in 95% of the subjects. No statistically significant correlation (p<0.01 between spleen length and body height, weight and BMI was found. The prevalence of accessory spleen was determined as 2.5% on ultrasound screening.Conclusion: It was found that in healthy Turkish men, mean spleen length was 10,76±1,8 cm. This data should be taken into consideration when the diagnosis of splenomegaly is established in Turkish males.

  2. Generation of a Tlx1(CreER-Venus) knock-in mouse strain for the study of spleen development.

    Nakahara, Ryo; Kawai, Yasuhiro; Oda, Akihisa; Nishimura, Miyuki; Murakami, Akikazu; Azuma, Takachika; Kaifu, Tomonori; Goitsuka, Ryo


    The spleen is a lymphoid organ that serves as a unique niche for immune reactions, extramedullary hematopoiesis, and the removal of aged erythrocytes from the circulation. While much is known about the immunological functions of the spleen, the mechanisms governing the development and organization of its stromal microenvironment remain poorly understood. Here we report the generation and analysis of a Tlx1(Cre) (ER) (-Venus) knock-in mouse strain engineered to simultaneously express tamoxifen-inducible CreER(T2) and Venus fluorescent protein under the control of regulatory elements of the Tlx1 gene, which encodes a transcription factor essential for spleen development. We demonstrated that Venus as well as CreER expression recapitulates endogenous Tlx1 transcription within the spleen microenvironment. When Tlx1(Cre) (ER) (-Venus) mice were crossed with the Cre-inducible reporter strain, Tlx1-expressing cells as well as their descendants were specifically labeled following tamoxifen administration. We also showed by cell lineage tracing that asplenia caused by Tlx1 deficiency is attributable to altered contribution of mesenchymal cells in the spleen anlage to the pancreatic mesenchyme. Thus, Tlx1(Cre) (ER) (-Venus) mice represent a new tool for lineage tracing and conditional gene manipulation of spleen mesenchymal cells, essential approaches for understanding the molecular mechanisms of spleen development.

  3. Benzo(a)pyrene metabolism by murine spleen microsomes

    Kawabata, T.T.; White, K.L. Jr. (Virginia Commonwealth Univ., Richmond (USA))


    The immunosuppressive actions of benzo(a)pyrene have been proposed to be mediated by reactive metabolites rather than the parent compound. Reactive metabolites which suppress splenic humoral immune responses are thought to be generated within the spleen rather than in distant tissues. Although the spleen has been shown to be capable of metabolizing benzo(a)pyrene, the relative amounts and types of metabolites generated have not been determined. In this study, high-pressure liquid chromatography was used to separate benzo(a)pyrene metabolites generated by splenic microsomes. The major metabolites generated by the splenic microsomal preparations of untreated female B6C3F1 mice were found to be the 9,10- and 7,8-dihydrodiols and 9-, 7-, and 3-hydroxy benzo(a)pyrene. The 1,3-, 3,6-, and 6,12-diones and 4,5-dihydrodiol constituted only a small fraction of the metabolites generated. The generation of all metabolites were inhibited by alpha-naphthoflavone and antiserum to NADPH-cytochrome P-450 reductase, whereas SKF 525-A had only a minimal effect. Dihydrodiol production was completely inhibited by the epoxide hydrolase inhibitor, trichloropropylene oxide. Benzo(a)pyrene pretreatment of mice produced a dramatic increase in the amount of metabolites formed; however, the pattern of metabolites remained similar to that generated by splenic microsomes of untreated mice. The role of prostaglandin synthetase in generating these metabolites was also examined. The addition of arachidonic acid in place of NADPH resulted in the formation of only quinones. Dihydrodiols and phenols were undetectable. The results of this study indicate that splenocytes may be capable of generating the 7,8-dihydrodiol, the precursor to the highly reactive 7,8-dihydrodiol-9,10-epoxide.

  4. The mouse spleen white pulp response to continuous hypoxia. A digital image processing analysis.

    Nessi de Aviñón, A C; Bengtsson, M C


    Ninety days old male mice of the CFW strain, placed under standard conditions for studies of periodicity, showed a 24 hours variation pattern in the spleen white pulp surface, in cross sections. This pattern was modified by hypoxia during the first 18 hours of continuous treatment. Since this time onwards a new steady state was reached, although the spleen of hypoxic animals was always smaller than in the controls. As the modifications were measured in pixel counts -a magnitude which can be easily transformed into square micrometers- they can be attributed to a real size variation and not to an apparent growth and decay due to environmental vasoactive phenomena.

  5. Function of the replanted spleen in dogs

    Velcek, F.T.; Kugaczewski, J.T.; Jongco, B.; Shaftan, G.W.; Rao, P.S.; Schiffman, G.; Kottmeier, P.K.


    The function of replanted splenic fragments was studied by comparing three groups of five dogs each, one group with intact spleens; one, post-splenectomy; and one with splenic replantation. Fifteen fragments were implanted into the omentum. Howell-Jolly bodies appeared after splenectomy but cleared in the replanted group after several months. /sup 125/I-tagged attenuated pneumococcal clearance studies showed a significant difference between control and replanted group compared with the splenectomized group. The increase of pneumococcal antibody titers after vaccination differed significantly between the splenectomized and the replanted group. All replanted fragments were viable and showed growth over a 2-year period. These studies demonstrate that omental replantation of the canine spleen leads to the maintenance of certain functional splenic parameters comparable to the normal spleen which are significantly different from the splenectomized animal.

  6. Morphological study of the dove spleen.

    Nasu, T; Shimizu, K; Nakai, M


    The spleen and vascular resin cast from doves were observed by a light and a scanning electron microscope for the purpose of studying the histological structure and the mode of the splenic blood microcirculation. The trabeculae of the dove spleen were poorly developed and the white and red pulps could not be distinguished from each other as is also the case of the chicken spleen. The luminal surface of the sinus was covered by continuous endothelial cells that had nuclear protrusion into the lumen. The blood cells passed to the sinus via the small gap of the luminal surface of the sinus. Irregular resin masses that connected the terminal portion of the artery with the venous sinus were observed. The direct connection between the arterial terminalis and venous sinus could not be recognized. When the resin was injected retrograde to blood flow from the vein, the sinus ended blindly.

  7. In vivo nitrogen dioxide exposure depresses spleen cell in vitro mitogenic responses: effects of sulfur compounds

    Azoulay-Dupuis, E.; Gougerot-Pocidalo, M.A.; Kraus, L.; Moreau, J.


    The in vivo mitogenic responses to lipopolysaccharide or concanavalin A by spleen cells of mice exposed to 20 ppm nitrogen dioxide (NO/sub 2/) for 96 hr, were evaluated. (/sup 3/H)Thymidine incorporation after addition of either mitogen, was significantly lower in spleen cells from acutely NO/sub 2/-exposed mice (NO/sub 2/SC) than from control mice, although cell viability was not affected. T- and B-cell mitogenic responses were inhibited to the same extent by NO/sub 2/ exposure. NO/sub 2/SC responses were protected by the thiol compounds 2-mercaptoethanol, L-cysteine, and selenomethionine. No restoration of mitogenic response was observed after treatment with reduced glutathione. Mechanisms accounting for this in vivo NO/sub 2/ immune toxicity, are discussed in terms of oxidative injury.

  8. 21 cases reports on haemangioma of spleen.

    Huang, Yuan; Mu, Guangchuan; Qin, Xingan; Lin, Jinling; Li, Shaosen; Zeng, Yanjun


    The growing activity of hemangioma of spleen keeps unknown. To search theoretical basis for whether to take the operation, this study analyzed clinical data of 21 hemangioma patients, and 16 surgical specimens were analyzed immunohistochemistry of Ki-67, Bcl-2 and vascular endothelial growth factor (VEGF). Both 14 cases of cavernous hemangioma were positive for VEGF, and negative in capillary hemangioma, there was statistical significant difference between two types of hemangioma (P Hemangioma of spleen was one benign tumor with a tendency of slow growth. Therefore, operation should be strictly selected, we recommend observation of patients with small, asymptomatic splenic lesions, which meet the radiologic criteria for hemangiomas.

  9. Ferritin surplus in mouse spleen 14 months after intravenous injection of iron oxide nanoparticles at clinical dose

    Alexandre Tamion; Matthias Hillenkamp; Arnaud Hillion; Valentin A.Maraloiu; Ioana D.Vlaicu; Mariana Stefan; Daniela Ghica


    In this study,we followed the biodegradation of ultra-small superparamagnetic iron oxide nanoparticles injected intravenously at clinical doses in mice.An advanced fitting procedure for magnetic susceptibility curves and lowtemperature hysteresis loops was used to fully characterize the magnetic size distribution as well as the magnetic anisotropy energy of the injected P904 nanoparticles (Guerbet Laboratory).Additional magnetometry measurements and transmission electronic microscopy observations were systematically performed to examine dehydrated samples from the spleen and liver of healthy C57B16 mice after nanoparticle injection,with sacrifice of the mice for up to 14 months.At 3 months after injection,the magnetic properties of the spleen and liver were dramatically different.While the liver showed no magnetic signals other than those also present in the reference species,the spleen showed an increased magnetic signal attributed to ferritin.This surplus of ferritin remained constant up to 14 months after injection.

  10. TRPV1 Antagonism by Capsazepine Modulates Innate Immune Response in Mice Infected with Plasmodium berghei ANKA

    Elizabeth S. Fernandes


    Full Text Available Thousands of people suffer from severe malaria every year. The innate immune response plays a determinant role in host’s defence to malaria. Transient receptor potential vanilloid 1 (TRPV1 modulates macrophage-mediated responses in sepsis, but its role in other pathogenic diseases has never been addressed. We investigated the effects of capsazepine, a TRPV1 antagonist, in malaria. C57BL/6 mice received 105 red blood cells infected with Plasmodium berghei ANKA intraperitoneally. Noninfected mice were used as controls. Capsazepine or vehicle was given intraperitoneally for 6 days. Mice were culled on day 7 after infection and blood and spleen cell phenotype and activation were evaluated. Capsazepine decreased circulating but not spleen F4/80+Ly6G+ cell numbers as well as activation of both F4/80+and F4/80+Ly6G+ cells in infected animals. In addition, capsazepine increased circulating but not spleen GR1+ and natural killer (NK population, without interfering with natural killer T (NKT cell numbers and blood NK and NKT activation. However, capsazepine diminished CD69 expression in spleen NKT but not NK cells. Infection increased lipid peroxidation and the release of TNFα and IFNγ, although capsazepine-treated group exhibited lower levels of lipid peroxidation and TNFα. Capsazepine treatment did not affect parasitaemia. Overall, TRPV1 antagonism modulates the innate immune response to malaria.

  11. Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl4-treated mice

    Kei Moriya; Masahide Yoshikawa; Ko Saito; Yukiteru Ouji; Mariko Nishiofuku; Noriko Hayashi; Shigeaki Ishizaka; Hiroshi Fukui


    AIM: To transplant undifferentiated embryonic stem (ES) cells into the spleens of carbon tetrachloride (CCl4)-treated mice to determine their ability to differentiate into hepatocytes in the liver.METHODS: CCU, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 (n = 12), 1 x 105 undifferentiated ES cells (0.1 mL of 1 x 106/mL solution), genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice (n = 12) were injected with 0.2 mL of saline twice a week, instead of CCU, and the same amount of ES cells was transplanted into the spleens. Group 3 mice (n = 6) were treated with CCU and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d (PD) 10, 20, and 30.RESULTS: Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice (CCl4-treated) on PD 10, however, not in those untreated with CCl4 (group 2). The GFP-positive cells were also immunopositive for albumin (ALB), alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period.CONCLUSION: Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth.

  12. SH-2-containing protein tyrosine phosphatase 1 is required for IL-4-induced IL-4R expression in spleen cells

    CAO Xin; HUANG Zan; FAN Jingyi


    To investigate the role of SH-2-containing protein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA expression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4RαmRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rαprotein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the percentages of CD4+, CD8+, and CD19+ cells expressing relatively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4RαmRNA expression was comparable in spleen cells of littermate control mice (+/() and mev/mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macrophages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis.

  13. Influence of thymodepressine on the course of autoimmune process in MRL/1 female mice

    V A Nassonova


    Full Text Available Objective. To assess efficacy of new immunoactive peptide thymodepressine (TD selectively inhibiting T-cell immunity in rheumatic diseases Methods. Spleen, kidneys and synovial membrane morphological changes and survival were assessed in 100 MRL/1 female mice. 20 and 40 per animal TD injections in doses 10 mcg/kg and 10+100 mcg/kg were made. Control group animals received placebo (saline solution. Results were assessed by double blind method. Results. Survival of treated mice (10+100 mcg/kg at the 6 months age was two times higher than in control group. Morphometric indices of immunogenesis in spleen of treated animals were comparable with parameters of one month age mice. White and red pulp area, number of mature and immature plasmacytes per 1 mm 2, number of megacariocytes were increased. Results of the spleen examination shows immunosuppressive action of TD suppressing lymphoprolipherative process and increasing survival of animals having lpr/lpr gen. But TD does not influence course of autoimmune process providing rheumatoid like changes in kidneys and synovial membrane of mice. Conclusion. TD has dose-dependent effect on survival and morphological indices in MRL/1 mice. Survival of animals at dose 10+100 mcg/kg was higher but dose 10 mcg/kg more expressively effected morphological indices of immuno- and hemopoiesis. Additional examinations are needed to determine optimal dose and scheme of treatment.

  14. Avermectin induced autophagy in pigeon spleen tissues.

    Liu, Ci; Zhao, Yanbing; Chen, Lijie; Zhang, Ziwei; Li, Ming; Li, Shu


    The level of autophagy is considered as an indicator for monitoring the toxic impact of pesticide exposure. Avermectin (AVM), a widely used insecticide, has immunotoxic effects on the pigeon spleen. The aim of this study was to investigate the status of autophagy and the expression levels of microtubule-associated protein1 light chain 3 (LC3), beclin-1, dynein, autophagy associated gene (Atg) 4B, Atg5, target of rapamycin complex 1 (TORC1) and target of rapamycin complex 2 (TORC2) in AVM-treated pigeon spleens. Eighty two-month-old pigeons were randomly divided into four groups: a control group, a low-dose group, a medium-dose group and a high-dose group, which were fed a basal diet spiked with 0, 20, 40 and 60 mg AVM/kg diet, respectively. Microscopic cellular morphology revealed a significant increase in autophagic structures in the AVM-treated groups. The expression of LC3, beclin-1, dynein, Atg4B and Atg5 increased, while mRNA levels of TORC1 and TORC2 were decreased in the AVM-treated groups relative to the control groups at 30, 60 and 90 days in the pigeon spleen. These results indicated that AVM exposure could up-regulate the level of autophagy in a dose-time-dependent manner in the pigeon spleen.

  15. Inflammatory pseudotumor of spleen: a case report

    Paúl Ugalde


    Conclusion: Inflammatory pseudotumor of spleen is a benign disease, in which diagnostic approach must bear in mind the possibility of a malignant lesion. For this reason, the surgical approach is appropriate to confirm the diagnosis and rule out malignancy with histology.

  16. Distal splenorenal shunt with partial spleen resection

    Gajin Predrag


    Full Text Available Introduction: Hypersplenism is a common complication of portal hypertension. Cytopenia in hypersplenism is predominantly caused by splenomegaly. Distal splenorenal shunt (Warren with partial spleen resection is an original surgical technique that regulates cytopenia by reduction of the enlarged spleen. Objective. The aim of our study was to present the advantages of distal splenorenal shunt (Warren with partial spleen resection comparing morbidity and mortality in a group of patients treated by distal splenorenal shunt with partial spleen resection with a group of patients treated only by a distal splenorenal shunt. Method. From 1995 to 2003, 41 patients with portal hypertension were surgically treated due to hypersplenism and oesophageal varices. The first group consisted of 20 patients (11 male, mean age 42.3 years who were treated by distal splenorenal shunt with partial spleen resection. The second group consisted of 21 patients (13 male, mean age 49.4 years that were treated by distal splenorenal shunt only. All patients underwent endoscopy and assessment of oesophageal varices. The size of the spleen was evaluated by ultrasound, CT or by scintigraphy. Angiography was performed in all patients. The platelet and white blood cell count and haemoglobin level were registered. Postoperatively, we noted blood transfusion, complications and total hospital stay. Follow-up period was 12 months, with first checkup after one month. Results In the first group, only one patient had splenomegaly postoperatively (5%, while in the second group there were 13 patients with splenomegaly (68%. Before surgery, the mean platelet count in the first group was 51.6±18.3x109/l, to 118.6±25.4x109/l postoperatively. The mean platelet count in the second group was 67.6±22.8x109/l, to 87.8±32.1x109/l postoperatively. Concerning postoperative splenomegaly, statistically significant difference was noted between the first and the second group (p<0.05. Comparing the

  17. 肝卵圆细胞与骨髓间质干细胞经脾移植治疗实验性小鼠肝纤维化的疗效比较%Compare the effect of hepatic oval cells and bone marrow mesenchymal stem cells transplanted by spleen to treat liver fibresis in mice

    刘波; 林楠; 胡鲲鹏


    目的 比较肝卵圆细胞(Hot)与骨髓间充质干细胞(MSC)治疗小鼠肝纤维化的疗效.方法 以含浓度为0.1%的3,5-二乙酯基-1,4二氢三甲基吡啶(DDC)喂养C57BL/6小鼠,建立小鼠肝卵圆细胞增殖模型,而后利用胶原酶原位灌注及percoll密度梯度离心法分离肝脏非实质细胞,再用免疫磁珠分离纯化出Sca-1阳性的肝卵圆细胞.利用四氯化碳(CCl4)皮下注射诱导小鼠肝纤维化模型.最后经脾分别输入卵圆细胞、骨髓间充质干细胞或生理盐水(NS).4周后观察肝功能各项指标、羟脯氨酸及肝脏的病理改变,比较各组间的差别.结果 在继续注射CCl4的情况下,HOC移植与MSC移植治疗均能改善肝纤维化小鼠的肝功能,降低肝脏羟脯氨酸含量,缓解肝纤维化,但HOC移植组更加明显(P0.05).结论 肝卵圆细胞经脾注射移植后,能改善肝硬化小鼠的肝功能,减轻其肝纤维化的程度,且效果比骨髓间充质干细胞更明显.%Objective To compare the effect of hepatic oval cells and bone marrow mesenchymal stem cells to treat liver fibrosis in mice. Methods The C57BL/6 mice were fed with 3,5-diethoxycarbonyl-1, 4-dihydro-collidine (DDC) in a standard food at a concentra-tion of 0.1% to activate the oval cells proliferation, then the nonparenchymal cells were separated by in situ perfusion and density gradient centrifugation, and finally Sca-1 antibody was used in conjunction with magnetic activated cell sorting (MACS) to separate the Sca-1 +cells. Other mice were injected subcutaneously with CCl4 to establish experimental liver fibrosis model. Finally, the fibrosis mice were trans-planted with HOC or MSC or saline by spleen injection according to the group they belonged to. Four weeks later, the liver function index, the hydroxyproline and the histopathological change among the groups were used to evaluate the effect of the treatment. Result The liver function index was improved after transplantation. HOC and MSE

  18. Dendritic cells derived exosomes migration to spleen and induction of inflammation are regulated by CCR7

    Wei, Gao; Jie, Yuan; Haibo, Liu; Chaoneng, Wu; Dong, Huang; Jianbing, Zhu; Junjie, Guo; Leilei, Ma; Hongtao, Shi; Yunzeng, Zou; Junbo, Ge


    Mature dendritic cells (DCs) home to secondary lymphoid organs through CC chemokine receptor 7 (CCR7). Exosomes derived from DCs (DC-exos) are reported to migrate to spleen and induce inflammation in vivo. In this study, we demonstrated that mature bone marrow DC-exos can activate immature DC and T cells in vitro. Then we intravenously injected DC-exos into C57BL/6 mice, observing that mature DC-exos accumulated more in spleen than immature DC-exos. These DC-exos in spleen could be uptaken by splenetic DCs and T cells and induce an inflammatory response. We further showed that the increased accumulation of mature DC-exos in spleen was regulated by CCR7, whose reduction led to a decrease of accumulation in spleen and attenuated inflammatory response in serum. These data provide us a new perspective to comprehensively understand exosomes, which might inherit some special functions from their parent cells and exert these functions in vivo. PMID:28223684

  19. Scrapie strains retain their distinctive characteristics following passages of homogenates from different brain regions and spleen.

    Carp, R I; Meeker, H; Sersen, E


    The molecular basis of differences among scrapie strains is unknown. The prion theory posits that there are differences in the conformation of the host protease-resistant protein (PrP) molecules and that these differences are responsible for scrapie strains. A corollary of this theory is that the origin of host PrP variation resides in different neuronal cell types. To assess this concept, preparations from three brain regions (cerebrum, cerebellum and olfactory bulb) and from spleen were passaged in C57BL mice by intracerebral injection. After three passages of three scrapie strains in this manner, homogenates of each brain region and spleen were tested for several of the characteristics that distinguish the three strains: (1) the rank order of incubation periods in C57BL mice, (2) induction of obesity in SJL mice and (3) comparative incubation periods in mice with three genotypes for the scrapie incubation period marker. Analysis revealed that virtually all of the criteria that distinguished the three strains prior to passages of the three brain regions and spleen were retained after this series of passages. This finding argues against cellular-based PrP differences providing a basis for strain specificity.

  20. Melanoma metastasis to the spleen: Laparoscopic approach

    Trindade Manoel Roberto


    Full Text Available We report a case of minimally invasive surgery in the management of metastasis to the spleen. A 67-year-old male patient with possible splenic soft tissue melanoma metastasis was referred to our hospital. He had a history of an excised soft tissue melanoma from his back eight months earlier, and the control abdominal computer tomography (CT scan revealed a hypodense spleen lesion. The patient underwent laparoscopic surgery to diagnose and treat the splenic lesion. The splenectomy was performed and the histological examination revealed a melanoma. The patient had a good postoperative course and was discharged on the second postoperative day. On his 12-month follow-up there was no sign of recurrence. The laparoscopic approach is a safe and effective alternative for treatment of splenic metastases.

  1. Melanoma metastasis to the spleen: Laparoscopic approach

    Trindade, Manoel Roberto Maciel; Blaya, Rodrigo; Trindade, Eduardo Neubarth


    We report a case of minimally invasive surgery in the management of metastasis to the spleen. A 67-year-old male patient with possible splenic soft tissue melanoma metastasis was referred to our hospital. He had a history of an excised soft tissue melanoma from his back eight months earlier, and the control abdominal computer tomography (CT) scan revealed a hypodense spleen lesion. The patient underwent laparoscopic surgery to diagnose and treat the splenic lesion. The splenectomy was performed and the histological examination revealed a melanoma. The patient had a good postoperative course and was discharged on the second postoperative day. On his 12-month follow-up there was no sign of recurrence. The laparoscopic approach is a safe and effective alternative for treatment of splenic metastases. PMID:19547681

  2. Inflammatory pseudotumor of spleen: a case report.

    Ugalde, Paúl; García Bernardo, Carmen; Granero, Pablo; Miyar, Alberto; González, Carmen; González-Pinto, Ignacio; Barneo, Luis; Vazquez, Lino


    Inflammatory pseudotumor of spleen is an extremely rare benign condition of uncertain etiology that presents with nonspecific symptoms or as an incidental finding in patients studied by other processes. Since the first description in 1984 by Cotelingam and Jaffe, only 114 cases have been reported. We present a case of a fifty-six years old woman with a splenic injury in ultrasound and computed tomography. The patient undergoes laparoscopic splenectomy and the histologic study of the specimen revealed findings consistent with inflammatory pseudotumor of spleen. This rare entity whose pathogenesis is still unknown, can present with nonspecific symptoms. Radiologic studies may lead the diagnosis being useful CT and MRI. The definitive diagnosis is established with the histological findings, characterized by the presence of inflammatory cells with areas of necrosis and fibrosis. There are multiple differentials diagnoses: metastasis, lymphoma, splenic infarction, hemangiomas, vascular malformations, lymphangioma, plasmacytoma, reactive lymphoid hyperplasia, abscess and infectious granulomatous processes; therefore suspicion of malignant neoplasm must be considered, being indicated splenectomy to confirm the diagnosis. Inflammatory pseudotumor of spleen is a benign disease, in which diagnostic approach must bear in mind the possibility of a malignant lesion. For this reason, the surgical approach is appropriate to confirm the diagnosis and rule out malignancy with histology. Copyright © 2015. Published by Elsevier Ltd.

  3. Measurement of spleen size using gamma camera scintigraphy in essential thrombocythaemia

    Revesz, P. (Department of Medicine, Oestra Hospital, University of Goeteborg, Goeteborg (Sweden)); Carneskog, J.; Wadenvik, H.; Kutti, J. (Haematology Section, Department of Medicine, Sahlgrenska Hospital, University of Goeteborg, Goeteborg (Sweden)); Jarneborn, L. (Department of Clinical Physiology, Oestra Hospital, University of Goeteborg, Goeteborg (Sweden))


    By using gamma camera imaging the spleen size was determined in 33 consecutive patients with essential thrombocythaemia (ET) and in 33 consecutive patients with reactive thrombocytosis (RT). All ET patients were newly diagnosed and had not received myelosuppressive treatment prior to study; they all fulfilled the criteria for ET as established by the Polycythemia Vera Study Group. In both posterior and lateral projections, the spleen area in the group of ET patients was significantly larger than in the RT patients. The present study has shown that 39% of ET patients at diagnosis have splenic enlargement. Evaluation of Spleen size is therefore a useful diagnostic test in patients presenting with unexplained thrombocytosis. (au) (15 refs.).

  4. Difference in gene expression of macrophage between normal spleen and portal hypertensive spleen idendified by cDNA microarray


    AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hypertension.

  5. Evaluation of spleen lymphocyte responsiveness to a T-cell mitogen during early infection with larval Taenia taeniaeformis.

    Letonja, T; Hammerberg, C; Schurig, G


    The effect of taeniid infection on the in vitro cellular response of the host was investigated. Infections of Taenia taeniaeformis decreased the ability of spleen cells from susceptible C3H/He mice to respond to the T-cell mitogen concanavalin A (Con A) as early as 2 days postinfection (pi) reaching a suppression peak at day 12 pi. Similar experiments performed with spleen cells from infected BALB/c mice, resistant to the infection, revealed little or no suppression of Con A stimulation. The results suggested that susceptibility to the parasite may be due to its ability to induce a partial suppression of the host's immune system. The role of adherent splenocytes from infected C3H/He mice in the production of a deficient response to Con A during early infection was studied by coculturing experiments. These experiments demonstrated that adherent populations from infected mice did not play a direct role in the Con A-suppressor mechanisms. Concomitant with the suppressor activity an increased background proliferation was observed with nonstimulated splenocytes from C3H/He mice infected with T. taeniaeformis. Plasma from infected mice was able to suppress the response of normal spleen cells to Con A and to stimulate a proliferative response in cultured splenocytes from noninfected animals. The results suggest the presence of factors in the plasma of infected mice which may be modulating the immune response to the parasite.

  6. [Inorganic pyrophosphatase activity of the mouse spleen in the immune response and after treatment with bis-phosphonates].

    Komissarenko, S V; Gulaia, N M; Gaĭvoronskaia, G G; Karlova, N P; Tarusova, N B


    The inorganic pyrophosphatase activity was determined in different tissues of mice. The immunization of mice by sheep erythrocytes increased the inorganic pyrophosphatase activity of the spleen. The in vivo administration of bisphosphonates (40 mg per 1 g of mass), which are structural analogs of inorganic pyrophosphate (methylene bisphosphonic acid--MBPA, hydroxyethylidene bisphosphonic acid--HEBPA and aminomethylene bisphosphonic acid--AMBPA), inhibited the inorganic pyrophosphatase activity only by MBPA in the thymus and spleen but not in liver. The addition of MBPA, HEBPA as well as of phosphonoacetic acid, imidobisphosphate, bis(phosphonomethyl)-phosphonic acid, MBPA and phosphoric acid monoanhydride to cytosol from the mouse spleen led to the competitive (relative to the [Mg (PPi)2-] complex) inhibition of the inorganic pyrophosphatase activity. AMBPA didn't possess the analogous effect.

  7. Immunoregulatory activities of Dendrobium huoshanense polysaccharides in mouse intestine, spleen and liver.

    Zha, Xue-Qiang; Zhao, Hong-Wei; Bansal, Vibha; Pan, Li-Hua; Wang, Zheng-Ming; Luo, Jian-Ping


    To evaluate the immunomodulating responses in intestine, spleen and liver, 50-200mg/kg of DHP was orally administrated to mice without or with methotrexate. The proliferation of marrow cells, which was performed with the addition of the supernatant of small intestinal lymphocytes isolated from the mice administrated orally with DHP, showed that the intestinal immune response was significantly enhanced in all DHP-treated groups. For the immune response in spleen, all tested doses of DHP remarkably promoted the proliferation of splenic cells and increased the secretion of interferon-γ (IFN-γ). For the immune responses in liver, DHP not only significantly stimulated the proliferation of hepatic cells and the secretion of IFN-γ at all tested doses of DHP, but also significantly elevated the secretion interleukin-4 (IL-4) at the doses of 100 and 200mg/kg. Moreover, DHP could recover methotrexate-injured small intestinal immune function (100 and 200mg/kg) and promoted cell proliferation and IFN-γ production (200mg/kg) in spleen and liver of methotrexate-treated mice. These results suggested that DHP after oral administration possessed immunomodulating effects both in small intestine immune system and in systemic immune system, which were further proved by the mRNA expression of IFN-γ and IL-4.

  8. Macrophages retain hematopoietic stem cells in the spleen via VCAM-1

    Hoyer, Friedrich Felix; Grigoryeva, Lubov S.; Sager, Hendrik B.; Leuschner, Florian; Courties, Gabriel; Borodovsky, Anna; Novobrantseva, Tatiana; Ruda, Vera M.; Fitzgerald, Kevin; Iwamoto, Yoshiko; Wojtkiewicz, Gregory; Sun, Yuan; Da Silva, Nicolas; Libby, Peter; Anderson, Daniel G.; Swirski, Filip K.; Weissleder, Ralph


    Splenic myelopoiesis provides a steady flow of leukocytes to inflamed tissues, and leukocytosis correlates with cardiovascular mortality. Yet regulation of hematopoietic stem cell (HSC) activity in the spleen is incompletely understood. Here, we show that red pulp vascular cell adhesion molecule 1 (VCAM-1)+ macrophages are essential to extramedullary myelopoiesis because these macrophages use the adhesion molecule VCAM-1 to retain HSCs in the spleen. Nanoparticle-enabled in vivo RNAi silencing of the receptor for macrophage colony stimulation factor (M-CSFR) blocked splenic macrophage maturation, reduced splenic VCAM-1 expression and compromised splenic HSC retention. Both, depleting macrophages in CD169 iDTR mice or silencing VCAM-1 in macrophages released HSCs from the spleen. When we silenced either VCAM-1 or M-CSFR in mice with myocardial infarction or in ApoE−/− mice with atherosclerosis, nanoparticle-enabled in vivo RNAi mitigated blood leukocytosis, limited inflammation in the ischemic heart, and reduced myeloid cell numbers in atherosclerotic plaques. PMID:25800955

  9. Genotoxicity evaluation of pesticide formulations containing alachlor and atrazine in multiple mouse tissues (blood, kidney, liver, bone marrow, spleen) by comet assay.

    Zeljezic, D; Garaj-Vrhovac, V


    Every year, in the European countries more than 2 million tons of pesticides are released into the environment. More than 60% of those substances appear to be herbicides. Due to extensive production and application of this chemical their putative detrimental effect on life should be known and minimized. In this study we applied the comet assay on blood and 4 mouse organs (kidney, liver, bone marrow, and spleen) to evaluate possible genome damage caused by two pesticide formulations (Bravo and Gesaprim) containing alachlor and atrazine as active ingredients. Five male CBA mice were assigned to each of 4 treatment groups and control group. Bravo and Gesaprim were injected intraperitoneally once. Two different doses of Bravo were used: 0.031 ml/kg and 0.021 microl/kg, so that doses of alachlor mice received within the pesticide formulation given were 15 mg/kg and 0.01 mg/kg. Also Gesaprim was given at two different doses: 1.08 ml/kg and 0.07 microl/kg so that the doses of atrazine contained within the pesticide formulation given were 540 mg/kg and 3.5 x 10(-2) mg/kg. Mice were sacrificed 24 hours after treatment. Alkaline comet assay on the blood samples, kidney, liver, bone marrow and spleen was performed. Statistically significant (ppesticides DNA of kidney and liver showed largest increase in migration. Also, distribution of tail length values for Bravo and Gesaprim for all mouse tissues examined showed a shift to the right when compared to the controls.

  10. Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

    Djukic, Marija; Sostmann, Nadine; Bertsch, Thomas; Mecke, Marianne; Nessler, Stefan; Manig, Anja; Hanisch, Uwe-Karsten; Triebel, Jakob; Bollheimer, L Cornelius; Sieber, Cornel; Nau, Roland


    Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured. Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation. Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

  11. 21 cases reports on haemangioma of spleen

    Yuan Huang


    Full Text Available The growing activity of hemangioma of spleen keeps unknown. To search theoretical basis for whether to take the operation, this study analyzed clinical data of 21 hemangioma patients, and 16 surgical specimens were analyzed immunohistochemistry of Ki-67, Bcl-2 and vascular endothelial growth factor (VEGF. Both 14 cases of cavernous hemangioma were positive for VEGF, and negative in capillary hemangioma, there was statistical significant difference between two types of hemangioma (P < 0.05. The most tumors had a low expression of Ki-67 with a mean ± standard deviation (SD of 6.62 ± 6.24%, whereas the mean ± SD of Bcl-2 labeling index was 36.06 ± 19.05%. According to the statistical results, the expression of Ki-67 and Bcl-2 did not correlate with age, gender, tumor size, amount of tumor and angiomatous types. Hemangioma of spleen was one benign tumor with a tendency of slow growth. Therefore, operation should be strictly selected, we recommend observation of patients with small, asymptomatic splenic lesions, which meet the radiologic criteria for hemangiomas.

  12. Contrast-enhanced ultrasound of the spleen.

    Omar, Asha; Freeman, Simon


    Abnormalities in the spleen are less common than in most other abdominal organs. However, they will be regularly encountered by ultrasound practitioners, who carefully evaluate the spleen in their abdominal ultrasound studies. Conventional grey scale and Doppler ultrasound are frequently unable to characterise focal splenic abnormalities; even when clinical and laboratory information is added to the ultrasound findings, it is often not possible to make a definite diagnosis. Contrast-enhanced ultrasound (CEUS) is easy to perform, inexpensive, safe and will usually provide valuable additional information about splenic abnormalities, allowing a definitive or short differential diagnosis to be made. It also identifies those lesions that may require further imaging or biopsy, from those that can be safely dismissed or followed with interval ultrasound imaging. CEUS is also indicated in confirming the nature of suspected accessory splenic tissue and in selected patients with abdominal trauma. This article describes the CEUS examination technique, summarises the indications for CEUS and provides guidance on interpretation of the CEUS findings in splenic ultrasound.

  13. Search for antisense copies of beta-globin mRNA in anemic mouse spleen

    Taylor John M


    Full Text Available Abstract Background Previous studies by Volloch and coworkers have reported that during the expression of high levels of β-globin mRNA in the spleen of anemic mice, they could also detect small but significant levels of an antisense (AS globin RNA species, which they postulated might have somehow arisen by RNA-directed RNA synthesis. For two reasons we undertook to confirm and possibly extend these studies. First, previous studies in our lab have focussed on what is an unequivocal example of host RNA-directed RNA polymerase activity on the RNA genome of human hepatitis delta virus. Second, if AS globin species do exist they could in turn form double-stranded RNA species which might induce post-transcriptional gene silencing, a phenomenon somehow provoked in eukaryotic cells by AS RNA sequences. Results We reexamined critical aspects of the previous globin studies. We used intraperitoneal injections of phenylhydrazine to induce anemia in mice, as demonstrated by the appearance and ultimate disappearance of splenomegaly. While a 30-fold increase in globin mRNA was detected in the spleen, the relative amount of putative AS RNA could be no more than 0.004%. Conclusions Contrary to earlier reports, induction of a major increase in globin transcripts in the mouse spleen was not associated with a detectable level of antisense RNA to globin mRNA.

  14. [The effect of physical loads of differing intensities on the lymphoid tissue elements of the thymus and spleen].

    Sapin, M R; Aminova, G G; Grigorenko, D E; Rusina, A K; Erofeeva, L M; Volkova, L V


    The amounts of blast, large lymphocytes and mitotically divided cells were histologically and morphometrically studied in the thymus and spleen in 24 BALB/c female mice during exercises of varying intensity which were induced by swimming and during restricted mobility. The latter was found to cause a greater increase in the above cells in the spleen. The similar changes, though less pronounced, were noted in the thymus during intensive exercises. Moderate exercises and restricted mobility led to a reduction of the number of divided cells in the thymus, but doubled blasts and large lymphocytes.

  15. The spleen in local and systemic regulation of immunity.

    Bronte, Vincenzo; Pittet, Mikael J


    The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity.

  16. Protease activity of legumain is inhibited by an increase of cystatin E/M in the DJ-1-knockout mouse spleen, cerebrum and heart

    Takuya Yamane


    Full Text Available Legumain (EC is an asparaginyl endopeptidase. Legumain activity has been detected in various mouse tissues including the kidney, spleen and epididymis. Legumain is overexpressed in the majority of human solid tumors and transcription of the legumain gene is regulated by the p53 tumor suppressor in HCT116 cells. The legumain activity is also increased under acid conditions in Alzheimer's disease brains. DJ-1/PARK7, a cancer- and Parkinson's disease-associated protein, works as a coactivator to various transcription factors, including the androgen receptor, p53, PSF, Nrf2, SREBP and RREB1. Recently, we found that legumain expression, activation and cleavage of annexin A2 are regulated by DJ-1 through p53. In this study, we found that the expression levels of legumain mRNA were increased in the cerebrum, kidney, spleen, heart, lung, epididymis, stomach, small intestine and pancreas from DJ-1-knockout mice, although legumain activity levels were decreased in the cerebrum, spleen and heart from DJ-1-knockout mice. Furthermore, we found that cystatin E/M expression was increased in the spleen, cerebrum and heart from DJ-1-knockout mice. These results suggest that reduction of legumain activity is caused by an increase of cystatin E/M expression in the spleen, cerebrum and heart from DJ-1-knockout mice.

  17. Spleen-preserving distal pancreatectomy with conservation of the spleen vessels

    MA Jin-ping; CHEN Chuang-qi; PENG Lin; ZHAO Gang; CAI Shi-rong; HU Shi-xiong; HE Yu-long; ZHAN Wen-hua


    Background Distal pancreatectomy traditionally included splenectomy; the spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation. The aim of this research was to study the feasibility,safety and clinical effects of spleen and splenic vessel-preserving distal pancreatectomy.Methods A retrospective review was performed for 26 patients undergoing distal pancreatectomy for benign or low grade malignant disease with splenectomy (n=13) or splenic preservation (n=13) at the First Hospital of Sun Yat-sen University and Guangdong General Hospital in Southern China from May 2002 to April 2009.Results All 26 pancreatectomies with splenectomy or splenic preservation were performed successfully. There was no statistically significant difference between two groups in mean operative time ((172±47) minutes vs. (157±52) minutes, P >0.05), intraoperative estimated blood loss ((183±68) ml vs. (160±51) ml, P >0.05), incidence of noninfectious and infection complication and mean length of postoperative hospital stay ((10.1±2.2) days vs. (12.1 ±4.6) days, P >0.05). The platelet counts examined one week after operation were significantly higher in the distal pancreatectomy with splenectomy group than the other group ((37.3±12.8)×109/L vs. (54.7±13.2)×109/L, P <0.05).Conclusions Spleen-preserving distal pancreatectomy appears to be a feasible and safe procedure. In selected cases of benign or low-grade malignant disease, spleen-preserving distal pancreatectomy is recommended.

  18. Spleen volume on CT and the effect of abdominal trauma.

    Cruz-Romero, Cinthia; Agarwal, Sheela; Abujudeh, Hani H; Thrall, James; Hahn, Peter F


    The aim of this study is to determine the magnitude of change in spleen volume on CT in subjects sustaining blunt abdominal trauma without hemorrhage relative to patients without disease and how the spleen volumes are distributed. Sixty-seven subjects with blunt abdominal trauma and 101 control subjects were included in this retrospective single-center, IRB-approved, and HIPAA-compliant study. Patients with an injured spleen were excluded. Using a semiautomatic segmentation program, two readers computed spleen volumes from CT. Spleen volume distribution in male and female trauma and control cohorts were compared nonparametrically. Spleen volume plotted against height, weight, and age were analyzed by linear regression. The number of females and males are, respectively, 35 and 32 in trauma subjects and 69 and 32 among controls. Female trauma patients (49.6 years) were older than males (39.8 years) (p = 0.02). Distributions of spleen volume were not normal, skewed above their means, requiring a nonparametric comparison. Spleen volumes in trauma patients were smaller than those in controls with medians of 230 vs 294 mL in males(p volume correlated positively with weight in females and with height in male controls, and negatively with age in male controls (p volume in controls was 245 mL, the largest ever reported. Spleen volume decreases in response to blunt abdominal trauma. Spleen volumes are not normally distributed. Our population has the largest spleen volume reported in the literature, perhaps a consequence of the obesity epidemic.

  19. Changes in mouse thymus and spleen after return from the STS-135 mission in space.

    Daila S Gridley

    Full Text Available Our previous results with flight (FLT mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM. Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01. Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05. In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6; 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc. In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa. Pathway analysis (apoptosis signaling and checkpoint regulation was used to map relationships among the cancer-related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA's Space Shuttle Program, exploration of space will undoubtedly continue.

  20. Suppression of Th1- and Th2-type immune responses in infant mouse spleen after prenatal and postnatal exposure to low-level toluene and peptidoglycan.

    Yamamoto, Shoji; Win-Shwe, Tin-Tin; Tin-Tin-Win-Shwe; Yoshida, Yasuhiro; Kunugita, Naoki; Arashidani, Keiichi; Fujimaki, Hidekazu


    The aim of the present study was to investigate the effect of low-level concentrations, under the occupational acceptable limits, of toluene exposure and peptidoglycan (PGN) stimulation on Th1/Th2 immunity in infant mice. Pregnant BALB/c mice and their offspring were exposed to low-level toluene inhalation (0, 5, and 50 ppm) for 4 wk (from the late prenatal stage to early postnatal stage) in a whole-body exposure chamber. Some of the pregnant mice and their offspring were stimulated with PGN during toluene exposure. We measured total immunoglobulins of different subclasses in plasma, and production and expression level of cytokines in the lung and spleen, and transcription factors related to Th1/Th2 immunity in the spleen of infant (3 wk old) mice. Exposure of mice to 5 or 50 ppm toluene resulted in increased immunoglobulin (Ig) G1 and decreased IgG2a and IgE antibodies in the plasma; significantly decreased T-bet, GATA-3, and Foxp3 mRNA in the spleen; and a tendency toward decreased interferon (IFN)-gamma mRNA in spleen. Exposure of mice to low-level toluene together with PGN stimulation resulted in decreased IgG1 as well as IgG2a antibodies in the plasma and Foxp3 mRNA in spleen as compared with control or PGN-treated mice. These findings suggest that low-level toluene exposure and PGN stimulation from the late prenatal to early postnatal stage suppressed the splenic parameter related to Th1/Th2 immunity in infant mice.

  1. The wandering spleen: CT findings and possible pitfalls in diagnosis

    Ben Ely, A.; Zissin, R.; Copel, L.; Vasserman, M.; Hertz, M.; Gottlieb, P.; Gayer, G


    Aim: To report the CT features of wandering spleen, a rare condition which can be incidentally detected as an abdominal or pelvic mass or can present with torsion, causing an acute abdomen. Materials and methods: The CT studies of seven patients, two children and five adults, with wandering spleen were reviewed. CT was performed urgently in three patients for acute abdomen, and electively in four. Results: CT findings of wandering spleen included absence of the spleen in its normal position and a mass located elsewhere in the abdomen or pelvis, i.e. an ectopic spleen, enhancing homogeneously in four cases and failing partially or completely to enhance in the other three, indicating infarction. A 'whirl' appearance representing the twisted splenic pedicle was seen in the three cases with torsion. Urgent splenectomy confirmed infarction secondary to torsion. Conclusion: The possible diagnosis of wandering spleen should be kept in mind when CT shows the spleen to be absent from its usual position and a mass is found elsewhere in the abdomen or pelvis. When, in addition, a 'whirl' or partial or no enhancement of this mass are seen in a case presenting with acute abdomen, torsion of a wandering spleen is a likely diagnosis.

  2. Clinical Application of the Spleen-stomach Theory

    ZHAO Hai-feng


    @@ The spleen-stomach theory is a very valuablecomposition of the TCM. It is originated from Neijing (), initiated in Jin-Yuan periods and the idea "spleen and stomach is the postnatal base of life" in Piweilun () written by LI Dong-yuan established its theoretical basis. Directed by this theory, the author cured several cases, and it is now reported below.

  3. Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis.

    Ji, H; Rabbi, M F; Labis, B; Pavlov, V A; Tracey, K J; Ghia, J E


    The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and α7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility complex II level and pro-inflammatory cytokine secretion by splenic CD11c⁺ cells mediated by α7nAChR signaling. The cholinergic anti-inflammatory efficacy was abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit controls intestinal inflammation and this regulation can be explored to develop novel therapeutic strategies.

  4. Spleen vagal denervation inhibits the production of antibodies to circulating antigens.

    Ruud M Buijs

    Full Text Available BACKGROUND: Recently the vagal output of the central nervous system has been shown to suppress the innate immune defense to pathogens. Here we investigated by anatomical and physiological techniques the communication of the brain with the spleen and provided evidence that the brain has the capacity to stimulate the production of antigen specific antibodies by its parasympathetic autonomic output. METHODOLOGY/PRINCIPAL FINDINGS: This conclusion was reached by successively demonstrating that: 1. The spleen receives not only sympathetic input but also parasympathetic input. 2. Intravenous trinitrophenyl-ovalbumin (TNP-OVA does not activate the brain and does not induce an immune response. 3. Intravenous TNP-OVA with an inducer of inflammation; lipopolysaccharide (LPS, activates the brain and induces TNP-specific IgM. 4. LPS activated neurons are in the same areas of the brain as those that provide parasympathetic autonomic information to the spleen, suggesting a feed back circuit between brain and immune system. Consequently we investigated the interaction of the brain with the spleen and observed that specific parasympathetic denervation but not sympathetic denervation of the spleen eliminates the LPS-induced antibody response to TNP-OVA. CONCLUSIONS/SIGNIFICANCE: These findings not only show that the brain can stimulate antibody production by its autonomic output, it also suggests that the power of LPS as adjuvant to stimulate antibody production may also depend on its capacity to activate the brain. The role of the autonomic nervous system in the stimulation of the adaptive immune response may explain why mood and sleep have an influence on antibody production.

  5. Platelet count/spleen diameter ratio to predict esophageal varices in Mexican patients with hepatic cirrhosis.

    González-Ojeda, Alejandro; Cervantes-Guevara, Gabino; Chávez-Sánchez, Manuela; Dávalos-Cobián, Carlos; Ornelas-Cázares, Susana; Macías-Amezcua, Michel Dassaejv; Chávez-Tostado, Mariana; Ramírez-Campos, Kenia Militzi; Ramírez-Arce, Anaís Del Rocío; Fuentes-Orozco, Clotilde


    To validate whether the platelet count/spleen size ratio can be used to predict the presence of esophageal varices in Mexican patients with hepatic cirrhosis. This was an analytical cross-sectional study to validate the diagnostic test for hepatic cirrhosis and was performed between February 2010 and December 2011. Patients with a diagnosis of hepatic cirrhosis were included and stratified using their Child-Pugh score. Biochemical parameters were evaluated, and ultrasound was used to measure the longest diameter of the spleen. The platelet count/spleen diameter ratio was calculated and analyzed to determine whether it can predict the presence of esophageal varices. Upper gastrointestinal endoscopy was used as the gold standard. Sensitivity and specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined, with the cutoff points determined by receiver-operating characteristic curves. A total of 91 patients were included. The mean age was 53.75 ± 12 years; 50 (54.9%) were men, and 41 (45.0%) women. The etiology of cirrhosis included alcohol in 48 (52.7%), virally induced in 24 (26.3%), alcoholism plus hepatitis C virus in three (3.2%), cryptogenic in nine (9.8%), and primary biliary cirrhosis in seven (7.6%). Esophageal varices were present in 73 (80.2%) patients. Child-Pugh classification, 17 (18.6%) patients were classified as class A, 37 (40.6%) as class B, and 37 (40.6%) as class C. The platelet count/spleen diameter ratio to detect esophageal varices independent of the grade showed using a cutoff value of ≤ 884.3, had 84% sensitivity, 70% specificity, and positive and negative predictive values of 94% and 40%, respectively. Our results suggest that the platelet count/spleen diameter ratio may be a useful tool for detecting esophageal varices in patients with hepatic cirrhosis.

  6. Engraftment of bone marrow-derived cells after nonlethal radiation in syngeneic C57BL/6mice%Engraftment of bone marrow-derived cells after nonlethal radiation in syngeneic C57BL/6 mice

    Wu Liao; Tan Li; Wang Yu; Liu Dengqun; Shi Chunmeng


    Objective To study the characteristics of cell engraftment in mice at a lower dose under nonlethal radiated condition.Methods A syngeneic C57BL/6 mouse model,transplanted with 1 × 107 bone marrow cells and exposed to 2.5 Gy whole body irradiation (WBI),was selected to study the chimerism of cells from green fluorescent protein positive (GFP +) transgenic mice.The control group was injected with GFP + cells without receiving irradiation.In addition,an allogenic transplantation model of BALB/c mice was also investigated which was infused by GFP + cells from C57BL/6 mice.The engraftment of bone marrow-derived cells (BMDCs) was detected by immunohistochemistry in bone marrow,liver,lung,small intestine and spleen.Results The transplanted bone marrow cells successfully grafted in the haematopoietic tissues from syngeneic GFP transgenic mice.The transplanted GFP+ cells were also detected in the non-haematopoietic tissues,such as the small intestine,liver,spleen and lung,after irradiation.However,a lethal dose irradiation of 8 Gy was required to establish successful chimerism in allogeneic transplantation model by infusing the bone marrow cells from C57BL/6 mice to BALB/c mice.Conclusions Bone marrow-derived cells can be successfully grafted into various recipient tissues receiving a 2.5 Gy dose of radiation in syngeneic mice,but not in allogeneic mice.This nonlethal model may help to further study the plasticity and mechanism of bone marrow-derived cells in tissue repair and regeneration after radiation injury.

  7. Spleen involvement in Hodgkin's lymphoma: assessment and risk profile.

    Rueffer, U; Sieber, M; Stemberg, M; Gossmann, A; Josting, A; Koch, T; Grotenhermen, F; Diehl, V


    Diagnostic laparotomy is no longer routinely performed in Hodgkin's lymphoma and noninvasive diagnosis of spleen involvement remains uncertain. In order to assess the probability of splenic involvement based on clinical parameters, we retrospectively analyzed data on patients of the German Hodgkin's Lymphoma Study Group (GHSG) who underwent staging laparotomy and for whom splenic weight and size were available. Our study included 376 patients with Hodgkin's lymphoma who underwent staging laparotomy and splenectomy according to the treatment policy of the GHSG between February 1981 and January 1993. Univariate and multivariate analyses of pretherapeutic clinical characteristics and splenic weight were performed in order to predict the probability of splenic involvement. Computed tomographic (CT) images of 25 patients were available and used to correlate radiological splenic size and pathological splenic weight. In 171 of 376 patients spleen involvement was found. Average weight of the spleens was 258 g (+/-257) ranging from 55 to 3290 g. All spleens with a weight above 2000 g showed disease involvement, while those under 150 g were never involved. In the multivariate analysis, splenic weight ( p<0.001), erythrocyte sedimentation rate ( p<0.001), and clinical stage ( p<0.01) were found to be independently prognostic for spleen involvement. Splenic weight was highly correlated with a spleen index defined as the product of length, width, and thickness measured by CT (correlation coefficient: 0.93). By applying the identified risk factors in clinically staged patients spleen involvement can be determined. Spleen weight can be estimated with the help of a spleen index. Above an index of 1000 the probability of spleen involvement is higher than 90%. This might be of outstanding importance for patients being scheduled for involved field radiation.

  8. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen

    Kentaro Kikuchi


    Full Text Available Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plasma cells in spleen increased by 100 fold after transplantation. Plasma cell numbers correlated with the detection of human IgM and IgG in serum, indicating that human B cells had differentiated into mature plasma cells in the murine spleen. In addition to CD19+ plasma cells, a distinct CD19- plasma cell population was detected, suggesting that downregulation of CD19 associated with maturation of plasma cells occurred. When purified human B cells were transplanted, those findings were not observed. Our results indicate that differentiation and maturation of human B cells and plasma cells can be investigated by transplantation of human PBMC into the spleen of NOD/SCID mice. The model will be useful for studying the differentiation of human B cells and generation of plasma cells.

  9. Phenylethanoid Glycosides of Cistanche on menopausal syndrome model in mice

    Shuo Tian


    Full Text Available Cistanche is the traditional and precious Chinese herbal, with two thousand years of use history in China. It has the effect on tonifying kidney, strong supplement to the liver and kidney, and replenishing essence and blood, known as the “desert ginseng”. Here, we explored the mechanism of Phenylethanoid Glycosides of Cistanche (PGC to the model mice of menopausal syndrome, as well as the therapeutic effect and characteristics of PGC to the menopausal syndrome. In this study, KM mice were reproduced by the complete resection of the ovaries on both sides of the back to establish the model mice of menopausal syndrome (MPS, and received distilled water or drugs, respectively. Model mice received distilled water. Mice received 200 mg/(kg day high doses of Phenylethanoid Glycosides of Cistanche (HPGC, and 100 mg/(kg day medium doses of Phenylethanoid Glycosides of Cistanche (MPGC, and 50 mg/(kg day low doses of Phenylethanoid Glycosides of Cistanche (LPGC. After 21 days, it could determine the number of independent activities and the number of standing, the latent period of first entering the dark room, and the electric number. It also calculated the viscera index of uterus, thymus, spleen, measured the levels of estradiol (E2, testosterone (T, luteinizing hormone (LH, and follicle-stimulating hormone (FSH in the serum. Furthermore, it observed the pathological changes of uterus, thymus, spleen and pituitary of mice. The results showed that behavioral indicators: Compared with the model group (MG, HPGC, MPGC, LPGC could increase the independent activities (P < 0.01; HPGC, MPGC could increase the number of standing, the latent period of first entering the dark room, and reduce the electric number (P < 0.01; LPGC could increase the number of standing (P < 0.05; Viscera index: Compared with MG, HPGC, MPGC could increase the viscera index of uterus, thymus, spleen (P < 0.01; LPGC could increase the viscera index of uterus (P < 0

  10. Comparison of CTL reactivity in the spleen and draining lymph nodes after immunization with peptides pulsed on dendritic cells or mixed with Freund's incomplete adjuvant

    Wang, Ming-Jun; Nissen, Mogens Holst; Buus, Søren


    OBJECTIVE: To compare CTL reactivity in the spleen and the draining lymph nodes (LN) from C57BL/6 mice after immunization with self and non-self peptides pulsed on autologous dendritic cells (DC) or mixed with Freund's incomplete adjuvant (FIA). METHODS: Peptides showing high to low binding...... in the draining LN, whereas non-self peptides mixed with FIA generated the strongest response in the spleen. CONCLUSIONS: DC-based immunization with non-self and self peptides is more efficient than immunization based on peptides mixed with FIA. DC-based immunization focuses the CTL response towards the spleen....... Immunization based on FIA focuses the response against self peptides towards the draining LN and non-self peptides towards the spleen....

  11. Loss of a major idiotype (CRIA) after repopulation of irradiated mice

    Willems, F.; Vansanten-Urbain, G.; De Wit, D.; Slaoui, M.; Urbain, J. (Universite Libre de Bruxelles (Belgium))


    The normal immune response of A/J mice against arsonate coupled to hemocyanin is characterized by a major recurrent cross-reactive Id, the CRIA. This Id is encoded by a single gene segment combination: VHidcr11-DFL16.1e-JH2 for the H chain and Vkidcr-Jk1 for the L chain. In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate. Different protocols were performed to repopulate the irradiated mice. First, lethally irradiated A/J mice were reconstituted by the transfer of syngeneic bone marrow cells. Second, A/J mice were lethally irradiated while their hind limbs were partially shielded. Third, lethally irradiated A/J mice received a transfer of syngeneic spleen cells. The three groups of mice produce high titers of antiarsonate antibodies completely devoid of CRIA DH-JH related idiotopes expression. Moreover, a lack of affinity maturation is observed in the secondary antiarsonate response of all irradiated and reconstituted mice. A transfer of syngeneic peritoneal cells or a transfer of primed T cells in irradiated and reconstituted A/J mice do not restore in a significant manner either the recurrent CRIA expression or the affinity maturation of the antiarsonate response. Our data suggest that the choice of this Id is not solely dictated by the Igh locus.

  12. Morphology and function of isolated hepatocytes transplanted into rat spleen.

    Mito, M; Ebata, H; Kusano, M; Onishi, T; Saito, T; Sakamoto, S


    Hepatocytes isolated by the collagenase digestive method were transplanted into the spleens of syngeneic rats. Morphology and function of the hepatocytes in the spleen were investigated for 12 to 17 months after transplantation. The transplanted hepatocytes proliferated and reconfigured in the spleen without direct perfusion of portal venous blood and with the presence of an intact host liver. Fourteen to 17 months after transplantation, the hepatocytes which had formed a demarcated nodule occupied approximately 40% of the area of the splenic parenchyma without undifferentiation on microscopic examination. However, the weight of the hepatized spleen did not increase beyond the weight of a normal spleen and the weight of the host liver that had normal morphology also did not differ from a normal liver. Light and electron microscopic studies demonstrated differentiated cord structure and normal architecture for each heptocyte. Furthermore, the hepatized spleen synthesized albumin and glycogen as demonstrated by immunofluorescence and histochemical studies. Ammonia tolerance and indocyanine green clearance tests revealed functioning hepatocytes in the spleen proper. These results indicate that our experimental model lends itself well to investigations in cell growth mechanism and that hepatocellular transplantation has potential clinical application to compensate for impaired hepatic function.

  13. Some putative prebiotics increase the severity of Salmonella enterica serovar Typhimurium infection in mice

    Petersen, Anne; Heegaard, Peter M. H.; Pedersen, Anna Lovmand;


    : The mice fed with diets containing fructo-oligosaccharide (FOS) or xylo-oligosaccharide (XOS) had significantly higher (P spleen and mesenteric lymph nodes when compared to the mice fed with the cornstarch-based control diet. Significantly...... increased amounts (P spleen and lymph nodes than animals from the control group (P

  14. The comparative immunotoxicity of mesoporous silica nanoparticles and colloidal silica nanoparticles in mice

    Lee, Soyoung; Kim, Mi-Sun; Lee, Dakeun; Kwon, Taeg Kyu; Khang, Dongwoo; Yun, Hui-Suk; Kim, Sang-Hyun


    Background Mesoporous silica (MPS) nanoparticles (NPs), which have a unique pore structure and extremely large surface area and pore volume, have received much attention because of their biomedical application potential. Using MPS NPs for biomedical devices requires the verification of their biocompatibility because the surface area of NPs is one of the most important determinants of toxicity, including the cellular uptake and immune response. We have previously reported that the cytotoxicity and inflammation potential of MPS NPs have been shown to be lower than those of general amorphous colloidal silica (Col) NPs in macrophages, but the low cytotoxicity does not guarantee high biocompatibility in vivo. In this study, we compared the in vivo immunotoxicity of MPS and Col NPs in the mouse model to define the effects of pore structural conditions of silica NPs. Materials and methods Both MPS and Col NPs (2, 20, and 50 mg/kg/day) were intraperitoneally administered in female BALB/c mice for 4 weeks, and clinical toxicity, lymphocyte population, serum IgG/IgM levels, and histological changes were examined. Results There was no overt sign of clinical toxicity in either MPS- or Col-treated mice. However, MPS NPs led to significant increases in liver and spleen weight and splenocyte proliferation. Mice treated with MPS NPs showed altered lymphocyte populations (CD3+, CD45+, CD4+, and CD8+) in the spleen, increased serum IgG and IgM levels, and histological changes. Despite slight changes in lymphocyte populations in the spleen, Col NPs did not alter other immunological factors. Conclusion The results indicate that in vivo exposure to MPS NPs caused more damage to systemic immunity than that of Col NPs through the dysregulation of the spleen. The results for in vivo data are inconsistent with those for in vitro data, which show lower cytotoxicity for MPS NPs. These results suggest the importance of verifying biocompatibility both in vitro and in vivo during the design of

  15. Diagnostic value of 18F-FDG uptake by spleen in acute radiation disease

    Shao-jie WU


    Full Text Available Objective To investigate whether 18F-FDG uptake can be applied in dosimetry to facilitate a rapid and accurate evaluation of individual radiation dosage after a nuclear accident. Methods Forty-eight Tibetan minipigs were randomly assigned into 6 groups, i.e., 0, 1, 2, 5, 8 and 11Gy groups. Animals in all except 0Gy group received total body irradiation (TBI with a 8MV X centrifugal linear accelerator, and 18F-FDG combined positron-emission tomography and computed tomography (PET/CT were carried out before TBI, and also at 6, 24 and 72h after receiving TBI in different doses ranging from 1 to 11Gy. Spleen tissues and blood samples were collected for histological examination, apoptosis, and routine blood analysis. Results Mean standardized uptake values (SUVs of the spleen showed significant differences between experimental groups and control group. The spleen SUVs at 6h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.95(P<0.01. Histopathological observations showed that the degree of splenic damage was proportional to the radiation dose. Moreover, flow cytometry revealed that apoptosis was one of the major forms of splenic lymphocyte death. Conclusion In the Tibetan minipig model, it was shown that radiation doses bear a close relationship with the 18F-FDG uptake of spleen. This finding suggests that 18F-FDG PET/CT may be useful for the rapid detection of individual radiation dosage after acute radiation disease (ARD. DOI: 10.11855/j.issn.0577-7402.2015.07.08

  16. [Lymphangiomatosis of the spleen. Report of a clinical case].

    Talarico, C; Cerasoli, V; Mancini, B; Mulieri, G; Cancellario D'Alena, F; Montemurro, L; Verna, F


    Lymphangiomatosis confined to the spleen is a very are condition. The authors in this article describes one new case and briefly reviews the literature. In this case, after the exclusion of an hydatidosis of the spleen, a total splenectomy was performed. The histologic findings confirmed the lymphangiomatosis of the spleen. The authors emphasize the surgical strategy in splenic lymphangiomyomatosis, infact the total splenectomy is mandatory, because the splenic parenchyma is nearly completely substitute by the cysts. For this reason is preferably, before surgery, to perform the antibateric profilaxis against the OPSI.

  17. Torsion of a wandering spleen: an unusual abdominal catastrophe.

    Riaz ul Haq, Muhammad; Elhassan, Elbagir; Mahdi, Diaa


    Wandering spleen is a rare clinical entity characterised by splenic hypermobility resulting from laxity or maldevelopment of the suspensory gastrosplenic, splenorenal, and phrenicocolic ligaments. Diagnosis is quite difficult, especially in children because of the lack of symptoms and signs until splenic torsion have occurred. An array of investigations is possible but US with color Doppler, CT with intravenous contrast and MRI are frequently being used to diagnose wandering spleen with or without torsion. We present a case of 5 years old child with torsion of wandering spleen to highlight the importance of prompt diagnosis and management.

  18. [Objective assessment of trauma severity in patients with spleen injuries].

    Alekseev, V S; Ivanov, V A; Alekseev, S V; Vaniukov, V P


    The work presents an analysis of condition severity of 139 casualties with isolated and combined spleen injuries on admission to a surgical hospital. The assessment of condition severity was made using the traditional gradation and score scale VPH-SP. The degree of the severity of combined trauma of the spleen was determined by the scales ISS. The investigation showed that the scale ISS and VPH-SP allowed objective measurement of the condition severity of patients with spleen trauma. The score assessment facilitated early detection of the severe category of the patients, determined the diagnostic algorithm and the well-timed medical aid.

  19. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen


    Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC) directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plas...

  20. Graft-versus-leukemia effects from donor lymphocyte infusion after nonmyeloablative allogeneic bone marrow transplantation in mice

    DU Bing; LI De-peng; XU Kai-lin; PAN Xiu-ying


    Background Nonmyeloablative allogeneic bone marrow transplantation has been used since the 1990s as a new hematological stem cell transplantation strategy for treating hematological diseases. The purpose of this study was to explore the graft-versus-leukemia (GVL) effects of donor lymphocyte infusions (DLIs) after nonmyeloablative allogeneic bone marrow transplantations, while assessing the declines in treatment-associated morbidity, mortality, and graft-versus-host disease (GVHD).Methods A total of 615 (H-2k) mice were injected with L615 tumor cells and received 500 cGy (60Coγ-ray) irradiation three days later, followed by an allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3×107 bone marrow cells and 1×107 spleen cells from BALB/C (H-2d) donor mice. Two days after the allo-BMT, the recipient mice were given 200 mg/kg of cyclophosphamide. Subsequently, recipient mice were infused with either donor spleen cells (2×107) on day 14 or 21, or donor spleen cells (5×107) pretreated with hydrocortisone and cyclosporin A (CsA) in vitro on day 14 post-BMT.Results The median survival time of mice that received DLI on day 21 and pretreated DLI on day 14 post-BMT was longer than that of controls and the day 14 DLI group (P<0.01). No evidence of severe GVHD was observed in the day 21 DLI group nor in the day 14 treated DLI group. Mixed chimerism was confirmed in the day 14 DLI group, the day 14 treated DLI group, and the day 21 DLI group on the thirteenth day post-transplantation; full donor chimerism was observed two weeks after DLI.Conclusion Donor lymphocyte infusion after nonmyeloablative bone marrow transplantation may reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.

  1. Antidiabetic activity of methanolic bark extract ofAlbizia odoratissima Benth. in alloxan induced diabetic albino mice

    Dinesh Kumar; Sunil Kumar; Sonia Kohli; Renu Arya; Jyoti Gupta


    Objective:To evaluate the antidiabetic potential of methanolic extract ofAlbizia odoratissima Benth. bark in alloxan induced diabetic mice.Methods: Group-Ⅰ (normal control) mice received only basal diet without any treatment. In Group-Ⅱ (Diabetic control) mice, diabetes was induced by alloxan (150 mg/kgi.p.) and received only Tween80, 5% v/v in normal saline. Group-Ⅲ and Group-Ⅳ mice received metformin (10 mg/kg) and gliclazide (10 mg/kg) as standard drugs. Group-Ⅴ and Ⅵ mice received methanolic bark extract ofAlbizia odoratissima at doses of250 and500 mg/kg body weightp.o., respectively.Results: The results of the study indicates thatAlbizia odoratissima bark extract significantly (P<0.01) reduced the blood sugar level. The bark extract also significantly reduced the levels of serum cholesterol, triglycerides, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, alkaline phosphatase and decreases level of total proteins in alloxan induced diabetic mice.Conclusions:Methanolic extract ofAlbizia odoratissima has protective effects on the protection of vital tissues (pancreas, kidney, liver, heart and spleen), thereby reducing the causation of diabetes in experimental animals.

  2. Effect of dietary gluten on dendritic cells and innate immune subsets in BALB/c and NOD mice.

    Jesper Larsen

    Full Text Available The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD but may also be important in type 1 diabetes (T1D, and could potentially explain the reduced incidence of T1D in mice receiving a gluten-free (GF diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD gluten containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR, if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found that a GF diet increased the percentage of macrophages in BALB/c spleen and of CD11c+ DCs in BALB/c and NOD spleen. Strictly gluten-free (SGF diet increased the percentage of CD103+ DCs in BALB/c mice and decreased percentages of CD11b+ DCs in mesenteric and pancreatic lymph nodes in BALB/c mice. SGF diet in BALB/c mice also decreased DC expression of CD40, CCR7 and MHC-II in pancreatic lymph nodes. In conclusion, GF diet changes the composition of the innate immune system in BALB/c and NOD mice and increases expression of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NOD mice. This mechanism may be important in development of type 1 diabetes, celiac disease and non-celiac gluten sensitivity.

  3. Spleen dynamic contrast-enhanced magnetic resonance imaging as a new method for staging liver fibrosis in a piglet model.

    Li Zhou

    Full Text Available OBJECTIVE: To explore spleen hemodynamic alteration in liver fibrosis with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI, and to determine how to stage liver fibrosis with spleen DCE-MRI parameters. MATERIALS AND METHODS: Sixteen piglets were prospectively used to model liver fibrosis staged by liver biopsy, and underwent spleen DCE-MRI on 0, 5th, 9th, 16th and 21st weekend after modeling this disease. DCE-MRI parameters including time to peak (TTP, positive enhancement integral (PEI, maximum slope of increase (MSI and maximum slope of decrease (MSD of spleen were measured, and statistically analyzed to stage this disease. RESULTS: Spearman's rank correlation tests showed that TTP tended to increase with increasing stages of liver fibrosis (r = 0.647, P0.05, and decreased from stage 2 to 4 (P0.05. Mann-Whitney tests demonstrated that TTP and PEI could classify fibrosis between stage 0 and 1-4, between 0-1 and 2-4, between 0-2 and 3-4, or between 0-3 and 4 (all P<0.01. MSD could discriminate between 0-2 and 3-4 (P = 0.006, or between 0-3 and 4 (P = 0.012. MSI could not differentiate between any two stages. Receiver operating characteristic analysis illustrated that area under receiver operating characteristic curve (AUC of TTP was larger than of PEI for classifying stage ≥1 and ≥2 (AUC = 0.851 and 0.783, respectively. PEI could best classify stage ≥3 and 4 (AUC = 0.903 and 0.96, respectively. CONCLUSION: Spleen DCE-MRI has potential to monitor spleen hemodynamic alteration and classify liver fibrosis stages.

  4. Immunomodulatory effect of gelatin-coated silver nanoparticles in mice: Ultrastructural evaluation.

    Ahmed, Omar Bauomy; Mahmoud, Usama Taha; Elganady, Sara; Nafady, Allam Mohamed; Afifi, Salah Mohamed Hassan


    Silver nanoparticles (SNP) are used in many pharmaceutical, cosmetic, and industrial products already available in the market. Although they are considered relatively safe, many toxic and pathological alterations in different organs including immune organs were reported after SNP administration. In this study, 10-week-old male mice (n = 20) were divided into two groups. Ten mice received greenly synthesized gelatin-coated silver nanoparticles in a dose of 10 mg/kg body weight for five consecutive days while the other 10 received 0.5 ml of distilled water daily for 5 days and kept as control. At the sixth day, all mice were sacrificed; blood and tissue samples were collected and prepared for pathological analysis. Liver and kidney lesions were in the form of degenerative and inflammatory changes. Interestingly, the immune organs were drastically affected by SNP treatment. Severe hyperplasia of the Peyer's patches was noticed in the intestines of intoxicated animals both in gross and microscopic examination. Spleen was enlarged and showed large number of megakaryocytes. The particles were encountered in membrane-bound phagosomes inside macrophages in different organs like lungs and spleen. Blood picture complied to morphological findings with an increase in monocytes and eosinophils accompanied by drop in the platelets count in the intoxicated animals.

  5. Protective Effect of Lycium ruthenicum Murr. Against Radiation Injury in Mice

    Yabin Duan


    Full Text Available The protective effect of Lycium ruthenicum Murr. against radiation injury was examined in mice. Kunming mice were randomly divided into a control group, model group, positive drug group and L. ruthenicum high dose (8 g/kg, L. ruthenicum middle dose (4 g/kg, L. ruthenicum low dose (2 g/kg treatment groups, for which doses were administered the third day, seventh day and 14th day after irradiation. L. ruthenicum extract was administered orally to the mice in the three treatment groups and normal saline was administered orally to the mice in the control group and model group for 14 days. The positive group was treated with amifostine (WR-2721 at 30 min before irradiation. Except for the control group, the groups of mice received a 5 Gy quantity of X-radiation evenly over their whole body at one time. Body weight, hemogram, thymus and spleen index, DNA, caspase-3, caspase-6, and P53 contents were observed at the third day, seventh day, and 14th day after irradiation. L. ruthenicum could significantly increase the total red blood cell count, hemoglobin count and DNA contents (p < 0.05. The spleen index recovered significantly by the third day and 14th day after irradiation (p < 0.05. L. ruthenicum low dose group showed a significant reduction in caspase-3 and caspase-6 of serum in mice at the third day, seventh day, and 14th day after irradiation and L. ruthenicum middle dose group experienced a reduction in caspase-6 of serum in mice by the seventh day after irradiation. L. ruthenicum could decrease the expression of P53. The results showed that L. ruthenicum had protective effects against radiation injury in mice.

  6. Inflammatory pseudotumour of the spleen associated with splenic tuberculosis.

    Prieto-Nieto, Maria Isabel; Pérez-Robledo, Juan Pedro; Díaz-San Andrés, Beatriz; Nistal, Manuel; Rodríguez-Montes, José Antonio


    Inflammatory pseudotumor (IPT) of the spleen is an uncommon entity with an uncertain aetiology. Inflammatory pseudotumors present diagnostic difficulties because the clinical and radiological findings tend to suggest a malignancy. The symptoms include weight loss, fever, and abdominal pain. Most cases of splenic IPT present solitary relatively large well circumscribed masses on imaging. The diagnosis in the majority of the cases is made after histopathologic study of splenectomy specimens. The IPTs that occur in the spleen and liver are typically associated with Epstein-Barr virus. Thirty-seven percent of all new cases of active tuberculosis infection are extrapulmonary tuberculosis and tuberculous lymphadenitis the most commonly occurring form of extrapulmonary tuberculosis. We report the case of an inflammatory pseudotumor of the spleen associated with splenic tuberculous lymphadenitis in a 50-year-old female patient who was preoperatively diagnosed with a malignant spleen tumour based on her history of breast of carcinoma.

  7. Sonographic assessment of the normal limits of the spleen in ...

    Sonographic assessment of the normal limits of the spleen in healthy school children in South-East Nigeria. ... Nigerian Journal of Clinical Practice ... The splenic length correlated best with BSA, followed by body WT and least with BMI.

  8. Inflammatory pseudotumour of the spleen associated with splenic tuberculosis

    Maria; Isabel; Prieto-Nieto; Juan; Pedro; Pérez-Robledo; Beatriz; Díaz-San; Andrés; Manuel; Nistal; José; Antonio; Rodríguez-Montes


    Inflammatory pseudotumor(IPT) of the spleen is an uncommon entity with an uncertain aetiology. Inflammatory pseudotumors present diagnostic difficulties because the clinical and radiological findings tend to suggest a malignancy. The symptoms include weight loss, fever, and abdominal pain. Most cases of splenic IPT present solitary relatively large well circumscribed masses on imaging. The diagnosis in the majority of the cases is made after histopathologic study of splenectomy specimens. The IPTs that occur in the spleen and liver are typically associated with Epstein-Barr virus. Thirtyseven percent of all new cases of active tuberculosis infection are extrapulmonary tuberculosis and tuberculous lymphadenitis the most commonly occurring form of extrapulmonary tuberculosis. We report the case of an inflammatory pseudotumor of the spleen associated with splenic tuberculous lymphadenitis in a 50-year-old female patient who was preoperatively diagnosed with a malignant spleen tumour based on her history of breast of carcinoma.

  9. Mechanisms of Coix seed compositions in the treatment of spleen ...

    Mechanisms of Coix seed compositions in the treatment of spleen deficiency and wet ... African Journal of Traditional, Complementary and Alternative Medicines ... The urine volume, the drinking volume and the water loading index in each ...

  10. Pectus excavatum defect on liver-spleen scintigraphy

    Moreno, A.J.; Turnbull, G.L.; Parker, A.L.; Fredericks, P.


    A 58-year-old man with a pectus excavatum demonstrated a photon-deficient defect within the left lobe of the liver on liver-spleen scintigraphy using Tc-99m SCOL. Computed tomography of the liver clearly revealed the abnormal defect seen on the liver-spleen scan to be due to the pectus excavatum. This case confirms the impression that these skeletal aberrations may cause false-positive hepatic defects.

  11. Oyster (Crassostrea gigas Hydrolysates Produced on a Plant Scale Have Antitumor Activity and Immunostimulating Effects in BALB/c Mice

    Yu-Zhong Zhang


    Full Text Available Oyster extracts have been reported to have many bioactive peptides. But the function of oyster peptides produced by proteolysis is still unknown. In this study, the oligopeptide-enriched hydrolysates from oyster (Crassostrea gigas were produced using the protease from Bacillus sp. SM98011 at laboratory level, and scaled up to pilot (100 L and plant (1,000 L levels with the same conditions. And the antitumor activity and immunostimulating effects of the oyster hydrolysates in BALB/c mice were investigated. The growth of transplantable sarcoma-S180 was obviously inhibited in a dose-dependent manner in BALB/c mice given the oyster hydrolysates. Mice receiving 0.25, 0.5 and 1 mg/g of body weight by oral gavage had 6.8%, 30.6% and 48% less tumor growth, respectively. Concurrently, the weight coefficients of the thymus and the spleen, the activity of natural killer (NK cells, the spleen proliferation of lymphocytes and the phagocytic rate of macrophages in S180-bearing mice significantly increased after administration of the oyster hydrolysates. These results demonstrated that oyster hydrolysates produced strong immunostimulating effects in mice, which might result in its antitumor activity. The antitumor and immunostimulating effects of oyster hydrolysates prepared in this study reveal its potential for tumor therapy and as a dietary supplement with immunostimulatory activity.

  12. Oyster (Crassostrea gigas) hydrolysates produced on a plant scale have antitumor activity and immunostimulating effects in BALB/c mice.

    Wang, Yu-Kai; He, Hai-Lun; Wang, Guo-Fan; Wu, Hao; Zhou, Bai-Cheng; Chen, Xiu-Lan; Zhang, Yu-Zhong


    Oyster extracts have been reported to have many bioactive peptides. But the function of oyster peptides produced by proteolysis is still unknown. In this study, the oligopeptide-enriched hydrolysates from oyster (Crassostrea gigas) were produced using the protease from Bacillus sp. SM98011 at laboratory level, and scaled up to pilot (100 L) and plant (1,000 L) levels with the same conditions. And the antitumor activity and immunostimulating effects of the oyster hydrolysates in BALB/c mice were investigated. The growth of transplantable sarcoma-S180 was obviously inhibited in a dose-dependent manner in BALB/c mice given the oyster hydrolysates. Mice receiving 0.25, 0.5 and 1 mg/g of body weight by oral gavage had 6.8%, 30.6% and 48% less tumor growth, respectively. Concurrently, the weight coefficients of the thymus and the spleen, the activity of natural killer (NK) cells, the spleen proliferation of lymphocytes and the phagocytic rate of macrophages in S180-bearing mice significantly increased after administration of the oyster hydrolysates. These results demonstrated that oyster hydrolysates produced strong immunostimulating effects in mice, which might result in its antitumor activity. The antitumor and immunostimulating effects of oyster hydrolysates prepared in this study reveal its potential for tumor therapy and as a dietary supplement with immunostimulatory activity.

  13. Effect of Curcumin on Immune Function of Mice


    To investigate the effect of curcumin on immune function of mice, the effect of curcumin was examined on the proliferation of spleen lymphocytes of mice and the function of phagocytosis of peritoneal macrophage by using MTT test and the expression of the nucleoprotein of NFκB p65 was determined in spleen lymphocytes by employing Western Blot. Our results showed that curcumin could enhance the phagocytosis of peritoneal macrophages. Lowdose curcumin could upregulate the proliferation of spleen lymphocytes of mice, and highdose curcumin could suppress the proliferation of spleen lymphocytes. Curcumin could suppress the expression of NFκB p65. Our study suggested that curcumin can regulate immune function of mice in a dosedependent manner. The possible underlying mechanism might be its ability to suppress the activity of NFκB p65.

  14. Sonographic determination of normal spleen size in an adult African population

    Mustapha, Zainab; Tahir, Abdulrahman [Department of Radiology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Tukur, Maisaratu [Department of Human Physiology, University of Maiduguri, Maiduguri, Borno State (Nigeria); Bukar, Mohammed [Department of Obstetrics and Gynaecology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Lee, Wai-Kit, E-mail: [Department of Medical Imaging, St. Vincent' s Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065 (Australia)


    Objective: The purpose of this study was to determine the normal range of spleen size in an adult African population, and compare the findings to published data to determine any correlation with ethnicity. Materials and methods: Three hundred and seventy-four African adults without conditions that can affect the spleen or splenic abnormalities were evaluated with ultrasonography. Spleen length, width and thickness were measured and spleen volume calculated. Spleen size was correlated with age, gender, height, weight, and body mass index. Results: The mean spleen volume was 120 cm{sup 3}. Spleen volume correlated with spleen width (r = 0.85), thickness (r = 0.83) and length (r = 0.80). Men had a larger mean spleen volume than women. No correlation was found between spleen volume and age, weight, height, or body mass index. Conclusion: Mean spleen volume in African adults is smaller than data from Western sources, and cannot be explained by difference in body habitus.

  15. Dexamethasone Regulates Macrophage and Cd4+Cd25+ Cell Numbers in the Chicken Spleen

    AS Calefi


    Full Text Available Abstract Dexamethasone (DEX is a corticoid hormone that is experimentally used to mimic the effects of increased levels of endogenous corticosterone observed during the stress response. Currently, stress is considered one of the major predisposing factors for diseases in the poultry industry. The aim of this study was to analyze the effects of DEX and/or of a 20-fold coccidial vaccine dose on leukocyte phenotypes in the spleen and cecal tonsils of chickens. Twenty specific-pathogen-free (SPF Leghorn chickens were divided into four groups: a non-treated group (NT, a DEX-treated group (Dex, a vaccinated group (V and a DEX-treated+vaccinated group (Dex+V. On experimental day (ED 42, each bird in the vaccinated groups received a anti-coccidial vaccine. DEX was injected in the birds of the Dex and Dex+V groups (0.9 mg/kg onED42 and ED45. The immunophenotyping was performed by flow cytometry analysis of splenocytes and cecal tonsils cells onED48. DEX treatment per se was unable to change CD4+CD8+, CD4+CD8+ and CD4-CD8+ populations with TCRgd or CD28 in the spleen, or macrophages and T lymphocytes in the cecal tonsils. V group birds presented higher numbers of splenic macrophages compared with those measured in the Dex+V group. The number of CD4+CD25+ cells in the spleen of birds of the V group was higher than those measured in the other experimental groups. Our data suggest that CD4+CD25+ cells and macrophages might be influenced by DEX treatment in spleen, but not in the cecal tonsils of chickens inoculated with Eimeria.

  16. Complex organizational defects of fibroblast architecture in the mouse spleen with Nkx2.3 homeodomain deficiency.

    Bovári, Judit; Czömpöly, Tamás; Olasz, Katinka; Arnold, Hans-Henning; Balogh, Péter


    The capacity of secondary lymphoid organs to provide suitable tissue environment for mounting immune responses is dependent on their compartmentalized stromal constituents, including distinct fibroblasts. In addition to various members of the tumor necrosis factor/lymphotoxin beta family as important morphogenic regulators of peripheral lymphoid tissue development, the formation of stromal elements of spleen is also influenced by the Nkx2.3 homeodomain transcription factor in a tissue-specific fashion. Here we extend our previous work on the role of Nkx2.3-mediated regulation in the development of spleen architecture by analyzing the structure of reticular fibroblastic meshwork of spleen in inbred Nkx2.3-deficient mice. Using immunohistochemistry and dual-label immunofluorescence we found both distributional abnormalities, manifested as poor reticular compartmentalization of T-zone and circumferential reticulum, and developmental blockade, resulting in the absence of a complementary fibroblast subpopulation of white pulp. The disregulated distribution of fibroblasts was accompanied with an increased binding of immunohistochemically detectable complement factor C4 by T-cell zone-associated reticular fibroblasts, distinct from follicular dendritic cells with inherently high-level expression of bound C4. These data indicate that the impact of Nkx2.3 gene deficiency on fibroblast ontogeny within the spleen extends beyond its distributional effects, and that the formation of various white pulp fibroblast subsets is differentially affected by the presence of Nkx2.3 activity, possibly also influencing their role in various immune functions linked with complement activation and deposition.

  17. Protective effects of phyllanthus emblica leaf extract on sodium arsenite-mediated adverse effects in mice.

    Sayed, Sadia; Ahsan, Nazmul; Kato, Masashi; Ohgami, Nobutaka; Rashid, Abdur; Akhand, Anwarul Azim


    Groundwater contamination of arsenic is the major cause of a serious health hazard in Bangladesh. No specific treatment is yet available to manage the large number of individuals exposed to arsenic. In this study, we evaluated the protective effects of Phyllanthus emblica (Indian gooseberry or Amla) leaf extract (PLE) on arsenic-mediated toxicity in experimental mice. Male Swiss albino mice were divided into three different groups (n=6/group). 'Control' mice received arsenic free water together with normal feed. Mice in the remaining two groups designated 'SA' and 'SA+PLE' were exposed to sodium arsenite (SA, 10 µg/g body weight/day) through drinking water in addition to receiving normal feed and PLE-supplemented feed, respectively. The weight gain of SA-exposed mice was decreased compared with the controls; however, this decrease in body weight gain was prevented when the feed was supplemented with PLE. A secondary effect of arsenic was enlargement of the liver, kidney and spleen of SA-group mice. Deposition of arsenic in those organs was demonstrated by ICP-MS. When PLE was supplemented in the feed the enlargement of the organs was minimized; however, the deposition of arsenic was not significantly reduced. These results indicated that PLE may not block arsenic deposition in tissue directly but rather may play a protective role to reduce arsenic-induced toxicity. Therefore, co-administration of PLE in arsenic-exposed animals might have a future therapeutic application for protecting against arsenic-mediated toxicity.

  18. Distinct CCR2(+) Gr1(+) cells control growth of the Yersinia pestis ΔyopM mutant in liver and spleen during systemic plague.

    Ye, Zhan; Uittenbogaard, Annette M; Cohen, Donald A; Kaplan, Alan M; Ambati, Jayakrishna; Straley, Susan C


    We are using a systemic plague model to identify the cells and pathways that are undermined by the virulence protein YopM of the plague bacterium Yersinia pestis. In this study, we pursued previous findings that Gr1(+) cells are required to selectively limit growth of ΔyopM Y. pestis and that CD11b(+) cells other than polymorphonuclear leukocytes (PMNs) are selectively lost in spleens infected with parent Y. pestis. When PMNs were ablated from mice, ΔyopM Y. pestis grew as well as the parent strain in liver but not in spleen, showing that these cells are critical for controlling growth of the mutant in liver but not spleen. In mice lacking expression of the chemokine receptor CCR2, wild-type growth was restored to ΔyopM Y. pestis in both organs. In spleen, the Gr1(+) cells differentially recruited by parent and ΔyopM Y. pestis infections were CCR2(+) Gr1(+) CD11b(+) CD11c(Lo-Int) MAC3(+) iNOS(+) (inducible nitric oxide synthase-positive) inflammatory dendritic cells (iDCs), and their recruitment to spleen from blood was blocked when YopM was present in the infecting strain. Consistent with influx of iDCs being affected by YopM in spleen, the growth defect of the ΔyopM mutant was relieved by the parent Y. pestis strain in a coinfection assay in which the parent strain could affect the fate of the mutant in trans. In a mouse model of bubonic plague, CCR2 also was shown to be required for ΔyopM Y. pestis to show wild-type growth in skin. The data imply that YopM's pathogenic effect indirectly undermines signaling through CCR2. We propose a model for how YopM exerts its different effects in liver and spleen.

  19. [The spleen in non-malignant haematological disorders].

    Rüfer, Axel; Wuillemin, Walter A


    The spleen functions as a filter of the circulating blood, removing aging or abnormal red blood cells, intraerythrocyte inclusions as well as foreign particals. As the spleen is composed of lymphocytic tissue, circulatory elements and mononuclear phagocytic cells it plays an important role in the nonspecific as well as the specific immune response. Additionally, the spleen serves as a reservoir for circulating blood cells, especially platelet sequestration by the spleen is well do cumented. The spleen produces blood cells during fetal development and in certain haematological disorders such as myelofibrosis. The destruction of red blood cells within the splenic cords releases iron in the circulation, which is recycled and used to manufacture new erythrocytes in the bone marrow. In several non-malignant haematological disorders antibody-coated cells are cleared from the circulation by phagocytic cells of the spleen. This involves erythrocytes in autoimmunhaemolytic anaemias, platelets in immunthrombocytopenia and neutrophils in Felty syndrome. In hereditary spherocytosis the spleen destroys the resulting defective, spherical red cells. In pyruvate kinase deficiency impaired production of adenosine triphosphate leads to destruction of red blood cells in the spleen or in the liver. In sickle cell anaemia the defective erythrocytes cause sludging and thrombosis in small vessels with infarcts for instance in the spleen, which over time can result in autosplenectomy. In thalassaemia major abnormal haemoglobin forms protein precipitates in the red cells with development of a severe hypochromic anaemia with haemolysis and intramedullary inef fective erythropoiesis. Therapeutic splenectomy can be an option in all of these mentioned non-malignant haematological disorders. The rationale and the pathophysiology of its role in thrombotic thrombocytopenic purpura is probably at least well understood. The use of new and effective drugs such as the monoclonal antibody rituximab or

  20. Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

    Chen J


    Full Text Available Jie Chen, Hao Wang, Wei Long, Xiu Shen, Di Wu, Sha-Sha Song, Yuan-Ming Sun, Pei-Xun Liu, Saijun Fan, Feiyue Fan, Xiao-Dong ZhangTianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of ChinaAbstract: Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles.Keywords: sex differences, toxicity, gold nanoparticles

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  1. A perisinusoidal niche for extramedullary haematopoiesis in the spleen

    Acar, Melih; Murphy, Malea M.; Richardson, James; Zhao, Zhiyu; Morrison, Sean J.


    Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here, we assessed the sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses. PMID:26570997

  2. Morphogenesis of the spleen during the human embryonic period.

    Endo, Aya; Ueno, Saki; Yamada, Shigehito; Uwabe, Chigako; Takakuwa, Tetsuya


    We aimed to observe morphological changes in the spleen from the emergence of the primordium to the end of the embryonic period using histological serial sections of 228 samples. Between Carnegie stages (CSs) 14 and 17, the spleen was usually recognized as a bulge in the dorsal mesogastrium (DM), and after CS 20, the spleen became apparent. Intrasplenic folds were observed later. A high-density area was first recognized in 6 of the 58 cases at CS 16 and in all cases examined after CS 18. The spleen was recognized neither as a bulge nor as a high-density area at CS 13. The mesothelium was pseudostratified until CS 16 and was replaced with high columnar cells and then with low columnar cells. The basement membrane was obvious after CS 17. The mesenchymal cells differentiated from cells in the DM, and sinus formation started at CS 20. Hematopoietic cells were detected after CS 18. The vessels were observed at CS 14 in the DM. Hilus formation was observed after CS 20. The parallel entries of the arteries and veins were observed at CS 23. The rate of increase in spleen length in relation to that of stomach length along the cranial-caudal direction was 0.51 ± 0.11, which remained constant during CSs 19 and 23, indicating that their growths were similar. These data may help to better understand the development of normal human embryos and to detect abnormal embryos in the early stages of development.

  3. A perisinusoidal niche for extramedullary haematopoiesis in the spleen.

    Inra, Christopher N; Zhou, Bo O; Acar, Melih; Murphy, Malea M; Richardson, James; Zhao, Zhiyu; Morrison, Sean J


    Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

  4. Wandering spleen: 'presentation in adolescent with high thrombotic risk'.

    Tchidjou, Hyppolite K; Castelluzzo, Maria A; Messia, Virginia; Luciani, Matteo; Monti, Lidia; Grimaldi, Chiara; Bernardi, Stefania; D'Argenio, Patrizia


    The term 'wandering spleen' refers to an abnormal hypermobility of the spleen, which may be congenital or acquired. The absence or abnormal laxity of splenic ligaments combined with an abnormally long and mobile vascular pedicle predispose to complications such as torsion of the splenic pedicle, infarction and splenic vein thrombosis. The clinical presentation of such disease is highly variable. In this case, we describe an asymptomatic case of wandering spleen in high thrombotic risk patients with cavernoma of splenic vein and infarction of the spleen. Physical examination was normal except the enlarged and no tender consistency spleen palpable at left iliac fossa. Ultrasonography revealed enlarged spleniform mass below its normal position suggesting vascular impairment and subsequently has been confirmed by colour Doppler ultrasound and computed tomography. The family history was positive for ischemic thrombotic vascular diseases and the screening for thrombotic risk has revealed hyperhomocysteinemia, thrombophilic homozygous gene mutations for factor V (H1299R) and MTHFR (C677T). For high thrombotic risk, prophylaxis postsplenectomy was suggested according to the international recommendations with subcutaneous low molecular weight heparin, associated with a preventive treatment with acetyl salicylic acid and folic acid along with B-vitamin. This case report may be helpful for clinicians involved in the care of splenectomized patients, because it has shown the importance of an appropriate pre and postoperative antithrombotic management to reduce as soon as possible the risk of thrombotic events in such patients after splenectomy.


    M. Lo Gatto


    Full Text Available Introduction. In closed trauma of the most frequent causes of injuries are haemoperitoneus of parenchymatous organs such as liver and spleen. Patients and methods. Clinical Case No.1. R.F. (spleen injury: 2nd degree sec. Moore, 1st degree sec. Buntain WL, Tc-based score of 2 is subject to clinical monitoring with ultrasound control, tc, and several blood exams with a satisfactory clinical outcome. Clinical Case No.2. A.C. presents a clinical picture attributable to 3rd grade sec. Moore and the 2nd grade sec. Buntain WL with a Tc-based score of 4, therefore, performed emergency splenectomy was not delayed, thus saving the patient at the death. Results. The rupture of the spleen is the most frequent complication of closed abdominal trauma (contusion or direct backlash. It appears as isolated lesion in 30-70% of cases. Conclusions. In our experience individual spleen injuries, undercapslular that does not involve the hilum and without spillage of liquid peritoneal deserve a conservative, on the other hand, the spleen injury in excess of 4 cm, manyfragments, with spreading of free peritoneal fluid in need of treatment Surgical sudden.

  6. Prion disease induced alterations in gene expression in spleen and brain prior to clinical symptoms

    Hyeon O Kim


    Full Text Available Hyeon O Kim1, Greg P Snyder1, Tyler M Blazey1, Richard E Race2, Bruce Chesebro2, Pamela J Skinner11Department of Veterinary and Biomedical Sciences, University of Minnesota, USA; 2NIH Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana, USAAbstract: Prion diseases are fatal neurodegenerative disorders that affect animals and humans. There is a need to gain understanding of prion disease pathogenesis and to develop diagnostic assays to detect prion diseases prior to the onset of clinical symptoms. The goal of this study was to identify genes that show altered expression early in the disease process in the spleen and brain of prion disease-infected mice. Using Affymetrix microarrays, we identified 67 genes that showed increased expression in the brains of prion disease-infected mice prior to the onset of clinical symptoms. These genes function in many cellular processes including immunity, the endosome/lysosome system, hormone activity, and the cytoskeleton. We confirmed a subset of these gene expression alterations using other methods and determined the time course in which these changes occur. We also identified 14 genes showing altered expression prior to the onset of clinical symptoms in spleens of prion disease infected mice. Interestingly, four genes, Atp1b1, Gh, Anp32a, and Grn, were altered at the very early time of 46 days post-infection. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as surrogate markers for the early detection and diagnosis of prion disease.Keywords: prion disease, microarrays, gene expression

  7. PARP inhibition delays progression of mitochondrial encephalopathy in mice.

    Felici, Roberta; Cavone, Leonardo; Lapucci, Andrea; Guasti, Daniele; Bani, Daniele; Chiarugi, Alberto


    Mitochondrial disorders are deadly childhood diseases for which therapeutic remedies are an unmet need. Given that genetic suppression of the nuclear enzyme poly (adenine diphosphate-ribose) polymerase(PARP)-1 improves mitochondrial functioning, we investigated whether pharmacological inhibition of the enzyme affords protection in a mouse model of a mitochondrial disorder. We used mice lacking the Ndufs4 subunit of the respiratory complex I (Ndufs4 knockout [ KO] mice); these mice undergo progressive encephalopathy and die around postnatal day 50. Mice were treated daily with the potent PARP inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride (PJ34); neurological parameters, PARP activity, and mitochondrial homeostasis were evaluated. We found that mice receiving N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-(N,N-dimethylamino)acetamide hydrochloride from postnatal day 30 to postnatal day 50 show reduced neurological impairment, and increased exploratory activity and motor skills compared with vehicle-treated animals. However, drug treatment did not delay or reduce death. We found no evidence of increased PARP activity within the brain of KO mice compared with heterozygous, healthy controls. Conversely, a 10-day treatment with the PARP inhibitor significantly reduced basal poly(ADP-ribosyl)ation in different organs of the KO mice, including brain, skeletal muscle, liver, pancreas, and spleen. In keeping with the epigenetic role of PARP-1, its inhibition correlated with increased expression of mitochondrial respiratory complex subunits and organelle number. Remarkably, pharmacological targeting of PARP reduced astrogliosis in olfactory bulb and motor cortex, but did not affect neuronal loss of KO mice. In light of the advanced clinical development of PARP inhibitors, these data emphasize their relevance to treatment of mitochondrial respiratory defects.

  8. Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes.

    Koh, Dong-In; Yoon, Jae-Hyeon; Kim, Min-Kyeong; An, Haemin; Kim, Min-Young; Hur, Man-Wook


    Kaiso was previously described as a methylated DNA-binding protein and a transcription repressor interacting with the corepressor protein complex NCoR. In the current study, we show that generation-3 Kaiso knockout mice show a phenotype of splenomegaly and large diffused germinal centers (GC). In the spleens of Kaiso knockout mice, Bcl6 (a transcriptional repressor that plays a critical role in GC development in spleen) and c-Myc were highly expressed, while the cell cycle arrest genes p27 (CDKN1B), p21 (CDKN1A) and Gadd45a were downregulated. Chromatin immunoprecipitation (ChIP) and transcription assays suggested that Kaiso represses Bcl6 expression, and in Kaiso knockout mice, derepressed Bcl6 increased cell proliferation by suppressing p27 (CDKN1B), p21 (CDKN1A) and Gadd45a, while upregulating the oncogene c-Myc. Further evidence for Kaiso regulation of splenomegaly was provided by B lymphocyte Ramos cells, in which ectopic KAISO repressed BCL6 and c-MYC expression, while concomitantly increasing the expression of the cell cycle arrestors p21, p27 and Gadd45a. In summary, derepressed Bcl6 expression may be responsible for increases in GC cell proliferation and splenomegaly of Kaiso knockout mice.

  9. Conservation of the ruptured spleen in children: an African series.

    Mabogunje, O A


    In the Zaria region of northern Nigeria, which is endemic for malaria and schistosomiasis, laparotomy was performed for traumatic rupture of the spleen in 27 children, 10 of whom had splenomegaly. Eleven of the children were pedestrians knocked down by motor vehicles while crossing the road and six were boys who fell off mango or guava trees. Using suture techniques, 17 ruptured spleens were repaired and one was partially resected: eight of them were enlarged. Total splenectomy was performed in nine cases. Five of the children in the splenic conservation group died within 4 days of surgery owing to severe associated injuries. It is concluded that splenorrhaphy is quite feasible in both normal-sized and enlarged spleens and should be encouraged in similar tropical countries where splenomegaly is a common response to endemic malaria and schistosoma.

  10. Littoral-cell angioma of the spleen: A case report


    Littoral-cell angioma (LCA) is a primary splenic vascular tumor that arises from the normal littoral cells lining the sinus channels of the splenic red pulp. We report a case of LCA of the spleen, which has been infrequently communicated in the literature. A 76-year-old man with a 2-wk history of weight loss, abdominal pain and changes in bowel habits was admitted to our hospital.Imaging studies (CT and MRI) showed multiple lesions in the spleen. Splenectomy was performed. Lining cells were positive for CD31/CD68 markers. Our case was associated with a serrated colonic adenoma. LCA is a benign vascular tumor of the spleen that needs to be included in the differential diagnosis of multiple splenic nodules.

  11. Clinical application of serial operations with preserving spleen

    Hong-Chi Jiang; Bei Sun; Hai-Quan Qiao; Jun Xu; Da-Xun Piao; Hang Yin


    AIM: To evaluate the clinical application of serial operations with preservation of spleen. METHODS: Serial operations with preserving spleen were performed on 211 cases in our hospital from 1980 to 2000.The patient's age ranged from 13 to 56 years, averaging 3years. Diseases included splenic injury in 171 cases, portal hypertension in 9 cases, splenic cyst in 10 cases, and the lesion of pancreatic body and tail in 21 cases. RESULTS: All the cases were cured, and 129 patients were followedup from 3 months to 3 years with the leukocyte phagocytosis test, detection of immunoglubin, CT, 99mTc scanning and ultrasonogrsphy. The results were satisfactory. CONCLUSION: The operations with preserving spleen were safe, feasible, and worth of clinical application.

  12. Candidiasis of the liver and spleen in childhood

    Miller, J.H. (Childrens Hospital of Los Angeles, CA); Greenfield, L.D.; Wald, B.R.


    Four children with acute leukemia and surgically documented candidiasis of the liver and/or spleen were examined with a combination of diagnostic imaging modalities including /sup 99m/Tc-sulfur colloid and /sup 67/Ga- citrate scintigraphy, gray-scale ultrasound, and body computed tomography (CT). Abnormalities were detected in every individual examined. /sup 99m/Tc-sulfur colloid scintigraphy revealed ''cold'' areas in the liver or spleen. With /sup 67/Ga scintigraphy, these areas were ''cold'' in some individuals and ''hot'' in others. Gray-scale ultrasound demonstrated hypoechoic lesions with central areas of increased echogenicity in hepatic involvement, and hypoechoic replacement of the spleen in splenic involvement. CT in one patient revealed low-density areas without contrast enhancement within the hepatic parenchyma and unsuspected renal involvement.

  13. Candidiasis of the liver and spleen in childhood

    Miller, J.H.; Greenfield, L.D.; Wald, B.R.


    Four children with acute leukemia and surgically documented candidiasis of the liver and/or spleen were examined with a combination of diagnostic imaging modalities including /sup 99/mTc-sulfur colloid and /sup 67/Ga-citrate scintigraphy, gray-scale ultrasound, and body computed tomography (CT). Abnormalities were detected in every individual examined. /sup 99/mTc-sulfur colloid scintigraphy revealed cold areas in the liver or spleen. With /sup 67/Ga scintigraphy, these areas were cold in some individuals and hot in others. Gray-scale ultrasound demonstrated hypoechoic lesions with central areas of increased echogenicity in hepatic involvement, and hypoechoic replacement of the spleen in splenic involvement. CT in one patient revealed low-density areas without contrast enhancement within the hepatic parenchyma and unsuspected renal involvement.

  14. Giant Accessory Right-Sided Suprarenal Spleen in Thalassaemia

    A. Arra


    Full Text Available An accessory spleen is defined as ectopic splenic tissue that develops due to failure of fusion of cells during embryonic development as they migrate from the midline to the left upper quadrant. While benign, complications may arise which include trauma, torsion, or infarction of the ectopic tissue. Additionally, patients who have had a splenectomy secondary to treatment for previous pathology such as a haematological malignancy or idiopathic thrombocytopenia purpura may experience persistent symptoms due to the accessory splenic tissue. The presence of an accessory spleen is therefore of significant diagnostic and therapeutic importance. To the best of the authors' knowledge, this case is the second and largest reported case of a giant right suprarenal accessory spleen and highlights the difficulty in differentiation of these masses from malignant adrenal tumours.

  15. Semiautomated spleen volumetry with diffusion-weighted MR imaging.

    Lee, Jeongjin; Kim, Kyoung Won; Lee, Ho; Lee, So Jung; Choi, Sanghyun; Jeong, Woo Kyoung; Kye, Heewon; Song, Gi-Won; Hwang, Shin; Lee, Sung-Gyu


    In this article, we determined the relative accuracy of semiautomated spleen volumetry with diffusion-weighted (DW) MR images compared to standard manual volumetry with DW-MR or CT images. Semiautomated spleen volumetry using simple thresholding followed by 3D and 2D connected component analysis was performed with DW-MR images. Manual spleen volumetry was performed on DW-MR and CT images. In this study, 35 potential live liver donor candidates were included. Semiautomated volumetry results were highly correlated with manual volumetry results using DW-MR (r = 0.99; P volumetry was significantly shorter compared to that of manual volumetry with DW-MR (P volumetry with DW-MR images can be performed rapidly and accurately when compared with standard manual volumetry.

  16. Microscopic study of human spleen in different age groups

    Lizamma Alex


    Full Text Available Background: The microscopic structure of spleen is variable depending on the developmental stage of the organ, and the age and immune status of the individual. The aim of the investigation was to study the microscopic structure of human spleen in different age groups, starting from a six month old foetus up to the eighth decade of life. Methods: Seventy formalin fixed human spleens obtained postmortem, were included in the study. They were classified into different age groups, in both sexes, for a detailed study of the microscopic details. Results: The white pulp of spleen showed peri-arteriolar lymphatic sheath (PALS and lymphatic follicles. The corona or mantle zone and the germinal centre were discernible in many of the Malpighian bodies. The marginal zone separating the red pulp from the white pulp also could be clearly demarcated. The marginal sinus and peri-follicular zone could be seen in some sections only. The capsule thickness, trabecular network, cellularity of white pulp and red pulp, the connective tissue framework seen in the red pulp etc., showed variations in the different age groups. Conclusion: The microscopic structure of spleen varies in different age groups, with the PALS and the white pulp showing scanty cellularity in the six month foetus, and almost uniform cellularity in all areas of spleen at full term. Thereafter the follicles showed increase in its cellularity up to the third decade, and then seemed becoming progressively atrophic. Further studies are required on age related changes in the cellular architecture of this organ correlating with its functions. [Int J Res Med Sci 2015; 3(7.000: 1701-1706

  17. Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation

    Yu X


    Full Text Available Xin Yu,1 Laijin Lu,1 Zhigang Liu,1 Teng Yang,2 Xu Gong,1 Yubo Ning,3 Yanfang Jiang4 1Department of Hand Surgery, 2Department of Orthopedics, The First Hospital of Jilin University, Changchun, 3Department of Orthopedics, Ningshi Orthopedics Hospital of Tonghua, Tonghua, 4Department of Central Laboratory, The First Hospital of Jilin University, Changchun, People’s Republic of China Background: Brain-derived neurotrophic factor (BDNF has been demonstrated to play an important role in survival, differentiation, and neurite outgrowth for many types of neurons. This study was designed to identify the role of BDNF during peripheral nerve xenotransplantation. Materials and methods: A peripheral nerve xenotransplantation from rats to mice was performed. Intracellular cytokines were stained for natural killer (NK cells, natural killer T (NKT cells, T cells, and B cells and analyzed by flow cytometry in the spleen of the recipient mouse. Serum levels of related cytokines were quantified by cytometric bead array. Results: Splenic NK cells significantly increased in the xenotransplanted mice (8.47±0.88×107 cells/mL compared to that in the control mice (4.66±0.78×107 cells/mL, P=0.0003, which significantly reduced in the presence of BDNF (4.85±0.87×107 cells/mL, P=0.0004. In contrast, splenic NKT cell number was significantly increased in the mice with xenotransplantation plus BDNF (XT + BDNF compared to that of control group or of mice receiving xenotransplantation only (XT only. Furthermore, the number of CD3+ T cells, CD3+CD4+ T cells, CD3+CD4- T cells, interferon-γ-producing CD3+CD4+ T cells, and interleukin (IL-17-producing CD3+CD4+ T cells, as well as CD3-CD19+ B cells, was significantly higher in the spleen of XT only mice compared to the control mice (P<0.05, which was significantly reduced by BDNF (P<0.05. The number of IL-4-producing CD3+CD4+ T cells and CD3+CD4+CD25+Foxp3+ T cells was significantly higher in the spleen of XT + BDNF

  18. Kaiso is a key regulator of spleen germinal center formation by repressing Bcl6 expression in splenocytes

    Koh, Dong-In; Yoon, Jae-Hyeon; Kim, Min-Kyeong; An, Haemin; Kim, Min-Young; Hur, Man-Wook, E-mail:


    Highlights: •Knockout of Kaiso results in concordant high expression of Bcl6 and c-Myc in spleen. •Kaiso binds the Bcl6 promoter and represses Bcl6 transcription by recruiting NCoR. •Upregulated Bcl6 increases splenocyte proliferation and causes large diffused GC. •Cell cycle-inhibition genes such as Cdkn1b and Cdkn1a are repressed by Bcl6. -- Abstract: Kaiso was previously described as a methylated DNA-binding protein and a transcription repressor interacting with the corepressor protein complex NCoR. In the current study, we show that generation-3 Kaiso knockout mice show a phenotype of splenomegaly and large diffused germinal centers (GC). In the spleens of Kaiso knockout mice, Bcl6 (a transcriptional repressor that plays a critical role in GC development in spleen) and c-Myc were highly expressed, while the cell cycle arrest genes p27 (CDKN1B), p21 (CDKN1A) and Gadd45a were downregulated. Chromatin immunoprecipitation (ChIP) and transcription assays suggested that Kaiso represses Bcl6 expression, and in Kaiso knockout mice, derepressed Bcl6 increased cell proliferation by suppressing p27 (CDKN1B), p21 (CDKN1A) and Gadd45a, while upregulating the oncogene c-Myc. Further evidence for Kaiso regulation of splenomegaly was provided by B lymphocyte Ramos cells, in which ectopic KAISO repressed BCL6 and c-MYC expression, while concomitantly increasing the expression of the cell cycle arrestors p21, p27 and Gadd45a. In summary, derepressed Bcl6 expression may be responsible for increases in GC cell proliferation and splenomegaly of Kaiso knockout mice.

  19. Spleen and liver enlargement in a patient with rheumatoid arthritis.

    Bedoya, María Eugenia; Ceccato, Federico; Paira, Sergio


    We describe the case of a 51-year-old woman with a seropositive, erosive, and non-nodular rheumatoid arthritis of 15 year of evolution. The patient had poor compliance with medical visits and treatment. She came to the clinic with persistent pancytopenia and spleen and liver enlargement. Liver and bone marrow biopsies were carried out and amyloidosis, neoplasias and infections were ruled out. We discuss the differential diagnosis of pancytopenia and spleen and liver enlargement in a long-standing rheumatoid arthritis patient. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. Assessment of spleen size using gamma camera scintigraphy in newly diagnosed patients with essential thrombocythaemia and polycythaemia vera

    Carneskog, J.; Wadenvik, H.; Kutti, J. [Univ. of Goeteborg, Sahlgrenska Univ. Hospital, Dept. of Medicine, Haematology Section, Goeteborg (Sweden); Fjaeelling, M. [Univ. of Goeteborg, Sahlgrenska Univ. Hospital, Dept. of Clinical Physiology, Section of Nuclear Med., Goeteborg (Sweden)


    By using gamma camera imaging the spleen size was assessed in 18 consecutive patients with essential thrombocythaemia (ET) and in 18 consecutive patients with polycythaemia vera (PV). All ET and PV patients were newly diagnosed and had not received any myelosuppressive therapy prior to study. The spleen areas in both posterior and left lateral projections were determined. Eighteen consecutive patients with idiopathic thrombocytopenic purpura (ITP) served as a control group since by definition they do not present with splenic enlargement; in these latter subjects the mean posterior and left lateral splenic areas were almost identical (48 {+-} 15 and 47 {+-} 17 cm{sup 2}, respectively). In comparison with this control group patients with ET an dPV had significantly larger spleens. In both ET and in PV patients the left lateral spleen scan area exceeded the posterior one. Patients with PV had larger splenic areas in both projections than did patients with ET, but the differences were not statistically significant. Compared to the ITP patients it was found that at least 50% of the ET patients and at least 61% of the PV patients at diagnosis presented with splenomegaly. (au) 35 refs.

  1. Organ Atrophy Induced by Sorafenib and Sunitinib – Quantitative Computed Tomography (CT) Evaluation of the Pancreas, Thyroid Gland and Spleen

    Takahashi, Hiroaki; Nasu, Katsuhiro; Minami, Manabu; Kojima, Takahiro; Nishiyama, Hiroyuki; Ishiguro, Toshitaka; Konishi, Takahiro


    Summary Background To evaluate organ atrophy induced by sorafenib and sunitinib, we retrospectively reviewed the CT scans of renal cell carcinoma (RCC) patients receiving molecular targeted therapy (MTT) using sorafenib or sunitinib, and performed volumetric analysis of the pancreas, thyroid gland, and spleen. Material/Methods Thirteen RCC patients receiving MTT were assigned as the evaluation cases (MTT group), while thirteen additional RCC patients not receiving MTT were retrieved as the Control group. We evaluated the baseline and follow-up CT studies. The volume of the three organs estimated by CT volumetry was compared between the baseline and follow-up CTs. The atrophic ratio of the organ volume in the follow-up CT to that in the baseline CT was calculated, and compared between the MTT and Control groups. Results All measured organs in the MTT group showed statistically significant volume loss, while no significant change was observed in the Control group. Mean atrophic ratio in the MTT group was 0.74, 0.58, and 0.82 for the pancreas, thyroid and spleen, respectively. The differences in atrophic ratios between both groups were all statistically significant (P<0.05). Conclusions Single-agent sorafenib or sunitinib therapy induced statistically significant atrophy in the pancreas, thyroid, and spleen. PMID:27956943

  2. Difference in gene expression of macrophage between normal spleen and portal hypertensive spleen idendified by cDNA microarray

    Feng Yan; Xiao-Min Wang


    AIM: To identify the difference in gene expression of microphage (Mφ) between normal spleen and portal hypertensive spleen using cDNA microarrays and find new gene functions associated with hypersplenism in portal hypertension.METHODS: The Biostar-H140s chip containing 14112 spots of cDNAs were used to investigate the difference of the expression. The total RNA extracted from macrophages isolated from both normal spleen and portal hypertensive spleen was reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5) labeled dCTP to prepare the hybridization probes.After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. That was repeated three times,and only the genes which had differential expression in all three chips were considered to be associated with hypersplenism in portal hypertension.RESULTS: Eight hundred and ninety-six, 1330 and 898 genes were identified to be differentially expressed in three chips, respectively. One hundred and twenty-one genes (0.86%) were identified to be differentially expressed in all three chips, including 21 up-regulated genes and 73 down-regulated genes. The differentially expressed genes were related to ionic channel and transport protein, cyclin, cytoskeleton, cell receptor, cell signal conduct, metabolism, immune, and so on. These genes might be related to the hypersplenism in portal hypertension.CONCLUSION: The investigations based on cDNA microarray can screen differentially expressed genes of macrophages between normal spleen and portal hypertensive spleen, thus may provide a new idea in studying the pathogenesis of hypersplenism in portal hypertension.

  3. Ultrasonography of sclerosing angiomatoid nodular transformation in the spleen


    We report three rare cases of sclerosing angiomatoid nodular transformation(SANT) in the spleen.We compared the conventional and contrast-enhanced ultrasonographic appearance.The conventional sonographic examinations exhibited solitary lesions without common respects,while contrast-enhanced ultrasonography(CEUS) revealed nodular appearance mimicking its pathologic characteristics.It suggests that CEUS can provide morphologic information for diagnosing SANT.

  4. Spontaneous rupture of the spleen after infectious mononucleosis

    Gulstad, Mikkel Bak; Thomsen, Henrik


    Non-traumatic rupture of the spleen (NRS) is a rare but serious complication to infectious mononucleosis (IM) and it is important to have in mind, when patients have IM. Although splenectomy has been advocated as the appropriate treatment for this problem, the trend goes towards conservative...

  5. Big liver and spleen disease in broiler breeders in Italy

    Gloria Torcoli


    Full Text Available For the first time in Italy, we have reported two outbreaks resembling big liver and spleen disease in broiler breeder flocks. The combination of clinical signs and pathological findings and the laboratory investigation results appeared corrisponde to previously recorded outbreaks in other countries.

  6. Sonographic biometry of spleen among school age children in ...


    Background: Normative value of spleen size among school age children is important for objective assessment of the ... subjects were recruited from some primary and secondary schools within Nsukka metropolis and also ... technology have advanced the use of this modality ..... textbook of body measurement for sports and.

  7. Hydatid disease of the spleen; Ultrasonography, CT and MR imaging

    Sinner, W.N. von; Stridbeck, H. (Dept. of Diagnostic Radiology, King Faisal Specialist Hospital, and Research Center, Riyadh (Saudi Arabia) Lund Univ. Hospital (Sweden))


    Seven patients with hydatid disease of the spleen were examined by radiography, ultrasound, CT, and in one case MR imaging. The observations were confirmed by patho-anatomic findings except in 2 patients where high indirect hemagglutination tests confirmed the diagnosis. (orig./MG).

  8. The human spleen. Development and role in the immune system.

    Timens, Willem


    In the present thesis an extensive in situ characterization is given of cellular constituents of the human spleen, that play a role in the human immune system. The development of immunocompetent cells in their micro-environment was studied in early embryonic life, fetal life, infancy and childhood,

  9. Role of spleen elastography in patients with chronic liver diseases.

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella


    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations.

  10. A Possible Explanation to Paradox in Horse Spleen Ferritins

    寇谡鹏; 梁九卿


    There are contradicting opinions about the tunnelling experiments in horse-spleen ferritin particles. By distinguish the coherent and incoherent tunnelling processes, we give a unified explanation to different experiments. As a result, a possible explanation to the paradox is proposed

  11. Comparative effects of the herbal constituent parthenolide (Feverfew on lipopolysaccharide-induced inflammatory gene expression in murine spleen and liver

    Smolinski Alexa T


    Full Text Available Abstract Background Parthenolide, a major sesquiterpene lactone present in extracts of the herb Feverfew, has been investigated for its inhibitory effects on mediators of inflammation, including the proinflammatory cytokines. Although parthenolide's anti-inflammatory effects have been investigated in vitro, little in vivo data are available. Moreover, the molecular mechanisms for these inhibitory effects are not fully understood. The objective of this study was to test the hypothesis that parthenolide suppresses lipopolysaccharide (LPS-induced serum (interleukin IL-6, tumor necrosis factor (TNF-α, IL-1β and cyclooxygenase (COX-2 expression in mice as indicated by reduced splenic and liver mRNA levels. Methods Mice were co-treated i.p. with LPS (1 mg/kg bw and parthenolide (5 mg/kg bw and blood, spleen and liver collected. Serum was analyzed for IL-6, TNF-α and IL-1β by ELISA. Total RNA was extracted from spleen and liver, and real-time RT-PCR was used to determine relative mRNA expression of IL-1β, IL-6, TNF-α and COX-2. Results LPS induced increases in serum IL-6 and TNF-α concentrations with only IL-6 being suppressed in parthenolide-treated mice. Induction of IL-6 mRNA was reduced, TNF-α and COX-2 mRNAs unchanged, and IL-1β mRNA increased in spleens of parthenolide plus LPS co-treated animals compared to LPS-only. No significant differences were observed in inflammatory gene expression between these two groups in liver samples. Overall, mRNA expression of each proinflammatory gene was much higher in spleen when compared to liver. Conclusion In summary, only one gene, IL-6, was modestly suppressed by parthenolide co-exposure which contrasts with many in vitro studies suggesting anti-inflammatory effects of this compound. Also, LPS evoked greater effects in spleen than liver on expression of proinflammatory genes. Further study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using model

  12. Induced prion protein controls immune-activated retroviruses in the mouse spleen.

    Marius Lötscher

    Full Text Available The prion protein (PrP is crucially involved in transmissible spongiform encephalopathies (TSE, but neither its exact role in disease nor its physiological function are known. Here we show for mice, using histological, immunochemical and PCR-based methods, that stimulation of innate resistance was followed by appearance of numerous endogenous retroviruses and ensuing PrP up-regulation in germinal centers of the spleen. Subsequently, the activated retroviruses disappeared in a PrP-dependent manner. Our results reveal the regular involvement of endogenous retroviruses in murine immune responses and provide evidence for an essential function of PrP in the control of the retroviral activity. The interaction between PrP and ubiquitous endogenous retroviruses may allow new interpretations of TSE pathophysiology and explain the evolutionary conservation of PrP.

  13. Spleen tyrosine kinase Syk is critical for sustained leukocyte adhesion during inflammation in vivo

    Poeschl Johannes


    Full Text Available Abstract Background During inflammation, β2-integrins mediate leukocyte adhesion to the endothelium accompanied by the activation of the spleen tyrosine kinase Syk. Results We investigated leukocyte adhesion and rolling in cremaster muscle venules before and during stimulation with fMLP using mice with a Syk-/- hematopoietic system. In unstimulated venules, Syk-/- leukocytes adhered less efficiently than control leukocytes while rolling was similar between Syk-/- and control leukocytes. During fMLP-superfusion, control mice showed significantly increased adhesion accompanied by reduced rolling. For Syk-/- leukocytes, an increase in adhesion with a concomitant decrease in rolling was only observed during the first three minutes during fMLP stimulation, but not at later time points. We also investigated leukocyte spreading against the vessel wall during fMLP stimulation and found a significant impairment of spreading for Syk-/- leukocytes. Additional in vitro experiments revealed that the adhesion and spreading defect seen in Syk-/- chimeric mice was due to compromised β2-integrin-mediated outside-in signaling. Conclusion We provide substantial evidence for an important role of Syk in mediating β2-integrin dependent outside-in signaling leading to sustained leukocyte adhesion and spreading during the inflammatory response in vivo.

  14. Cell apoptosis of caprine spleen induced by toxicity of cadmium with different levels of molybdenum.

    Gu, Xiaolong; Chen, Rongrong; Hu, Guoliang; Zhuang, Yu; Luo, Junrong; Zhang, Caiying; Guo, Xiaoquan; Huang, Aiming; Cao, Huabin


    In order to clarify the effects of the combination of Mo and Cd on goat and relationship between the two elements, combined chronic toxicity of cadmium with different levels of molybdenum in vivo on apoptosis gene and ultrastructure of spleen was evaluated with the methods of RT-qPCR and transmission electron microscopy. A total of thirty-six goats were randomly distributed in equal number into four groups. These groups were randomly assigned with one of three oral treatments of CdCl2 (0.5 mgCd kg(-1)) and [(NH4)6Mo7O24·4H2O] (15 mg Mo kg(-1), group I; 30 mg Mo kg(-1), group II; 45 mg Mo kg(-1), group III), while the control group received deionized water. Spleen tissues were taken from individual goat at different time intervals to measure the levels of apoptosis genes including Bcl-2, Bax, Cyt c, Caspase-3, Smac and ceruloplasmin (Cp). The results revealed that a significant suppression in Bcl-2 expression and increase in Cyt c, Caspase-3 and Cp expression in splenic cells. The Bax expression in group I and II was up-regulated, however, it displayed reduction in group III, whereas no statistical significance was observed on Smac expression. In addition, histopathologic injury revealed remarkable morphplogical changes on the splenocytes in the means of apoptosis including fragmentized nucleus, apoptotic body and vesiculation of cytoplasma and mitochondria. Taken together, combined chronic toxicity of cadmium with different levels of molybdenum induce goat spleen cell apoptosis associated with mitochondrial intrinsic pathway, and the two elements showed possible antergic relationship.

  15. Immunotoxicity of the organochlorine pesticide methoxychlor in female ICR, BALB/c, and C3H/He mice.

    Hayashi, Koichi; Fukuyama, Tomoki; Ohnuma, Aya; Tajima, Yukari; Kashimoto, Yukiko; Yoshida, Toshinori; Kosaka, Tadashi


    Several types of pesticides, including organochlorines, are known to suppress or modulate immune responses. The present study evaluated the immunotoxicity of the organochlorine pesticide methoxychlor (MXC) in female BALB/c, C3H/He, and ICR mice. Mice were given oral MXC doses of 0, 30, 100, and 300 mg/kg each day for 7 consecutive days. On day 4, the mice also received an intravenous injection of sheep red blood cells (SRBC). The splenic plaque-forming cell (PFC) IgM response and the serum anti-SRBC IgM antibody titer were evaluated while splenic lymphocytes were counted by flow cytometry and the spleen underwent histopathological analysis. Significant decreases in IgM PFC responses were seen in BALB/c, C3H/He, and ICR mice that received MXC doses of 100 and 300 mg/kg. Similar changes in serum anti-SRBC IgM antibody titers occurred in three strain mice. Flow cytometric analysis revealed significantly decreased splenic T-cell (CD3+) populations in a dose dependent manner in BALB/c mice, and in the 300 mg/kg of MXC-treated group of C3H/He mice. Germinal center (GC) B-cell (CD19+PNA+) populations were significantly decreased in the 300 mg/kg of MXC-treated groups of all three mouse strains and in the 30 and 100 mg/kg of MXC-treated groups of BALB/c and C3H/He strain mice. Histopathological analysis revealed decreased cellularity of the periarteriolar lymphoid sheath (PALS; T-cell area) and decreased GC development in all three strains of mice treated with 300 mg/kg MXC. These results suggest that MXC has an immune-suppressive effect in mice, and that our protocol may be useful for rapidly detecting immunosuppression induced by environmental chemicals.

  16. Postnatal events in intestinal gene expression and splenic cell composition is altered in NOD mice

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Kristensen, Matilde Bylov


    , cellular composition in spleen and liver. At PND1 and 2, the number of Ly-6G and CD11b positive cells in NOD mice was significantly (p=0.05) higher as compared to C57/bl6. Furthermore, gene expression analyses of liver, spleen and intestine showed differences between the two mouse strains in the early...

  17. Depletion of spleen macrophages delays AA amyloid development: a study performed in the rapid mouse model of AA amyloidosis.

    Katarzyna Lundmark

    Full Text Available AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM, marginal zone macrophages (MZM, metallophilic marginal zone macrophages (MMZM. MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.

  18. Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and Abrogate Chronic Inflammation in Stroke.

    Acosta, Sandra A; Tajiri, Naoki; Hoover, Jaclyn; Kaneko, Yuji; Borlongan, Cesar V


    Adult stem cell therapy is an experimental stroke treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow stromal cells (hBMSCs) in chronic stroke. At 60 days post stroke, adult Sprague-Dawley rats received intravenous hBMSCs (4×10(6) labeled or nonlabeled cells) or vehicle (saline). A sham surgery group served as additional control. In vivo imaging was conducted between 1 hour and 11 days post transplantation, followed by histological examination. Labeled hBMSCs migrated to spleen which emitted significantly higher fluorescent signal across all time points, especially during the first hour, and were modestly detected in the head region at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused stroke animals, or sham (Pcells in gray and white matter, and a 43% diminution in tumor necrosis factor-α cell density in the spleen of transplanted stroke animals compared with vehicle-infused stroke animals (Pstroke possibly by abrogating the inflammation-plagued secondary cell death. © 2015 The Authors.


    Morphological difference in spleen and thymus are closely related to functional immune differences. Hormonal regulation of the immune system has been demonstrated in reptilian splenic and thymic tissue. Spleens and thymus were obtained from juvenile alligators at two reference si...

  20. Accessory wandering spleen: Report of a case of laparoscopic approach in an asymptomatic patient

    Alessandro Perin


    CONCLUSION: We suggest performing surgery with a laparoscopic approach in patients with accessory wandering spleen, though asymptomatic, because of the risk of serious complications in case of accessory spleen torsion.


    Morphological difference in spleen and thymus are closely related to functional immune differences. Hormonal regulation of the immune system has been demonstrated in reptilian splenic and thymic tissue. Spleens and thymus were obtained from juvenile alligators at two reference si...


    刘爱莲; 朱萍; 李学均; 张丽; 迟凤琴; 吴振铎; 宋雁南; 张亚坤


    Reciprocal interations between hemopoietic stromal cells and immature hemopoietic cells in human spleens obtained from 20 fetuses of 10-28 weeks gestation were observed by transmission electron microscopy and scanning electron microscopy.The close association of stromal cells with immature hemopoietic cells was confirmed under the electron microscope and a preasumptive HIM(Hemopoietic inductive mocroenvironment) was visualized.In regions of immature hemopoietice cell-reticular cell,endothelial cell,macrophage and interdigitating cell contact,some communicating structures were found between the plasma membranes of adjacent cells.moreovcer,the cytoplasm of these four stromal cells were full of various kinds of organelles.These results suggest that reticular cells,endothelial cells,macrophages and interdigitating cells are component parts of the HIM of human fetal spleen and that these cells have a nurturing function in relation to hemopoietic cells.

  3. Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis.

    Gong, Yu; Zou, Lin; Cen, Dongzhi; Chao, Wei; Chen, Dunjin


    Objective Immune dysfunction, including prominent apoptosis of immune cells and decreased functioning of the remaining immune cells, plays a central role in the pathogenesis of sepsis. Sterile α and HEAT/armadillo motif-containing protein (SARM) is implicated in the regulation of immune cell apoptosis. This study aimed to elucidate SARM contributes to sepsis-induced immune cell death and immunosuppression. Methods A mouse model of polymicrobial sepsis was generated by cecum ligation and puncture (CLP). SARM gene and protein expression, caspase 3 cleavage and intracellular ATP production were measured in the mouse spleens. Results CLP-induced polymicrobial sepsis specifically attenuated both the gene and protein expression of SARM in the spleens. Moreover, the attenuation of SARM expression synchronized with splenocyte apoptosis, as evidenced by increased caspase 3 cleavage and ATP depletion. Conclusions These findings suggest that SARM is a potential regulator of sepsis-induced splenocyte apoptosis.

  4. Malignant melanoma with liver and spleen metastases: case report

    Laura Cotta Ornellas


    Full Text Available CONTEXT: The diagnosis of primary melanoma is easily confirmed after histological analysis of the lesion, whereas it is rarely diagnosed when the patient even has distant metastases. DESIGN: Case report CASE REPORT: Malignant melanoma is responsible for about 1% of all deaths caused by cancer in the USA and only 3% of all malig-nant skin diseases. Malignant melanoma is a rare disease, although it corresponds to 65% of all deaths caused by skin cancer. The liver and spleen are rarely the first sites of melanoma metastases. This paper reports on the clinical picture of a patient with fatal malignant melanoma and hepatic and spleen metastases. As this was an un-usual presentation, the melanoma diagnosis could only be made after pathological analysis of the skin and hepatic lesions.

  5. IL-6 Compared to Young Mice

    Jihyun Park


    Full Text Available Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly.

  6. Research Progress on Metastatic Carcinoma of the Spleen

    Zhaoxiang Zhang


    ABSTRACT Metastatic carcinoma of the spleen (MCS) is a rare condition which is frequency misdiagnosed. Research progress on the prevalence,clinicopathological features and diagnosis of MCS from the Chinese and English medical literature was reviewed to increase understanding of all aspects related to MCS. It is hoped that a better comprehension of MCS will increase the diagnotic level and the rate of MCS detection.

  7. Electronic warfare receivers and receiving systems

    Poisel, Richard A


    Receivers systems are considered the core of electronic warfare (EW) intercept systems. Without them, the fundamental purpose of such systems is null and void. This book considers the major elements that make up receiver systems and the receivers that go in them.This resource provides system design engineers with techniques for design and development of EW receivers for modern modulations (spread spectrum) in addition to receivers for older, common modulation formats. Each major module in these receivers is considered in detail. Design information is included as well as performance tradeoffs o

  8. Horse spleen segmentation technique as large animal model of preclinical trials

    Foz Filho, Roberto P. P.; Martin, Benedito W. de; Ana Rita De Lima; Maria Angelica Miglino


    The parenchymal distribution of the splenic artery was studied in order to obtain anatomical basis for partial splenectomy. Thirty two spleens were studied, 26 spleens of healthy horses weighing 320 to 450kg, aged 3 to 12 years and 6 spleens of fetus removed from slaughterhouse. The spleens were submitted to arteriography and scintigraphy in order to have their vascular pattern examined and compared to the external aspect of the organ aiming establish anatomo-surgical segments. All radiograph...

  9. Membranoproliferative Glomerulonephritis and Inflammatory Pseudotumour of the Spleen

    U. Hadimeri


    Full Text Available Inflammatory pseudotumour is a rare condition that can affect various organs. The clinical and histologic appearance of the pseudotumour may mimic haematological, lymphoproliferative, paraneoplastic or malignant processes. A previously healthy 39-year-old man presented with nephrotic syndrome. He had a history of headaches, nausea and swollen ankles. Computed tomography of the abdomen revealed a 6-cm mass in the spleen. Following a renal biopsy, a diagnosis of membranoproliferative glomerulonephritis (MPGN type I was made. Splenectomy was performed and the examination revealed a mixed population of lymphocytes with predominantly T-cells, B-cells and lymphoplasmacytoid cells. Immunostaining confirmed that the small cells were mostly T-cells positive for all T-cell markers including CD2, CD3, CD4, CD5, CD7 and CD8. A diagnosis of inflammatory pseudotumour was established. The removal of the spleen was followed by remission of glomerulonephritis, but it was complicated by a subphrenic abscess and pneumonia. This association between an inflammatory pseudotumour of the spleen and MPGN has not been previously described. Abnormal immune response due to the inflammation leading to secondary glomerulonephritis might be the main pathogenic mechanism.

  10. Standards of the Polish Ultrasound Society - update. Spleen examination.

    Walczyk, Joanna; Walas, Maria Krystyna


    Ultrasound scan of the spleen is an integral part of the overall abdominal examination. Due to its anatomical position, physical examination of the spleen is frequently supplemented with an ultrasound which plays a special role in the differential diagnostics of splenic diseases and facilitates the determination of further diagnostic and therapeutic procedures. Similarly to other types of ultrasound scans, the examiner should be familiar with all significant clinical information as well as results of examinations and tests conducted so far. This enables to narrow the scope of search for etiological factors and indicate specific disease entities in the findings as well as allows for accurate assessment of coexistent pathologies. The article presents the standards of the Polish Ultrasound Society concerning the apparatus, preparation for the examination, technique and description of the findings. The authors discuss the normal anatomy of the spleen and the most common pathologies ranging from splenomegaly to splenic traumas. The indications for the contrast-enhanced ultrasound and characteristic patterns of enhancement of individual focal lesions are presented. This article is supplemented with photographic documentation, which provides images of the discussed lesions. The ultrasound examination, if carried out in compliance with current standards, allows for accurate interpretation of detected changes. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011) and updated with the current knowledge.

  11. Abscesses of the spleen: Report of three cases

    Constantin Fotiadis; Giagkos Lavranos; Pavlos Patapis; Gabriel Karatzas


    Abscess of the spleen is a rare discovery, with about 600 cases in the international literature so far. Although it may have various causes, it is most usually associated with trauma and infections of the spleen. The latter are more common in the presence of a different primary site of infection, especially endocarditis or in cases of ischemic infarcts that are secondarily infected.Moreover, immunosuppression is a major risk factor.Clinical examination usually reveals a combination of fever, left-upper-quadrant abdominal pain and vomiting.Laboratory findings are not constant. Imaging is a necessary tool for establishing the diagnosis, with a choice between ultrasound and computed tomography.Treatment includes conservative measures, and surgical intervention. In children and in cases of solitary abscesses with a thick wall, percutaneous catheter drainage may be attempted. Otherwise, splenectomy is the preferred approach in most centers. Here, we present three cases of splenic abscess. In all three,splenectomy was performed, followed by rapid clinical improvement. These cases emphasize that current understanding of spleen abscess etiology is still limited,and a study for additional risk factors may be necessary.

  12. Standards of the Polish Ultrasound Society – update. Spleen examination

    Walas, Maria Krystyna


    Ultrasound scan of the spleen is an integral part of the overall abdominal examination. Due to its anatomical position, physical examination of the spleen is frequently supplemented with an ultrasound which plays a special role in the differential diagnostics of splenic diseases and facilitates the determination of further diagnostic and therapeutic procedures. Similarly to other types of ultrasound scans, the examiner should be familiar with all significant clinical information as well as results of examinations and tests conducted so far. This enables to narrow the scope of search for etiological factors and indicate specific disease entities in the findings as well as allows for accurate assessment of coexistent pathologies. The article presents the standards of the Polish Ultrasound Society concerning the apparatus, preparation for the examination, technique and description of the findings. The authors discuss the normal anatomy of the spleen and the most common pathologies ranging from splenomegaly to splenic traumas. The indications for the contrast-enhanced ultrasound and characteristic patterns of enhancement of individual focal lesions are presented. This article is supplemented with photographic documentation, which provides images of the discussed lesions. The ultrasound examination, if carried out in compliance with current standards, allows for accurate interpretation of detected changes. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011) and updated with the current knowledge. PMID:26672802

  13. Standards of the Polish Ultrasound Society – update. Spleen examination

    Joanna Walczyk


    Full Text Available Ultrasound scan of the spleen is an integral part of the overall abdominal examination. Due to its anatomical position, physical examination of the spleen is frequently supplemented with an ultrasound which plays a special role in the differential diagnostics of splenic diseases and facilitates the determination of further diagnostic and therapeutic procedures. Similarly to other types of ultrasound scans, the examiner should be familiar with all significant clinical information as well as results of examinations and tests conducted so far. This enables to narrow the scope of search for etiological factors and indicate specific disease entities in the findings as well as allows for accurate assessment of coexistent pathologies. The article presents the standards of the Polish Ultrasound Society concerning the apparatus, preparation for the examination, technique and description of the findings. The authors discuss the normal anatomy of the spleen and the most common pathologies ranging from splenomegaly to splenic traumas. The indications for the contrast-enhanced ultrasound and characteristic patterns of enhancement of individual focal lesions are presented. This article is supplemented with photographic documentation, which provides images of the discussed lesions. The ultrasound examination, if carried out in compliance with current standards, allows for accurate interpretation of detected changes. This article has been prepared on the basis of the Ultrasound Examination Standards of the Polish Ultrasound Society (2011 and updated with the current knowledge.

  14. Evaluation of infection course in mice induced by L. major in presence of positively charged liposomes containing CpG ODN

    Hesamoddin Hoseinjani


    Full Text Available Abstract An inoculation of virulent Leishmania major is known as leishmanization (LZ which is proven to be the most effective control measure against Cutaneous Leishmaniasis (CL. However, using LZ is restricted due to various side effects such as uncontrolled lesion development. In the present research, the efficacy of cationic nanoliposomes containing CpG oligodeoxynucleotides (CpG ODN as an improved adjuvant delivery system was studied to diminish the lesion development and infection course of L. major after inoculation into the mice. BALB/c mice were inoculated subcutaneously (SC with L. major plus empty DSPC, DSPC (CpG ODN, DSPC (Non CpG ODN, empty DMPC, DMPC (CpG ODN, DMPC (Non CpG ODN or HEPES buffer. The results showed that group of mice received DMPC (CpG ODN nanoliposomes developed a significantly smaller lesion and showed minimum number of L. major in the spleen and draining lymph nodes. In addition, using DMPC (CpG ODN liposomes resulted in a Th1 type of immune response with a preponderance of IgG2a isotype which is concurrent with the production of DMPC (CpG induced IFN-γ in the spleen of the mice. Taken together, the results suggested that immune modulation using DMPC (CpG ODN nanoliposomes might be a practical approach to improve the safety of LZ

  15. File list: ALL.Oth.20.AllAg.Spleen [Chip-atlas[Archive

    Full Text Available ALL.Oth.20.AllAg.Spleen hg19 All antigens Others Spleen SRX347277,SRX263894,SRX1369...8960,SRX263904,SRX188949 ...

  16. File list: ALL.Oth.05.AllAg.Spleen [Chip-atlas[Archive

    Full Text Available ALL.Oth.05.AllAg.Spleen hg19 All antigens Others Spleen SRX134736,SRX347277,SRX2638...7283,SRX134738,SRX188949 ...

  17. File list: ALL.Oth.50.AllAg.Spleen [Chip-atlas[Archive

    Full Text Available ALL.Oth.50.AllAg.Spleen hg19 All antigens Others Spleen SRX347277,SRX263894,SRX1369...3904,SRX134738,SRX188949 ...

  18. File list: ALL.Oth.10.AllAg.Spleen [Chip-atlas[Archive

    Full Text Available ALL.Oth.10.AllAg.Spleen hg19 All antigens Others Spleen SRX134736,SRX347277,SRX2638...4738,SRX263904,SRX188949 ...

  19. Extracellular Vesicles Mediate Radiation-Induced Systemic Bystander Signals in the Bone Marrow and Spleen

    Szatmári, Tünde; Kis, Dávid; Bogdándi, Enikő Noémi; Benedek, Anett; Bright, Scott; Bowler, Deborah; Persa, Eszter; Kis, Enikő; Balogh, Andrea; Naszályi, Lívia N.; Kadhim, Munira; Sáfrány, Géza; Lumniczky, Katalin


    Radiation-induced bystander effects refer to the induction of biological changes in cells not directly hit by radiation implying that the number of cells affected by radiation is larger than the actual number of irradiated cells. Recent in vitro studies suggest the role of extracellular vesicles (EVs) in mediating radiation-induced bystander signals, but in vivo investigations are still lacking. Here, we report an in vivo study investigating the role of EVs in mediating radiation effects. C57BL/6 mice were total-body irradiated with X-rays (0.1, 0.25, 2 Gy), and 24 h later, EVs were isolated from the bone marrow (BM) and were intravenously injected into unirradiated (so-called bystander) animals. EV-induced systemic effects were compared to radiation effects in the directly irradiated animals. Similar to direct radiation, EVs from irradiated mice induced complex DNA damage in EV-recipient animals, manifested in an increased level of chromosomal aberrations and the activation of the DNA damage response. However, while DNA damage after direct irradiation increased with the dose, EV-induced effects peaked at lower doses. A significantly reduced hematopoietic stem cell pool in the BM as well as CD4+ and CD8+ lymphocyte pool in the spleen was detected in mice injected with EVs isolated from animals irradiated with 2 Gy. These EV-induced alterations were comparable to changes present in the directly irradiated mice. The pool of TLR4-expressing dendritic cells was different in the directly irradiated mice, where it increased after 2 Gy and in the EV-recipient animals, where it strongly decreased in a dose-independent manner. A panel of eight differentially expressed microRNAs (miRNA) was identified in the EVs originating from both low- and high-dose-irradiated mice, with a predicted involvement in pathways related to DNA damage repair, hematopoietic, and immune system regulation, suggesting a direct involvement of these pathways in mediating radiation

  20. Anti-allergic effect of intranasal administration of type-A procyanidin polyphenols based standardized extract of cinnamon bark in ovalbumin sensitized BALB/c mice.

    Aswar, Urmila M; Kandhare, Amit D; Mohan, Vishwaraman; Thakurdesai, Prasad A


    The objective of the present work was to evaluate anti-allergic effects of intranasal administration of type-A procynidines polyphenols (TAPP) based standardized hydroalcoholic extract of Cinnamomum zeylanicum bark (TAPP-CZ) in ovalbumin (OVA)-induced experimental allergic rhinitis (AR) in BALB/c mice. Sixty male BALB/c mice were divided into six groups of ten each (G1-G6). The mice from G1 were nonsensitized and maintained as normal group. Remaining mice (G2-G6) were sensitized with OVA (500 μL solution, intraperitoneal) on alternate days for 13 days and had twice daily intranasal treatment from day 14-21 as follows: G2 (AR control) received saline, G3 (positive control, XLY) received xylometazoline (0.5 mg/mL, 20 μL/nostril) and G4-G6 received TAPP-CZ (3, 10 and 30 µg/kg in nostril), respectively. On day 21, mice were challenged with OVA (5 μL/nostril, 5% solution) and assessments (nasal signs, biochemical and histopathological) were performed. Treatment with TAPP-CZ (10 and 30 µg/kg in nostril) showed significant attenuation in OVA-induced alterations of the nasal (number of nasal rubbing and sneezing), biochemical markers (serum IgE and histamine), haematological, morphological (relative organ weight of spleen and lung) and histopathological (nasal mucosa and spleen) parameters. In conclusion, TAPP-CZ showed anti-allergic efficacy in animal model of AR.

  1. Traumatic spinal cord injury in mice with human immune systems.

    Carpenter, Randall S; Kigerl, Kristina A; Marbourg, Jessica M; Gaudet, Andrew D; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G


    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in the blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI

  2. Sex Differences in the Effect of Resveratrol on DSS-Induced Colitis in Mice

    Alexandra Wagnerova


    Full Text Available Resveratrol is a natural polyphenol studied for its possible protective properties in inflammatory bowel diseases. Moreover, it has been shown to interact with estrogen receptors. In the present study, we aimed to investigate possible diverse effects of resveratrol on female and male mice in DSS-induced colitis. Thirty-seven C57BL/6 mice (21 female and 16 male were divided into three groups for each sex. The first group received pure water (CTRL. The other two groups received 1.5% dextran sulfate sodium (DSS to induce colitis from which one group was treated with resveratrol (DSS + RSV. Intake of 1.5% DSS caused weight loss in all DSS groups compared to control mice. Weight loss, stool consistency, and discomfort did not show any protective effect of resveratrol in males and showed even adverse effects in females. In females, the activity of myeloperoxidase was lower compared to that in males. However, colon length and spleen weight showed no sex differences, which can indicate the induction of only mild colitis in mice. Resveratrol did not have any effect on TNF-alpha levels. Taken together, these results for the first time propose possible diverse effects of resveratrol in DSS-induced colitis model depending on the sex of the animal. However, this conclusion must be confirmed by further analyses.

  3. Dietary L-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus.

    Ren, Wenkai; Luo, Wei; Wu, Miaomiao; Liu, Gang; Yu, Xinglong; Fang, Jun; Li, Teijun; Yin, Yulong; Wu, Guoyao


    Porcine circovirus type 2 (PCV2) causes reproductive failure in swine. As glutamine can enhance immune function in animals, this study was conducted with mice to test the hypothesis that dietary glutamine supplementation will improve pregnancy outcome in PCV2-infected dams. Beginning on day 0 of gestation, mice were fed a standard diet supplemented with 1.0% L-glutamine or 1.22% L-alanine (isonitrogenous control). All mice were infected with PCV2 (2000 TCID50) on day 10 of gestation. On day 17 of gestation, six mice from each group were euthanized to obtain maternal tissues and fetuses for hematology and histopathology tests. The remaining mice continued to receive their respective diets supplemented with 1.0% L-glutamine or 1.22% L-alanine through lactation. The PCV2 virus was present in maternal samples (serum and lung) of most mice in the control group but was not detected in the glutamine-supplemented mice. Dietary glutamine supplementation reduced abortion, decreased fetal deaths, and enhanced neonatal survival. The glutamine treatment also reduced concentrations of interleukin-6, while increasing concentrations of tumor necrosis factor-α and C-reactive protein, in the maternal serum of mice. Furthermore, glutamine supplementation attenuated microscopic lesions in maternal tissues (lung, spleen, and liver). Collectively, these results indicate that dietary glutamine supplementation is beneficial for ameliorating reproductive failure in virus-infected mice. The findings support the notion that gestating dams require adequate amounts of dietary glutamine for the optimal survival and growth of embryos, fetuses, and neonates, and have important implications for nutritional support of mammals (including swine and humans) during gestation and lactation.

  4. Environmentally Relevant Chronic Low-Dose Tritium and Gamma Exposures do not Increase Somatic Intrachromosomal Recombination in pKZ1 Mouse Spleen.

    Bannister, Laura; Serran, Mandy; Bertrand, Lindsey; Klokov, Dmitry; Wyatt, Heather; Blimkie, Melinda; Gueguen, Yann; Priest, Nicholas; Jourdain, Jean-René; Sykes, Pamela


    The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision. In this study, we investigated potential cytotoxic and genotoxic effects in mouse spleen after one month and eight months of chronic exposure to low-dose tritiated water (HTO). The dose regimes studied were designed to mimic human chronic consumption of HTO at levels of 10 kBq/l, 1 MBq/l and 20 MBq/l. The total doses from these radiation exposures ranged from 0.01 to 180 mGy. We also compared the biological effects of exposure to HTO with equivalent exposure to external whole-body (60)Co gamma rays. Changes in spleen weight and somatic intrachromosomal recombination (DNA inversions) in spleen tissue of pKZ1(Tg/+) mice were monitored. Our results showed no overall changes in either spleen organ weights and no increase mouse splenic intrachromosomal recombination frequencies, indicating that current drinking water standards for tritium exposure in the form of HTO are likely to be adequately protective against cytotoxic and genotoxic damage in spleen. These results demonstrate no evidence for cytotoxicity or genotoxicity in mouse spleen following chronic exposures to HTO activities (or equivalent gamma doses) up to 20 MBq/L.

  5. Transcriptional Profiling of Dibenzo[def,p]chrysene-induced Spleen Atrophy Provides Mechanistic Insights into its Immunotoxicity in MutaMouse.

    Chepelev, Nikolai L; Long, Alexandra S; Williams, Andrew; Kuo, Byron; Gagné, Rémi; Kennedy, Dean A; Phillips, David H; Arlt, Volker M; White, Paul A; Yauk, Carole L


    Dibenzo[def,p]chrysene (DBC) is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) examined to date. We investigated the immunotoxicity of DBC, manifested as spleen atrophy, following acute exposure of adult MutaMouse males by oral gavage. Mice were exposed to 0, 2.0, 6.2, or 20.0 mg DBC /kg-bw per day, for 3 days. Genotoxic endpoints (DBC-DNA adducts and lacZ mutant frequency in spleen and bone marrow, and red blood cell micronucleus frequency) and global gene expression changes were measured. All of the genotoxicity measures increased in a dose-dependent manner in spleen and bone marrow. Gene expression analysis showed that DBC activates p53 signaling pathways related to cellular growth and proliferation, which was evident even at the low dose. Strikingly, the expression profiles of DBC exposed mouse spleens were highly inversely correlated with the expression profiles of the only published toxicogenomics dataset of enlarged mouse spleen. This analysis suggested a central role for Bnip3l, a pro-apoptotic protein involved in negative regulation of erythroid maturation. RT-PCR confirmed expression changes in several genes related to apoptosis, iron metabolism, and aryl hydrocarbon receptor signaling that are regulated in the opposite direction during spleen atrophy versus benzo[a]pyrene-mediated splenomegaly. In addition, benchmark dose modeling of toxicogenomics data yielded toxicity estimates that are very close to traditional toxicity endpoints. This work illustrates the power of toxicogenomics to reveal rich mechanistic information for immunotoxic compounds and its ability to provide information that is quantitatively similar to that derived from standard toxicity methods in health risk assessment.

  6. PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes.

    Liu, Qian; Lv, Yi; Zhao, Min; Jin, Yiduo; Lu, Jiangyang


    This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition.

  7. Chimerism of allogeneic mesenchymal cells in bone marrow, liver, and spleen after mesenchymal stem cells infusion.

    Meleshko, Alexander; Prakharenia, Irina; Kletski, Semen; Isaikina, Yanina


    Although an infusion of culture-expanded MSCs is applied in clinic to improve results of HSCs transplantation and for a treatment of musculoskeletal disorders, homing, and engraftment potential of culture-expanded MSC in humans is still obscure. We report two female patients who received allogeneic BM transplantation as a treatment of hematological diseases and a transplantation of MSCs from third-party male donors. Both patients died within one yr of infectious complications. Specimens of paraffin-embedded blocks of tissues from transplanted patients were taken. The aim of the study was to estimate possible homing and engraftment of allogeneic BM-derived MSCs in some tissues/organs of recipient. Sensitive real-time quantitative PCR analysis was applied with SRY gene as a target. MSC chimerism was found in BM, liver, and spleen of both patients. We conclude that sensitive RQ-PCR analysis is acceptable for low-level chimerism evaluation even in paraffin-embedded tissue specimens.

  8. Contents of corticotropin-releasing hormone and arginine vasopressin immunoreativity in the spleen and thymus during a chronic inflammatory stress

    Chowdrey, H.S.; Lightman, S.L.; Harbuz, M.S.;


    Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin......Corticotropin-releasing hormone, spleen, thymus, immune system, stress, arthritis, arginine vasopressin...

  9. SPECT/CT analysis of splenic function in genistein-treated malaria-infected mice.

    Ha, Young Ran; Kang, Sung-A; Ryu, Jeongeun; Yeom, Eunseop; Kim, Mun Ki; Lee, Sang Joon


    Spleen traps malaria-infected red blood cells, thereby leading to splenomegaly. Splenomegaly induces impairment in splenic function, i.e., rupture. Therefore, splenomegaly inhibition is required to protect the spleen. In our previous study, genistein was found to have an influence on malaria-induced splenomegaly. However, the effect of genistein in malaria-induced splenomegaly, especially on the function of spleen, has not been fully investigated. In this study, hematoxylin and eosin (H&E) staining images show that genistein partially prevents malaria-induced architectural disruption of spleen. In addition, genistein decreases transgenic Plasmodium parasites accumulation in the spleen. Genistein treatment can protect splenic function from impairment caused by malaria infection. To examine the functions of malaria-infected spleen, we employed single-photon emission computed tomography/computed tomography (SPECT/CT) technology. Red blood cells are specifically radiolabeled with Technetium-99m pertechnetate ((99m)TcO4(-)) and trapped inside the spleen. The standardized uptake values (SUVs) in the spleen of infected mice are higher than those of naive and genistein-treated mice. However, genistein reduces the malaria-induced trapping capacity of spleen for heat-damaged radiolabeled RBCs, while exhibiting a protective effect against malaria. Considering these results, we suggested that genistein could be effectively used in combination therapy for malaria-induced splenic impairment.

  10. Organ-specific responses of total body irradiated doxycycline-inducible manganese superoxide dismutase Tet/Tet mice.

    Rhieu, Byung Han; Shinde, Ashwin; Epperly, Michael W; Dixon, Tracy; Wang, Hong; Chaillet, Richard; Greenberger, Joel S


    We evaluated doxycycline-inducible manganese superoxide dismutase (MnSOD(tet/tet)) mice after 9.25 Gy total-body irradiation (TBI) or 20 Gy thoracic irradiation. Six-week-old MnSOD(tet/tet) or control C57BL/6NHsd mice on or off doxycycline (doxy) in food received 9.25 Gy TBI, were sacrificed at day 19 and bone marrow, brain, esophagus, heart, intestine, kidney, liver, lung, spleen and tongue harvested, total RNAs extracted and transcripts for irradiation response genes quantitated by real time-polymerase chain reaction (RT-PCR). MnSOD(tet/tet) mice only survived with daily injections of doxy beginning 5 days after birth until weaning, at which time they were placed on food containing doxy. Manganese superoxide dismutase (MnSOD) transcript levels were reduced in all tissues except the lung. Adult mice survived with low MnSOD levels, but induced by doxy or TBI. Thoracic-irradiated MnSOD(tet/tet) mice survived past day 120. MnSOD(tet/tet) mice should be valuable for elucidating the role of MnSOD in growth and irradiation response. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  11. Splenic Stromal Cells from Aged Mice Produce Higher Levels of IL-6 Compared to Young Mice

    Park, Jihyun; Miyakawa, Takuya; Shiokawa, Aya; Nakajima-Adachi, Haruyo; Hachimura, Satoshi


    Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly. PMID:24729663

  12. Mucormycosis resulting in a pseudoaneurysm in the spleen

    Nevitt, P.C.; Das Narla, L. [Medical College of Virginia, Virginia Commonwealth Univ., Richmond (United States); Hingsbergen, E.A. [Children' s Radiologic Institute, Children' s Hospital, Columbus, OH (United States)


    Mucormycosis is an uncommon and frequently fatal fungal infection. It characteristically affects patients with diabetes mellitus or patients with severe immunosuppression. The hallmark of mucormycosis infection is tissue infarction and vascular invasion. We present clinical data and imaging studies of a 16 year-old child with acute lymphoblastic leukemia complicated by disseminated mucormycosis resulting in a pseudoaneurysm of the spleen. This was successfully managed by a combination of systemic antifungal therapy (Amphotericin B) and surgery (splenectomy). This entity has not been described in the literature. (orig.)

  13. Errors made in the ultrasound diagnostics of the spleen.

    Walczyk, Joanna; Walas, Maria Krystyna


    Ultrasonography, like any imaging method, entails the risk of errors. From among all means of imaging, it is the most subjective and dependent on the examiner's knowledge and experience. This paper presents the causes of examiner-dependent errors as well as those which result from technical settings and preparation of the patient for the examination. Moreover, the authors discuss the most frequent errors in the diagnosis of splenic conditions, which result from insufficient knowledge concerning anatomical variants of this organ, wrong measurements and incorrect examination technique. The mistakes made in the differentiation of focal lesions of the spleen and its hilum are also discussed. Additionally, the differentiation of collateral circulation, lymph nodes and accessory spleens is mentioned. The authors also draw attention to erroneous interpretation of the left liver lobe as a fragment of the spleen as well as the prominent tail of the pancreas filled with gastric contents and intestinal loops as abnormal masses or fluid cisterns in the area of the splenic hilum. Furthermore, the pathologies of the hilum are discussed such as tumors of the splenic flexure of the colon, lesions arising from the left kidney or the left adrenal gland. The authors list characteristic imaging features of the most common focal lesions visualized in a standard ultrasound scan as well as enhancement patterns appearing in contrast-enhanced examinations. The article discusses the features and differentiation of, among others, infarction, splenic cysts including hydatid ones, abscesses and angiomas. The ultrasound appearance of lymphoma and secondary involvement of the spleen by other malignant neoplasms is also mentioned. Moreover, the authors provide useful tips connected with imaging techniques and interpretation of the findings. The ultrasound examination carried out in compliance with current standards allows for an optimal assessment of the organ and reduction of the error

  14. Errors made in the ultrasound diagnostics of the spleen

    Joanna Walczyk


    Full Text Available Ultrasonography, like any imaging method, entails the risk of errors. From among all means of imaging, it is the most subjective and dependent on the examiner’s knowledge and experience. This paper presents the causes of examiner-dependent errors as well as those which result from technical settings and preparation of the patient for the examination. Moreover, the authors discuss the most frequent errors in the diagnosis of splenic conditions, which result from insufficient knowledge concerning anatomical variants of this organ, wrong measurements and incorrect examination technique. The mistakes made in the differentiation of focal lesions of the spleen and its hilum are also discussed. Additionally, the differentiation of collateral circulation, lymph nodes and accessory spleens is mentioned. The authors also draw attention to erroneous interpretation of the left liver lobe as a fragment of the spleen as well as the prominent tail of the pancreas filled with gastric contents and intestinal loops as abnormal masses or fluid cisterns in the area of the splenic hilum. Furthermore, the pathologies of the hilum are discussed such as tumors of the splenic flexure of the colon, lesions arising from the left kidney or the left adrenal gland. The authors list characteristic imaging features of the most common focal lesions visualized in a standard ultrasound scan as well as enhancement patterns appearing in contrast-enhanced examinations. The article discusses the features and differentiation of, among others, infarction, splenic cysts including hydatid ones, abscesses and angiomas. The ultrasound appearance of lymphoma and secondary involvement of the spleen by other malignant neoplasms is also mentioned. Moreover, the authors provide useful tips connected with imaging techniques and interpretation of the findings. The ultrasound examination carried out in compliance with current standards allows for an optimal assessment of the organ and

  15. Critical role of IFN-gamma in CFA-mediated protection of NOD mice from diabetes development.

    Mori, Yoshiko; Kodaka, Tetsuro; Kato, Takako; Kanagawa, Edith M; Kanagawa, Osami


    IFN-gamma signaling-deficient non-obese diabetic (NOD) mice develop diabetes with similar kinetics to those of wild-type NOD mice. However, the immunization of IFN-gamma signaling-deficient NOD mice with CFA failed to induce long-term protection, whereas wild-type NOD mice receiving CFA remained diabetes-free. CFA also failed to protect IFN-gamma receptor-deficient (IFN-gammaR(-/-)) NOD mice from the autoimmune rejection of transplanted islets, as it does in diabetic NOD mice, and from disease transfer by spleen cells from diabetic NOD mice. These data clearly show that the pro-inflammatory cytokine IFN-gamma is necessary for the CFA-mediated protection of NOD mice from diabetes. There is no difference in the T(h)1/T(h)17 balance between IFN-gammaR(-/-) NOD and wild-type NOD mice. There is also no difference in the total numbers and percentages of regulatory T (Treg) cells in the lymph node CD4(+) T-cell populations between IFN-gammaR(-/-) NOD and wild-type NOD mice. However, pathogenic T cells lacking IFN-gammaR are resistant to the suppressive effect of Treg cells, both in vivo and in vitro. Therefore, it is likely that CFA-mediated protection against diabetes development depends on a change in the balance between Treg cells and pathogenic T cells, and IFN-gamma signaling seems to control the susceptibility of pathogenic T cells to the inhibitory activity of Treg cells.

  16. Dietary lutein absorption from marigold extract is rapid in BALB/c mice.

    Park, J S; Chew, B P; Wong, T S


    Even though lutein can stimulate immunity and decrease cancer growth, no systematic studies are available on the uptake of lutein in mice. We studied the uptake of lutein in 8-wk-old female BALB/c mice fed a diet containing 0, 0.05, 0.1, 0.2 or 0.4% lutein. Mice were killed on d 0, 3, 7, 14, 21 and 28 (n = 6/period), and blood, spleen and liver were collected. Food intake and body, liver and spleen weights did not differ among treatment groups. Lutein + zeaxanthin were not detectable in the plasma, liver and spleen of unsupplemented mice. Mice fed lutein showed very rapid lutein + zeaxanthin absorption. On d 3, concentrations of plasma lutein + zeaxanthin had rapidly increased (P Plasma lutein + zeaxanthin concentrations did not differ among lutein-fed mice by d 7 (2.58 +/- 0.2 micromol/L). Even though maximal uptake of plasma lutein + zeaxanthin was observed by d 3, uptake of lutein + zeaxanthin by the liver and especially by the spleen generally continued to increase (P +/- 0.001 (spleen) and 0.71 +/- 0. 0002 (liver) nmol/g. Therefore, dietary lutein is readily absorbed into the plasma and taken up by liver and spleen of mice. Plasma lutein + zeaxanthin concentrations were higher than in human studies; however, mice were fed lutein at a level several hundredfold greater than in humans. The liver is a major storage organ for lutein + zeaxanthin in mice. Uptake of lutein + zeaxanthin by the spleen suggests a role for lutein in modulating immunity.

  17. Data from quantitative label free proteomics analysis of rat spleen

    Khadar Dudekula


    Full Text Available The dataset presented in this work has been obtained using a label-free quantitative proteomic analysis of rat spleen. A robust method for extraction of proteins from rat spleen tissue and LC-MS-MS analysis was developed using a urea and SDS-based buffer. Different fractionation methods were compared. A total of 3484 different proteins were identified from the pool of all experiments run in this study (a total of 2460 proteins with at least two peptides. A total of 1822 proteins were identified from nine non-fractionated pulse gels, 2288 proteins and 2864 proteins were identified by SDS-PAGE fractionation into three and five fractions respectively. The proteomics data are deposited in ProteomeXchange Consortium via PRIDE PXD003520, Progenesis and Maxquant output are presented in the supported information. The generated list of proteins under different regimes of fractionation allow assessing the nature of the identified proteins; variability in the quantitative analysis associated with the different sampling strategy and allow defining a proper number of replicates for future quantitative analysis.

  18. Asymptomatic lymphangioma involving the spleen and retroperitoneum in adults

    Sook Hee Chung; Young Sook Park; Yun Ju Jo; Seong Hwan Kim; Dae Won Jun; Byoung Kwan Son; Jun Young Jung; Dae Hyun Baek; Dong Hee Kim; Yoon Young Jung; Won Mi Lee


    Lymphangioma, a benign neoplasm of the lymphatic system, is common in children but rare in adults. Its clinical manifestations include abdominal pain, nausea,vomiting and a palpable mass. However, abdominal sonography or abdominal computed tomography (CT) scan can also incidentally reveal lymphangioma. A larger or symptomatic lymphangioma is treated with total resection to prevent recurrence, infection, torsionand enlargement. Although lymphangioma rarely becomes malignant, its prognosis is generally good.We report a cystic lymphangioma of the spleen and retroperitoneum, which was incidentally found in a 56-year-old man who was hospitalized due to a colon mass. Physical examination showed no specific findings.Abdominal CT revealed a 5.7 cm, non-enhanced multilobulated cystic mass with multiple septa in the spleen and a 10 cm lobulated cystic mass in the paraaorticarea. Splenectomy and retroperitoneal resectionof the cystic mass were conducted. The endothelium of splenic and retroperitoneal cyst was immunohistochemically stained with D2-40 antibody. The patient was finally diagnosed with splenic cystic and retroperitoneal cavernous lymphangioma.

  19. Data from quantitative label free proteomics analysis of rat spleen.

    Dudekula, Khadar; Le Bihan, Thierry


    The dataset presented in this work has been obtained using a label-free quantitative proteomic analysis of rat spleen. A robust method for extraction of proteins from rat spleen tissue and LC-MS-MS analysis was developed using a urea and SDS-based buffer. Different fractionation methods were compared. A total of 3484 different proteins were identified from the pool of all experiments run in this study (a total of 2460 proteins with at least two peptides). A total of 1822 proteins were identified from nine non-fractionated pulse gels, 2288 proteins and 2864 proteins were identified by SDS-PAGE fractionation into three and five fractions respectively. The proteomics data are deposited in ProteomeXchange Consortium via PRIDE PXD003520, Progenesis and Maxquant output are presented in the supported information. The generated list of proteins under different regimes of fractionation allow assessing the nature of the identified proteins; variability in the quantitative analysis associated with the different sampling strategy and allow defining a proper number of replicates for future quantitative analysis.

  20. [Pathogenesis and morphology of hemophagocytic syndrome in the spleen].

    Gattenlöhner, S; Müller-Hermelink, H K


    Hemophagocytic syndrome (macrophage activation syndrome) is a group of disorders characterized by clinical, histological and biological symptoms of T-lymphocytes/NK cell-driven macrophage stimulation with subsequent hemophagocytosis which can be observed in various organs, particularly in the bone marrow and spleen. The main clinical symptoms include cytopenia, multiple organ dysfunction, fever unresponsive to antibiotics, hepatosplenomegaly and rash. Besides rare inherited immune system anomalies (primary hemophagocytic syndrome), the most prevalent etiologies of hemophagocytic syndrome are infections (viral, bacterial and parasitic), cancers, lymphoproliferative disorders and systemic diseases. Hemophagocytic syndrome is treated with immunosuppressives, cytostatic drugs, plasmapheresis and intravenous immunoglobulins/anti-TNF antibodies and due to the multiorgan involvement and the associated high mortality, recognition of early serum changes, such as very high levels of ferritin is mandatory. The most relevant histological changes are the increase of histiocytes showing evidence of phagocytosis of erythroid cells, platelets and granulocytes as well as in the spleen a rarefaction of the white pulpa with lack of lymph follicles and abundant lymphocytes, plasma cells and plasma cell precursors in the pulpa cords.

  1. Genomic DNA characterization of pork spleen by Raman spectroscopy

    Guzmán-Embús, D. A.; Orrego Cardozo, M.; Vargas-Hernández, C.


    In this paper, the study of Raman signal enhancement due to interaction between ZnO rods and pork spleen DNA is reported. ZnO microstructures were synthesized by the Sol-Gel method and afterward combined with porcine spleen DNA extracted in the previous stages, following standardized cell lysis, deproteinization, and precipitation processes. Raman spectroscopy was used for the characterization of structures of ZnO and ZnO-DNA complex, and the results show the respective bands of ZnO wurtzite hexagonal phase for modes E2 (M), A1(TO), E2(High), E1(LO), and 2LO. Due to the SERS effect in the spectral range from 200 to 1800 cm,-1 Raman bands caused by vibrations of the deoxyribose C-O-C binding were also observed, producing deformation of the ring as shown in the 559 cm-1 peak. The broad band at 782 cm-1, together with the complex vibration of the string 5'-COPO-C3', is over a wide band of thymine (790 cm-1) or cytosine (780 cm-1). A prominent band near 1098 cm-1 assigned to symmetric stretching vibration phosphodioxy group (PO2-) DNA backbone is most favoured in intensity by the addition of ZnO particles originated by the SERS effect. This effect suggests a possible mechanism for enhancing the Raman signal due to the electromagnetic interaction between a DNA molecule and the flat surface of the ZnO rod.

  2. Dynamics of Red Cells in Spleen: How Does Vesiculation Happen?

    Zhu, Qiang; Salehyar, Sara; Cabrales, Pedro; Asaro, Robert


    Vesiculation of red blood cells as a result of local separation between lipid bilayer and cytoskeleton is known to happen in vivo, most likely inside spleen where they sustain large mechanical loads during the passage through venus slits. There is, however, little knowledge about the detailed scenario and condition. We address this question via a fluid-cell interaction model by coupling a multiscale model of the cell membrane (including molecular details) with a fluid dynamics model based on boundary-integral equations. A numerical flow channel is created where the cell is driven through a narrow slit by pressure (imitating the transit through venus slits in spleen). The concentration is the occurrence of large dissociation (negative) pressure between the skeleton/membrane connection that promotes separation, a precursor of vesicle formation. Critical levels for the negative pressure are estimated using published data. By following the maximum range of pressure, we conclude that for vesiculation to happen there must be biochemical influences (e.g. binding of degraded haemoglobin) that significantly reduce effective attachment density. This is consistent with reported trends in vesiculation that are believed to occur in cases of various hereditary anemias and during blood storage. Our findings also suggest the criticality of understanding the biochemical phenomena involved with cytoskeleton/membrane attachment.

  3. The spleen in the sickling disorders: an update

    Khatib, Rana; Sarnaik, Sharada A. [Wayne State University School of Medicine, Children' s Hospital of Michigan, Carmen and Ann Adams Department of Pediatrics, Detroit, MI (United States); Rabah, Raja [Wayne State University School of Medicine, Department of Pathology, Detroit, MI (United States)


    In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal ''autosplenectomy'' emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management. (orig.)

  4. Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus.

    Mitra, Soham; Keswani, Tarun; Dey, Manali; Bhattacharya, Shaswati; Sarkar, Samrat; Goswami, Suranjana; Ghosh, Nabanita; Dutta, Anuradha; Bhattacharyya, Arindam


    Copper is an essential trace element for human physiological processes. To evaluate the potential adverse health impact/immunotoxicological effects of this metal in situ due to over exposure, Swiss albino mice were treated (via intraperitoneal injections) with copper (II) chloride (copper chloride) at doses of 0, 5, or 7.5 mg copper chloride/kg body weight (b.w.) twice a week for 4 wk; these values were derived from LD₅₀ studies using copper chloride doses that ranged from 0 to 40 mg/kg BW (2×/wk, for 4 wk). Copper treated mice evidenced immunotoxicity as indicated by dose-related decreases and increases, respectively, in thymic and splenic weights. Histomorphological changes evidenced in these organs were thymic atrophy, white pulp shrinkage in the spleen, and apoptosis of splenocytes and thymocytes; these observations were confirmed by microscopic analyses. Cell count analyses indicated that the proliferative functions of the splenocytes and thymocytes were also altered because of the copper exposures. Among both cell types from the copper treated hosts, flow cytometric analyses revealed a dose related increase in the percentages of cells in the Sub-G₀/G₁ state, indicative of apoptosis which was further confirmed by Annexin V binding assay. In addition, the copper treatments altered the expression of selected cell death related genes such as EndoG and Bax in a dose related manner. Immunohistochemical analyses revealed that there was also increased ubiquitin expression in both the cell types. In conclusion, these studies show that sublethal exposure to copper (as copper chloride) induces toxicity in the thymus and spleen, and increased Sub G₀/G₁ population among splenocytes and thymocytes that is mediated, in part, by the EndoG-Bax-ubiquitin pathway. This latter damage to these cells that reside in critical immune system organs are likely to be important contributing factors underlying the immunosuppression that has been documented by other

  5. Role of color Doppler flow imaging in applicable anatomy of spleen vessels

    Wei-Li Xu; Suo-Lin Li; Yan Wang; Meng Li; Ai-Guo Niu


    AIM: To explore the role of color Doppler flow imaging (CDFI) in visualization of spleen vessels and to define its value for spleen micro-invasive operation. METHODS: A total of 36 patients requiring laparoscopic splenectomy (LS) for various hematopathies and autoimmune diseases were randomly selected from April 2005 to May 2008. Anatomic types of spleen pedicle, adjacent relations between spleen vessels and pancreas, diameters of spleen artery and vein were detected and recorded by preoperative CDFI. Different operative procedures were performed according to different anatomic frameworks. The parameters were recorded by telerecording during LS and compared with those by preoperative CDFI using Chi-square test. RESULTS: Two anatomic types of spleen pedicle and four different adjacent relations between spleen vessels and pancreas were detected by CDFI. The diameters of spleen artery and vein detected by CDFI were 0.46 ± 0.09 cm and 0.85 ± 0.35 cm, respectively. There was no statistical difference between the parameters recorded by CDFI and by telerecording (χ2 = 0.250, 0.677, P > 0.05). LS was successfully performed following the anatomic information provided by preoperative CDFI.CONCLUSION: Different anatomic frameworks of spleen vessels can be provided by preoperative CDFI,which instructs micro-invasive operation of spleen and increase the safety of operation.

  6. Bone marrow response in treated patients with Gaucher disease: evaluation by T1-weighted magnetic resonance images and correlation with reduction in liver and spleen volume

    Terk, M.R. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology; LAC/USC Imaging Science Center, Los Angeles, CA (United States); Dardashti, S. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology; Liebman, H.A. [University of Southern California, Los Angeles, CA (United States). Dept. of Medicine


    Purpose. To determine whether T1-weighted magnetic resonance (MR) images can demonstrate response in the marrow of patients with type 1 Gaucher disease treated with enzyme replacement therapy (ERT) and to determine whether a relationship exists between liver and spleen volume reductions and visible marrow changes.Patients. Forty-two patients with type 1 Gaucher disease were evaluated on at least two occasions. Thirty-two patients received ERT. Of these patients, 15 had a baseline examination prior to the initiation of ERT. The remaining 10 patients did not receive ERT.Design. T1-weighted and gradient recalled echo (GRE) coronal images of the femurs and hips were obtained. Concurrently, liver and spleen volumes were determined using contiguous breath-hold axial gradient-echo images. T1-weighted images of the hips and femurs were evaluated to determine change or lack of change in the yellow marrow.Results. Of the 32 patients receiving ERT, 14 (44%) demonstrated increased signal on T1-weighted images suggesting an increase in the amount of yellow marrow. If only the 15 patients with a baseline examination were considered, the response rate to ERT was 67%. Using Student's t-test a highly significant correlation (P<0.005) was found between marrow response and reduction in liver and spleen volume.Conclusions. Marrow changes in patients receiving ERT can be detected by T1-weighted images. This response correlated with reductions in visceral volumes (P<0.0005). (orig.)

  7. Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

    Wang, Yuehai [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Huang, Ziyang, E-mail: [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Lu, Huixia [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Huili; Wang, Zhenhua [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Chen, Xiaoqing [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Ouyang, Qiufang [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Tang, Mengxiong; Hao, Panpan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Ni, Jingqin [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Xu, Dongming [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Zhang, Mingxiang; Zhang, Qunye [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Ling [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); and others


    Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-} mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The

  8. Immunomodulating Effect of Cyclophosphamide on the Mice Infected with Candida albicans

    aziz japoni


    Full Text Available Background & Objectives: Cyclophosphamide is an alkylating agent that stops the replication of DNA, which is used to treat various types of cancer and some autoimmune disorders. This study was aimed at then evaluating the immunomodulating effect of cyclophosphamide (Cy on the immune system of vaccinated and non-vaccinated mice.Materials & Methods: The  study was performed on three groups of mice consisting of vaccinated, non-vaccinated and control groups. Vaccination was carried out by three separated courses of C. albicans injection intraperitoneally.  Then,  the  vaccinated group  received Cy  on  day  zero  and  were  challenged  with  lethal  doses of  C. albicans  on  days  zero, one, 3, 6 and 12 post-Cy injection. Non-vaccinated group received Cy on day zero and similar to vaccinated ones were challenged with lethal doses of the organism. The control groups received  just  Cy  on  day  zero  and  were  sacrificed  on days  post-Cy injection. Then, the hemogram and the spleen and the renal tissues were studied microscopically and macroscopically.Results: In the vaccinated group, an increase in survival time, the number of polymorphonuclear and the significant hyperplasia in the white pulp on days 6 and 12 post-Cy injection were noticed. In non-vaccinated ones, these factors had significant decrease on days 1 and 3. Conclusion: It is concluded that the hyperplasia in the white pulp of spleen and an increasing in peripheral polymorphonuclear due to the selective effects of Cy could effectively protect the animal against C. albicans infection.

  9. Spleen tyrosine kinase inhibitors for rheumatoid arthritis: where are we now?

    Scott, Ian C; Scott, David L


    The development of small-molecule inhibitors of inflammatory cascade signaling kinases offers a potential approach to treating rheumatoid arthritis (RA). Spleen tyrosine kinase is one such tyrosine kinase. Recent research efforts have focussed on the development and testing of a spleen tyrosine kinase inhibitor, fostamatinib. We reviewed the results of the clinical trials of fostamatinib in RA with the aim of outlining its clinical efficacy and the nature and frequency of its main adverse events. To date, this drug has been evaluated in over 3,200 RA patients enrolled in three phase II, one phase IIb and three phase III trials. These studies showed fostamatinib was effective. In four trials in which patients received 100 mg twice daily, fostamatinib reduced inflammatory synovitis; the relative risks of achieving American College of Rheumatology Responder rates compared with placebo in the combined studies ranged from 1.6 for 20 % of responders to 3.7 for 70 % of responders. There was a similar relative risk of achieving a clinically meaningful reduction in disability of 1.6 for the chance of patients achieving a reduction in health assessment questionnaire scores of 0.22 or more. Three of the trials examined the impact of fostamatinib on erosive radiographic damage using changes in the modified total Sharp score. None of them provided any evidence for a significant effect of fostamatinib on erosive damage over 6 months. All the trials included descriptions of adverse events. Hypertension was common, involving over 40 % of patients treated. Other common adverse events included diarrhoea, neutropenia and increases in hepatic enzyme levels. Some patients developed infections. On the conclusion of the phase III trials, one of the main pharmaceutical sponsors decided not to further develop fostamatinib for RA.

  10. Donor MHC gene to mitigate rejection of transplantation in recipient mice

    LI Tong; ZHANG Zhi-tai; LI Hui; YAN Jun; TAN Jia-li; L(U) Yue-ping; HOU Sheng-cai; LI Shen-tao; XU Qing; TONG Xue-hong; DING Jie


    Background Donor organ rejection continues to be a significant problem for patients receiving transplants.We therefore tested whether transferring a donor's major histocompatibility complex (MHC) gene to the recipient would mitigate the rejection of transplanted hearts in mice.Methods H-2Kkgene from donor mice was amplified using nested polymerase chain reaction (PCR) and ligated into a mammalian expression vector,which was then transfected into thymus ground mass cells collected from the recipients.Clones stably expressing the transgene were then injected into the recipients' thymus visualized using ultrasound.Control mice were administered cells previously transfected with empty vector.Following heart transplantation,cardiac activity was monitored electrocardiographically.Recipient thymus cells were tested for MHC antigenicity using flow cytometry and spleen cells were subjected to mixed lymphocyte culture tests.Finally,the transplanted hearts were sectioned,stained and examined under light microscopy.Results Southern analysis following nested PCR revealed clear expression of H-2Kk gene.Following transplantation,electrocardiosignals were detectable highly significantly longer in recipients administered thymal cells expressing donor H-2Kk than in those receiving control cells.Flow cytometric analysis using an anti-H-2Kk antibody confirmed its expression in H-2Kk treated recipients but not in control mice.Mixed lymphocyte cultures containing H-2Kk treated cells showed significantly less proliferation than those containing control cells.Hearts from control mice showed substantially greater lymphocyte infiltration than those from H-2Kk treated mice and large areas of necrosis.Conclusion Rejection of transplanted hearts can be mitigated substantially by introducing the donor's MHC into the recipient.

  11. Wandering spleen, gastric and pancreatic volvulus and right-sided descending and sigmoid colon.

    Flores-Ríos, Enrique; Méndez-Díaz, Cristina; Rodríguez-García, Esther; Pérez-Ramos, Tania


    Wandering spleen is a rare condition, characterized by a mobile spleen that is attached only by an elongated vascular pedicle, allowing it to migrate to any part of the abdomen or pelvis. Mesenteroaxial gastric volvulus usually occurs in children and may be associated with wandering spleen. Both entities result from abnormal laxity or absence of the peritoneal attachments due to abnormal fusion of the peritoneal mesenteries. Pancreatic volvulus is a very rare anomaly, with only a few isolated case reports described in association with wandering spleen. Anomalous right sided descending and sigmoid colon is a very rare entity and its association with wandering spleen has not been previously reported. We report a case of wandering spleen associated with mesenteroaxial gastric volvulus, pancreatic volvulus and rightward shift of the splenic flexure of the colon and right sided descending and sigmoid colon in a young female.

  12. The Therapeutic Effects of the Chinese Herbal Medicine, Lang Chuang Fang Granule, on Lupus-Prone MRL/lpr Mice

    Kai-Peng Huang


    Full Text Available Systemic lupus erythematosus (SLE is a chronic autoimmune disease that leads to severe multiorgan damage. Lang Chuang Fang (LCF is a Chinese herbal medicine that is clinically prescribed for treating SLE. In this study, we examined the therapeutic effects of LCF granule on lupus-prone MRL/lpr mice. Female mice were randomly separated into six groups, and LCF treatment groups received LCF granule at the dosage of 0.97 g/kg/d, 1.95 g/kg/d, and 3.90 g/kg/d, respectively. Here, we found that, compared to the MRL/lpr mice, both the spleen coefficient and thymus coefficient were reduced in the LCF granule-treated mice. There was a marked downregulation in CRP and anti-dsDNA autoantibody and an evident upregulation of CH50 in LCF granule-treated mice. LCF granule treatment also obviously reduced the proteinuria, BUN, and SCr levels in MRL/lpr mice at the dosage of 0.97 g/kg/d, 1.95 g/kg/d, and 3.90 g/kg/d, indicating that LCF granule alleviated the renal injury of MRL/lpr mice. Furthermore, LCF granule decreased p65 NF-κB levels and increased Sirt1 and Nrf2 levels in the kidney tissues of MRL/lpr mice, which might elucidate the beneficial effects of LCF on lupus nephritis. In conclusion, this study demonstrates that LCF granule has therapeutic effects on lupus-prone MRL/lpr mice.

  13. Spontaneous rupture of tuberculous spleen in a HIV seropositive patient on maintenance hemodialysis

    Rathore Shubhra


    Full Text Available Spontaneous rupture of the spleen usually occurs secondary to infection, hematolo-gical disorders or infiltrative lesions of the spleen. In patients with positive human immuno-deficiency virus (HIV antibodies and the acquired immunodeficiency syndrome (AIDS who pre-sent with acute abdomen, splenic rupture should be considered as a possible cause and should addi-tionally be investigated for co-infection with tuberculosis. Spontaneous rupture of spleen in asymp-tomatic patients requires a high index of suspicion for diagnosis. We herein report on a HIV-positive patient on maintenance hemodialysis, who presented with spontaneous rupture of a tuberculous spleen.

  14. Interactions between Biliverdin, Oxidative Damage, and Spleen Morphology after Simulated Aggressive Encounters in Veiled Chameleons.

    Butler, Michael W; Ligon, Russell A


    Stressors frequently increase oxidative damage--unless organisms simultaneously mount effective antioxidant responses. One putative mitigative mechanism is the use of biliverdin, an antioxidant produced in the spleen during erythrocyte degradation. We hypothesized that both wild and captive-bred male veiled chameleons (Chamaeleo calyptratus), which are highly aggressive to conspecifics, would respond to agonistic displays with increased levels of oxidative damage, but that increased levels of biliverdin would limit this increase. We found that even just visual exposure to a potential combatant resulted in decreased body mass during the subsequent 48-hour period, but that hematocrit, biliverdin concentration in the bile, relative spleen size, and oxidative damage in plasma, liver, and spleen were unaffected. Contrary to our predictions, we found that individuals with smaller spleens exhibited greater decreases in hematocrit and higher bile biliverdin concentrations, suggesting a revision to the idea of spleen-dependent erythrocyte processing. Interestingly, individuals with larger spleens had reduced oxidative damage in both the liver and spleen, demonstrating the spleen's importance in modulating oxidative damage. We also uncovered differences in spleen size and oxidative damage between wild and captive-bred chameleons, highlighting environmentally dependent differences in oxidative physiology. Lastly, we found no relationship between oxidative damage and biliverdin concentration, calling into question biliverdin's antioxidant role in this species.

  15. Transient reduction of spleen density in acute pancreatitis: case reports and literature review.

    Jiang, Xing Yue; Bian, Jia; Zhang, Cheng Zhou; Wang, Shan Shan; Nie, Tai Ming; Zhang, Lin


    A healthy spleen has density stable on computed tomographic (CT) scan; in some patients, spleen infarction can be associated with acute pancreatitis. Here, we report 2 patients with acute pancreatitis associated with transient reduction of spleen density that were confirmed in our hospital. The clinical data of the 2 patients were retrospectively analyzed, and the relevant literature was reviewed. Acute pancreatitis with transient reduction of splenic density has certain characteristics in clinical and radiological aspects. After clinical treatment, the spleen density can be restored. Its mechanism may be related to glucose and lipid metabolism, transient thrombosis formation in splenic vessels, and so on.

  16. Pattern of distribution and kinetics of accumulation of gold nanorods in mouse spleen

    Di Lascio, Nicole; Avigo, Cinzia; Armanetti, Paolo; Stea, Francesco; Cavigli, Lucia; Ratto, Fulvio; Pini, Roberto; Kusmic, Claudia; Menichetti, Luca; Faita, Francesco


    Gold nanorods (GNRs) offer a tunable optical absorption in the near infra-red wavelength region due to their plasmon resonance, which results in strong photoacoustic (PA) signal and make them suitable as contrast agent by means of PA imaging. The aim of this study was to examine the performance of synthesized polyethilene glicol (PEG)-GNRs as contrast agent for in vivo PA imaging and to evaluate their accumulation and distribution real time. Two-three month old FVB female mice were enrolled for the study, a bolus of 200μL of synthesized PEG-GNRs (53 nm length and 11 nm axial diameter, plasmon resonance at 840 nm, 1 mM Au concentration) solution was injected intravenously and detected with PA imaging. The accumulation of GNRs in the spleen was studied by means of the amplitude dynamic variation of the PA signal during time. GNRs contrast was clearly distinguished from endogenous background thanks to the nanoparticle spectroscopic specificity. Our results suggest that PA imaging could allow an efficient and noninvasive tool for in vivo detection of GNRs content and for the assessment of the kinetic parameters in target organs. The coregistration of μ-ultrasound and PA imaging is crucial for the real time evaluation of the GNRs distribution in different organs.

  17. Xanthohumol feeding does not impair organ function and homoeostasis in mice.

    Dorn, Christoph; Bataille, Frauke; Gaebele, Erwin; Heilmann, Jörg; Hellerbrand, Claus


    Xanthohumol, the major prenylated chalcone found in hops, is known to exert several beneficial effects but only few studies evaluated the safety profile of this natural compound with in part discrepant results. Here, we fed female BALB/c mice with a standard diet supplemented with xanthohumol for 3 weeks, and thus, achieved a daily dose of approximately 1000 mg xanthohumol/kg body weight. There were no significant differences in body weight or food intake between mice on standard diet and animals receiving the same diet supplemented with xanthohumol. Histopathological examination of liver, kidney, colon, lung, heart, spleen and thymus revealed no signs of xanthohumol-toxicity, and biochemical serum analysis confirmed normal organ function. Further, xanthohumol treatment did not affect hepatic glycogen content CYP2E1 and CYP1A2 expression levels, but CYP3A11 mRNA was approximately 30% reduced. Expression of several genes indicative of early hepatic inflammation and fibrosis, a hallmark of chronic liver injury, did not differ between xanthohumol treated and control mice. In summary, these results indicate that oral administration of xanthohumol exhibits no adverse effects on major organ function and homoeostasis in mice. Particularly, hepatotoxic effects could be ruled out confirming a good safety profile of xanthohumol as prerequisite for further studies in humans.

  18. Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice

    Lima Leandro C F


    Full Text Available Abstract Background Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/- mouse. Methods Spleen-derived MNCs were isolated from green fluorescent protein (GFP-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC or vehicle (Cuff-Vehicle and were compared with sham-operated animals (Sham. Results The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 ± 4; Vehicle, 20 ± 4; Sham, 55 ± 2 x103 μm2; p -/- mice. Conclusion In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.

  19. Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

    Zhen Gong


    Full Text Available Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID. Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 107 cells/mouse i.p. and human bladder cancer cells (3 × 106 cells/mouse s.c.. Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3+ cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.

  20. Evaluation in mice of the capillary leak syndrome (CLS) mediated by the systemic administration of recombinant interleukin-2 (IL-2)

    Ettinghausen, S.E.; Rosenstein, M.; Rosenberg, S.A.


    Since a CLS with interstitial pulmonary edema has been the major toxicity of IL-2 administration in humans, the authors studied this CLS in mice by quantitating the IL-2 mediated, tissue extravasation (Ex) of intravenously injected /sup 125/I-bovine serum albumin (BSA). Mice received saline (HBSS) or 200,000 U of IL-2 intraperitoneally thrice daily from day 0-6 before tissues were counted. A permeability index (PI) was calculated by dividing the mean counts per minute (CPM) from tissues of treated mice by those from controls. In a representative experiment, increased BSA Ex was noted in the lungs of mice treated with IL-2 when compared with HBSS (6187 +/- 141 and 638 +/- 64 CPM +/- SEM, respectively; p2 < .001; PI = 9.7). Other tissues with increased BSA Ex included the liver, spleen, kidneys and mesenteric lymph nodes (PI = 6.7, 10.0, 6.3, 6.0, respectively). BSA Ex, which did not occur with the excipient control, was dependent upon the dose and the duration of IL-2. Serial lung weights showed dramatic increases in water weight induced by IL-2. Treatment of mice with radiation (500R), cyclophosphamide, or cortisone acetate significantly reduced IL-2 mediated BSA Ex. Thus, IL-2 induced a generalized CLS which is mediated directly or indirectly by cellular mechanisms.

  1. Identification of (+)-erythro-mefloquine as an active enantiomer with greater efficacy than mefloquine against Mycobacterium avium infection in mice.

    Bermudez, Luiz E; Inderlied, Clark B; Kolonoski, Peter; Chee, Christopher B; Aralar, Priscilla; Petrofsky, Mary; Parman, Toufan; Green, Carol E; Lewin, Anita H; Ellis, William Y; Young, Lowell S


    Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+)-erythro-, (-)-erythro-, (+)-threo-, and (-)-threo-mefloquine were 32 μg/ml, 32 μg/ml, 64 μg/ml, and 64 μg/ml, respectively. The postantibiotic effect for (+)-erythro-mefloquine was 36 h (MIC) and 41 h for a concentration of 4× MIC. The mefloquine postantibiotic effect was 25 h (MIC and 4× MIC). After baseline infection was established (7 days), the (+)- and (-)-isomers of the diastereomeric threo- and erythro-α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol were individually used to orally treat C57BL/6 bg(+)/bg(+) beige mice that were infected intravenously with M. avium. Mice were also treated with commercial mefloquine and diluent as controls. After 4 weeks of treatment, the mice were harvested, and the number of bacteria in spleen and liver was determined. Mice receiving (+)- or (-)-threo-mefloquine or (-)-erythro-mefloquine had numbers of bacterial load in tissues similar to those of untreated control mice at 4 weeks. Commercial mefloquine had a bactericidal effect. However, mice given the (+)-erythro-enantiomer for 4 weeks had a significantly greater reduction of bacterial load than those given mefloquine. Thus, (+)-erythro-mefloquine is the active enantiomer of mefloquine against M. avium and perhaps other mycobacteria.

  2. Effects of Hypericum perforatum extract on IgG titer, leukocytes subset and spleen index in rats

    Tahereh Aghili


    Full Text Available Objectives: Hypericum perforatum L. is a medicinal plant containing many polyphenolic compounds, ‎including flavonoids and phenolic acids with antidepressant and anti-inflammatory properties. ‎This study was investigated the effects of Hypericum perforatum extract (HPE on immunity, ‎body weight (BW, and spleen index (SI in rats.‎ Materials and Methods: A total of 24 Wistar male rats were randomly received 4 different doses (6 rats each of HPE ‎‎(0, 100, 200 and 400 mg/kg BW intraperitoneally for 14 days using a completely ‎randomized design. On days 1 and 7, rats were received 0.5 ml SRBC (10% injection. Blood ‎samples were collected on day 14 to evaluate IgG titer and leukocyte count. On days 1, 7 and ‎‎14, the BW and on day 14 spleen were weighted for SI. ‎ Results: The IgG titer increased with higher doses of HPE. The HPE increased number of ‎lymphocytes at 200 mg but decreased at 400 mg, number of neutrophils decreased at 200 mg ‎but increased at 400 mg, and number of monocytes increased at 100 mg and 200 mg but ‎decreased at 400 mg (p

  3. Long-term effects on the histology and function of livers and spleens in rats after 33% toploading of PEG-PLA-nano artificial red blood cells.

    Liu, Zun Chang; Chang, Thomas M S


    This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens.

  4. {sup 18}F-FDG uptake by spleen helps rapidly predict the dose level after total body irradiation in a Tibetan minipig model

    Wang, Yu Jue; Gu, Wei Wang [Southern Medical University, Department of Laboratory Animal Center, Guangzhou, Guangdong (China); Wu, Shao Jie; Guo, Kun Yuan; Chen, Chi [Southern Medical University, Department of Hematology, Zhujiang Hospital, Guangzhou, Guangdong (China); Xie, Qiang; Cai, Liang [Chinese People' s Armed Police Forces, Department of Oncology and PET/CT, Guangdong Provincial Corp Hospital, Guangzhou, Guangdong (China); Zou, Fei [Southern Medical University, School of Public Health and Tropical Medicine, Guangzhou, Guangdong (China)


    To investigate whether {sup 18}F- FDG uptake can be applied in dosimetry to facilitate the rapid and accurate evaluation of individual radiation doses after a nuclear accident. Forty-eight Tibetan minipigs were randomised into a control group (n = 3) and treatment groups (n = 45). {sup 18}F-FDG combined positron-emission tomography and computed tomography (PET/CT) were carried out before total body irradiation (TBI) and at 6, 24 and 72 h after receiving TBI doses ranging from 1 to 11 Gy. Spleen tissues and blood samples were also collected for histological examination, apoptosis and blood analysis. Mean standardised uptake values (SUVs) of the spleen showed significant differences between the experimental and the control groups. Spleen SUV at 6 h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.97 (P < 0.01). Histological observations showed that damage to the splenic lymphocyte became more severe with an increase in the radiation dose. Moreover, apoptosis was one of the major routes of splenic lymphocyte death, which was also confirmed by flow cytometry analysis. In the Tibetan minipig model, radiation doses have a close relationship with the {sup 18}F-FDG uptake of the spleen. This finding suggests that {sup 18}F-FDG PET/CT may be useful for the rapid detection of individual radiation doses. (orig.)

  5. Identifying protective host gene expression signatures within the spleen during West Nile virus infection in the collaborative cross model

    Richard Green


    Full Text Available Flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. Like Zika virus, West Nile Virus (WNV is a flavivirus for which no approved vaccine exists [1]. The role host genetics play in early detection and response to WNV still remains largely unexplained. In order to capture the impact of genetic variation on innate immune responses, we studied gene expression following WNV infection using the collaborative cross (CC. The CC is a mouse genetics resource composed of hundreds of independently bred, octo-parental recombinant inbred mouse lines [2]. To accurately capture the host immune gene expression signatures of West Nile infection, we used the nanostring platform to evaluate expression in spleen tissue isolated from CC mice infected with WNV over a time course of 4, 7, and 12 days' post-infection [3]. Nanostring is a non-amplification based digital method to quantitate gene expression that uses color-coded molecular barcodes to detect hundreds of transcripts in a sample. Using this approach, we identified unique gene signatures in spleen tissue at days 4, 7, and 12 following WNV infection, which delineated distinct differences between asymptomatic and symptomatic CC lines. We also identified novel immune genes. Data was deposited into the Gene Expression Omnibus under accession GSE86000.

  6. Differential control of immune cell homeostasis by Foxp3(+) regulatory T cells in murine peripheral lymph nodes and spleen.

    Milanez-Almeida, Pedro; Klawonn, Frank; Meyer-Hermann, Michael; Huehn, Jochen


    Foxp3(+) regulatory T cells (Tregs) hamper efficient immune responses to tumors and chronic infections. Therefore, depletion of Foxp3(+) Tregs has been proposed as therapeutic option to boost immune responses and to improve vaccinations. Although Treg-mediated control of T cell homeostasis is well established, Foxp3(+) Treg interaction with other immune cell subsets is only incompletely understood. Thus, the present study aimed at examining dynamic effects of experimental Foxp3(+) Treg depletion on a broad range of immune cell subsets, including B cells, natural killer cells, and myeloid cells. Striking differences were observed when peripheral lymph nodes (LN) and spleen were compared. B cells, for example, showed a massive and long-lasting accumulation only in LN but not in spleen of transiently Treg-depleted mice. In contrast, monocyte-derived dendritic cells, which are potent inducers of T cell responses, also accumulated selectively, but only transiently in LN, suggesting that this cell population is under very strict control of Foxp3(+) Tregs. In summary, the observations described here provide insights into the dynamics of immune cells after selective depletion of Foxp3(+) Tregs. This will allow a better prediction of the impact of Treg ablation in translational studies that aim at boosting immune responses and vaccinations.

  7. Diffuse Hepatic and Spleen Uptake of Tc-99m MDP on Bone Scintigraphy Resembling Liver-Spleen Scintigraphy in a Patient of Plasma Cell Tumor.

    Ravanbod, Mohammad Reza; Nemati, Reza; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid


    The present case demonstrates a diffuse intense hepatic and, to a lesser degree, spleen, Tc-99m MDP uptake on a routine bone scintigraphy resembling liver-spleen imaging. A 49-year-old female with a history of anaplastic plasma cell tumor and suffering from bone pain was referred for bone scintigraphy to evaluate possible bone metastases. The bone scintigraphy showed diffuse hepatic and spleen uptake of Tc-99m MDP resembling liver-spleen imaging. Furthermore, bone uptake of Tc-99m MDP was significantly diminished and there were no abnormal foci throughout the skeleton. The bone scintigraphy of the present case of an anaplastic plasma cell tumor suggests the possible presence of amyloidosis.

  8. Regeneration of hemopoietic and lymphoid tissues following total-body irradiation and therapeutic administration of thiamin diphosphate. [Mice, gamma radiation

    Vavrova, J.; Nouza, K.; Petjrek, P.


    Analysis was made of the mechanism of therapeutic application of thiamine diphosphate (TDP) in radiation sickness in mice. This agent increased the number of endogenous colonies in the spleen and incorporation of /sup 59/Fe in spleen and bone marrow with sublethal doses of radiation (500 and 600 R) and has no effect with a lethal dose (750 R). After administration of TDP to mice exposed to 500 R radiation, there is faster DNA synthesis in the spleen, thymus and bone marrow, as well as reliable increase in number of nuclear cells in femoral marrow.

  9. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J. (Department of Veterinary Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States))


    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 {times} 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.

  10. Highly Sensitive Optical Receivers

    Schneider, Kerstin


    Highly Sensitive Optical Receivers primarily treats the circuit design of optical receivers with external photodiodes. Continuous-mode and burst-mode receivers are compared. The monograph first summarizes the basics of III/V photodetectors, transistor and noise models, bit-error rate, sensitivity and analog circuit design, thus enabling readers to understand the circuits described in the main part of the book. In order to cover the topic comprehensively, detailed descriptions of receivers for optical data communication in general and, in particular, optical burst-mode receivers in deep-sub-µm CMOS are presented. Numerous detailed and elaborate illustrations facilitate better understanding.


    Xiu Wen P'ng, Gabriel Akyirem Akowuah and Jin Han Chin*


    Full Text Available Clinacanthus nutans Lindau (Family: Acanthaceae has attracted public interest recently due to its high medicinal values for the treatment of cancer, inflammation and various skin problems. This study was aimed to determine the oral LD50 value of the methanol leaves extract of C. nutans and identify the targeted organs in mice. This acute oral toxicity study was conducted in accordance to OECD 423 guidelines by using male Swiss albino mice weighing 25-35 g. First group was served as control group which received distilled water (vehicle while second and third group were orally treated with single daily dose of 0.9 g/kg and 1.8 g/kg of methanol leaves extract of C. nutans, respectively. All the animals were closely observed for 14 days. Body weight for each mouse was recorded at day-0, day-3, day-7 and day-14. Relative organ weights for liver, kidney, spleen, lung and heart were also determined. All the results were presented as mean ± standard deviation and analyzed using Dunnett’s Test after ANOVA test. From the results obtained, no mortality was observed in both treatment groups either post 24 hours or 14 days of oral administration of C. nutans. Body weight for each mouse and relative organ weight showed insignificant difference when compared to the control group. In conclusion, acute exposure of 1.8 g/kg of C. nutans was safe in male mice without causing any adverse effects or mortality. The oral LD50 of methanol leaves extract of C. nutans was suggested to be greater than 1.8 g/kg bw in male mice.

  12. Myostatin expression, lymphocyte population, and potential cytokine production correlate with predisposition to high-fat diet induced obesity in mice.

    Jeri-Anne Lyons

    Full Text Available A strong relationship exists between increased inflammatory cytokines and muscle insulin resistance in obesity. This study focused on identifying a relationship between metabolic propensity and myostatin expression in muscle and spleen cells in response to high-fat diet intake. Using a comparative approach, we analyzed the effects of high-fat diet intake on myostatin and follistatin expression, spleen cell composition, and potential cytokine expression in high-fat diet induced obesity (HFDIO resistant (SWR/J and susceptible (C57BL/6 mice models. Results demonstrated overall increased myostatin expression in muscle following high-fat diet intake in HFDIO-susceptible mice, while myostatin expression levels decreased initially in muscle from high-fat diet fed resistant mice. In HFDIO-resistant mice, myostatin expression decreased in spleen, while myostatin increased in spleen tissue from HFDIO-susceptible mice. Proinflammatory cytokine (IL-17, IL-1β, and IFNγ potential increased in splenocytes from HFDIO-susceptible mice. In comparison, C57BL/6 mice fed a high-fat diet exhibited higher frequencies of CD4(+/CD44(hi and CD8(+/CD44(hi cells in the spleen compared to control fed mice. Together, these results suggest that susceptibility to high-fat diet induced obesity could be influenced by local myostatin activity in a tissue-specific manner and that splenocytes exhibit differential cytokine production in a strain-dependent manner. This study sets the stage for future investigations into the interactions between growth, inflammation, and metabolism.

  13. Monoclonal B-cell hyperplasia and leukocyte imbalance precede development of B-cell malignancies in uracil-DNA glycosylase deficient mice

    Andersen, Sonja; Ericsson, Madelene; Dai, Hong Yan;


    causes a significant reduction of T-helper cells, and 50% of the young Ung(-/-) mice investigated have no detectable NK/NKT-cell population in their spleen. The immunological imbalance is confirmed in experiments with spleen cells where the production of the cytokines interferon gamma, interleukin 6...

  14. Subchronic toxicity of triethylenetetramine dihydrochloride in B6C3F1 mice and F344 rats.

    Greenman, D L; Morrissey, R L; Blakemore, W; Crowell, J; Siitonen, P; Felton, P; Allen, R; Cronin, G


    Triethylenetetramine dihydrochloride (trien-2HCl; CAS No. 38260-01-04), a chelating agent used to treat Wilson's disease patients who are intolerant of the drug of choice, was tested for subchronic toxicity in B6C3F1 mice and F344 rats. Mice and rats received trien-2HCl in the drinking water at concentrations of 0, 120, 600, or 3000 ppm for up to 92 days. Twenty mice and 18 rats of each sex were assigned to each dose group fed either a cereal-based (NIH-31) or a purified (AIN-76A) diet, both containing nutritionally adequate levels of copper. An additional control group of rats and mice received a Cu-deficient AIN-76A diet. This low copper diet resulted in Cu-deficiency symptoms, such as anemia, liver periportal cytomegaly, pancreatic atrophy and multifocal necrosis, spleen hematopoietic cell proliferation, and increased heart weight, together with undetectable levels of plasma copper in rats but not in mice. Trien-2HCl lowered plasma copper levels some-what (at 600 and 3000 ppm) in rats fed the AIN-76A diet, but did not induce the usual signs of copper deficiency. Trien-2HCl caused an increased frequency of uterine dilatation at 3000 ppm in rats fed AIN-76A diet that was not noted in females fed the Cu-deficient diet. Trien-2HCl toxicity occurred only in mice in the highest dose group fed an AIN-76A diet. Increased frequencies of inflammation of the lung interstitium and liver periportal fatty infiltration were seen in both sexes, and hematopoietic cell proliferation was seen in the spleen of males. Kidney and body weights were reduced in males as was the incidence of renal cytoplasmic vacuolization. There were no signs of copper deficiency in mice exposed to trien-2HCl. The only effect of trien-2HCl in animals fed the NIH-31 diet was a reduced liver copper level in both rat sexes, noted at 3000 ppm.

  15. Effects of boron on structure and antioxidative activities of spleen in rats.

    Hu, Qianqian; Li, Shenghe; Qiao, Enmei; Tang, Zhongtao; Jin, Erhui; Jin, Guangming; Gu, Youfang


    In order to determine the relationship between boron and development of the spleen, especially in the promoting biological effects, we examined the effects of different levels of boron on weight, organ index, microstructure, and antioxidative activities of the spleen in rats. Sprague-Dawley (SD) rats were selected and treated with different concentrations of boron, and then, the organs were resected and weighed. One half of the tissue was fixed and embedded in paraffin to observe tissue structure changes. The other half of the tissue was homogenated for determining the antioxidant activities. The results showed that 40 mg/L of boron could increase weight, organ indexes, and antioxidant capacity of spleens and improve the spleen tissue structure, while the boron concentration above 80 mg/L could decrease weight, organ indexes, and antioxidant capacity of spleens and damage the spleen tissue structure. The higher the concentration, the more serious the damage was. Especially at the concentration of 640 mg/L, it could significantly inhibit the development of the spleen and even exhibit toxic effect. Hence, low boron concentration played a protective role in the development of the spleen, while high boron concentration could damage the organs and even produce toxic effect.

  16. CT Scan Mapping of Splenic Flexure in Relation to Spleen and its Clinical Implications.

    Saber, Alan A; Dervishaj, Ornela; Aida, Samer S; Christos, Paul J; Dakhel, Mahmoud


    Splenic flexure mobilization is a challenging step during left colon resection. The maneuver places the spleen at risk for injury. To minimize this risk, we conducted this study for CT scan mapping of splenic flexure in relation to the spleen. One hundred and sixty CT scans of abdomen were reviewed. The level of the splenic flexure was determined in relation to hilum and lower pole of spleen. These levels were compared with patient demographics. Statistical analysis was performed using Fisher's exact test. The splenic flexure was above the hilum of the spleen in 95 patients (67.86%), at the splenic hilum level in 11 patents (7.88%), between the hilum and lower pole of the spleen in 12 (8.57%), at the lower pole of the spleen in 15 (10.7%) patients and 7 (5%) patients has a splenic flexure that lied below the lower pole of the spleen. Patient demographics showed no statistical significance in regard to splenic flexure location. Splenic flexure lies above the hilum of the spleen in majority of patients. This should be considered as part of operative strategies for left colon resection.

  17. Accessory spleen presenting as acute abdomen: A case report and operative management

    A. Landmann


    Full Text Available Accessory spleens are found in 10–30% of patients and are asymptomatic. Rarely, torsion of an accessory spleen can cause abdominal pain and acute abdomen. We present the case of an 8-year-old girl who arrives to the emergency room with left upper quadrant abdominal pain. CT scan revealed a non-enhancing soft tissue mass and multiple small splenules. Laparoscopy revealed a torsed accessory spleen and malrotation. Accessory spleen is a common congenital anomaly that is frequently asymptomatic. Rarely, an accessory spleen may become torsed around its vascular pedicle resulting in severe abdominal pain. Treatment is surgical resection. Torsion of accessory splenic tissue is a rare cause of acute abdomen in pediatric patients.

  18. Spleen Segmentation and Assessment in CT Images for Traumatic Abdominal Injuries.

    Reza Soroushmehr, S M; Davuluri, Pavani; Molaei, Somayeh; Hargraves, Rosalyn Hobson; Tang, Yang; Cockrell, Charles H; Ward, Kevin; Najarian, Kayvan


    Spleen segmentation is especially challenging as the majority of solid organs in the abdomen region have similar gray level range. Physician analysis of computed tomography (CT) images to assess abdominal trauma could be very time consuming and hence, automating this process can reduce time to treatment. The proposed method presented in this paper is a fully automated and knowledge based technique that employs anatomical information to accurately segment the spleen in CT images. The spleen detection procedure is proposed to locate the spleen in both healthy and injured cases. In the presence of hemorrhage and laceration, the edge merging technique is used. The accuracy of the method is measured by some criteria such as mis-segmented area, accuracy, specificity and sensitivity. The results show that the proposed spleen segmentation method performs well and outperforms other methods.

  19. Horse spleen segmentation technique as large animal model of preclinical trials.

    Foz Filho, Roberto P P; Martin, Benedito W de; Lima, Ana Rita de; Miglino, Maria Angélica


    The parenchymal distribution of the splenic artery was studied in order to obtain anatomical basis for partial splenectomy. Thirty two spleens were studied, 26 spleens of healthy horses weighing 320 to 450 kg, aged 3 to 12 years and 6 spleens of fetus removed from slaughterhouse. The spleens were submitted to arteriography and scintigraphy in order to have their vascular pattern examined and compared to the external aspect of the organ aiming establish anatomo-surgical segments. All radiographs were photographed with a digital camera and the digital images were submitted to a measuring system for comparative analysis of areas of dorsal and ventral anatomo-surgical segments. Anatomical investigations into the angioarchitecture of the equine spleen showed a paucivascular area, which coincides with a thinner external area, allowing the organ to be divided in two anatomo-surgical segments of approximately 50% of the organ each.

  20. Horse spleen segmentation technique as large animal model of preclinical trials

    Roberto P.P. Foz Filho


    Full Text Available The parenchymal distribution of the splenic artery was studied in order to obtain anatomical basis for partial splenectomy. Thirty two spleens were studied, 26 spleens of healthy horses weighing 320 to 450kg, aged 3 to 12 years and 6 spleens of fetus removed from slaughterhouse. The spleens were submitted to arteriography and scintigraphy in order to have their vascular pattern examined and compared to the external aspect of the organ aiming establish anatomo-surgical segments. All radiographs were photographed with a digital camera and the digital images were submitted to a measuring system for comparative analysis of areas of dorsal and ventral anatomo-surgical segments. Anatomical investigations into the angioarchitecture of the equine spleen showed a paucivascular area, which coincides with a thinner external area, allowing the organ to be divided in two anatomo-surgical segments of approximately 50% of the organ each.

  1. Improved Retroviral Vector Design Results in Sustained Expression after Adult Gene Therapy in Mucopolysaccharidosis I Mice

    Herati, Ramin Sedaghat; Ma, Xiucui; Tittiger, Mindy; Ohlemiller, Kevin K; Kovacs, Attila; Ponder, Katherine P.


    Background Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease due to α-L-iduronidase (IDUA) deficiency that results in the accumulation of glycosaminoglycans (GAG). Gene therapy can reduce most clinical manifestations, but mice that receive transfer as adults lose expression unless they receive immunosuppression. Increasing liver specificity of transgene expression has reduced immune responses to other genes. Methods A gamma retroviral vector was generated with a liver-specific human α1-antitrypsin promoter and the canine IDUA cDNA inverted relative to the retroviral long-terminal repeat. Adult MPS I mice received the vector intravenously at 6 weeks of age and were assessed for expression via serial serum IDUA assays. Functional testing and organ analysis were performed at 8 months. Results This vector resulted in high specificity of expression in liver, and serum IDUA activity was stable in 90% of animals. Although the average serum IDUA activity was relatively low at 12.6 ± 8.1 units/mL in mice with stable expression, a relatively high percentage of enzyme contained the mannose 6-phosphorylation necessary for uptake by other cells. At 6.5 months after transduction, most organs had high IDUA activity and normalized GAG levels. There was complete correction of hearing and vision abnormalities and significant improvements in bone, although the aorta was refractory to treatment. Conclusions Stable expression of IDUA in adult MPS I mice can be achieved without immunosuppression by modifying the vector to reduce expression in the spleen. This approach may be effective in patients with MPS I or other lysosomal storage diseases. PMID:18613275

  2. Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

    Mahévas, Matthieu; Michel, Marc; Vingert, Benoit; Moroch, Julien; Boutboul, David; Audia, Sylvain; Cagnard, Nicolas; Ripa, Julie; Menard, Cédric; Tarte, Karin; Mégret, Jérôme; Le Gallou, Simon; Patin, Pauline; Thai, Lan; Galicier, Lionel; Bonnotte, Bernard; Godeau, Bertrand; Noizat-Pirenne, France; Weill, Jean-Claude; Reynaud, Claude-Agnès


    Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen.

  3. Osteopontin exacerbates Pseudomonas aeruginosa-induced bacteremia in mice.

    Piao, Zhenghao; Yuan, Haiying


    Osteopontin (OPN) is a multifunctional protein involved in various pathophysiological processes. However, the role of OPN in Pseudomonas aeruginosa-related sepsis is not yet clear. Here, we found that OPN expression was elevated in plasma and spleen samples from P. aeruginosa-infected mice. To determine the function of OPN in sepsis, we used wild-type (WT) and OPN-knockout (KO) mice with P. aeruginosa-induced bacteremia. We found that OPN-KO mice exhibited reduced mortality compared with WT mice and that OPN exacerbated spleen bleeding and functional impairment. OPN-KO mice exhibited reduced secretion of pro-inflammatory cytokines, such as interferon-γ, interleukin (IL)-1β, IL-12, and tumor necrosis factor-α, whereas levels of anti-inflammatory cytokine IL-10 and the leukocyte trafficking mediator macrophage inflammatory protein (MIP)-2 were not altered. Additionally, the percentages and absolute numbers of B cells were elevated in the spleens of OPN-KO mice. Thus, OPN promoted sepsis in P. aeruginosa-infected mice and potentially blocked B cell-dependent immunity. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice.

    Liu, Jing-yu; Feng, Cui-ping; Li, Xing; Chang, Ming-chang; Meng, Jun-long; Xu, Li-jing


    To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF-α, IFN-γ, and IL-1β mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. A murine model for human immune thrombocytopenic purpura and comparative analysis of multiple gene expression in bone marrow and spleen

    Hong Wei; Xinchun Ding; Jiangong Ren; Ka Liu; Pingping Tan; Daquan Li; Runlin Z.Ma


    Homeostasis of platelet number in human and other mammals is well maintained for prevention of minor bleeding and for other im-munological functions, but the exact molecular mechanism responsible for immune thrombocytopenic purpura (ITP) has not been fullyunderstood. In an effort to identify genetic factors involved in initiation of platelet production in response to bleeding injury or plateletdestruction, we have successfully generated an animal model of human ITP via intraperitoneal injection of anti-platelet antibody into theBalb/c mouse. Platelet counts were dropped dramatically in animals that received antibody injection within 4 h, maintained at the mini-mum level for a period of 44 h, started to rebound after 48 h, and reached to the maximum at 144 h (6 days). Final homeostasis reached atapproximately 408 h (17 days), following a minor cycle of platelet number fluctuation. Using semi-quantitative RT-PCR, we assessed andcompared mRNA level of CD41, c-myb, c-mpl, caspase-3, caspase-9, GATA-1, and Bcl-xl in bone marrow and spleen. Alteration ofmRNA expression was correlated with the change of platelet level, and an inverse relationship was found for expression of the genes be-tween bone marrow and spleen. No transcription was detectable for any of the seven genes in bone marrow at the time when plateletnumber reached the maximum (144 h). In contrast, mRNA transcripts of the seven genes were found to be at the highest level in spleentissue. This is the first study of simultaneous detection of multiple platelet related genes in a highly reproducible ITP animal model. Ourresults provided the supportive evidence that expression of the above seven genes are more related to negative regulation of plateletnumber in spleen tissue, at least in the model animals.

  6. Spleen histology in children with sickle cell disease and hereditary spherocytosis: hints on the disease pathophysiology.

    Pizzi, Marco; Fuligni, Fabio; Santoro, Luisa; Sabattini, Elena; Ichino, Martina; De Vito, Rita; Zucchetta, Pietro; Colombatti, Raffaella; Sainati, Laura; Gamba, Piergiorgio; Alaggio, Rita


    Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histologic and morphometric features of HS and SCD spleens, to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS, and control patients, the following parameters were considered: (i) macroscopic features, (ii) lymphoid follicle (LF) density, (iii) presence of perifollicular marginal zones, (iv) presence of Gamna-Gandy bodies, (v) density of CD8-positive sinusoids, (vi) density of CD34-positive microvessels, (vii) presence/distribution of fibrosis and smooth muscle actin (SMA)-positive myoid cells, and (viii) density of CD68-positive macrophages. SCD and HS spleens had similar macroscopic features. SCD spleens had lower LF density and fewer marginal zones than did HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than did controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, most HS spleens clustered with controls, whereas SCD grouped separately. A multiparametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS, and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.

  7. Immune signatures of protective spleen memory CD8 T cells.

    Brinza, Lilia; Djebali, Sophia; Tomkowiak, Martine; Mafille, Julien; Loiseau, Céline; Jouve, Pierre-Emmanuel; de Bernard, Simon; Buffat, Laurent; Lina, Bruno; Ottmann, Michèle; Rosa-Calatrava, Manuel; Schicklin, Stéphane; Bonnefoy, Nathalie; Lauvau, Grégoire; Grau, Morgan; Wencker, Mélanie; Arpin, Christophe; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline


    Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy.

  8. Immune signatures of protective spleen memory CD8 T cells

    Brinza, Lilia; Djebali, Sophia; Tomkowiak, Martine; Mafille, Julien; Loiseau, Céline; Jouve, Pierre-Emmanuel; de Bernard, Simon; Buffat, Laurent; Lina, Bruno; Ottmann, Michèle; Rosa-Calatrava, Manuel; Schicklin, Stéphane; Bonnefoy, Nathalie; Lauvau, Grégoire; Grau, Morgan; Wencker, Mélanie; Arpin, Christophe; Walzer, Thierry; Leverrier, Yann; Marvel, Jacqueline


    Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in their ability to protect the host. In order to identify the whole range of qualities uniquely associated with protective memory cells we compared the gene expression signatures of two qualities of memory CD8 T cells sharing the same antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express classical phenotypic memory markers and are polyfunctional, only Flu-TM protects against a lethal viral challenge. Protective memory CD8 T cells express a unique set of genes involved in migration and survival that correlate with their unique capacity to rapidly migrate within the infected lung parenchyma in response to influenza infection. We also enlighten a new set of poised genes expressed by protective cells that is strongly enriched in cytokines and chemokines such as Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8 T cells. These immune signatures are also induced by two other pathogens (vaccinia virus and Listeria monocytogenes). The immune signatures associated with immune protection were identified on circulating cells, i.e. those that are easily accessible for immuno-monitoring and could help predict vaccines efficacy. PMID:27883012

  9. Low complexity MIMO receivers

    Bai, Lin; Yu, Quan


    Multiple-input multiple-output (MIMO) systems can increase the spectral efficiency in wireless communications. However, the interference becomes the major drawback that leads to high computational complexity at both transmitter and receiver. In particular, the complexity of MIMO receivers can be prohibitively high. As an efficient mathematical tool to devise low complexity approaches that mitigate the interference in MIMO systems, lattice reduction (LR) has been widely studied and employed over the last decade. The co-authors of this book are world's leading experts on MIMO receivers, and here they share the key findings of their research over years. They detail a range of key techniques for receiver design as multiple transmitted and received signals are available. The authors first introduce the principle of signal detection and the LR in mathematical aspects. They then move on to discuss the use of LR in low complexity MIMO receiver design with respect to different aspects, including uncoded MIMO detection...

  10. Life cycle of Cystoisospora felis (Coccidia: Apicomplexa) in cats and mice

    Cystoisospora felis is a ubiquitous apicomplexan protozoon of cats. The endogenous development of C. felis was studied in cats after feeding them infected mice. For this, 5 newborn cats were killed at 24, 48, 72, 96, and 120 h after having been fed mesenteric lymph nodes and spleens of mice that wer...

  11. Delphi Accounts Receivable Module -

    Department of Transportation — Delphi accounts receivable module contains the following data elements, but are not limited to customer information, cash receipts, line of accounting details, bill...

  12. DNA vaccine encoding Der p 2 allergen generates immunologic protection in recombinant Der p 2 allergen-induced allergic airway inflammation mice model

    LI Guo-ping; LIU Zhi-gang; QIU Jing; RAN Pi-xin; ZHONG Nan-shan


    Background DNA immunization is a promising novel type of immunotherapy against allergy. An estimated 79.2% patients with asthma, wheezing and/or rhinitis suffer from Dermatophagoides pteronyssinus group 2 (Der p 2) allegen. The aim of the present study was to determine whether DNA vaccine encoding Der p 2 could generate immunologic protection in recombinant Der p 2 (rDer p 2) allergen-induced allergic airway inflammation mice model and to understand the role of DNA vaccination in specific-allergen immunotherapy for asthma. Methods After DNA vaccination, BALB/c mice were sensitized by intraperitoneal injection (i.p) and challenged by intranasal instillation of rDer p 2. The lung tissues were assessed using hematoxylin and eosin. Mucus-producing goblet cells were identifed using periodic acid-Schiff(PAS)/alcian blue. The total cell number and composition of bronchoalveolar lavage samples were determined. The levels of the cytokines IL-4 and IFN-γ, as well as IgE and IgG2a in the serum were determined by enzyme-linked immunosorbent assay. Allergen-specific IL-4 and IFN-γ production by spleen cells were also measured by enzyme-linked immunosorbent assay. Expression of signal transducer and activator of transcription 6 (STAT6) in splenocytes were determined by Western blot. Results DNA vaccine encoding Der p 2 allergen inhibited extensive infiltration of inflammatory cells and production of mucin induced by allergen. The influx of eosinophils into the lung interstitium was significantly reduced after administration of DNA vaccine. Significant reductions of IL-4 and increase in levels of IFN-γ in bronchoalveolar lavage fluid were observed. The allergen-specific IgE was markedly decreased in mice receiving DNA vaccination. Allergen could induce higher IFN-γ, weaker IL-4 in cultured spleen cells from mice receiving DNA vaccine. DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. Conclusion These results indicated that DNA vaccine encoding

  13. [A Case of Pancreatic Metastasis of Osteosarcoma Resected Using Laparoscopic Spleen Preserving Distal Pancreatectomy].

    Toyama, Hirochika; Asari, Sadaki; Goto, Tadahiro; Terai, Sachio; Shirakawa, Sachiyo; Nanno, Yoshihide; Mizumoto, Takuya; Fukumoto, Takumi; Ajiki, Tetsuo; Kido, Masahiro; Tanaka, Motofumi; Matsumoto, Taku; Kinoshita, Hisoka; Kuramitsu, Kaori; Ku, Yonson


    A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

  14. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat.

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J


    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague-Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation.

  15. Study on the pathological basis of classification of spleen deficiency in chronic gastritis

    尹光耀; 张武宁; 沈小静; 何雪芬; 陈一


    Background Spleen in Traditional Chinese Medicine (TCM) is not actually the spleen in the anatomic sense designated in western medicine because its functions basically belong to the physiological category of digestive system in modern medicine, and it represents a macroscopic concept of digestion, absorption and nutrition metabolism. Spleen deficiency syndrome refers to the clinical phenomena such as hypofunction of digestion, absorption and nutrition metabolism. By integrating TCM with modern medicine , this paper is intended to explore the pathological basis of classification of spleen deficiency in chronic gastritis.Method By means of optical microscope, scanning electron microscope (SEM), transmission electron microscope (TEM) and histochemical staining, we conducted histopathological and subcellular ultrastructural (nuclei and mitochondrial) analysis of gastric mucosa of 188 patients of spleen deficiency, and that of 42 voluntary blood donors without clinical symptoms. Results The gastric mucosa of patients with spleen Qi deficiency (SQD) and spleen yang deficiency (SyangD) could either be affected by organic lesion (type G-occurring on the basis of chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG)) or unaffected (type F-chiefly belonging to functional indigestion); spleen yin deficiency (SyinD) and spleen deficiency with Qi stagnation (SDQS) both occurred on the basis of CSG and CAG; and the degree of mucosa inflammatory cells infiltration, the degree of decrease in glands propria, and the incidence of IMⅡb in CSG and CAG were more serious than those of G-SQD and G-SyangD, P<0.05-0.01.Conclusion Spleen deficiency syndrome is likely to occur on the basis of organic lesion of gastric mucosa (disease with symptoms of both CSG or CAG and spleen deficiency symptoms), as well as on the basis of inorganic lesion of gastric mucosa (nondisease with symptoms, which is, despite spleen deficiency symptoms, there is no CSG or CAG). Besides, the

  16. Heterogeneous profiles of a factor that renders neutrophils cytotoxic obtained from a concanavalin A-stimulated spleen cell culture in partial purification process

    Fujii, Y.; Inoue, T.; Ito, M.; Kimura, S.; Fuyama, S.; Arai, S.; Naiki, M.; Sendo, F.


    Concanavalin A (Con A)-stimulated rat spleen cells were cultured in a serum-free conditioned medium. This culture supernatant contained a certain factor(s) that renders neutrophil cytotoxic for various tumor cells. The factor was tentatively termed neutrophil-activating factor (NAF). NAF activity was eluted in broad fractions by the ion exchange chromatography and the gel filtration. Moreover, on the Con A column, some NAF activities were bound to the column, but other activities passed through the column. These results showed the heterogeneity or polydispersity of NAF activity in both molecular size and charge-based separation properties. Monoclonal antibodies were produced by fusing BALB/c myeloma cells (P3-X63 Ag8.653) with spleen cells from syngeneic mice immunized with partially purified NAF (pNAF) obtained from the gel filtration. Absorbent beads which were linked with one monoclonal antibody (ANAF-10) partially absorbed NAF activity from supernatants of a Con A-stimulated spleen cell culture. By further purification of pNAF the NAF activity was concentrated about 10,000-fold. Heterogeneity of NAF activity, however, did not disappear in even this affinity chromatography. On the other hand, /sup 125/I-labeled material of the final product migrated to one major band corresponding with an m.w. of about 20,000 as determined by SDS-PAGE analysis, and NAF activity was detected in the same band.


    Xiao-lei Zou; Zeng-yu Zhao; Yun-yang Wang; Zhi-qiang Su; Ming Xiang


    Objective To investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes meilitus(T1DM) in BALB/c mice.Methods Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin(STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 ( IL-2 ) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTr, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-γ, IL-4, and IL-10) levels, and pathological changes in pancreatic islets.Results As few as 3 × 106 diabetogenic T cells successfully induced diabetes meilitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenie splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-γ and IL-2 in the supematants of diabetogenie T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-γ secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer.Conclusions A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4M+ T cells with interferon-γ may promote the onset of diabetes mellitus.

  18. Immunomodulatory properties of aloe vera gel in mice

    Madan Jyotsana


    Full Text Available Administration of Aloe vera extract to swiss albino mice (300 mg/kg i.p. daily for five days, significantly (P < 0.01 increases the total white blood cells count. Further, it increases humoral immune response, as demonstrated from the increase in plaque-forming cells in the spleen and circulating antibody titre.

  19. [Uncommon etiology of acute abdomen in pediatric age: the torsion of spleen].

    Marinaccio, F; Caldarulo, E; Nobili, M; Magistro, D; Marinaccio, M


    The torsion of spleen on its vascular shank represents an uncommon problem, responsible of acute and chronic pain. The mobile spleen is fixed only through hilus vessels the gastrosplenic ligament. The incidence is unknow, greater in the male with an M:F ratio 6.1 in the first ten years of life, even if an episode of intrauterine torsion has been reported. The diagnosis can be performed with ultrasonography, angiography, scintigraphy and CT scan. There are reported two cases: male of 2.5 years female of 14 years who presented with recurrent pain to the left side, vomit diarrhoea and fever. Objectively a palpable mass was present. Ultrasonography and angio-CT scan of abdomen revealed splenomegaly, ptosis of the spleen and malrotation with signs of obstruction of the vessels. The treatment in both cases was splenectomy. The spleen appeared rotated on its shank and increased of volume, deprived of anatomical structures of fixation. The histological report confirmed the haemorrhagic infarction. The excessive mobility of the spleen, from insufficiency or absence of the ligamentous attachments is case of abdominal pain or acute abdomen, that can complicate with the infarction of the spleen. Angio-CT scan, in the cases here reported, has shown to greater sensibility in comparison to the ultrasonography. The Authors believe that the video-laparoscopic splenopexy, when the diagnosis is made of "wandering spleen" with painful repeated episodes, can be finalized, to the preservation of organ.

  20. Recommendations for gross examination and sampling of surgical specimens of the spleen.

    O'Malley, Dennis P; Louissaint, Abner; Vasef, Mohammad A; Auerbach, Aaron; Miranda, Roberto; Brynes, Russell K; Fedoriw, Yuri; Hudnall, S David


    This review examines handling and processing of spleen biopsies and splenectomy specimens with the aim of providing the pathologist with guidance in optimizing examination and diagnosis of splenic disorders. It also offers recommendations as to relevant reporting factors in gross examination, which may guide diagnostic workup. The role of splenic needle biopsies is discussed. The International Spleen Consortium is a group dedicated to promoting education and research on the anatomy, physiology, and pathology of the spleen. In keeping with these goals, we have undertaken to provide guidelines for gross examination, sectioning, and sampling of spleen tissue to optimize diagnosis (Burke). The pathology of the spleen may be complicated in routine practice due to a number of factors. Among these are lack of familiarity with lesions, complex histopathology, mimicry within several types of lesions, and overall rarity. To optimize diagnosis, appropriate handling and processing of splenic tissue are crucial. The importance of complete and accurate clinical history cannot be overstated. In many cases, significant clinical history such as previous lymphoproliferative disorders, hematologic disorders, trauma, etc, can provide important information to guide the evaluation of spleen specimens. Clinical information helps plan for appropriate processing of the spleen specimen. The pathologist should encourage surgical colleagues, who typically provide the specimens, to include as much clinical information as possible.

  1. 脾阴虚小议%Discussion on Spleen-Yin Deficiency



    Spleen-yin deficiency is explored as insufficient Fm-blood of spleen from objective existence of spleen- Yin deficiency, clinical manifestations and pathological mechanism of spleen- Yin deficiency, the relation between spleen-Yin deficiency and other viscera. The symptoms mainly include restless fever of hands and feet, dry mouth and don't want to drink, dysphoria, poor appetite and constipation, etc. Yin deficiency of spleen and stomach is the common type, treated with moistening spleen and regulating Qi.%从脾阴虚的客观存在、脾阴虚的临床表现及病理机制、脾阴虚与他脏的关系3 方面探讨脾阴虚乃脾之阴血不足证,证见手足烦热、口干不欲饮、烦满、不思食、大便秘结等,辨证分型以脾胃阴虚型多见,治宜滋脾兼调气.

  2. Factors influencing liver and spleen volume changes after donor hepatectomy for living donor liver transplantation

    Bae, Ji Hee; Ryeom, Hunku; Song, Jung Hup [Kyungpook National University Hospital, Daegu (Korea, Republic of)


    To define the changes in liver and spleen volumes in the early postoperative period after partial liver donation for living-donor liver transplantation (LDLT) and to determine factors that influence liver and spleen volume changes. 27 donors who underwent partial hepatectomy for LDLT were included in this study. The rates of liver and spleen volume change, measured with CT volumetry, were correlated with several factors. The analyzed factors included the indocyanine green (ICG) retention rate at 15 minutes after ICG administration, preoperative platelet count, preoperative liver and splenic volumes, resected liver volume, resected-to-whole liver volume ratio (LV{sub R}/LV{sub W}), resected liver volume to the sum of whole liver and spleen volume ratio [LV{sub R}/(LV{sub W} + SV{sub 0})], and pre and post hepatectomy portal venous pressures. In all hepatectomy donors, the volumes of the remnant liver and spleen were increased (increased rates, 59.5 ± 50.5%, 47.9 ± 22.6%). The increment rate of the remnant liver volume revealed a positive correlation with LV{sub R}/LV{sub W} (r = 0.759, p < 0.01). The other analyzed factors showed no correlation with changes in liver and spleen volumes. The spleen and remnant liver volumes were increased at CT volumetry performed 2 weeks after partial liver donation. Among the various analyzed factors, LV{sub R}/LV{sub W} influences the increment rate of the remnant liver volume.

  3. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail:, e-mail:; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail:; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail:


    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  4. Evaluation of the proliferative activity of methanol extracts from six medicinal plants in murine spleen cells

    Rodrigo Hermes Zandonai


    Full Text Available A number of natural compounds have been used as immunomodulatory agents, enabling the function of the immune system to be modified by stimulating or suppressing it. There has been increasing interest in the study of therapeutic action of plant extracts regarding their immunomodulatory activity. The aim of this study was to identify and evaluate the action of extracts of the medicinal plants Calophyllum brasiliense, Ipomoea pes-caprae, Matayba elaeagnoides, Maytenus robusta, Rubus imperialis and Vernonia scorpioides on the development of spleen cells from mice, using the in vitro cellular proliferation assay. The cells, obtained by mechanical rupture of mice spleen (5x10(4 cells/mL, were incubated with methanol extracts (10, 50, 100 and 200 µg/mL and phytohemagglutinin (PHA, 5 µg/mL. The basal control for proliferation consisted of cells alone, while the positive control consisted of cells and PHA. The cell culture was kept at 37 ºC in 5% CO2 for 72 hours, and cell proliferation was revealed by the blue tetrazolium reduction assay (MTT. The results were expressed as percentage of growth and were analyzed using the Kruskal-Wallis and Mann-Whitney tests. The C. brasiliense, I. pes-caprae and M. elaeagnoides extracts showed dose-dependent induction of cell proliferation, with a significant increase in cell proliferation (pVárias substâncias de origem natural têm sido utilizadas como agentes imunomoduladores, permitindo modificar a função do sistema imune e propiciando o estudo de atividades terapêuticas de extratos de plantas. Este trabalho objetivou identificar a atividade imunomodulatória dos extratos de seis plantas medicinais da flora brasileira, Calophyllum brasiliense, Ipomoea pes-caprae, Matayba elaeagnoides, Maytenus robusta, Rubus imperialis e Vernonia scorpioides, sobre a proliferação de células esplênicas de camundongos. As células esplênicas murinas obtidas por ruptura mecânica do baço (5x14³ células/mL foram

  5. Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis

    Campanelli, Rita; Fois, Gabriela; Catarsi, Paolo; Poletto, Valentina; Villani, Laura; Erba, Benedetta Gaia; Maddaluno, Luigi; Jemos, Basilio; Salmoiraghi, Silvia; Guglielmelli, Paola; Abbonante, Vittorio; Di Buduo, Christian Andrea; Balduini, Alessandra; Iurlo, Alessandra; Barosi, Giovanni; Rosti, Vittorio; Massa, Margherita


    Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph−) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62−CCR2− (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ. PMID:27281335

  6. Response of colony-forming units-spleen to heavy charged particles.

    Ainsworth, E J; Kelly, L S; Mahlmann, L J; Schooley, J C; Thomas, R H; Howard, J; Alpen, E L


    Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET infinity). In in vitro irradiation experiments. CFU-S suspensions were exposed to 220 kVp X rays or to 20Ne (372 MeV/micron) or 40Ar (447 MeV/micron) particles in the plateau portion of the Bragg curve. In in vivo irradiation experiments, donor mice from which CFU-S were harvested were exposed to 12C (400 MeV/micron). 20Ne (400 or 670 MeV/micron), or 40Ar (570 MeV/micron) particles in Bragg peaks spread to 4 or 10 cm by spiral ridge filters. Based on RBE at 10 survival, the maximum RBE of 2.1 was observed for 40Ar particles characterized by an LET infinity of approximately 100 keV/micron. Lower RBEs were determined at lower or higher estimated values of LET infinity and ranged from 1.1 for low energy 40Ar particles to 1.5-1.6 for low energy 12C and 20Ne. The responses of CFU-S are compared with responses of other model systems to heavy charged particles and with the reported sensitivity of CFU-S to neutrons of various energies. The maximum RBE reported here, 2.1 for high energy 40Ar particles, is somewhat lower than values reported for fission-spectrum neutrons, and is appreciably lower than values for monoenergetic 0.43-1.8 MeV neutrons. Low energy 12C and 20Ne particles have RBEs in the range of values reported for 14.7 MeV neutrons.

  7. Knowledge of the anatomy and physiology of the spleen throughout Antiquity and the Early Middle Ages.

    Paraskevas, George K; Koutsouflianiotis, Konstantinos N; Nitsa, Zoi; Demesticha, Theano; Skandalakis, Panagiotis


    The evolution of knowledge regarding the anatomy and physiology of the spleen throughout Antiquity and the Early Middle Ages is described, and general perceptions about this organ during different eras along this time line are presented. The original words of great physicians from the period of time stretching from Ancient Egypt to the Avicennan era are quoted and discussed to demonstrate how knowledge of the spleen has evolved and to present the theories that dominated each era. Furthermore, theories about illnesses relating to the spleen are reported, which show how this organ was perceived-in terms of its function and anatomy-during each era.

  8. The Study on Morphological and Functional Changes of Thymus, Spleen and T Lymphocytes in Vasectomized Rabbits

    刘睿智; 李璐; 赵丹; 赵雪检; 丛琦; 郑志超; 潘淑琴


    The morphology and functional changes of thymus, spleen and T lymphocytes were studied in vasectomlzed rabbits. The results showed that: (t) A significant low weight of thymus and spleen, and a slight or medium atrophy of thymic lobules and shrinked splenic nodules and lymphoid tissues were observed in the rabbits vasectomized for 6 months (VG6 rabbits), (2) Spontaneous-proliferation of thymus could not be affected by vasectomy, (3) The lowest activity of IL 2 was detected in the supernatant of spleen ceil culture of VG6 rabbits.

  9. [A method of extracorporeal perfusion of the sections of xenogeneic spleen].

    Borisov, A E; Zhidkov, K P; Dmitriev, N V; Domanskaia, I A


    A method of extracorporeal perfusion of sections of the swine spleen developed by the authors is described. Perfusion of the swine spleen sections was performed in the small volume perfusion chamber (100 cm3) with a 80-100 ml/min rate for 30-60 min with the help of a roller pump. The extracorporeal contour was connected with the major veins of the patient. An experience with the treatment of 23 patients with pyo-septic diseases with the use of extracorporeal perfusion of the swine spleen sections shows the efficiency, simplicity and safety of the proposed method.

  10. Spontaneous rupture of a normal spleen following bronchoplastic left lung lower lobectomy.

    Stupnik, Tomaz; Vidmar, Stanko; Hari, Petra


    Rupture of the spleen is a common event associated with trauma, infectious diseases, neoplasia and many systemic disorders affecting the reticuloendothelial system. A rare subtype of rupture occurring spontaneously and arising from a normal spleen was recognized as a distinct clinicopathologic entity. It has been reported in association with trivial insults such as vomiting and coughing. We report a case of a patient with spontaneous rupture of a normal spleen observed after severe coughing on the 3rd postoperative day following bronchoplastic left lung lower lobectomy combined with S4, S5 segmentectomy.

  11. 《伤寒论》治脾法%Methods of Treating the Spleen in Treatise on Cold Damage



    Under the theoretical guidance of syndrome differentiation on zang-fu organs, the relevant terms in Treatise on Cold Damage are analyzed and the following methods of treating the spleen are categorized, including supporting earth to restrict water, regulating qi and invigorating spleen, invigorating spleen and draining water, clearing upper and warming middle (spleen), warming spleen to strength middle, purging liver and supporting spleen, clearing gall bladder and warming spleen, invigorating spleen to regulate middle, invigorating spleen and descending adverse qi, warming middle and releasing exterior, warming spleen and dredging collaterals as well as warming spleen and consolidating fluid. Besides, the idea of protecting stomach qi in Treatise on Cold Damage also involves the spleen.%在《伤寒论》中亦有脏腑辨证的理论指导下,对论中有关条文进行分析,归纳出培土制水、理气健脾、健脾利水、清上温中(脾)、温脾建中、泻肝扶脾、清胆温脾、健脾理中、健脾降逆、温中和表、温脾通络、温脾摄津等治脾法.另外,《伤寒论》中“顾护胃气”的思想,也包括脾在内.

  12. Lack of cardiac differentiation in c-kit-enriched porcine bone marrow and spleen hematopoietic cell cultures using 5-azacytidine

    M.L. Ramirez (Mario); T. McMorrow (Tara); T.M. Sanderson (Thomas M.); C.J. Lancos (C.); Y.-L. Tseng (Y.); D.K.C. Cooper (David); F.J.M.F. Dor (Frank)


    textabstractThe adult spleen is a source of early hematopoietic stem cells (HSC). We therefore studied whether culturing spleen or bone marrow (BM) HSC in medium containing 5-azacytidine could induce a cardiac phenotype. c-kit enrichment and depletion of adult pig spleen and BM mononuclear cells wer

  13. The anti-infective activity of punicalagin against Salmonella enterica subsp. enterica serovar typhimurium in mice.

    Li, Guanghui; Feng, Yuqing; Xu, Yunfeng; Wu, Qian; Han, Qi'an; Liang, Xiujun; Yang, Baowei; Wang, Xin; Xia, Xiaodong


    Punicalagin, a major bioactive component of pomegranate peel, has been proven to have antioxidant, antiviral, anti-apoptosis, and hepatoprotective properties. The aim of this study was to investigate the anti-infective activity of punicalagin in a mouse model. C57BL/6 mice were initially challenged with Salmonella enterica subsp. enterica serovar typhimurium (S. typhimurium) and then treated with punicalagin. Food and water consumption and body weight were recorded daily. On day 8 post infection, the mice were sacrificed to examine pathogen counts in tissues, hematological parameters, cytokine levels, and histological changes. Compared to mice only infected with S. typhimurium, punicalagin-treated mice had more food consumption and less weight loss. A higher survival rate and lower counts of viable S. typhimurium in feces, liver, spleen, and kidney were found in the punicalagin-treated mice. The enzyme linked immunosorbent assay showed that the levels of IL-6, IL-10, and IFN-γ in serum and the spleen and TNF-α in serum, the spleen and the liver were reduced by punicalagin. Moreover, more neutrophils and higher neutrophil-to-mononuclear cell ratios in the punicalagin-treated mice were observed. Histological examination showed that punicalagin protected cells in the liver and spleen from hemorrhagic necrosis. It is concluded that punicalagin has a beneficial effect against S. typhimurium infection in mice. The anti-infective properties, together with other nutritionally beneficial effects, make punicalagin a promising supplement in human food or animal feeds to prevent disease associated with S. typhimurium.

  14. 营养型鸡精对拘束应激小鼠免疫功能的改善作用%Effects of Chicken Essence on Immune Activity in Restraint Stressed Mice

    李怡芳; 曾怀苇; 陈邦添; 何蓉蓉; 栗原博


    作者研究了营养型鸡精对拘束负荷小鼠免疫功能的改善作用.将小鼠随机分为正常对照组,拘束应激组,25 mg/kg RU486(糖皮质激素受体拮抗剂组),1 mL/hg BEC(营养型鸡精)组及2mL/hg BEC组,每组10只.除正常对照组外,其余各组连续灌胃给药5 d后拘束负荷18 h,拘束恢复3 d后取血取脾脏测定相关指标.结果显示:BEC不仅可以明显改善拘束应激时小鼠脾脏的损伤,提高脾淋巴细胞总数,而且能显著降低应激小鼠血浆中皮质酮的含量,抑制相关凋亡因子的基因表达,提高线粒体膜电位,减少细胞色素C的释放.BEC可以通过抑制应激小鼠脾淋巴细胞的凋亡来维护脾淋巴细胞数目和功能,改善应激负荷引起的免疫抑制作用.%This study aims to study the effect of BEC (BRANDS Chicken Essence, BEC) on immune system in restraint stressed mice. Mice were randomly divided into 5 groups with 10 mice each group: normal control group, restraint control group, 25 mg/kg RU486 (GR antagonist)group, 1 mL/100 g BEC and 2 mL/100 g BEC. The treatment groups were orally administrated with BEC or RU486 for consecutive 5 days, while normal control and stress control groups were given the same volume of water. On the 5th day, all mice were restraint for 18 h except normal group. After 3 days recovery, mice were sacrificed. Blood was distilled and spleens were received to prepare lymphocytes for following tests. The results showed that BEC not only could protect the reduced spleen index and spleen lymphocytes, but also could inhibit the elevated content of corticosterone in plasma. RT-PCR analysis showed that BEC also could recover GR mRNA, Bcl2 mRNA and Bax mRNA in spleen lymphocytes nearly to normal. Meantime, the mitochondrion membrane potential (△Ψmt), the content of CytC in cytoplasm or mitochondrion of spleen lymphocytes were also recovered to normal when compared to stressed mice. All of these results indicated that BEC could protect

  15. Induction of apoptosis in murione spleen lymphocytes using carbon ion beam; Induction de l'apoptose dans les lymphocytes spleniques de souris par un faisceau d'ions carbone

    Holl, V.; Coelho, D. [Lab. de Cancerologie Experimentale et de Radiobiologie, LCER, Inst. de Recherche contre les Cancers de l' Appareil Digestif, Hopitaux Universitaires, Strasbourg (France); Weltin, D. [Faculte de Medecine, Strasbourg (France); Dufour, P. [Lab. de Cancerologie Experimentale et de Radiobiologie, LCER, Inst. de Recherche contre les Cancers de l' Appareil Digestif, Hopitaux Universitaires, Strasbourg (France); Denis, J.M. [Faculte de Medecine, Univ. Catholique de Louvain, Bruxelles (Belgium); Florentin, I. [Centre National de la Recherche Scientifique, CNRS, Unite de Recherche Associee, Hopital Cochin, Paris (France); Mathieu, J. [Centre de Recherche du Service de Sante des Armees, CRSSA, La Tronche (France); Gueulette, J. [Faculte de Medecine, Univ. Catholique de Louvain, Bruxelles (Belgium); Bischoff, P. [Lab. de Cancerologie Experimentale et de Radiobiologie, LCER, Inst. de Recherche contre les Cancers de l' Appareil Digestif, Hopitaux Universitaires, Strasbourg (France)


    To assess the capacity of heavy ions to induce apoptosis in lymphocytes, mice have been irradiated with accelerated carbon ions (95 MeV/nucleon) at doses ranging from 0.1 to 4 Gy. Their spleens were removed 24 h later and gently dissociated to prepare a single cell suspension. Mononuclear cells were then maintained in culture at 37{sup o}C, and the occurrence of apoptosis in these cells was analysed 24 h later. Lymphocytes were also irradiated in vitro, in the presence of Ac-DEVD-CHO, a potent caspase-3 and -7 inhibitor. Results from three experiments performed at the Grand Accelerateur National d'Ions Lourds (GANIL, Caen, France) are reported here. They indicate that carbon ions induce a marked, dose-dependent, reduction of the spleen weight and cellularity. However, in sharp contrast with spleen cells prepared from X-ray irradiated mice, only a slight increase of apoptosis is evidenced in cultured lymphocytes from mice irradiated with heavy ions. The significance of such results is discussed. So far, few data exist concerning the biological effects of heavy ions, in particular their capacity to induce apoptosis in lymphocytes; the present study provides useful clues for further investigations. (author)

  16. Vitamin D improves immune function in immunosuppressant mice induced by glucocorticoid

    Wang, Zongye; Wang, Ying; Xu, Bingxin; Liu, Junli; Ren, Ye; Dai, Zhuojie; Cui, Di; Su, Xiaoming; Si, Shaoyan; Song, Shu Jun


    Vitamin D is an essential fat-soluble vitamin with multiple functions. Vitamin D receptor has been shown to be expressed in several types of immune cells suggesting vitamin D may have immune regulatory roles. Vitamin D insufficiency has been suggested to increase the risk of autoimmune diseases. However, little is known regarding its immunomodulatory effects in the condition of immune suppression. The aim of the present study was to investigate the regulatory effects of vitamin D on immune function in immunosuppressant mice. An immunosuppressant mouse model was induced by intraperitoneal injection with glucocorticiod for 3 days. Immunosuppressant mice were intragastrically administered with 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3; 0,4, 6 or 10 IU/g body weight] for 7 days. On day 8, the mice were decapitated. The body weight and the weights of thymus and spleen were measured. Thymus and spleen indexes were calculated. The ratio of CD4+/CD8+ T lymphocytes in the peripheral blood, proliferation and interleukin-2 (IL-2) production of spleen T lymphocytes was detected. Compared with the mice in the control group, the body weight, thymus and spleen indexes, the ratios of CD4+/CD8+ in peripheral blood and IL-2 production and proliferation of spleen T lymphocytes were decreased in immunosuppressant mice induced by glucocorticiod. However, in vitamin D-treated mice, the thymus indexes, the ratios of CD4+/CD8+, secretion of IL-2 and the proliferation index of spleen T lymphocytes were significantly increased (P2D3, 6 IU/g was most effective in improving the immune function. These results indicate that vitamin D supplementation can improve immune recovery in immunosuppressant mice by stimulating T-cell proliferation and elevating IL-2 production. PMID:28123720

  17. The spleen microenvironment influences disease transformation in a mouse model of KITD816V-dependent myeloproliferative neoplasm

    Pelusi, Natalie; Kosanke, Maike; Riedt, Tamara; Rösseler, Corinna; Seré, Kristin; Li, Jin; Gütgemann, Ines; Zenke, Martin; Janzen, Viktor; Schorle, Hubert


    Activating mutations leading to ligand-independent signaling of the stem cell factor receptor KIT are associated with several hematopoietic malignancies. One of the most common alterations is the D816V mutation. In this study, we characterized mice, which conditionally express the humanized KITD816V receptor in the adult hematopoietic system to determine the pathological consequences of unrestrained KIT signaling during blood cell development. We found that KITD816V mutant animals acquired a myeloproliferative neoplasm similar to polycythemia vera, marked by a massive increase in red blood cells and severe splenomegaly caused by excessive extramedullary erythropoiesis. Moreover, we found mobilization of stem cells from bone marrow to the spleen. Splenectomy prior to KITD816V induction prevented expansion of red blood cells, but rapidly lead to a state of aplastic anemia and bone marrow fibrosis, reminiscent of post polycythemic myeloid metaplasia, the spent phase of polycythemia vera. Our results show that the extramedullary hematopoietic niche microenvironment significantly influences disease outcome in KITD816V mutant mice, turning this model a valuable tool for studying the interplay between functionally abnormal hematopoietic cells and their microenvironment during development of polycythemia vera-like disease and myelofibrosis. PMID:28128288

  18. Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA mutator mouse.

    Lloye M Dillon

    Full Text Available Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs and PPAR γ coactivator-1α (PGC-1α pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of premature aging including hair loss, anemia, osteoporosis, sarcopenia and decreased lifespan. They also have increased mtDNA mutations and marked mitochondrial dysfunction. We found that mutator mice treated with bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging-like phenotypes. Although we observed an increase in markers of fatty acid oxidation in these tissues, we did not detect a generalized increase in mitochondrial markers. On the other hand, there were no improvements in muscle function or lifespan of the mutator mouse, which we attributed to the rodent-specific hepatomegaly associated with fibrate treatment. These results showed that despite its secondary effects in rodent's liver, bezafibrate was able to improve some of the aging phenotypes in the mutator mouse. Because the associated hepatomegaly is not observed in primates, long-term bezafibrate treatment in humans could have beneficial effects on tissues undergoing chronic bioenergetic-related degeneration.

  19. Effect of Yiqi Jianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role

    Li-Ran Fu; Sheng-Wei Guo; Xian-Hui Liu


    Objective:To observe the effect ofYiqiJianpi plus anticancer herbs on spleen deficiency in colorectal cancer and its anti-tumor role.Methods:Human intestinal cancer cellHT29 xenograft of nude mice model was established.The expression ofEGF,VEGF, gastric cancer tumor growth in mice were observed.Results:Protein kinaseC expression in in theYiqiJianpi group andYiqi Jianpi anti-tumor group was significantly better than the model group(P<0.01,P<0.05).There was significantly more apoptotic cells inYiqiJianpi anti-tumor group thanYiqiJianpi group and model group(P<0.01).Epidermal growth factor and vascular endothelial growth factor expression inYiqiJianpi group was significantly lower thanYiqiJianpi group and model group(P<0.05). Conclusions:Tumor can inhibit the expression ofPKC inhibition.YiqiJianpi and anticancer treatment can reduce this inhibition.Besides this treatment can also inhibit expression of tumor related genes such as epidermal growth factor and vascular endothelial growth factor.

  20. Kinetics of Trypanosoma cruzi destruction in the mouse spleen

    Zulmira M.S. Cordeiro


    Full Text Available Massive destruction of parasitized splenic macrophages was histologically observed at the height of a virulent infection caused by Trypanosoma cruzi (Y strain in the mouse. This was coincident with a sudden drop in parasitemic curve. Most of the animals died at this point, probably due to the liberation of toxic products, such as TNF, following the massive destruction of parasitized cells. However, parasitized-cell destruction indicated the transition from susceptibility to resistance. Although it has been extensively studied in vitro, this study contributes with the morphological counterpart observed in vivo by optical and electron microscopy. When infected animals were specifically treated during early infection transition to chronic phase was immediately observed without splenic parasitism. Animals that apparently recovered from massive cell-destruction in the spleen showed evidences of a rapid restoration of splenic architecture.Um estudo histologico sequenciado mostrou que o parasitismo dos macrófagos esplênicos por uma cepa virulenta (cepa Y do Trypanosoma cruzi tem um curso progressivo, mas chega até um ponto em que todos as células parasitadas são subitamente destruídas. Tal achado coincidiu com uma quéda brusca da curva parasitêmica e com a morte da maioria dos animais, provavelmente devido à liberação de produtos tóxicos (como o TNF pelas células desintegradas. O achado foi interpretado como o auge da transição entre uma fase de susceptibilidade e outra de resistência. Embora esta transição tenha sido bem estudada in vitro, este estudo contribui com os dados do substrato morfológico observados in vivo, através da microscopia ótica e eletrônica. O tratamento específico e supressivo feito na fase inicial da infecção acarreta uma transição imediata para a fase crônica e aí o parasitismo esplênico desaparece completamente. Os animais que aparentemente se recuperaram expontaneamente após a fase de destrui

  1. Transcriptome analysis of orange-spotted grouper (Epinephelus coioides) spleen in response to Singapore grouper iridovirus

    Huang, Youhua; Huang, Xiaohong; Yan, Yang; Cai, Jia; Ouyang, Zhengliang; Cui, Huachun; Wang, Peiran; Qin, Qiwei


    .... coioides infected with Singapore grouper iridovirus (SGIV). Using 454 pyrosequencing, we obtained abundant high-quality ESTs from two spleen-complementary DNA libraries which were constructed from SGIV-infected (V...

  2. letter to editor: Torsion of a Wandering Spleen: A Pediatric Acute Abdominal Presentation

    Sharath GG


    Full Text Available Dear editor:"n"nWandering spleen is a rare pediatric emergency. Persistent torsion of the splenic pedicle causes splenic infarction, which results as an acute abdomen and severe pain. An abdominal mass is present in the majority of cases. We emphasize that whenever a pediatric patient comes with acute abdomen and the spleen is not in the usual position and a mass is found elsewhere in the abdomen or pelvis, the possible diagnosis of wandering spleen with acute torsion should be kept in mind. Ultrasonography (US is the initial study of choice, but CT scan of the liver and the spleen are excellent adjuncts when the diagnosis remains in question.    

  3. Torsion of a Wandering Pelvic Spleen; Acute Abdomen in a Child

    Metin GUNDUZ


    Full Text Available Wandering spleen is an uncommon clinical entity. Acute splenic torsion of wandering spleen is a potentially fatal surgical emergency case, and its correct and early identification continues to represent a challenge especially in children. A 11 years old girl was taken to the operative room for an explorative laparotomy due to abdominal pain, tenderness, and a midabdominal mass. Preoperative computerise tomography showed a torsion of an enlarged wandering pelvic spleen which was in a serious ischemic suffering due to a 720 degrees clock torsion around its exceptionally long pedicle. Splenectomy has been the treatment for symptomatic wandering spleen as in our case. [J Contemp Med 2012; 2(2.000: 115-117

  4. Imaging of liver and spleen candidiasis in patients with acute leukemia

    Seino, Yasuo; Tamakawa, Y.; Kato, T.; Kimura, Y.; Miyazaki, S.; Miura, R.; Ishida, H.


    Four patients with acute leukemia were found to have candidal abscess of liver and spleen. CT and US showed hepatosplenomegaly and microabscess. These findings might be useful in diagnosis of visceral candidiasis.

  5. Sclerosing angiomatoid nodular transformation of the spleen presenting rapid growth after adrenalectomy: Report of a case

    Yasuo Nagai


    Conclusion: Decreases in glucocorticoid concentrations following adrenalectomy may have contributed to the rapid growth of SANT of the spleen, because SANT is considered to be related to immunoglobulin G4-associated disease.

  6. Microscopic Appearance of Human Spleen at Different Gestational Age Groups: A Fetal Histological Study

    Anne D Souza


    Results: The microscopic anatomy of the spleen was observed at different gestational age. At first trimester the spleen was covered with a capsule. The lymphoid aggregations were observed throughout the spleen without any well differentiated red pulp. At second trimester the lymphoid aggregations started differentiating around the central arteriole forming the periarteriolar lymphoid sheath by 20 weeks. The red pulp was distinctly observed containing the RBCs and sinusoids and the white pulp containing lymphoid follicles were observed by 23rd week. At third trimester distinct red and white pulp was observed. By 30th week well developed lymphoid follicles with central arteriole were seen. At 36 weeks the central arteriole was seen at the periphery of the lymphoid follicle. Conclusion: A detailed description of the development of parenchymal and vascular components is essential in understanding the normal development of spleen. [Cukurova Med J 2015; 40(1.000: 36-41

  7. Administration of sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate conjugated GP100{sub 25–33} peptide-coupled spleen cells effectively mounts antigen-specific immune response against mouse melanoma

    Chang, Xiaoli [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Xia, Chang-Qing, E-mail: [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing (China); Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL32610 (United States)


    It remains a top research priority to develop immunotherapeutic approaches to induce potent antigen-specific immune responses against tumors. However, in spite of some promising results, most strategies are ineffective because they generate low numbers of tumor-reactive cytotoxic T lymphocytes (CTLs). Here we designed a strategy to enhance antigen-specific immune response via administering sulfosuccinimidyl-4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-SMCC)-conjugated melanoma tumor antigen GP100{sub 25–33} peptide-coupled syngeneic spleen cells in a mouse model of melanoma. We found that infusion of GP100{sub 25–33} peptide-coupled spleen cells significantly attenuated the growth of melanoma in prophylactic and therapeutic immunizations. Consistent with these findings, the adoptive transfer of spleen cells from immunized mice to naïve syngeneic mice was able to transfer anti-tumor effect, suggesting that GP100{sub 25–33} peptide-specific immune response was induced. Further studies showed that, CD8+ T cell proliferation and the frequency of interferon (IFN)-γ-producing CD8+ T cells upon ex vivo stimulation by GP100{sub 25–33} were significantly increased compared to control groups. Tumor antigen, GP100{sub 25–23} specific immune response was also confirmed by ELISpot and GP100-tetramer assays. This approach is simple, easy-handled, and efficiently delivering antigens to lymphoid tissues. Our study offers an opportunity for clinically translating this approach into tumor immunotherapy. - Highlights: • Infusion of GP100{sub 25–33}-coupled spleen cells leads to potent anti-melanoma immunity. • GP100{sub 25–33}-coupled spleen cell treatment induces antigen-specific IFN-γ-producing CD8 T cells. • This approach takes advantage of homing nature of immune cells.

  8. Combination of Radiation and Burn Injury Alters FDG Uptake in Mice

    Carter, Edward A.; Winter, David; Tolman, Crystal; Paul, Kasie; Hamrahi, Victoria; Tompkins, Ronald; Fischman, Alan J.


    Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure, on glucose metabolism in mice using [18F] Fluorodeoxyglucose (18FDG). Groups of male mice weighing approximately 30g were studied. Group 1 was irradiated with a 137Cs source (9 Gy). Group 2 received full thickness burn injury on 25% total body surface area followed by resuscitated with saline (2mL, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 µCi of 18FDG. One hour post injection, the mice were sacrificed and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in 18FDG uptake by many tissues. In the heart, brown adipose tissue (BAT) and spleen, radiation plus burn produced a much greater increase (p<0.0001) in 18FDG accumulation than either treatment separately. All three treatments produced moderate decreases in 18FDG accumulation (p<0.01) in the brain and gonads. Burn injury, but not irradiation, increased 18FDG accumulation in skeletal muscle; however the combination of burn plus radiation decreased 18FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns + irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation. PMID:23143615

  9. Experimental study of G-CSF alleviating graft-versus-host disease after mixed bone marrow transplantation in mice%粒细胞集落刺激因子减轻混合骨髓移植后移植物抗宿主病的实验研究


    Objective: How to reduce the incidence and severity of acute graft-versus-host disease (aGVHD) is a crucial step to improve the overall survival of allogeneic bone marrow transplantation (allo-BMT). The low incidence of severe aGVHD observed in allogeneic peripheral blood stem cell transplantation (allo-PBSCT), which may be related to modulating immune function of T lymphocytes by granulocyte colony-stimulating factor (G-CSF) primed donors. The study aimed to explore whether aGVHD could be alleviated by syngeneic bone marrow mixed with G-CSF-mobilized H-2 haploidentical marrow grafting. Methods: Female BALB/c mice and neonatal BALB/c mice were recipients and male (BALB/c × C57BL/6)F1(BCF1)mice were donor mice respectively. Donor mice were injected subcutaneously with G-CSF daily at 0.01 μg/g body weight or saline for 6 days, and splenocytes were harvested on day 6. Spleen index (SI) represented GVHD in neonatal mice after the intraperitoneal injection of mixed spleen cells. Lethally irradiated (60Co, 8.5 Gy) adult mice were transplanted with a mixture of syngeneic plus G-CSF-mobilized (control diluents) H-2 haploidentical marrow cells. Survival time and survival rate of the recipients were observed after mixed marrow transplantation (MBMT). GVHD was assessed by observing signs of weight loss, ruffled fur, diarrhea and histological change of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) method was used to detect cytokines (IL-2, IL-4 and INF-Y). Fluorescence-activated cell sorting (FACS) analysis was used to detect T cells phenotype. Results: (1) The neonatal mice subject to injection of 2:1 and 1:1 mixed spleen cells and H-2 haploidentical spleen cells all suffered from aGVHD. The severity of aGVHD in recipient mice receiving G-CSF-mobilized splenocytes was dramatically reduced. (2) The aGVHD signs and histological change were observed in most mice of 2:1 and 1:1 MBMT groups. However, the survival time of G-CSF-mobilized MBMT was

  10. Study on the pathophysiologic basis of classification of 'spleen' deficiency in chronic gastritis

    YIN Guang-yao; CHEN Yi; SHEN Xiao-jing; HE Xue-fen; ZHANG Wu-ning


    Background Most of the studies on traditional Chinese medicine (TCM)‘spleen’deficiency syndrome in the recent 30 years were conducted only on the basis of single functional index, neglecting the study on the pathophysiologic internal relationship between spleen deficiency syndrome and gastric diseases in modern medicine. But it was at the subcellular molecular biological level that we explored the pathophysiologic basis of classification of spleen deficiency in chronic gastritis by detecting the bioactive substances in gastric mucosa nuclei and mitochondria. Methods By means of optical microscope, scanning electron microscope (SEM), transmission electron microscopy (TEM) and histochemical staining, we conducted histopathological, subcellular ultrastructural analysis and nuclei and mitochondrial ultrastructural analysis of gastric mucosa of 188 spleen deficiency patients and of 42 voluntary blood donors. At the same time, bioactive substances were measured by means of X-ray energy dispersive analysis system (EDAX) image analysis system, radioimmunoassay method and chemiluminescence method. Results The content of cAMP, superoxide dismutase (SOD), Zn and Cu in gastric mucosa, and the content of Zn and Cu in mitochondria decreased progressively in order of groups: healthy control (HC), spleen Qi deficiency without organic lesion (F-SQD), spleen Yang deficiency without organic lesion (F-SyangD), disease without symptoms group, spleen Qi deficiency with organic lesion (G-SQD), spleen Yang deficiency with organic lesion (G-SyangD), spleen Yin deficiency (SyinD) and spleen deficiency with Qi stagnation (SDQS), chronic spleen deficiency gastritis (CSG) and chronic atrophic gastritis (CAG); decreased in order of HC, intestinal metaplasia (IM)Ⅰa, IMⅠb, IMⅡa and IMⅡb, P<0.05. The content of DNA, Zn and Cu in nuclei progressively increased in order mentioned above, P<0.05.Conclusions The quantitative changes of gastric mucosal cAMP, SOD, Zn, Cu, of mitochondrial Zn

  11. Influence of radiation field and fractionation schedule of total lymphoid irradiation (TLI) on the induction of suppressor cells and stable chimerism after bone marrow transplantation in mice

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.


    When BALB/c mice received 17 daily fractions of 2 Gy each of total lymphoid irradiation (TLI, total dose 34 Gy) and 30 x 10/sup 6/ C/sub 57/ B1 bone marrow cells (BM) on the day after the last fraction, stable bone marrow chimerism without signs of graft-vs-host disease (GVHD) was obtained in 84% of the animals. On the contrary, in BALB/c mice receiving only seven fractions of TLI (total dose 14 Gy), all bone marrow grafts were rejected. When the last two fractions of a 14-Gy TLI course were given without shielding the extra lymphatic tissues (combined total lymphoid + total body irradiation, TLBI), chimerism could be induced in 53% of the animals. When this 14-Gy TLBI schedule was used, it was even possible to administer four fractions per day (multiple fractions per day schedule, MFD), thus reducing the overall treatment time to 2 consecutive days. After this concentrated form of TLBI, chimerism was detected in 35% of the animals. As in the 34-Gy TLI schedule, graft-vs-host reaction could not be prevented in the 14-Gy TLBI schedule when spleen lymphocytes (10 x 10/sup 6/) were added to the BM inocolum. Leucopenia or suppression of the phytohaemagglutinin (PHA)-induced blastogenesis could not predict which schedule would result in a successful allogeneic bone marrow take. Suppressor cells of the mixed lymphocyte reaction, on the other hand, were only found in the spleen of BALB/c mice treated with the TLI or TLBI schedules, which also resulted in stable bone marrow chimerism.

  12. Experimentally transmitted marble spleen disease in pen-raised wild turkeys.

    Iltis, J P; Jakowski, R M; Wyand, D S


    Pen-raised North American wild turkeys (Meleagris gallopavo L.) were experimentally infected with marble spleen disease (MSD) to determine their susceptibility to this disease. Gross and microscopic lesions were consistent with experimental MSD in pheasants and domestic turkeys: an enlarged mottled spleen, intranuclear inclusion bodies, and absence of pulmonary edema and hemorrhage. Detectable levels of viral antigen were not demonstrable in sera of turkeys using the agar gell precipitin test.

  13. The Great Pretender: Pediatric Wandering Spleen: Two Case Reports and Review of the Literature.

    Radillo, Lucia; Taddio, Andrea; Ghirardo, Sergio; Bramuzzo, Matteo; Pederiva, Federica; Maschio, Massimo; Barbi, Egidio


    Wandering spleen is a rare condition, typically not only due to embryological defects of the splenic ligaments, but also secondary to trauma and splenomegaly. The most common presentation is acute abdomen with a mobile abdominal mass or recurrent abdominal pain. However, the spleen may be temporary in its normal position, and patients could be asymptomatic. A familiarity, if present, strengthens the diagnostic suspect.Abdominal ultrasonography and computed tomography are the examination of choice, and the management is surgical.

  14. Computed tomography of the abdomen in Saanen goats: II. liver, spleen, abomasum, and intestine


    This study describes the results of computed tomography (CT) of the liver, spleen, abomasum, small intestine and large intestine in 30 healthy Saanen goats. CT examination and anatomical slice preparation postmortem were performed as described in the first communication. After subjective evaluation of the CT images, various variables including the length/size, volume and density of the liver, spleen and gallbladder, the wall thickness of the abomasum, small intestine and large intestine and t...

  15. Post-gastrectomy spleen enlargement and esophageal varices: Distal vs total gastrectomy

    Takatsugu; Oida; Kenji; Mimatsu; Hisao; Kano; Atsushi; Kawasaki; Youichi; Kuboi; Nobutada; Fukino; Sadao; Amano


    AIM: To study the relationship between platelet count-to-spleen diameter ratio and post-gastrectomy esopha-geal varices (EVs) development in patients without liver cirrhosis or hepatitis. METHODS: We retrospectively studied 92 patients who underwent gastrectomy. They were divided into 2 groups on the basis of the surgical treatment: the distal gastrectomy (DG) group and total gastrectomy (TG) group. The incidence of EVs was determined and postoperative platelet counts, spleen diameters, and platelet count-t...

  16. Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells

    Jun-li YU; De-qiang DOU; Xiao-hong CHEN; Hong-zhen YANG; Na GUO; Gui-fang CHENG


    AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism.METHODS: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-γ, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method. Effects of ginsenosideF3 on mRNA level of cytokines IL-4, IFN-γ, and transcription factors T-bet and GATA-3 were evaluated by RTPCR analysis. Effect of ginsenoside-F3 on NF-κB DNA binding activity in murine spleen cells was investigated by electrophoretic mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100μmol/L not only promoted the murine spleen cell proliferation, but also increased the production of IL-2 and IFN-γ, while decreased the production of IL-4 and IL-10 from murine spleen cells with the maximal effect at 10μmol/L. RT-PCR analysis displayed that ginsenoside-F3 enhanced the IFN-γ and T-bet gene expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed that ginsenoside-F3 10μmol/L enhanced the NF-κB DNA binding activity induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1 cytokines and type 2 cytokines in murine spleen cells.

  17. Neem tree (Azadirachta indica) extract specifically suppresses the growth of tumors in H22-bearing Kunming mice.

    He, Zhenxiang; Jiang, Cuihua; Zhang, Jian; Yin, Zhiqi; Yin, Zengfang; Zhu, Yunfeng; Fu, Jie


    Recently, neem tree (Azadirachta indica) extract (NTE) has been reported to have various antitumor activities against gastric, breast, prostate, and skin cancer, respectively. The current study was designed to evaluate the effect of NTE on hepatic cancer in a mouse model. The possible side effects elicited by NTE were also evaluated. The components in NTE were analyzed by liquid chromatography-mass spectrometry (LC-MS). H22 cells-bearing Kumming mice were generated by injecting H22 cells subcutaneously into the right forelimb armpit of the mice. Then the mice were treated daily for 27 days with NTE (150, 300, and 600 mg/kg body weight) by intragastric administration, using carboxymethyl cellulose (CMC, 1%) as blank control and cyclophosphamide (CTX, 20 mg/kg) as positive control. The antitumor effect of NTE was evaluated by assessment of survival rate, body weight, tumor volume and weight, tumor histology, thymus and spleen indexes, and liver histology. The tumor weight and volume in groups of NTE and CTX were significantly lower than those in the CMC group. The survival rate in the NTE group receiving the high dose (600 mg/kg) was significantly higher than that in the CTX and CMC groups. Compared with CTX, NTE was observed to have a tumor-specific cytotoxicity without impairing the normal liver tissue. Additionally, the higher indexes of thymus and spleen indicated that NTE could facilitate the growth of immune organs. The results indicate that NTE is a promising candidate for the antitumor treatment with high efficacy and safety.

  18. MCS-18, a natural product isolated from Helleborus purpurascens, inhibits maturation of dendritic cells in ApoE-deficient mice and prevents early atherosclerosis progression.

    Dietel, Barbara; Muench, Rabea; Kuehn, Constanze; Kerek, Franz; Steinkasserer, Alexander; Achenbach, Stephan; Garlichs, Christoph D; Zinser, Elisabeth


    Inflammation accelerates both plaque progression and instability in the pathogenesis of atherosclerosis. The inhibition of dendritic cell (DC) maturation is a promising approach to suppress excessive inflammatory immune responses and has been shown to be protective in several autoimmune models. The aim of this study was to investigate the immune modulatory effects of the natural substance MCS-18, an inhibitor of DC maturation, regarding the progression of atherosclerosis in ApoE-deficient mice. ApoE-deficient mice were fed for twelve weeks with a Western-type diet (n = 32) or normal chow (control group; n = 16). Animals receiving high-fat diet were treated with MCS-18 (500 μg/kg body weight, n = 16) or saline (n = 16) twice a week. After 12 weeks, animals were transcardially perfused and sacrificed. The percentage of mature DCs (CD3(-)/CD19(-)/CD14(-)/NK1.1(-)/CD11c(+)/MHCII(+)/CD83(+)/CD86(+)) and T cell subpopulations (CD4(+)/CD25(+)/Foxp3(+), CD3/CD4/CD8) was analyzed in peripheral blood and in the spleen using flow cytometry. Plaque size was determined in the aortic root and the thoracoabdominal aorta using en-face staining. Immunohistochemical stainings served to detect inflammatory cells in the aortic root. Several cytokines and chemokines were determined in serum using multiplex assays. In splenic cells derived from saline-treated atherosclerotic mice an increased DC maturation, reflected by the upregulation of CD83 and CD86 expression, was observed. The enhanced expression of both maturation markers was absent in MCS-18 treated atherosclerotic mice. While the percentage of splenic Foxp3 expressing Treg was increased in animals receiving MCS-18 compared to saline-treated atherosclerotic mice, cytotoxic T cells were reduced in the spleen and in atherosclerotic lesions of the aortic root. Furthermore, proatherogenic cytokines (e.g. IL-6 and IFN-γ) and chemokines (e.g. MIP-1β) were decreased in serum of MCS-18-treated animals when compared to saline

  19. Correlation between contrast enhancement of portal vein and spleen size in dual-phase spiral CT

    Ahn, Seung Eon; Choi, Jong Cheol; Nam, Kyung Jin; Jung, Won Jung; Goo, Bong Sik; Park, Byung Ho; Lee, Young Ii; Chung, Duck Hwan [Donga Univ. College of Medicine, Pusan (Korea, Republic of)


    To evaluate using spiral CT the effect of spleen size on blood flow in the portal venous system and to know the usefulness of this evaluation. Fifty-one patients without evidence on spiral CT scan of abnormality thought to affect portal venous flow presented between December 1994 and June 1995. We measured spleen size and Hounsfield units of portal vein in dual-phase, and calculated the ratio of the unit in the portal phase to that in the arterial phase. Spleen size was measured, using the length of X-axis by that of Z-axis on spiral CT scan. We then measured the correlation between the two values. CT was performed with a Somatom Plus-S scanner(Siemens, Erlangen, Germany). A total dose of 120ml of non-ionic contrast material(Ultravist) was administered at a rate of 3 ml/sec. Arterial and portal phase were obtained after 30 seconds and 60 seconds from the begining of the contrast agent injection. The correlation between spleen size and contrast enhancement of the portal vein was relatively significant(Pearson's correlation coefficient(r)=0.41801). Spleen size significantly affects portal venous flow on spiral CT scan. The evaluation of spleen size and contrast enhancement of the portal vein could be useful in the differential diagnosis of diseases which affect portal venous flow.

  20. Age dependence of spleen- and muscle-corrected hepatic signal enhancement on hepatobiliary phase gadoxetate MRI

    Matoori, Simon [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Froehlich, Johannes M. [Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zurich (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Breitenstein, Stefan [Cantonal Hospital Winterthur, Department of Surgery, Clinic for Visceral and Thoracic Surgery, Winterthur (Switzerland); Doert, Aleksis [Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Pozdniakova, Viktoria [Stavanger University Hospital, Department of Radiology, Stavanger (Norway); Koh, Dow-Mu [Royal Marsden Hospital, Department of Radiology, Surrey, England (United Kingdom); Gutzeit, Andreas [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland)


    To identify correlations of signal enhancements (SE) and SE normalized to reference tissues of the spleen, kidney, liver, musculus erector spinae (MES) and ductus hepatocholedochus (DHC) on hepatobiliary phase gadoxetate-enhanced MRI with patient age in non-cirrhotic patients. A heterogeneous cohort of 131 patients with different clinical backgrounds underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013. After exclusion of cirrhotic patients, a cohort of 75 patients with no diagnosed diffuse liver disease was selected. The ratio of signal intensity 20 min post- to pre-contrast administration (SE) in the spleen, kidney, liver, MES and DHC, and the SE of the kidney, liver and DHC normalized to the reference tissues spleen or MES were compared to patient age. Patient age was inversely correlated with the liver SE normalized to the spleen and MES SE (both p < 0.001) and proportionally with the SE of the spleen (p = 0.043), the MES (p = 0.030) and the kidney (p = 0.022). No significant correlations were observed for the DHC (p = 0.347) and liver SE (p = 0.606). The age dependence of hepatic SE normalized to the enhancement in the spleen and MES calls for a cautious interpretation of these quantification methods. (orig.)


    Rossi, Federica; Fina, Caroline; Stock, Emmelie; Vanderperren, Katrien; Duchateau, Luc; Saunders, Jimmy H


    Contrast-enhanced ultrasound of the spleen enables the dynamic assessment of the perfusion of this organ, however, both subjective and quantitative evaluation can be strongly influenced by sedative agent administration. The purpose of this prospective, experimental study was to test effects of two sedative agents on splenic perfusion during contrast-enhanced ultrasound of the spleen in a sample of healthy dogs. Contrast-enhanced ultrasound of the spleen was repeated in six healthy Beagles following a cross-over study design comparing three protocols: awake, butorphanol 0.2 mg/Kg intramuscular (IM), and dexmedetomidine 500 μg/m(2) IM. After intravenous injection of a phospholipid stabilized sulfur hexafluoride microbubble solution (SonoVue®, Bracco Imaging, Milano, Italy), the enhancement intensity and perfusion pattern of the splenic parenchyma were assessed and perfusion parameters were calculated. Normal spleen was slightly heterogeneous in the early phase, but the parenchyma was homogeneous at a later phase. Sedation with butorphanol did not modify perfusion of the spleen. Dexmedetomidine significantly reduced splenic enhancement, providing diffuse parenchymal hypoechogenicity during the entire examination. Measured parameters were significantly modified, with increased arrival time (AT; (spleen in the early venous phase was determined to be a normal finding.

  2. Ultrasonographic appearance of histoplasmosis identified in the spleen in 15 cats.

    Atiee, Genna; Kvitko-White, Heather; Spaulding, Kathy; Johnson, Mark


    Histoplasmosis is the second most common fungal infection reported in the cat. The disseminated form involving lung, liver, lymph nodes, spleen, and bone marrow is a frequent manifestation of the disease. Limited information is available in the literature regarding the ultrasonographic appearance of the spleen in cats with disseminated or splenic histoplasmosis. A retrospective review of splenic ultrasound images from 15 cats confirmed to have histoplasmosis by splenic aspirates was performed. Size, echotexture, echogenicity, margin appearance, presence of nodules, and the overall shape of the spleen were reported in each case. Splenomegaly was documented in all cases (15/15) and a hypoechoic appearance of the spleen was documented in 14/15 of cases. The spleen was diffusely and uniformly affected in 14/15 (six homogenous and eight with a subtle mottled appearance) and had discrete nodules in 1/15 cats. Histoplasmosis should be included in the differential list for an enlarged and hypoechoic spleen in cats with consistent clinical findings. Additionally, ultrasound guided splenic aspirate may be a useful method to obtain a cytology sample for diagnosis.

  3. Intrapancreatic Accessory Spleen: Investigative Dilemmas and Role of EUS-Guided FNA for Diagnostic Confirmation

    Somashekar G Krishna


    Full Text Available Context We submit a case of intrapancreatic accessory spleen. Case report A 33-year-old patient with history of dyspepsia underwent imaging studies suggestive of a neuroendocrine tumor. After referral to our institute, endoscopic ultrasound guided fine needle aspiration (EUS-FNA confirmed diagnosis as intrapancreatic accessory spleen. Discussion An accessory spleen may develop from estranged mesenchymal cells due to fusion failure of the splenic anlage. The prevalence of an accessory spleen is 10-30% with 80% of them present at the splenic hilum and 17% in the pancreatic tail. Intrapancreatic accessory spleen is commonly misdiagnosed as a pancreatic tumor. Since, the differential diagnosis includes pancreatic neuroendocrine tumors, additional investigation with EUS-FNA should be considered when radiological diagnosis is not definitive. Conclusion For diagnosis of intrapancreatic accessory spleen, radiographic imaging is useful, but lacks specificity without tissue diagnosis. Diagnosis can be safely and reliably established with EUS-FNA, leading to a benign prognosis and avoidance of unnecessary surgical intervention.

  4. A minimally invasive approach to spleen histopathology in dogs: A new method for follow-up studies of spleen changes in the course of Leishmania infantum infection.

    Santos, Silvana Ornelas; Fontes, Jonathan L M; Laranjeira, Daniela F; Vassallo, José; Barrouin-Melo, Stella Maria; Dos-Santos, Washington L C


    Severe forms of zoonotic visceral leishmaniosis (ZVL) are associated with disruption of the spleen structure. However, the study of spleen histology requires splenectomy or necropsy. In this work, we present a minimally invasive cell-block technique for studying spleen tissue histology in dogs with ZVL. We examined 13 dogs with and seven dogs without Leishmania infantum infection. The dogs with Leishmania infection had a lower frequency of lymphoid follicles (2/13, Fisher's test, P<0.02) and a higher density of plasma cells (score 3, Fisher's test, P<0.02) than uninfected dogs (5/7 exhibiting lymphoid follicles and a plasma cell score of 1). The dogs with Leishmania infection also presented with granulomas (8/13) and infected macrophages (5/13). These differences in the histological presentations of spleen tissue from infected and uninfected dogs corresponded to changes observed in conventional histology. Hence, the cell-block technique described here may be used in the follow-up care and study of dogs with ZVL and other diseases in both clinical practice and research.

  5. Wideband CMOS receivers

    Oliveira, Luis


    This book demonstrates how to design a wideband receiver operating in current mode, in which the noise and non-linearity are reduced, implemented in a low cost single chip, using standard CMOS technology.  The authors present a solution to remove the transimpedance amplifier (TIA) block and connect directly the mixer’s output to a passive second-order continuous-time Σ∆ analog to digital converter (ADC), which operates in current-mode. These techniques enable the reduction of area, power consumption, and cost in modern CMOS receivers.

  6. Tumorigenicity, Motility and Liver Metastasis of Human Gastric Carcinoma Lines with High Metastatic Potential in the Liver of Nude Mice


    To analyze the human gastric carcinoma metastasis to the liver, a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ521 were expanded in vitro and subsequently injected into the spleens of nude mice. By repeating these proce-dures five times, we were able to obtain a cell line, designated AZ-H5c, with high metastatic potential in nude mice. It was observed that animals had liver metastasis in 10 of 12 (83%) c...

  7. Zero-power receiver

    Brocato, Robert W.


    An unpowered signal receiver and a method for signal reception detects and responds to very weak signals using pyroelectric devices as impedance transformers and/or demodulators. In some embodiments, surface acoustic wave devices (SAW) are also used. Illustrative embodiments include satellite and long distance terrestrial communications applications.

  8. Sender-Receiver Games

    Peeters, R.J.A.P.; Potters, J.A.M.


    Standard game-theoretic solution concepts do not guarantee meaningful commu- nication in cheap-talk games. In this paper, we define a solution concept which guarantees communication for a large class of games by designing a behavior pro- tocol which the receiver uses to judge messages sent by the

  9. Variants of Sporothrix schenckii with attenuated virulence for mice.

    de Lima, Renata Ferretti; Schäffer, Guido Vidal; Borba, Cintia de Moraes


    Strains of Sporothrix schenckii preserved under mineral oil were examined for virulence in BALB/c mice. The mice were inoculated with S. schenckii conidia and development of cutaneous lesions, signs of inactivity, weight loss, survival rates, number of viable yeast cells in lung and spleen, splenomegaly and organ lesions were evaluated. After intravenous injection of 7.5 x 10(6) conidia, two of five S. schenckii strains were unable to induce systemic disease and to kill the mice, only producing cord-like lesions on the tail that regressed with mouse maturation. Very small numbers of viable cells isolated from the spleen confirmed the lower invasive ability of these strains when compared with other strains studied here. These results suggest a relationship between the attenuation of virulence and the storage method under mineral oil after long periods of time.

  10. Expression of JunB Induced by X-rays in Mice



    To explore JunB gene expression in spleen cells of mice after the whole body irradiation as well as in normal hematopoietic and leukemia cells in the primary culture after different dosages of X-ray irradiation. Methods Spleen cells were isolated from the mice irradiated with 3 Gy X-rays. Primary cultured cells from mice were incubated in different intervals after X-irradiation at different dosages. Total RNA was extracted from the cells and the fluctuation of JunB mRNA level was assessed by the RNA ratio of JunB/β-actin measured by quantitative Northern blot hybridization. Results After the mice were exposed to 3 Gy X-rays irradiation, JunB expression in spleen cells was remarkably and rapidly increased, and reached its peak 0.5 h later in C3H/He mice and 1 h later in Balb/c mice. In the primary culture of normal spleen and leukemia cells, JunB mRNA levels increased 30 min after irradiation. The enhanced levels of JunB mRNA were returned to a normal level within 240 min after irradiation. Conclusions JunB gene is responsive to ionizing irradiation and is induced at immediate-early phase after the stimulation. This suggests that the JunB gene plays an important role in the early process of the cells against radiation.

  11. NTP Toxicity Studies of Cyclohexanone Oxime Administered by Drinking Water to B6C3F1 Mice (CAS No. 100-64-1).


    Cyclohexanone oxime is used primarily as a captive intermediate in the synthesis of caprolactam for the production of polycaprolactam (Nylon-6) fibers and plastics and also in a variety of industrial applications. Cyclohexanone oxime was selected for study because of the potential for human exposure and the interest in oximes as a chemical class. Toxicity studies of cyclohexanone oxime (approximately 99% pure) were carried out in male and female B6C3F1 mice; the compound was administered in drinking water for 2 weeks or 13 weeks. In addition, the genetic toxicity of cyclohexanone oxime was evaluated by determining mutagenicity in Salmonella typhimurium and induction of chromosomal aberrations in cultured Chinese hamster ovary cells in vitro, with and without S9 activation. The frequency of micronucleated normochromatic erythrocytes in the bone marrow and peripheral blood of mice from the 13-week study was also determined. In the 2-week study, groups of five male and five female mice were given drinking water containing 0, 106, 312, 625, 1,250, or 2,500 ppm cyclohexanone oxime. No deaths occurred, and there was no decrease in weight gain in any group. No gross lesions were observed; there were significant increases in relative spleen weights of males and females in the 2,500 ppm group and increases in the relative liver weight of male mice exposed to 312 ppm or greater. In the 13-week studies, groups of 10 male and 10 female mice were given drinking water containing 625, 1,250, 2,500, 5,000 or 10,000 ppm cyclohexanone oxime. Deaths occurred in the 10,000 ppm groups and weight gain was depressed in males and females given 10,000 ppm and in females given 5,000 ppm. There were significant increases in relative spleen weight at exposure levels of 5,000 and 10,000 ppm and significant increases in the relative liver weights of males and females that received 10,000 ppm. Microscopically, hematopoietic cell proliferation was observed in the spleen of males and females in

  12. Reserve spleen up and descend parts of spleen resections of pole at reserve the application in the spleen surgical operation%保留脾上极和下极的部分脾切除术19例应用分析

    李安云; 徐登科; 成玉滨; 苏芹芹; 王洪波; 姜希宏


    Objective: The summary reserves spleen up, parts of spleen resections descending a pole protect spleen surgical operation at the grass-roots hospital in of applied effect. Methods: To 19 reservation spleens up and very with(or) descend parts of resections (protect a spleen set) of the spleen of poles and 20 spleen whole resections, spleen slice transplantation (slice a spleen set) the blood platelets, immunity index sign and the reservation spleen organization survival circumstance carry on contrast analysis after sufferer operation. Results: protect a spleen set Blood platelets' heating up range weremore obviously small than to slice a spleen set, the immunity index sign IgG,IgM and IgA's more slicing a spleen set instauration were quick. Conclusion: Reserve spleen up, descend parts of spleen resections of pole are safe in the middle of protecting spleen surgical operation credibility, compare the all of spleen cut off, spleen slice transplantation can better reservation spleen function, there is good clinical application value at the grass-roots hospital.%目的:总结保留脾上、下极的部分脾切除术在基层医院保脾手术中的应用效果.方法:对19例保留脾上极和(或)下极的脾部分切除术(保脾组)及20例脾全切除、脾片移植术(切脾组)患者术后情况进行对比分析.结果:保脾组患者脾血小板升高幅度明显小于切脾组(P<0.05),免疫指标lgG、lgM、lgA较切脾组恢复快(P<0.05).术后腹部B超或CT复查显示保脾组患者脾组织存活率高.结论:保留脾上、下极的部分脾切除术在保脾手术中安全可靠,较脾全切除、脾片移植术能更好保留脾脏功能,在基层医院有良好的临床应用价值.

  13. Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA.

    Yamanaka, Takahiro; Tamauchi, Hidekazu; Suzuki, Yusuke; Suzuki, Hitoshi; Horikoshi, Satoshi; Terashima, Masazumi; Iwabuchi, Kazuya; Habu, Sonoko; Okumura, Ko; Tomino, Yasuhiko


    We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli.

  14. Peromyscus leucopus mice: a potential animal model for haematological studies.

    Sun, Yu; Desierto, Marie J; Ueda, Yasutaka; Kajigaya, Sachiko; Chen, Jichun; Young, Neal S


    Peromyscus leucopus mice share physical similarities with laboratory mice Mus musculus (MM) but have higher agility and longer lifespan. We compared domesticated P. leucopus linville (PLL) and M. musculus C57BL/6 (MMB6) mice for cellular composition of peripheral blood (PB), bone marrow (BM) and spleen. PLL mice had significantly fewer platelets and significantly more monocytes in the blood, and notably fewer megakaryocytes in the BM. Spleens of PLL mice were significantly smaller, with 50% fewer cells and reduced 'red pulp'. There was no obvious haematological change in PLL mice between 2-8 and 16-26 months of age, except for a significant increase in blood monocytes. Cellular reactive oxygen species (ROS) content showed no change with age but differed significantly between different cell types. Treating two to eight month-old PLL mice with antioxidant N-acetylcysteine in drinking water for three months did not affect cellular ROS content, but increased blood leucocytes especially the concentration of monocytes. The low platelets, low megakaryocytes, high monocytes and low splenic erythropoiesis in PLL mice resemble human measurements better than the values seen in MMB6.

  15. Spleen-Preserving Distal Pancreatectomy for Pancreatic Trauma: A Series of Six Cases

    Thakur Deen Yadav


    Full Text Available Context Spleen-preserving distal pancreatectomy is a well-accepted procedure for benign tumors of the distal pancreas. Its safety and feasibility have been proven. However many doctors have not used this procedure due to the trauma involved. Objective We present our experience of six cases of distal pancreatic trauma where we managed to preserve the spleen during distal pancreatectomy in an emergency procedure. Design Prospective analysis of the data. Participants Patients with distal pancreatic trauma admitted to the Department of Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh between July 2001 and June 2005. Intervention A spleen-preserving distal pancreatectomy was performed by preserving the splenic vessels to maintain a reliable splenic blood flow. Patients who were unstable after adequate resuscitation were excluded. Main outcome measures The preoperative characteristics, intraoperative findings and postoperative complications with follow-up were studied. Results Six patients were found suitable for spleen-preserving distal pancreatectomy based on their general condition and a preoperative spleen CECT. Five patients had been injured in car accidents and one patient had sustained a stab injury. The average duration of the surgery was 4.75±0.25 hours. All patients had associated hollow viscus injury which was repaired along with the spleen-preserving distal pancreatectomy. The most common post-operative complication was fever with basal atelectasis. One patient died postoperatively from hemodynamic instability. The other five patients are doing well and have not developed pancreatic endocrine insufficiency. Conclusion Although technically demanding, a spleen-preserving distal pancreatectomy can be performed safely in an emergency, and it avoids splenectomy-related problems in the post-operative period.

  16. The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes.

    Fukuda, Kenji; Sugihara, Ayako; Nakasho, Keiji; Tsujimura, Tohru; Yamada, Naoko; Okaya, Atsuhito; Sakagami, Masafumi; Terada, Nobuyuki


    Transplantation of rat hepatocytes into the syngeneic rat spleen results in the appearance of cytokeration (CK)-19-positive biliary cells that form ductules. The exact origin of CK-19-positive cells is not known and the possibility that they are derived from biliary cells or precursors of oval cells in transplanted hepatocyte preparations has been raised. In the present study, we found that the number of CK-19-positive biliary cells increased rapidly after transplantation of hepatocytes, reached the maximum at 4 weeks, and then gradually decreased. However, a Ki-67 labeling index of CK-19-positive biliary cells was low and showed no significant changes throughout the experimental period. In addition, no or few CK-19-positive cells appeared in the spleen after transplantation of nonparenchymal liver cells enriched with biliary cells. These results showed that biliary cells were not the source of CK-19-positive cells in the spleen. Impairment of precursors of oval cells in the liver by administration of 4,4'-diaminodiphenylmethane 24 h before transplantation of hepatocytes did not prevent the appearance of CK-19-positive biliary cells in the spleen. Moreover, transplantation of nonparenchymal cells carrying an increased number of oval cells by means of treatment with 2-acetylaminofluorene and partial hepatectomy resulted in no appearance of CK-19-positive biliary cells in the spleen. These results ruled out oval cells as the origin of CK-19-positive biliary cells in the spleen. Because CK-19-positive biliary cells appeared in the spleen only when hepatocyte fractions were transplanted, we suggest transdifferentiation of heptocytes may be the mechanism by which CK-19-positive biliary cells are generated.

  17. Age dependent course of EAE in Aire-/- mice.

    Aharoni, Rina; Aricha, Revital; Eilam, Raya; From, Ido; Mizrahi, Keren; Arnon, Ruth; Souroujon, Miriam C; Fuchs, Sara


    This study explores the consequences of deficiency in the autoimmune regulator (Aire) on the susceptibility to experimental autoimmune encephalomyelitis (EAE). Increased susceptibility to EAE was found in Aire knockout (KO) compared to wild type (WT) in 6month old mice. In contrast, 2month old Aire KO mice were less susceptible to EAE than WT mice, and this age-related resistance correlated with elevated proportions of T regulatory (Treg) cells in their spleen and brain. Combined with our previous findings in experimental autoimmune myasthenia gravis, we suggest an age-related association between Aire and Treg cells in the susceptibility to autoimmunity. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Acute cadmium administration to rats exerts both immunosuppressive and proinflammatory effects in spleen.

    Demenesku, Jelena; Mirkov, Ivana; Ninkov, Marina; Popov Aleksandrov, Aleksandra; Zolotarevski, Lidija; Kataranovski, Dragan; Kataranovski, Milena


    Conflicting data (both suppression and augmentation as well as lack of the effect) exist in respect to cadmium (Cd) and splenic T cell-based immune cell activity. Spleen is also the site of innate immune responses but impact of Cd on this type of immunity has been less explored. In the present study the effects of acute Cd administration on basic aspects of both T cell-based and innate immune spleen cell activity were examined in rats. Intraperitoneal injection of 1mg of Cd/kg resulted in decrease in concanavalin A (ConA) induced proliferation which seems to be more related to altered spleen cells responsiveness to IL-2 than to apoptosis. Differential effects on proinflammatory T cell derived cytokines were observed (decreases of IFN-γ gene expression and ConA-stimulated production, but increases in IL-17 mRNA levels with no effect on concentrations of protein product). Reduction of IFN-γ production seemed not to rely on IL-4 and IL-10, but at least partly on nitric oxide (NO). Increased activity relevant for innate immunity (granulocyte and CD11b(+) cell accumulation in the spleen, inducible nitric oxide synthase/iNOS expression and NO production by spleen cells) was observed, but there was a decrease in respiratory burst (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT reduction). Increases of TNF-α and IL-1β gene expression and IL-1β protein product were noted as well. Administration of 0.5mg Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack of the effect (IFN-γ production) on spleen T cell activities and on innate activities (granulocyte accumulation, NO production) as well. However, increases of spleen cell respiratory burst activity and IL-1β production were observed. Effects of lower cadmium doses (5ppm and 50ppm) on several aspects of spleen cell immune activity were observed in intermediate period of exposure (30 days, oral intake) as well. Differential effects of Cd on immune activities of spleen cells might


    O. Dunaevskaya


    Full Text Available Purpose. Study of the microscopic structure and morphometric parameters of European catfish spleen. Methodology. For the study, we used the spleen of clinically healthy age-2 European catfish (Silurus glanis L.. We determined the absolute and relative weight of the organ or the index of spleen development. For the histological studies, pieces of the material were preserved in 10-12 % cooled neutral formalin solution, with subsequent filling in paraffin. Paraffin sections were prepared using a sledge microtome, with a thickness of no more than 10 microns. To determine the cell and tissue morphology under light microscopy, we the staining of histological sections with hematoxylin and eosin. Determination of spleen linear dimensions, morphometric measurements were carried out using the "Master of Morphology". Quantitative parameters were analyzed in "Statistica 6.0". Findings. European catfish spleen corresponded to general regularities of fish spleen structure: we identified support-contractile apparatus, white and red pulp and inherent cellular composition. Peculiarities of the microscopic structure of this organ in European catfish is underdevelopment of radial trabeculae, poor development of periarterial lymphoid sheaths, absence of the differentiation to zones in lymphoid nodules. The most developed was red pulp (70.82 ± 10.76%, the least developed — support-contractile apparatus (7.04 ± 0.65%. The base of the white pulp (22.14 ± 6.61% is lymphoid nodules without propagation center. The support-contractile apparatus of the spleen, which includes capsule and trabecular system, is developed unevenly. E.g., the capsule thickness in different parts of the body is not the same, the biggest thickness is in porta, where it attains 21.85 ± 7.44 micrometers, its relative area is 3.06 ± 0.32%. Relative area of the trabecular system is 3.98 ± 2.57%, the most developed are vascular trabeculae. Originality. We found the peculiarities of spleen

  20. Survival of motor neurone protein is required for normal postnatal development of the spleen.

    Thomson, Alison K; Somers, Eilidh; Powis, Rachael A; Shorrock, Hannah K; Murphy, Kelley; Swoboda, Kathryn J; Gillingwater, Thomas H; Parson, Simon H


    Spinal muscular atrophy (SMA), traditionally described as a predominantly childhood form of motor neurone disease, is the leading genetic cause of infant mortality. Although motor neurones are undoubtedly the primary affected cell type, the severe infantile form of SMA (Type I SMA) is now widely recognised to represent a multisystem disorder where a variety of organs and systems in the body are also affected. Here, we report that the spleen is disproportionately small in the 'Taiwanese' murine model of severe SMA (Smn(-/-) ;SMN2(tg/0) ), correlated to low levels of cell proliferation and increased cell death. Spleen lacks its distinctive red appearance and presents with a degenerated capsule and a disorganised fibrotic architecture. Histologically distinct white pulp failed to form and this was reflected in an almost complete absence of B lymphocytes necessary for normal immune function. In addition, megakaryoctyes persisted in the red pulp. However, the vascular density remained unchanged in SMA spleen. Assessment of the spleen in SMA patients with the infantile form of the disease indicated a range of pathologies. We conclude that development of the spleen fails to occur normally in SMA mouse models and human patients. Thus, further analysis of immune function is likely to be required to fully understand the full extent of systemic disease pathology in SMA.

  1. Effects of avermectin on immune function and oxidative stress in the pigeon spleen.

    Liu, Ci; Li, Ming; Cao, Ye; Qu, Jian-Ping; Zhang, Zi-Wei; Xu, Shi-Wen; Li, Shu


    Avermectin (AVM) is a pesticide that can accumulate in the environment through spray-drift, runoff or field drainage. Residues of AVM or its metabolites in livestock feces have toxic effects on non-target aquatic and terrestrial organisms. In this study, changes in oxidative stress and immunity in pigeon spleen tissues were detected after subchronic exposure to AVM for 30, 60, and 90 days. In pigeon spleen, the activities of total anti-oxidation capability (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased significantly, whereas the levels of malondialdehyde (MDA), protein carbonyl (PCO), and DNA-protein crosslink (DPC) coefficients increased. Additionally, obvious ultrastructure alterations were observed. These results indicated that AVM induced oxidative stress and damaged the normal structure of spleen cells. The exposure to AVM could lead to increases in the mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4), as well as a decrease in the mRNA level of interferon-γ (IFN-γ), in a dose-time-dependent manner in pigeon spleen. The results imply that AVM induces immunosuppression in the spleen tissue of pigeons. The information presented in this study may be helpful for understanding the mechanism of AVM-induced immunotoxicity in birds.

  2. Identification and structural composition of the blood-spleen barrier in chickens.

    Zhang, Qian; Chen, Bing; Yang, Ping; Zhang, Linli; Liu, Yi; Ullah, Shakeeb; Wu, Li; Waqas, Yasir; Le, Yuan; Chen, Wei; Chen, Qiusheng


    To identify the existence and composition of the blood-spleen barrier (BSB) in chickens, the microanatomical features of the spleen were investigated by light and transmission electron microscopy, intravenous injection of ink, acid phosphatase reaction, and silver impregnation. The results showed that the white pulp in chicken spleen consists of lymphoid nodules, periarteriolar lymphatic sheaths (PALS) and periellipsoidal lymphatic sheaths (PELS). There was no evidence for the presence of a marginal zone. The splenic ellipsoid was a unique structure, which functioned as a barrier for filtering and phagocytosis. Uptake of carbon particles was limited to the ellipsoid and PELS, 60 min after injection of carbon particles. Reticular fibres were densely distributed in the ellipsoid and extended into the PELS. Ellipsoid-associated cells (EACs), reticular cells and macrophages were acid phosphatase positive. The sheathed capillaries, surrounded by the ellipsoid, were similar to high endothelial venules (HEVs). These findings suggest that the BSB of chickens is present in the ellipsoid and PELS, protecting the spleen from invasion from circulating pathogens. The BSB was a reticular framework, between the arterial and venous vessels, which included cuboidal-shaped endothelial cells, supporting cells, EACs, macrophages, reticular cells and fibres. Lymphocyte migration into the spleen parenchyma is most likely via the HEV-like vessels. These research findings contribute to better understanding of avian immunology and provide an insight into evolutionary differences in the immune system.

  3. Atheroprotector role of the spleen based on the teaching of Avicenna (Ibn Sina).

    Emtiazy, Majid; Choopani, Rasool; Khodadoost, Mahmood; Tansaz, Mojgan; Nazem, Esmaiel


    Many studies have proven atherosclerosis is an inflammatory immune disease. The spleen plays an important immune role in the human body. Splenectomy is often used in several clinical disorders; but recent studies have shown that splenectomy may be effective in the development of atheroma lesions. Ibn Sina or Avicenna was known as one of the greatest philosopher and physician in Islam and in Medicine. He is remembered for his masterpiece, The "Al-Qanun fi al-Tibb" or "Qanun of medicine". According to the "Al-Qanun fi al-Tibb", spleen as storage organ plays an important role in absorption and secretion of the black bile in the human body. Therefore any disruption in the function of the spleen can lead to various diseases such as atherosclerosis. Based on his description, it is clear that Ibn Sina first described the role of spleen in prevention of atherosclerosis. In this review, we discuss the Avicenna (Ibn Sina) aspect of atheroprotector role of the spleen. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. [Functional morphology of conjunctive tissue stroma of spleen in the age aspect].

    Al'fonsova, E V


    The article presents the data on the structural and functional changes of conjunctive tissue of the spleen in postnatal ontogenesis of a person. The study was performed on 125 cadaveric spleens of the people of both sexes, who died from traumas and diseases not causing pathologic changes in the spleen. Definition of ontogenetic phases and chronological confines of age periods was identified according to Bunak V. V. (1965). The measurement of linear dimensions and mass of organ, histological, histochemical study and morphometry were performed. According to factual evidence, at the age from birth to 4 years the content of lymphatic follicles increases against a background of decrease of conjunctive tissue component and red pulp in the area of spleen section. By 8 or 10 years the part of lymphoid tissue decreases, but the part of conjunctive tissue and red pulp increases. Ageing symptoms are revealed at the age of 18, the increase of volume of conjunctive tissue component and destruction of external elastic membrane of trabecular artery of spleen take place. The destruction of elastic and reticulin fibers of soft skeleton, reduction of cellular elements (cells, fibroblasts and fibrocytes) and conjunctive tissue stroma collagenization are observed at a mature and old age.

  5. Treating insomnia from spleen and stomach%从脾胃辨治不寐



      Stomach function disorders can cause insomnia, variety of symptoms of Shizhi Yongzu, movements disorders;overwork spleen injury, lack of effort;spleen loss of transportation metaplasia phlegm. Treatment should be based on the Xiaodao Hewei;Spleen Qi, nourishing the nerves;spleen to help transport qi and phlegm method to restore the function of the spleen and stomach, sleep soundly at night of course just fine, and to focus on treatment seeking nature.%  脾胃功能失调均能引起不寐,其中各症分别为食滞壅阻,升降失调;过劳伤脾,心血不足;脾虚失运,化生痰湿。治疗以消导和胃,调畅气机;益气补脾,养血安神;健脾助运,行气化痰;为方法,恢复脾胃功能,则夜寐自安,并要注重治病求本。

  6. Trivial trauma and delayed rupture of a normal spleen: a case report

    Sowers Nicholas


    Full Text Available Abstract Introduction Although a majority of splenic ruptures present acutely with a known mechanism of injury, a minority of patients present days to weeks following trauma with a delayed rupture. Also uncommon is the atraumatic rupture, the vast majority of which occur in patients with underlying splenic pathology. A handful of cases of apparently spontaneous rupture of a normal spleen are reported; however, there is debate about whether these actually represent delayed ruptures following a history of trauma that is not elicited. Although a few cases of delayed rupture of the spleen following trivial trauma have been reported, the majority of these present evidence of an underlying disease process. We found only two such cases that documented a normal spleen and three cases where underlying splenic pathology was not reported. We review the literature and discuss the phenomenon of delayed rupture of the normal spleen following trivial trauma. Case presentation A 27-year-old Caucasian man with no underlying splenic pathology presented with splenic rupture one week after playfully wrestling with his partner. The patient did not present at the time of the injury and only recalled it upon repeated questioning after computed tomography diagnosis. Conclusions This case lends support to the theory that the normal spleen can rupture some time after trivial trauma, which seems like a more plausible explanation than rupture without cause. However, given the dearth of similar reports in the literature, the possibility remains that the association we have observed is not causational.

  7. Ratio of spleen diameter to red blood cell distribution width: a novel indicator for celiac disease.

    Balaban, Daniel Vasile; Popp, Alina; Lungu, Andrei Marian; Costache, Raluca Simona; Anca, Ioana Alina; Jinga, Mariana


    Celiac disease (CD) is currently considerably underdiagnosed, setting the need for developing tools to select patients with probability of CD, who warrant further testing. Red blood cell distribution width (RDW) has been shown in previous studies to be a sensitive predictor for CD, but it lacks specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim was to evaluate if spleen diameter to RDW ratio can be used as an indicator for CD. We evaluated 15 newly diagnosed CD patients, 52 patients with inflammatory bowel disease, and 35 patients with irritable bowel syndrome (IBS). We evaluated the differences in spleen diameter, RDW, and their ratio among the four groups. Two-thirds of the CD patients had elevated RDW, compared to 9% in the IBS group. A small spleen was seen in 80% of the celiacs, compared to 21.9% in the ulcerative colitis group, 10% in the Crohn disease group, and 9% in the IBS group. A spleen diameter to RDW ratio under 6 had a sensitivity of 73.3% and specificity of 88.5% in predicting CD, with an AUROC of 0.737. Spleen diameter to RDW ratio is a simple, widely available score, which can be used to select adult patients with probability of CD.

  8. Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose

    Zhang, Ming; Dong, Chunsheng; Xiong, Sidong


    Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development. PMID:28224119

  9. Effect of Xinnaoning Tablets on Spleen Tissue%心脑宁片对脾脏组织的影响

    吕宏迪; 王灵; 郝少君; 张正臣


    Objective:To observe the effect of Xinnaoning tablets on D-galactose subacute aging model mice spleen tissue. Methods:72 mice were randomly divided into 6 groups,12 rats in each group(male and female),of which one group as control group,daily subcuta-neous injection of the same volume of physiological saline;the other 5 groups(model group,Nao'an tablet group,large dose group of Xinnaoning piece,middle dose group,small dose group)production the subacute aging model induced by D-galactose,daily subcutane-ous injection of D-galactose(saline match 5% ,injection volume was 0. 025 mL·g - 1 )the production of glucose metabolism in aging model,daily injection of one,continuous 40 days. From the beginning of the eleventh day,Xinnaoning large dose group,medium dose group,low dose group were intragastrically Xinnaoning tablets suspension(2. 24 g·kg - 1 ,1. 12 g·kg - 1 ,0. 56 g·kg - 1 ,112 g·L - 1 , 56 g·L - 1 ,28 g·L - 1 ,equivalent to the clinical doses of 30,15,7. 5 times),Nao'an tablets suspension(0. 53 g·kg - 1 ,26. 5 g· L - 1 ,0. 02 mL·g - 1 ,15 times equivalent to the clinical dosage)and saline of the same volume;blank control group saline perfusion of the same volume. On the fortieth day after medication,measuring the size of spleen nodules,lymphocyte count,and the changes were ob-served under the light microscope splenic tissue morphology. Results:compared with the model group,high dose group of Xinnaoning piece,middle dose group and Nao'an tablets group significantly increased the number of spleen lymphocyte(P < 0. 01),on the splenic nodules,only increasing trend;Xinnaoning piece of high dose,middle dose group of lymphoid cells in the spleen of mouse D-galactose aging model to increase the number of role optimal. Conclusion:Xinnaoning tablets has the improving effect on D-galactose subacute ag-ing model mice spleen tissue.%目的:观察心脑宁片对 D-半乳糖亚急性衰老模型小鼠脾脏组织的影响。方法:72只小鼠随机分为6

  10. Lovastatin protects against experimental plague in mice.

    Saravanan Ayyadurai

    Full Text Available BACKGROUND: Plague is an ectoparasite-borne deadly infection caused by Yersinia pestis, a bacterium classified among the group A bioterrorism agents. Thousands of deaths are reported every year in some African countries. Tetracyclines and cotrimoxazole are used in the secondary prophylaxis of plague in the case of potential exposure to Y. pestis, but cotrimoxazole-resistant isolates have been reported. There is a need for additional prophylactic measures. We aimed to study the effectiveness of lovastatin, a cholesterol-lowering drug known to alleviate the symptoms of sepsis, for plague prophylaxis in an experimental model. METHODOLOGY: Lovastatin dissolved in Endolipide was intraperitoneally administered to mice (20 mg/kg every day for 6 days prior to a Y. pestis Orientalis biotype challenge. Non-challenged, lovastatin-treated and challenged, untreated mice were also used as control groups in the study. Body weight, physical behavior and death were recorded both prior to infection and for 10 days post-infection. Samples of the blood, lungs and spleen were collected from dead mice for direct microbiological examination, histopathology and culture. The potential antibiotic effect of lovastatin was tested on blood agar plates. CONCLUSIONS/SIGNIFICANCE: Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5% and lovastatin-treated mice (3/15; 20% was significant (P<0.004; Mantel-Haenszel test. Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague. Field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague.

  11. Digital Receiver Phase Meter

    Marcin, Martin; Abramovici, Alexander


    The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

  12. Pressure difference receiving ears

    Michelsen, Axel; Larsen, Ole Næsbye


    of such pressure difference receiving ears have been hampered by lack of suitable experimental methods. In this review, we review the methods for collecting reliable data on the binaural directional cues at the eardrums, on how the eardrum vibrations depend on the direction of sound incidence, and on how sound...... waves behave in the air spaces leading to the interior surfaces of eardrums. A linear mathematical model with well-defined inputs is used for exploring how the directionality varies with the binaural directional cues and the amplitude and phase gain of the sound pathway to the inner surface...

  13. Cell-mediated immune response to Leishmania chagasi experimental infection of BALB/c immunosuppressed mice

    JG Machado


    Full Text Available Leishmaniasis, a zoonosis of worldwide distribution, presents a significant impact on immunosupressed patients. This study aimed to evaluate Leishmania chagasi infection in BALB/c mice immunosuppressed with dexamethasone. Spleen cells stimulated or not with L. chagasi were cultured for cytokine quantification (IFN-γ, IL-2, IL-4 and IL-10 by sandwich ELISA. Parasite loads in the spleen and liver were determined by means of culture microtitration. Immunosuppressed groups showed statistically lower spleen weight and CD4-cell percentage in blood on the day of infection and produced Th1 and Th2 cytokines on other days of the study. The other infected groups, weather immunosupressed or not, also produced Th1 and Th2 cytokines. Parasite loads in the spleen and liver were not statistically different among the groups. It was concluded that L. chagasi infection was not affected by dexamethasone-induced immunosuppression, probably due the reversible effect of the treatment.

  14. Multidetector computed tomography findings of mesenteroaxial gastric volvulus combined with torsion of wandering spleen: A case report and literature review

    Youn, In Kyung; Ku, Young Mi; Lee, Su Lim [Dept. of Radiology, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu (Korea, Republic of)


    Gastric volvulus, defined as an abnormal rotation of stomach, may be idiopathic or secondary to abnormal fixation of intraperitoneal visceral ligaments. Wandering spleen is a movable spleen resulting from absence or underdevelopment of the splenic supporting ligaments that suspend the spleen to its normal position in the left part of the supramesocolic compartment of the abdomen. Wandering spleen increases the risk of splenic torsion. Both gastric volvulus and splenic torsion are potentially life-threatening if not urgently managed with surgery. Prompt and accurate diagnosis based on multidetector computed tomography (MDCT) is crucial to prevent unforeseen complications. Gastric volvulus and coexistent torsion of wandering spleen is a very rare condition. Herein, we described a case of gastric volvulus associated with wandering spleen and intestinal non-rotation in a 15-year-old girl focusing on MDCT findings.

  15. An experimental method for rapid growth of liver in spleen. The survival and proliferation of chemically induced preneoplastic hepatocytes in spleen.

    Finkelstein, S. D.; Lee, G.; Medline, A.; Tatematsu, M; Makowka, L.; Farber, E.


    Cellular suspensions (2 x 10(6) cells) of isolated preneoplastic liver cells, obtained from carcinogen-treated rats, were injected in the spleens of syngeneic rats divided into groups on the basis of no treatment, partial hepatectomy (PH), and/or feeding regimens including 2-acetylaminofluorene (AAF). Recipient rats undergoing both PH and AAF showed significantly more rapid proliferation of the preneoplastic liver cell implant, compared with other treatment groups and control. The theoretic b...

  16. The effects of G-CSF combined with SB203580 on the immune system of mice received 4 Gy total body irradiation%G-CSF联合SB203580对4Gy照射小鼠免疫系统的作用

    李德冠; 路璐; 吴红英; 张俊伶; 孟爱民


    Objective To observe the effects of G-CSF combined with SB203580(SB) on the immune system of mice received 4 Gy total body irradiation (TBI).Methods Thirty male C57BL/6 mice were randomly divided into control group,irradiated group,combined group.The mice in irradiated and combined group received 4 Gy TBI.In combined group,G-CSF (1 μg/each) was intraperitoneally (ip) injected twice one day for 5 days,SB (15 mg/kg) was ip injected every other day after 4 Gy TBI for 5 times.After 4 Gy TBI 10 days,the peripheral bloods were counted,the CD4,CD8,B220 cells in WBC and CD4,CD8 in thymocytes were analyzed by flowcytometry.The reactive oxygen species levels (ROS) of bone marrow cells were detected by microplate reader.Results Compared to the control group,the proportion of CD8,B220 and WBC in the irradiated mice significantly decreased,CD4+CD8+ thymocytes and ROS levels of bone marrow cells increased significantly.Compared to irradiation group,red blood,platelet,CD4 and CD8 cells in peripheral blood,CD4+CD8+ thymocytes decreased in the combined group.Conclusion G-CSF combined with SB has protective effects on the radiation-induced injury in immune system.%目的 研究G-CSF联合p38抑制剂SB203580 (SB)对免疫细胞辐射损伤的作用.方法 C57BL/6雄性小鼠按体质量随机分为对照组、照射组和给药组.照射组和给药组给予4 Gy全身照射.给药组小鼠给予腹腔注射G-CSF和SB,G-CSF于4Gy照射后2h和6h给药(1μg/只),每天2次,连续给药5d,SB于照射后24h给药(15 mg/kg),隔日给药,共给药5次.照射后10d测外周血计数,进行白细胞CD4、CD8、B220检测、胸腺细胞CD4、CD8检测和骨髓细胞活性氧检测.结果 照射组外周血计数和CD8、B220比例下降,而胸腺细胞中CD4+CD8+细胞比例及骨髓细胞活性氧水平显著增加.与照射组相比,联合给药组外周血红细胞数、血小板、CD4、CD8细胞比例升高,胸腺细胞中CD4+CD8+细胞比例下降.结论 G-CSF联合SB对4 Gy照射

  17. Enlargement of the human spleen in graft-versus-host disease.

    Dilly, S A; Sloane, J P


    The spleens of 49 patients who had undergone allogeneic bone marrow transplantation for leukemia were compared at autopsy to determine the pathological changes associated with graft-versus-host disease (GVHD). The only significant finding was an increase in weight of about 1.7 times that of spleens from patients without GVHD. This was not explained by differences in the patients' sex, length of survival after transplantation, presence of infection, or liver pathology. On histological examination, there was no detectable increase in congestion, siderosis, or numbers of lymphocytes, macrophages, antigen-presenting cells, blast cells, pyknotic cells, plasma cells, or hemopoietic cells to explain the increase in spleen weight. On the contrary, there was actually a reduction in CD8+ T lymphocytes. No proliferative phase of GVHD could be identified, possibly due to a lack of specimens examined less than 8 days after transplantation and to prophylactic measures undertaken to minimize GVHD. The pathogenesis of splenomegaly in human GVHD is unclear.

  18. Extra-adrenal myelolipoma presenting in the spleen: A report of two cases

    N.S. Aguilera


    Full Text Available Myelolipoma is a rare neoplasm composed of mature fat and bone marrow occurring most frequently in the adrenal gland with rare occurrences in extra adrenal locations including lung, liver, retroperitoneum, mediastinum and testes. Splenic myelolipomas are seen most commonly in non-human species including cat and dog. Only rare cases of splenic myelolipoma in humans have been reported previously. We present two cases of myelolipoma in the spleen. The first is a 62 year old female presenting with abdominal pain and a splenic mass. The second is a 44 year old male presenting with hematuria and a mass in the spleen. Both cases showed trilineage bone marrow elements with mature fat. These cases demonstrate that myelolipoma do rarely occur in human spleen and we highlight the distinction from extramedullary hematopoiesis, mature extramedullary myeloid tumor (myeloid sarcoma, lipoma and well differentiated liposarcoma.

  19. Yersinia enterocolitica-associated generalized microinfarctions of bone and spleen in a child

    Reiss-Zimmermann, Martin; Sorge, Ina; Hirsch, Wolfgang [University Hospital Leipzig, Paediatric Radiology, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Schille, Regine [University Hospital Leipzig, Paediatric Department, Leipzig (Germany); Beer, Joerg [University of Leipzig, Institute for Medical Microbiology and Epidemiology of Infectious Diseases, Leipzig (Germany)


    We report a case of unusual extraintestinal yersiniosis in a 16-year-old girl with generalized microinfarctions of the bone and spleen. For the past 2 years she had been repeatedly admitted to our hospital with reactive arthritis, erythema nodosum and iridocyclitis of unknown aetiology. Ultrasound showed multiple round hypoechoic lesions in the spleen that were shown to have low T2 signal on MRI. MRI also showed disseminated nodular lesions of the skeleton that were low T1 and high T2 signal and demonstrated inhomogeneous contrast enhancement. The patient is currently in good health on low-dose nonsteroidal immunosuppressive therapy. This is a unique case of microinfarctions of the skeleton and spleen caused by a severe postinfectious autoimmune reaction following extraintestinal Yersinia enterocolitica infection. (orig.)

  20. Inflammatory pseudotumor of the liver and spleen diagnosed by percutaneous needle biopsy

    Tsukasa Kawaguchi; Kiyoshi Mochizuki; Takashi Kizu; Masanori Miyazaki; Takayuki Yakushijin; Shusaku Tsutsui; Eiichi Morii; Tetsuo Takehara


    An inflammatory pseudotumor (IPT) is a relatively rare lesion characterized by chronic infiltration of inflammatory cells and areas of fibrosis. IPTs are difficult to diagnose because of the absence of specific symptoms or of characteristic hematological or radiological findings. In this study, a case of a woman aged over 70 years was reported, who presented with a general malaise lasting more than two months. A computed tomography scan demonstrated a diffusely spread lesion of the liver with a portal vein occlusion and a splenic lesion surrounded by a soft density layer. Since the percutaneous liver biopsy showed findings that suggested an IPT, although the radiological findings did not exclude the possibility of a malignancy, we performed a percutaneous spleen biopsy to enable a more definitive diagnosis. The microscopic findings from the spleen specimen lead us to a diagnosis of IPT involving the liver and spleen. Subsequent Subsequent steroid pulse therapy was effective, and rapid resolution of the disease was observed.

  1. Statistical shape analysis of the human spleen geometry for probabilistic occupant models.

    Yates, Keegan M; Lu, Yuan-Chiao; Untaroiu, Costin D


    Statistical shape models are an effective way to create computational models of human organs that can incorporate inter-subject geometrical variation. The main objective of this study was to create statistical mean and boundary models of the human spleen in an occupant posture. Principal component analysis was applied to fifteen human spleens in order to find the statistical modes of variation, mean shape, and boundary models. A landmark sliding approach was utilized to refine the landmarks to obtain a better shape correspondence and create a better representation of the underlying shape contour. The first mode of variation was found to be the overall volume, and it accounted for 69% of the total variation. The mean model and boundary models could be used to develop probabilistic finite element (FE) models which may identify the risk of spleen injury during vehicle collisions and consequently help to improve automobile safety systems.

  2. Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels for pancreatic adenocarcinoma

    Yan-Guo Zheng


    Full Text Available Background: A laparoscopic surgery can be beneficial in a spleen-preserving distal pancreatectomy. Aims: This report shows a 60-year-old woman who presented to her persistent upper abdominal and bilateral lumbodorsal distending pain for one year. A computed tomography scan demonstrated a 4cm×5cm×5cm solid space-occupying mass in the distal pancreas. The patient was referred to minimally invasive surgery service for resection of the pancreatic lesion. Methods: A laparoscopic spleen-preserving distal pancreatectomy was performed. Results: The mass was completely excised, the pathological examination revealed pancreatic adenocarcinoma with grade II. The postoperative advantages of this approach were the early return of bowel function, minimal complications, and early resumption of normal activities. Conclusions: This case illustrates that minimally invasive surgery in the performance of a spleen-and-splenic-vessel preserving distal pancreatectomy is a feasible procedure without compromising the splenic function.

  3. Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 C-acclimated hamsters

    Jones, S. B.; Musacchia, X. J.


    The relationship of norepinephrine (NE) concentration and endogenous turnover rates in both myocardial and spleen tissues in the golden hamster is examined as a function of chronic exposure to either high or low ambient temperatures. Changes in myocardial and spleen NE turnover values are discussed in terms of functional alterations in sympathetic nerve activity and the importance of such changes in temperature acclimation. It is found that acclimation of hamsters to 7 C for 7-10 weeks results in decreased myocardial NE concentration and an apparent increase in myocardial NE turnover. In contrast, exposure to 34 C for 6-8 weeks results in increased myocardial NE concentration and an apparent decrease in NE turnover in both myocardial and spleen tissues. The implication of altered NE synthesis is that sympathetic nerve activity is reduced with heat acclimation and is enhanced with cold acclimation.

  4. Protective effects of rosmarinic acid against radiation-induced damage to the hematopoietic system in mice.

    Xu, Wenqing; Yang, Fujun; Zhang, Yujie; Shen, Xiu


    Rosmarinic acid (RA) is an ester of caffeic acid and 3, 4-dihydroxyphenyl lactic acid. It is a potent antioxidant that functions by scavenging free radicals. Here, we used a 30-day survival assay to investigate the radioprotective effects of RA. Mice were treated with RA once per day for 10 consecutive days starting at 3 days before gamma irradiation at 7.5 Gy until 7 days post irradiation. Mice treated with 100 and 200 mg/kg body weight (bw) of RA had 30-day survival rates of 89% and 72%, respectively, compared with 32% in the control group, and the differences were statistically significant (P = 0.0008 and 0.0421, respectively). Spleen colony-forming units (CFU-S), the number of nucleated cells in the bone marrow (BMNC), bone marrow DNA content, and hematological parameters of the peripheral blood were measured to investigate the radioprotective effect of RA on the hematopoietic system. The treatment groups that received RA at 50, 100 and 150 mg/kg bw and whole-body exposure to 5.5 Gy of (137)Cs γ- radiation had significantly higher CFU-S, BMNC and DNA content than the irradiation-only group. Assessment of hematological parameters in the peripheral blood showed that the treatment groups receiving RA at doses of 50, 100 and 150 mg/kg bw had higher white blood cell counts, hemoglobin and platelets than the radiation-only group. These results suggested that the administration of RA promoted the recovery of peripheral blood cells in irradiated mice.

  5. Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

    Choi Jin-Ok


    Full Text Available Abstract Background Enzyme replacement therapy (ERT with α-galactosidase A (α-Gal A is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT. Methods A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3 levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted. Results Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT. Conclusions The rAAV2/8-hAGA mediated α-Gal A gene

  6. Salmonella Levels in Turkey Neck Skins, Drumstick Bones, and Spleens in Relation to Ground Turkey.

    Cui, Yue; Guran, Husnu S; Harrison, Mark A; Hofacre, Charles L; Alali, Walid Q


    The objective of this study was to determine Salmonella levels (presence and numbers) in turkey drumstick bone, spleen, and neck skin samples in relation to Salmonella contamination levels in ground turkey at the flock level. Over a 10-month period, a total of 300 samples of each turkey part (i.e., neck skin, spleen, and drumstick) from 20 flocks were collected at a commercial turkey processing plant after the evisceration step. Turkey flocks included in this study were classified as "targeted" and "nontargeted" based on the company's historical ground turkey contamination data. A flock that originated from a turkey farm that had previously produced one or more flocks with ≥20% Salmonella prevalence in ground turkey was labeled as a targeted flock (n = 13). The remaining seven flocks with Salmonella presence and numbers by using most-probable-number and selective enrichment methods. Further genotypic analysis (pulsed-field gel electrophoresis) of the isolates was performed. Ground turkey samples were collected and analyzed for Salmonella levels by the cooperating turkey company. The outside surface of bone and spleen were sterilized prior to Salmonella analysis. The overall Salmonella prevalence in neck skin, drumstick bone, spleen, and ground turkey samples was 42.0, 9.3, 6.7, and 14.5%, respectively. Salmonella prevalence in neck skin, spleen, drumstick bone, and ground turkey from the targeted flocks was significantly (P Salmonella presence in neck skin (when most probable numbers were ≥2 log) and Salmonella-positive ground turkey lot. Based on our findings, Salmonella was detected internally in drumstick bones and spleens at low levels, whereas Salmonella presence at higher levels in neck skin may indicate a flock with greater potential for Salmonella contamination of ground turkey.

  7. Experimental injury to the spleen study of interaction: contamination/preservation.

    Manssur, R; Margarido, N F; Nahas, S C; Lourenção, J L; de Tolosa, E M


    Ablation of the spleen leads to a significant risk of postsplenectomy invasive sepsis. This concept has become very important in the last three decades because of awareness of the spleen's important role in immunological functions. Hence, this has led many research centers to study hemostasis of the injured spleen in order to preserve its function. The objective of this study is to analyze the use of nylon mesh for preservation of the wounded spleen in the presence or absence of local contamination. Twenty dogs were operated, randomly divided into two groups and followed postoperatively for eight weeks. A standard splenic injury was produced in all animals and hemostasis accomplished by attaching nylon mesh to the organ. Postoperatively, in one of the groups the "wounded organ + mesh" was contaminated with a bacterial count proportional to the animal's weight. The other group was not contaminated, maintaining it as control. Both groups were studied as to interaction of contamination/preservation, i.e., body weight, surgical findings, splenic size and histology, blood and tissue culture and hematological data. The dogs adequately withstood the standardized trauma regardless of local contamination. And the nylon mesh effectively arrested bleeding in all animals. At sacrifice inoculated germs were confirmed in the contaminated group by histological methods or tissue cultures. A cellular infiltrate of lymphocytes and plasmocytes was present close to the mesh only in the latter. The mesh attached to the injured spleen did not lead to abscesses, intrasplenic or intraperitoneal fluid collections. Based on analysis of the data, we can infer that local contamination of the injured spleen and the presence of non-absorbable material (nylon mesh) did not markedly alter the overall behavior of the dogs compared to the uncontaminated group.


    Ivan F. Charas Santos


    Full Text Available The aim of the study was to analyze and compare the characteristics and ultrasound measurements of the spleen of healthy puppies and kittens, establishing normal standards and landmarks. We used 15 healthy male dogs and 15 healthy male cats, mixed breed and average age of six months. They were divided into two groups: G1 with 15 puppies with an average weight of 3 kg and G2 with  15 kittens with an average weight of 2 kg. The animals underwent ultrasound examination of the spleen for visualization of internal characteristics and measurement of the organ. The structural characteristics was analyzed and compared between the two species through the images obtained in the exam. The measurements were compared statistically using the SPSS program, with analysis of variance (ANOVA followed by Tukey test (P ˂ 0.05. In both groups, we observed the splenic artery showed smaller diameter than the splenic veins. In puppies and kittens, the echotexture was visualized homogeneous and finely granular. The puppy’s spleen tends to be bigger in length   (6.87 ± 0.03 cm and width (5.95 ± 0.07 cm in relation to spleen length (4,53 ± 0,02 cm and width  (4.55 ± 0.04 in kittens. We concluded there is no difference of echotexture and splenic echogenicity between puppies and kittens, and the spleen of puppies showed bigger dimensions than in kittens. Keywords: echogenicity; size; small animals; spleen;   ultrasound.

  9. Developmental changes of melatonin receptor expression in the spleen of the chicken, Gallus domesticus.

    Guo, Qingyun; Dong, Yulan; Cao, Jing; Wang, Zixu; Zhang, Ziqiang; Chen, Yaoxing


    Melatonin plays an essential role in development and immunoregulation of the avian spleen through its receptors; however, the variations in the expression of the melatonin receptor subtypes in the developing avian spleen are still unclear. The objective of the present study was not only to investigate the distribution patterns and development changes of the expression of the melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) in the chicken spleen but also to identify the correlation between the plasma melatonin concentration and the expression of the melatonin receptor subtypes. The immunohistochemical results indicated that Mel1a was mainly distributed in the red pulp and capillaries, Mel1b was predominantly distributed in the periarterial lymphatic sheath (PALS) and splenic nodule, and Mel1c was widely located in the red pulp, PALS and splenic nodule. From P0 to P21, the mRNA and protein expressions of Mel1a, Mel1b and Mel1c in the spleen were increased (P0.05). Furthermore, the mRNA levels of Mel1b and Mel1c between P0 and P14 raised more quickly than Mel1a. The plasma melatonin concentration increased in an age-dependent manner in the chicken from P0 to P42 (Pspleen. These results suggest the existence of age-related and region-specific changes in the expression of the melatonin receptor subtypes within the spleen of the chicken, and this characteristic pattern may be involved in the development and functional maturation of the avian spleen.

  10. Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen.

    Rosche, Kristin L; Aljasham, Alanoud T; Kipfer, James N; Piatkowski, Bryan T; Konjufca, Vjollca


    Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella) causes systemic inflammatory disease and enlargement of the spleen (splenomegaly). Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs) and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP), marginal zone (MZ), and red pulp (RP) is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM), we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines.

  11. Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen.

    Kristin L Rosche

    Full Text Available Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella causes systemic inflammatory disease and enlargement of the spleen (splenomegaly. Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP, marginal zone (MZ, and red pulp (RP is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM, we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines.

  12. Lung Tumors in Mice Receiving Different Schedules of Urethane


    tumors, but this phenotypic expression did become markedly segregated. Thus, there are strains such as A, in which almost all animals develop pulmonary...urethane," Khanolkar Felicitation Volume, Bombay , Indian Cancer Research Center, 1963, pp. 158-181. [11] P. S. HENSHAW and H. L. MEYER, "Further

  13. Locally advanced leiomyosarcoma of the spleen. A case report and review of the literature

    Recchia Franco


    Full Text Available Abstract Background Leiomyosarcomas are rare tumours, predominantly localized in the stomach, small intestine and retroperitoneum. Only one case of primary leiomyosarcoma of the spleen is described in human beings in literature. Case presentation We report a case of locally advanced primary leiomyosarcoma of the spleen in a 54 year-old woman, diagnosed only after splenectomy, performed with the suspicion of splenic haematoma. Conclusion Due to the lack of cases, no specific chemotherapy regimen has been tested to provide a longer survival.

  14. Sclerosing angiomatoid nodular transformation of the spleen:report of five cases and review of literature

    WANG Hao-lu; LI Ke-wei; WANG Jian


    Sclerosing angiomatoid nodular transformation (SANT) of the spleen,a newly defined primary lesion of the spleen,is very rare.Immunohistochemistry is the only way to confirm the diagnosis of SANT.We present the clinical characteristics and postoperative outcomes of five SANT cases that underwent splenectomy from January 2007 to October 2010.Although SANT had specific imaging findings,differential diagnosis from other splenic tuomrs or malignant lesions preoperatively was difficult.The hand-assisted laparoscopic splenectomy was a useful and effective technique for the management and postoperative diagnosis of SANT.All SANT patients had good prognosis without recurrence after splenectomy.

  15. Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins.

    Kirschke, H; Wiederanders, B; Brömme, D.; Rinne, A


    Cathepsin S was detected in bovine kidney, spleen, lymph nodes and lung by immunochemical methods. The immunostaining of cathepsin S in kidney was concentrated to the cells of the proximal tubule, where the enzyme was present in cytoplasmic granules. The purification method for cathepsin S from bovine spleen involved (NH4)2SO4 fractionation, chromatography on CM-Sephadex C-50, gel filtration on Sephacryl S-200 and chromatofocusing (pH 8.0-6.0). The enzyme was partially destroyed by autolysis ...

  16. Using ovality to predict nonmutagenic, orally efficacious pyridazine amides as cell specific spleen tyrosine kinase inhibitors.

    Lucas, Matthew C; Bhagirath, Niala; Chiao, Eric; Goldstein, David M; Hermann, Johannes C; Hsu, Pei-Yuan; Kirchner, Stephan; Kennedy-Smith, Joshua J; Kuglstatter, Andreas; Lukacs, Christine; Menke, John; Niu, Linghao; Padilla, Fernando; Peng, Ying; Polonchuk, Liudmila; Railkar, Aruna; Slade, Michelle; Soth, Michael; Xu, Daigen; Yadava, Preeti; Yee, Calvin; Zhou, Mingyan; Liao, Cheng


    Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of cancers and autoimmune diseases such as asthma, rheumatoid arthritis, and systemic lupus erythematous. We report the structure-guided optimization of pyridazine amide spleen tyrosine kinase inhibitors. Early representatives of this scaffold were highly potent and selective but mutagenic in an Ames assay. An approach that led to the successful identification of nonmutagenic examples, as well as further optimization to compounds with reduced cardiovascular liabilities is described. Select pharmacokinetic and in vivo efficacy data are presented.

  17. Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension

    Jansen, Christian; Bogs, Christopher; Verlinden, Wim


    BACKGROUND & AIMS: Clinically significant portal hypertension (CSPH) is associated with severe complications and decompensation of cirrhosis. Liver stiffness measured either by transient elastography (TE) or Shear-wave elastography (SWE) and spleen stiffness by TE might be helpful in the diagnosis...... correlate with portal pressure and can both be used as a non-invasive method to investigate CSPH. Even though external validation is still missing, these algorithms to rule-out and rule-in CSPH using sequential SWE of liver and spleen might change the clinical practice....




    Full Text Available BACKGROUND Volvulus of wandering spleen is a rare clinical occurrence with fewer than 500 cases reported and an incidence of less than 0.2%. We present a case of a 27-year-old man, who complained of a short history of severe abdominal pain with the background of recurrent abdominal pain. Ultrasound revealed wandering spleen with splenic vein thrombosis. An abdominal contrast enhanced computerized tomography scan revealed a torted wandering spleen with splenic vein thrombosis with infarction. This required a splenectomy due to splenic infarction. This report highlights the investigations including USG and CECT necessary for a patient who presents with an ischaemic torted wandering spleen.

  19. Extract of Gynostemma pentaphyllum enhanced the production of antibodies and cytokines in mice.

    Huang, Wen-Chung; Kuo, Ming-Ling; Li, Ming-Liang; Yang, Rong-Chi; Liou, Chian-Jiun; Shen, Jiann-Jong


    Gynostemma pentaphyllum is a popular herbal tea in China and some Asian countries. The modulatory function of G. pentaphyllum total plant extracts on immune cells was evaluated in this study. The extract was intraperitoneally injected into mice for 5 consecutive days. The production of antibodies from B cells or cytokines from T cells was determined mainly with ELISA. After the treatment, serum IgM and IgG2a were significantly enhanced and showed dose-dependent effect. Moreover, serum IgA and IgG1 were also increased when received the extract at the doses of 0.05 or 0.50 g/kg/day. In addition to the serum levels, the injection of the extract enhanced the production of all antibodies from LPS-activated spleen cells. Furthermore, more cytokines were secreted from Con A-stimulated splenocytes of G. pentaphyllum-treated mice. Our results suggest that the extract of G. pentaphyllum might promote immune responses through the activation of T and B cells.

  20. Effects of beer administration in mice on acute toxicities induced by X rays and carbon ions

    Monobe, Manami [Chiba Univ. (Japan). Graduate School of Science and Technology; Koike, Sachiko; Uzawa, Akiko; Ando, Koichi [National Inst. of Radiological Sciences, Chiba (Japan)


    We have investigated the tissue specificity of radioprotection by beer, which was previously found for human lymphocytes. C3H/He female mice, aged 14 weeks, received an oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min before whole-body irradiation with {sup 137}Cs {gamma} rays or 50 keV/{mu}m carbon ions. The dicentrics of chromosome aberrations in spleen cells were significantly (p<0.05) reduced by beer and ethanol-administration for {gamma}-ray irradiation, but not for carbon-ion irradiation. The number of jejunal crypts plotted against the dose showed that both beer and ethanol significantly increased D{sub 0} (slope of a dose-survival curve) for {gamma} rays and carbon ions as well. Beer administration significantly (p<0.05) increased LD{sub 50/30} (radiation dose required to kill 50% of mice within 30 days) for {gamma} rays and carbon ions. Ethanol-administration also significantly (p<0.05) increased the LD{sub 50/30} value for {gamma} rays, but not for carbon ions. It is concluded that beer administration reduces the radiation injury caused by photons and carbon ions, depending on the tissue type. Radioprotection by beer administration is not solely due to OH radical-scavenging action by the ethanol contained in beer. (author)

  1. Allogeneic Th1 cells home to host bone marrow and spleen and mediate IFNγ-dependent aplasia.

    Chewning, Joseph H; Zhang, Weiwei; Randolph, David A; Swindle, C Scott; Schoeb, Trenton R; Weaver, Casey T


    Bone marrow graft failure and poor graft function are frequent complications after hematopoietic stem cell transplantation and result in significant morbidity and mortality. Both conditions are associated with graft-versus-host disease (GVHD), although the mechanism remains undefined. Here we show, in 2 distinct murine models of GVHD (complete MHC- and class II-disparate) that mimic human peripheral blood stem cell transplantation, that Th1 CD4(+) cells induce bone marrow failure in allogeneic recipients. Bone marrow failure after transplantation of allogeneic naïve CD4(+) T cells was associated with increased CD4(+) Th1 cell development within bone marrow and lymphoid tissues. Using IFNγ-reporter mice, we found that Th1 cells generated during GVHD induced bone marrow failure after transfers into secondary recipients. Homing studies demonstrated that transferred Th1 cells express CXCR4, which was associated with accumulation within bone marrow and spleen. Allogeneic Th1 cells were activated by radiation-resistant host bone marrow cells and induced bone marrow failure through an IFNγ-dependent mechanism. Thus, allogeneic Th1 CD4(+) cells generated during GVHD traffic to hematopoietic sites and induce bone marrow failure via IFNγ-mediated toxicity. These results have important implications for prevention and treatment of bone marrow graft failure after hematopoietic stem cell transplantation. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Comparison of Human Hematopoietic Reconstitution in Different Strains of Immunodeficient Mice.

    Beyer, Ashley I; Muench, Marcus O


    Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34(+) cells: NSG, NSG-3GS, hSCF-Tg-NSG, and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen, and liver was evaluated by flow cytometry 12 weeks after transplant. The highest levels of human engraftment were observed in the liver, spleen, and bone marrow, whereas peripheral blood cell chimerism was notably less. The highest levels of tissue engraftment were in hSCF-Tg-NSG mice, but NSG mice exhibited the highest blood leukocyte engraftment. hSCF-Tg-NSG mice also exhibited the highest levels of CD133(+)CD34(++) stem cells. hSIRPα-DKO engrafted poorly and exhibited poor breeding. Myelopoiesis was greatest in NSG-3GS mice, followed by hSCF-Tg-NSG and NSG mice, whereas B cell engraftment exhibited the opposite pattern. Engraftment of CD3(+) T cells, CD3(+)CD161(+) T cells, and CD3(-)CD56(+) NK cells was greatest in NSG-3GS mice. Mast cell engraftment was highest in hSCF-Tg-NSG mice, but was also elevated in spleen and livers of NSG-3GS mice. Basophils were most abundant in NSG-3GS mice. Overall, hSCF-Tg-NSG mice are the best recipient mice for studies requiring high levels of human hematopoiesis, stem cell engraftment, and an intermediate level of myelopoiesis, whereas NSG and NSG-3GS mice offer select advantages in the engraftment of certain blood cell lineages.

  3. Immune modulatory effects of the foodborne contaminant citrinin in mice.

    Islam, Mohammad Rafiqul; Roh, Yoon-Seok; Cho, Ara; Kim, Jinho; Kim, Jong-Hoon; Eo, Seong-kug; Lim, Chae-Woong; Kim, Bumseok


    The mycotoxin citrinin can cause mycotoxic nephropathy, cytotoxicity and genotoxicity. To investigate the immune modulatory effects, CTN was orally administered to female BALB/c mice at the dose of 1, 5, or 10 mg/kg body weight for 14 days, and several immunotoxicity tests were performed. The populations of F4/80+ cells and CD19+ cells were significantly decreased in spleen and MLN. In MLN, CD4+, CD8+, and CD4+CD25+Foxp3+ cell populations were increased. CD8+ cells were increased but CD19+ cells were decreased in intra-epithelial, lamina propria and Peyer's patches lymphocytes. In a cell proliferation assay, along with the increased proliferative capacities of ConA-induced splenocytes and MLN cells, IFN-γ production was increased. The expression of TLR 2 was increased in spleen, but TLR 3 expression in MLN was decreased. The level of serum IgM was reduced. Furthermore, apoptosis was induced in spleen, MLN and Peyer's patches and promoted by the change in the ratio of Bax/Bcl-2 activities. Autophagy gene Atg5 and Beclin-1 were up-regulated in spleen. The expressions of IL-1β, IL-10, and TNF-α were inhibited in murine macrophage cells pre-exposed with TLR ligands. These results indicate that CTN has multiple immune modulatory effects in mice that may alter normal functions of immune system.

  4. NTP Toxicology and Carcinogenesis Studies of Glycidol (CAS No. 556-52-5) In F344/N Rats and B6C3F1 Mice (Gavage Studies).


    low dose female mice was similar to that of vehicle controls; survival of female mice that resurvival of male mice and low dose female mice was similar to that of vehicle controls; survival of female mice that received 50 mg/kg was lower than that of vehicle controls after week 101 (final survival--male: 33/50; 25/50; 27/50; female: 29/50; 27/50; 17/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Chemical-related nonneoplastic lesions in both rats and mice included hyperkeratosis and epithelial dysplasia of the forestomach. Fibrosis of the spleen was also present in rats of each sex, and cysts of the preputial gland and kidney were present in male mice. Exposure to glycidol induced dose-related increases in the incidences of neoplasms in numerous tissues in both rats and mice (see summary table on page 5 of the Technical Report). In male rats, mesotheliomas arising in the tunica vaginalis and frequently metastasizing to the peritoneum were considered the major cause of early death. Early deaths in female rats were associated with the presence of mammary gland neoplasms. Genetic Toxicology: Glycidol was mutagenic in a variety of in vitro and in vivo short-term tests. Mutagenic activity was observed in S. typhimurium strains TA97, TA98, TA100, TA1535, and TA1537 exposed to glycidol with and without exogenous metabolic activation. Glycidol was positive in the absence of exogenous metabolic activation in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y/TK cells; it was not tested with activation. In cytogenetic tests with CHO cells, glycidol induced both sister chromatid exchanges and chromosomal aberrations in the presence and absence of exogenous metabolic activation. Glycidol induced sex-linked recessive lethal mutations and reciprocal translocations in the germ cells of male D. melanogaster exposed by feeding. The incidence of micronucleated polychromatic erythrocytes was increased in the bone marrow of male B6C3F1

  5. Acute arsenic exposure induces inflammatory responses and CD4(+) T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF-kB, and Nrf2.

    Duan, Xiaoxu; Gao, Shuang; Li, Jinlong; Wu, Liuzhong; Zhang, Yang; Li, Wei; Zhao, Lu; Chen, Jinli; Yang, Shan; Sun, Guifan; Li, Bing


    Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice were used as a model to systemically administration 2.5, 5 and 10mg/kg NaAsO2 intra-gastrically for 24h. We found that arsenic significantly decreased the spleen and thymus weights and indices, and flow cytometry revealed that arsenic decreased the relative frequency of CD4(+) T cell subpopulation and the ratios of CD4/CD8 in spleen. In contrast, serum concentration of tumor necrosis factor α (TNF-α), IL-1β and IL-6 as well as the mRNA of key inflammatory mediators in spleen and thymus, including transforming growth factor β (Tgf-β), Tnf-α, Il-12, Il-1β and Il-6 were significantly increased in arsenic-treated mice compared to the control as assayed by ELISA and real time PCR, respectively. In addition, arsenic increased the expression of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) -associated transcription factors and cytokines as well as decreased Th17-associated transcription factors and cytokines. Moreover, arsenic enhanced oxidative stress and induced the activation of extracellular-signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 and their downstream transcription factors nuclear factor kappa B (NF-kB) and nuclear factor E2-related factor 2 (Nrf2), which comprise important mechanistic pathways involved in immune-inflammatory manifestations. Together, these results provide a novel strategy to block the arsenic-dependent impairments in immune responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

    Yun Seong-Jo


    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  7. Guipi decoction effects on brain somatostatin levels and receptor mRNA expression in rats with spleen deficiency

    Huinan Qian; Le Wang; Libo Shen; Xueqin Hu


    BACKGROUND:Somatostatin is abundant in the hypothalamus,cerebral cortex,limbic system,and mesencephalon.Somatostatin mRNA expression in the brain of rats with spleen deficiency is noticeably reduced,as well as attenuation of cognitive function. OBJECTIVE:To observe the interventional effect of Guipi decoction on somatostatin level and somatostatin receptor 1(SSTRI)mRNA expression in different encephalic regions of rats with spleen deficiency,and to compare the interventional effects of Guipi decoction,Chaihu Shugan powder,and Tianwang Buxin pellet. DESIGN:A randomized controlled observation. SETTING:Basic Medical College,Beijing University of Traditional Chinese Medicine.MATERIALS:Fifty adult Wistar male rats,of clean grade,weighing(160 ± 10)g,were provided by Beijing Weitong Lihua Laboratory Animal Technology Co.,Ltd.The protocol was performed in accordance with ethical guidelines for the use and care of animals.Somatostatin 1 polyclonal anti-rabbit antibody and SSTR1 in situ hybridization kit were provided by Department of Neuroanatomy,Shanghai Second Military Medical University of Chinese PLA.The drug for developing rat models of spleen deficiency was composed of Dahuang,Houpu and Zhishi,and prepared at 2:1:1.Guipi decoction,Chaihu Shugan powder,and Tianwang Buxin pellet recipes were made according to previous studies.METHODS:This study was performed at the Basic Medical College,Beijing University of Traditional Chinese Medicine from March 2002 to March 2005.The rats were randomly divided into 5 groups,with 10 rats in each group:normal,model,Guipi decoction,Chaihu Shugan powder,and Tianwang Buxin pelletgroups.Rat models of the latter 4 groups were developed by methods of purgation with bitter and cold nature drugs,improper diet,and overstrain.The rats received 7.5 g/kg of the drugs each morning and were fasted every other day,but were allowed free access to water at all times,The rats were forced to swim in 25℃ water until fatigued.Rats in the normal group

  8. M tuberculosis in the adjuvant modulates time of appearance of CNS-specific effector T cells in the spleen through a polymorphic site of TLR2.

    Chiara Nicolò

    Full Text Available DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called "immunoscope" mostly reach the spleen by day 28 after immunization ("late relocation" in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis ("early relocation". The C57Bl/6 background confers a dominant "early relocation" phenotype to F1 (SJL×C57Bl/6 mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for "early/late" relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.

  9. Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells

    Diana Magalhães de Oliveira


    Full Text Available Nitric oxide (NO is an important effector molecule involved in immune regulation and defense. NO produced by cytokine-activated macrophages was reported to be cytotoxic against the helminth Schistosoma mansoni. Identification and characterization of S. mansoni antigens that can provide protective immunity is crucial for understanding the complex immunoregulatory events that modulate the immune response in schistosomiasis. It is, then, essential to have available defined, purified parasite antigens. Previous work by our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP, named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to SEA (soluble egg antigen or to SWAP. In the present work we report the effect of different in vivo trials with mice on their spleen cells ability to produce NO. We demonstrate that PIII-immunization is able to significantly increase NO production by spleen cells after in vitro stimulation with LPS. These data suggest a possible role for NO on the protective immunity induced by PIII.

  10. Altered natural killer cell biology in C57BL/6 mice after leukemogenic split-dose irradiation. [/sup 137/Cs

    Parkinson, D.R.; Brightman, R.P.; Waksal, S.D.


    Natural killer (NK) cell activity was examined in the spleens of C57BL/6 mice given leukemogenic split-dose irradiation. The radiation protocol resulted in severe depression of spontaneous NK cell activity; this activity was not fully restored after treatment with the interferon inducer poly I:C. In vitro mixing studies provided no evidence for active suppression in vivo as a mechanism for this decrease in activity. In addition, spontaneous activity was restored towards control levels after bone marrow transfusion from nonirradiated mice. The results are most compatible with the radiation-induced loss of a cell with normal NK activity from spleen and bone marrow after the split-dose radiation protocol. In addition, a population of cells able to competitively block normal NK cell lysis of YAC-1 tumor cells is found in the bone marrow, spleen, and thymus of the irradiated mice lacking NK cell activity.

  11. Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

    Bancroft, A.J.; Devaney, E. (Liverpool School of Tropical Medicine, Liverpool (United Kingdom)); Grencis, R.K.; Else, K.J. (Univ. of Manchester (United Kingdom))


    BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-[gamma] by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs.

  12. Effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation

    Jing Liu; Yi Gao; Shuan Wang; Er-Wei Sun; Yu Wang; Zhi Zhang; Yi-Qiang Shan; Shi-Zheng Zhong


    AIM: To study effect of operation-synchronizing transfusion of apoptotic spleen cells from donor rats on acute rejection of recipient rats after liver transplantation.METHODS: Two of Wistar rats were chosen randomly for normal liver pathology control and ten of SD rats chosen randomly for liver function control as blank group (no operation). The rest of Wistar and SD rats were divided into four groups: control group (only liver transplantation),Dex group (donors receiving intraperitoneal injection of dexamethasone), SpC group (recipients receiving infusion of spleen cells of donors), Dex-SpC group (recipients receiving infusion of apoptotic spleen cells of donors),with each group except blank group, containing 10 SD rats and 10 Wistar rats, respectively. Wistar rats received liver transplantation from SD rats, in the meantime they received infusion of spleen cells of donors, which were induced by an intraperitoneal injection of dexamethasone The serum alanine transaminase (ALT), total bilirubin (T bili), liver pathological changes and survival time were analysed. Statistical analysis was carried out using SPSS 10.0 for Windows. Differences of the parametric data of ALT in means were examined by one-way ANOVA.Differences of ALT between two groups were examined by LSD. Differences of the nonparametric data of T bili in means and scores of pathology classification for acute rejection were examined by Kruskal-Willis H test. The correlations between ALT and T bili were analysed by Bivariate. Kaplan-Meier curves were used to demonstrate survival distribution. The log-rank test was used to compare the survival data.RESULTS: There were significant differences in ALT of the five groups (F= 23.164 P= 0.000), and ALT in DexSpC group was significantly higher than that in blank control, control, Dex, and SpC groups (P = 0.000), and ALT in SpC group was significantly higher than that in blank control (P = 0.000), control (P = 0.004), and Dex groups (P = 0.02). Results of

  13. Immune regulation effect of Ganodermapolysaccharide capsule on immunosuppressed mice

    Ding-wen JIANG


    Full Text Available Objective  To investigate the immune regulation effect of Ganoderma polysaccharide capsule (GPC on immunosuppressed mice. Methods  Sixty mice were randomly divided into 6 groups (10 each: normal control group, model group, Lentinan group and 20mg/(kg.d GPC group, 60mg/(kg.d GPC group and 180mg/(kg.d GPC group. The drugs were administrated by intragastric infusion for mice, respectively, once a day for 15 days. From the 13th days, the mice in each group except for control group were injected with cyclophosphamide at a dosage of 80mg/kg, once a day for 3 days. And then the number of peripheral blood cells was counted with veterinary hematology analyzer, the spleen and thymus were weighed and their index were calculated. The T lymphocyte proliferation induced by Con A and LPS was detected with MTT method, NK cytotoxicity was tested with LDH method, carbon clearance was tested by using carbon granules clearance test, and the expressions of IL-2 and IFN-γmRNA in spleen lymphocytes were detected with RT-PCR. Results  Peripheral blood WBC in 180mg/(kg.d GPC group, peripheral blood PLT in 60mg/(kg.d group, the spleen index in 20mg/(kg.d and 60mg/(kg.d groups, and thymus index in 20mg/(kg.d group were increased remarkably when compared with those in model group (P<0.05. Spleen T lymphocyte proliferation induced by Con A and LPS, spleen NK cytotoxicity and carbon clearance in 20mg/(kg.d, 60mg/(kg.d and 180mg/(kg.d GPC groups were increased notably when compared with those in the model group (P<0.05 or P<0.01. The expressions of IFN-γmRNA in spleen lymphocytes in 20mg/(kg.d and 180mg/(kg.d groups increased markedly when compared with that in the model group (P<0.01. Conclusion  GPS may enhance immune function and increase peripheral blood WBC and PLT in immunosuppressed mice. DOI: 10.11855/j.issn.0577-7402.2016.09.04

  14. Assessment of genotoxic effects of flumorph by the comet assay in mice organs.

    Zhang, T; Zhao, Q; Zhang, Y; Ning, J


    The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice. The DNA damage, measured as comet tail length (µm), was determined using the alkaline comet assay. The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model. Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed. The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight. Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm. Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.

  15. Status of ammonia, glutamate, lactate and pyruvate during Plasmodium yoelii infection and pyrimethamine treatment in mice.

    Agarwal, A; Tripathi, L M; Pandey, V C


    Ammonia, lactate, glutamate and pyruvate levels in blood, liver, brain, spleen and kidney were determined during Plasmodium yoelii infection and pyrimethamine treatment in mice. Ammonia and lactate levels showed significant increase with rise in parasitaemia except in spleen where decrease in the lactate levels was observed. The glutamate level displayed a marked decrease in blood, liver and splenic tissues, whereas, significant increase in glutamate level in kidney was observed, although its level in cerebral tissue remained unaltered. The pyruvate level in blood and liver showed a noticeable decrease but brain, spleen and kidney registered an elevation of the same due to the parasitic infection. Pyrimethamine (oral) treatment (10 mg/kg body weight) to infected mice (5-10%) for four days brought back the altered levels of the above cellular constituents in different tissues to normal, a week after cessation of drug treatment.

  16. CERN apprentice receives award


    Another CERN apprentice has received an award for the quality of his work. Stéphane Küng (centre), at the UIG ceremony last November, presided over by Geneva State Councillor Pierre-François Unger, Head of the Department of Economics and Health. Electronics technician Stéphane Küng was honoured in November by the Social Foundation of the Union Industrielle Genevoise (UIG) as one of Geneva’s eight best apprentices in the field of mechatronics. The 20-year-old Genevan obtained his Federal apprentice’s certificate (Certificat fédéral de capacité - CFC) in June 2007, achieving excellent marks in his written tests at the Centre d’Enseignement Professionnel Technique et Artisanal (CEPTA). Like more than 200 youngsters before him, Stéphane Küng spent part of his four-year sandwich course working at CERN, where he followed many practical training courses and gained valuable hands-on experience in various technical groups and labs. "It’ always very gr...

  17. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  18. Transplantation tolerance mediated by regulatory T cells in mice

    冯宁翰; 吴宏飞; 吴军; 张炜; 眭元庚; 贺厚光; 张春雷; 郑峻松


    Background With potent suppressive effect on responder T cells, CD4+CD25+ regulatory T (Treg) cells have become the focus of attention only recently and they may play an important role in transplantation tolerance. However, the mechanism of action is not clear. This study was designed to assess the possibility of using CD4+CD25+ Treg cells to induce transplantation tolerance and to investigate their mechanism of action.Methods CD4+CD25+ Treg cells were isolated using magnetic cell separation techniques. Mixed lymphocyte reactions were used to assess the ability of Treg cells to suppress effector T cells. Before skin transplantation, various numbers of CD4+CD25+Treg cells, which have been induced using complex skin antigens from the donor, were injected into the host mice either intraperitoneally (0.5×105, 1×105, 2×105, 3×105, 4×105, or 5×105) or by injection through the tail vein (5×103, 1×104, 2×104, 5×104, 1×105, 2×105). Skin grafts from two different donor types were used to assess whether the induced Treg cells were antigen-specific. The survival time of the allografts were observed. Single photon emission computed tomography was also used to determine the distribution of Treg cells before and after transplantation.Results Treg cells have suppressive effect on mixed lymphocyte reactions. Grafts survived longer in mice receiving CD4+CD25+ Treg cell injections than in control mice. There was a significant difference between groups receiving intraperitoneal injection of either 2×105 or 3×105 CD4+CD25+Treg cells and the control group (P<0.05, respectively). Better results were achieved when Treg cells were injected via the tail vein than when injected intraperitoneally. The transplantation tolerance induced by CD4+CD25+ Treg cells was donor-specific. Analysis of the localization of Treg cells revealed that Treg cells mainly migrated from the liver to the allografts and the spleen.Conclusions CD4+CD25+Treg cells can induce donor

  19. Presence of bluetongue virus in the marginal zone of the spleen in acute infected sheep.

    Lee, Fan; Chen, Jiun-Liang; Lin, Chun-Ming; Wang, Fun-In


    Bluetongue virus, a member of the genus Orbivirus of the family Reoviridae, is the causative agent of bluetongue, which is a non-contagious Culicoides mediated blood-borne disease. The present study characterizes the pathogenicity of a Taiwan prototype BTV2/KM/2003 in Corriedale sheep inoculated subcutaneously into the ear pinna. Histologically, multifocal petechiated hemorrhage, with mild to moderate inflammation and edema, were present in the contralateral ear pinna, tongue, and facial skin, without remarkable lesions in lymphoid organs. By days post-infection (DPI) 7, viral VP7 antigen, detected by immunohistochemistry, presented in the spleen, chiefly located in the outer rim of macrophages bordering the marginal zone and red pulp, and T lymphocytes of the red pulp. By DPI 11, viral signals shifted from the marginal zone to macrophages and small lymphocytes within follicles of the spleen. In situ hybridization with VP7 gene probe detected strong signals in the spleen, chiefly spanning the whole width of 5-10 cell thickness of the marginal zone, including the marginal zone macrophages and marginal zone B cells, as well as macrophages of sheathed capillaries in the red pulp. This study demonstrates molecular as well as morphologic evidence of the presence of bluetongue virus in the marginal zone of the spleen, most likely associated with viremia in acute infection, as previously demonstrated by the authors.

  20. Noninvasive assessment of esophageal-gastric varices by spleen stiffness in liver cirrhosis patients



    Objective To investigate the value of spleen stiffness measured by transient elastography(FibroScan,FS) for diagnosing esophageal-gastric varices in liver cirrhosis patients. Methods A total of 259 cirrhotic patients in Tianjin Third Central Hospital rom Apr 2011 to Apr 2012,and 30 healthy controls were enrolled

  1. Biomechanics of red blood cells in human spleen and consequences for physiology and disease

    Pivkin, Igor V.; Peng, Zhangli; Karniadakis, George E.; Buffet, Pierre A.; Dao, Ming; Suresh, Subra


    Red blood cells (RBCs) can be cleared from circulation when alterations in their size, shape, and deformability are detected. This function is modulated by the spleen-specific structure of the interendothelial slit (IES). Here, we present a unique physiological framework for development of prognostic markers in RBC diseases by quantifying biophysical limits for RBCs to pass through the IES, using computational simulations based on dissipative particle dynamics. The results show that the spleen selects RBCs for continued circulation based on their geometry, consistent with prior in vivo observations. A companion analysis provides critical bounds relating surface area and volume for healthy RBCs beyond which the RBCs fail the “physical fitness test” to pass through the IES, supporting independent experiments. Our results suggest that the spleen plays an important role in determining distributions of size and shape of healthy RBCs. Because mechanical retention of infected RBC impacts malaria pathogenesis, we studied key biophysical parameters for RBCs infected with Plasmodium falciparum as they cross the IES. In agreement with experimental results, surface area loss of an infected RBC is found to be a more important determinant of splenic retention than its membrane stiffness. The simulations provide insights into the effects of pressure gradient across the IES on RBC retention. By providing quantitative biophysical limits for RBCs to pass through the IES, the narrowest circulatory bottleneck in the spleen, our results offer a broad approach for developing quantitative markers for diseases such as hereditary spherocytosis, thalassemia, and malaria. PMID:27354532

  2. Body mass, spleen mass and level of thyroid hormones in juvenile hypothyroid rats

    Roksandić Dragutin


    Full Text Available In this paper, the effect of hypothyroidism on body mass and spleen mass of rats was examined during the prenatal and early juvenile periods. Hypothyroidism was induced by the application of propylthiouracil (PTU in drinking water to the mothers from the first day of gravidity and during lactation, and the offspring were sacrificed on the 14th and 21st days after birth. The body mass of the juvenile rats was measured just before they were sacrificed. The concentrations of triiodothyronine (T3 and thyroxine (T4 in blood serum were determined in control and treated juvenile rats. The results indicate that PTU leads to a reduction in T3 and T4 serum concentrations in treated juvenile rats. Treated juvenile rats had a bigger body mass and spleen mass in comparison with control animals. These data indicate that hypothyroidism induced in the prenatal and early juvenile period leads to an increase in the body mass and spleen mass and disrupts the normal development of the spleen in the course of the examined period. .

  3. Spleen morphology and vascularization in the alligator (Caiman crocodilus yacare – Daudin, 1802

    Alan Peres Ferraz de Melo


    Full Text Available The Caiman crocodilus yacare is found from northern Argentina to the southern Amazon basin, mainly occurring in Pantanal. Its food consists of fishes and other aquatic vertebrates and invertebrates, such as crabs, winkles, and insects. Its length can reach 3 meters and this species is important because it provides biological control of other animal species, by feeding on weak, old, and ill individuals, unable to escape its attack. A total of 15 alligators were used, young males and females, using histological techniques; injection techniques with Neoprene latex 450 and vinyl acetate; and radiographic techniques to observe particularities of spleen in this species. The organ has a conical shape, being thicker at its cranial end and tapering at its caudal end. Spleen involved the cranial mesenteric artery, which went towards the intestines, from its origin in the celiac artery until its middle third, through the splenic parenchyma in all preparations. Spleen irrigation in the alligator was originated from the celiac artery, through its branch, the cranial mesenteric artery, which branched into splenic arteries, only within this organ. The splenic veins showed up as the cranial, craniomedial, medial, and caudal splenic veins which drain from the splenic capsule to the medullary region, going through the cortical region and going towards the hepatic portal vein. Spleen in the alligator showed no correspondence between the arteries and veins responsible for the vascularization of a certain splenic territory, but one observed arteries irrigating and veins draining particular areas of the splenic parenchyma.

  4. Shape-constrained multi-atlas segmentation of spleen in CT

    Xu, Zhoubing; Li, Bo; Panda, Swetasudha; Asman, Andrew J.; Merkle, Kristen L.; Shanahan, Peter L.; Abramson, Richard G.; Landman, Bennett A.


    Spleen segmentation on clinically acquired CT data is a challenging problem given the complicity and variability of abdominal anatomy. Multi-atlas segmentation is a potential method for robust estimation of spleen segmentations, but can be negatively impacted by registration errors. Although labeled atlases explicitly capture information related to feasible organ shapes, multi-atlas methods have largely used this information implicitly through registration. We propose to integrate a level set shape model into the traditional label fusion framework to create a shape-constrained multi-atlas segmentation framework. Briefly, we (1) adapt two alternative atlas-to-target registrations to obtain the loose bounds on the inner and outer boundaries of the spleen shape, (2) project the fusion estimate to registered shape models, and (3) convert the projected shape into shape priors. With the constraint of the shape prior, our proposed method offers a statistically significant improvement in spleen labeling accuracy with an increase in DSC by 0.06, a decrease in symmetric mean surface distance by 4.01 mm, and a decrease in symmetric Hausdorff surface distance by 23.21 mm when compared to a locally weighted vote (LWV) method.

  5. Recruitment of macrophages from the spleen contributes to myocardial fibrosis and hypertension induced by angiotensin II

    Ning-Ping Wang


    Full Text Available Introduction: The purpose of this study was to determine whether macrophages migrated from the spleen are associated with angiotensin II-induced cardiac fibrosis and hypertension. Methods: Sprague-Dawley rats were subjected to angiotensin II infusion in vehicle (500 ng/kg/min for up to four weeks. In splenectomy, the spleen was removed before angiotensin II infusion. In the angiotensin II AT1 receptor blockade, telmisartan was administered by gastric gavage (10 mg/kg/day during angiotensin II infusion. The heart and aorta were isolated for Western blot analysis and immunohistochemistry. Results: Angiotensin II infusion caused a significant reduction in the number of monocytes in the spleen through the AT1 receptor-activated monocyte chemoattractant protein-1. Comparison of angiotensin II infusion, splenectomy and telmisartan comparatively reduced the recruitment of macrophages into the heart. Associated with this change, transforming growth factor β1 expression and myofibroblast proliferation were inhibited, and Smad2/3 and collagen I/III were downregulated. Furthermore, interstitial/perivascular fibrosis was attenuated. These modifications occurred in coincidence with reduced blood pressure. At week 4, invasion of macrophages and myofibroblasts in the thoracic aorta was attenuated and expression of endothelial nitric oxide synthase was upregulated, along with a reduction in aortic fibrosis. Conclusions: These results suggest that macrophages when recruited into the heart and aorta from the spleen potentially contribute to angiotensin II-induced cardiac fibrosis and hypertension.

  6. Floating spleen with chronic torsion of the pedicle causing splenomegaly and secondary hypersplenism

    Čolović Radoje B.


    Full Text Available If the spleen is not fixed within the left subphrenic space, it gradually passes into the lower abdomen, where is much more exposed to trauma. Torsion of the splenic pedicle can also occur, causing the infarct necessitating an immediate surgery. Venous stasis causes splenomegaly and sometimes secondary hypersplenism. The authors present 16.5-year old girl with torsion of the splenic pedicle of floating spleen for 720°: in spite of that, the patient had neither splenic infarct nor splenic vein thrombosis, possibly due to thrombocytopenia, but she had splenomegaly and secondary hypersplenism with pancytopenia causing bleeding, sideropenic anemia and mild jaundice. After treatment with iron, the patient underwent splenectomy which resulted in almost immediate rise of the number of all blood cells, and even thrombocytosis. The authors suggest early surgical treatment of the floating spleen, preferably splenopexy, before development of severe complications when splenectomy had to be performed in the majority of patients. Accessory spleens, if present, should be saved.

  7. Torted and Ruptured Wandering Spleen Presenting as a Surgical Emergency in Pregnancy

    A. Parvaiz


    Full Text Available Wandering spleen (WS is characterised by incomplete fixation of the spleen to its supporting linorenal and gastrosplenic ligaments. It can predispose to life-threatening complications due to torsion of its vascular pedicle, splenic infarction, portal hypertension, and haemorrhage. A 27-year-old, 36-week prima gravida underwent emergency caesarean section for tachycardia and hypotension. A healthy baby girl was delivered. However, she remained shocked despite aggressive fluid therapy and intraoperatively it was noted that there was significant intraperitoneal bleeding and the on-call surgical team was summoned. Midline laparotomy revealed a lacerated, infarcted, hypermobile spleen found with free intraperitoneal bleeding. The unsalvageable spleen was resected and the patient went on to make an excellent recovery. The aetiology of WS is contentious. With an increased frequency among multiparous females of reproductive age, some suggest the hormonal effects of pregnancy as contributing factors. Clinical presentations range from an asymptomatic abdominal mass to acute abdominal pain with hypovolaemic shock. WS poses a serious threat to life due to thrombosis, bleeding, or infarction. Ultrasound scan and CT scan are equally effective in the diagnosis. Patients with asymptomatic WS should be treated with elective splenopexy, however, in the acute presentation, splenectomy is the procedure of choice.

  8. A protein in pig spleen similar to immune suppressive protein of stress

    FUHong-Yan; ZHANGJie; DINGGui-Feng; FANShao-Guang


    AIM:To purify a protein in pig spleens, which was similar to immune suppressive protein of stress (ISPS), and characterize its properties and functions. METHODS: 1)Pig spleen was extracted in dilute hydrochloric acid. 2) The extract was ultra-filtrated for having high molecular weight proteins (Mr>30000). 3) The filtrates were purified with FPLC affinity chromatography. 4)The elute from FPLC was used for T-lymphocyte proliferation and ELISA test. 5) Lastly, SDS-PAGE was used to determine the molecular weight and purity of the final product. RESULTS: A protein purified from pig spleen (the pig ISPS homologue) inhibited concanavalin A(Con A)-induced mouse lymphocyte proliferation. The molecular weight of this protein was about Mr 190000. It has a stronger selectivity against T-lymphocyte line such as Jurkat cell line and mastocyte line (P815) and has a weaker inhibitory activity on macrophage line (U937). CONCLUSION: A protein similar to rat/mouse ISPS was found in pig spleen. This may provide an opportunity to study its roles in tumors and autoimmune diseases.

  9. Neural Crest Cells Contribute an Astrocyte-like Glial Population to the Spleen

    Barlow-Anacker, Amanda J.; Fu, Ming; Erickson, Christopher S.; Bertocchini, Federica; Gosain, Ankush


    Neural crest cells (NCC) are multi-potent cells of ectodermal origin that colonize diverse organs, including the gastrointestinal tract to form the enteric nervous system (ENS) and hematopoietic organs (bone marrow, thymus) where they participate in lymphocyte trafficking. Recent studies have implicated the spleen as an anatomic site for integration of inflammatory signals from the intestine with efferent neural inputs. We have previously observed alterations in splenic lymphocyte subsets in animals with defective migration of NCC that model Hirschsprung’s disease, leading us to hypothesize that there may be a direct cellular contribution of NCC to the spleen. Here, we demonstrate that NCC colonize the spleen during embryogenesis and persist into adulthood. Splenic NCC display markers indicating a glial lineage and are arranged anatomically adjacent to blood vessels, pericytes and nerves, suggesting an astrocyte-like phenotype. Finally, we identify similar neural-crest derived cells in both the avian and non-human primate spleen, showing evolutionary conservation of these cells. PMID:28349968

  10. Imaging findings in Langerhans` cell histiocytosis of the liver and the spleen in an adult

    Mampaey, S. [Dept. of Radiology, Aalsters Stedelijk Ziekenhuis, Aalst (Belgium)]|[Dept. of Radiology, University of Antwerp (Belgium); Warson, F. [Dept. of Anatomopathology, Aalsters Stedelijk Ziekenhuis, Aalst (Belgium); Hedent, E. van [Dept. of Radiology, Aalsters Stedelijk Ziekenhuis, Aalst (Belgium); Schepper, A.M. de [Dept. of Radiology, University of Antwerp (Belgium)


    We present a case of Langerhans` cell histiocytosis (LCH) of the liver and spleen in an adult. The imaging features are different from those in the few previously reported cases of individual organ involvement by LCH. (orig.) (orig.) With 2 figs., 5 refs.

  11. Malignant lymphoma of spleen presenting as acute pancreatitis: A case report

    Chao-Ming Wu; Lung-Chih Cheng; Gin-Ho Lo; Kwok-Hung Lai; Chia-Ling Cheng; Wen-Cheng Pan


    This is a case report of a patient who presented with acute pancreatitis without the common causes. A pancreatic biopsy revealed large B cell lymphoma. Spleen lymphoma with pancreatic involvement inducing acute pancreatitis, which is a rare disorder, was diagnosed.Here we also review the few similar cases reported in the literature.

  12. Coexisting Sclerosing Angiomatoid Nodular Transformation of the Spleen with Multiple Calcifying Fibrous Pseudotumors in a Patient

    Jen-Chieh Lee


    Full Text Available Primary tumor or tumor-like lesions of the spleen are rare. Among them, vascular lesions are the most common. Vascular tumor of the spleen is different from the usual hemangioma of soft tissue because the vascular structure of the spleen is unique. Sclerosing angiomatoid nodular transformation (SANT is a recently described vascular lesion of the spleen. Grossly, it is a multinodular, well-circumscribed tumor containing a hypervascular core. Microscopically, it comprises three types of vessels, and each type recapitulates the immunohistochemical characteristics of the normal vascular elements of the splenic red pulp, i.e. capillaries, sinusoids, and small veins, respectively. Because of the rarity of this entity, its actual pathogenesis is still unknown. In this study, we report a case of SANT occurring in a 43-year-old woman, in whom there were also multiple calcifying fibrous pseudotumors (CFPTs in the abdominal cavity. Both SANT and CFPT are thought to be variants of inflammatory pseudotumor. Coexistence of these two rare entities in a patient has never been reported, and this fact suggests that there might be a common mechanism contributing to the formation of these two types of lesions. [J Formos Med Assoc 2007;106(3:234-239

  13. Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

    Nell, Sjoerd; Brunaud, Laurent; Ayav, Ahmet; Bonsing, Bert A.; Groot Koerkamp, Bas; Nieveen van Dijkum, Els J.; Kazemier, Geert; de Kleine, Ruben H J; Hagendoorn, Jeroen; Molenaar, I. Quintus; Valk, Gerlof D.; Borel Rinkes, Inne H M; Vriens, Menno R.


    Background: Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. Objective: To describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. Methods: Robot-assisted

  14. Robot-assisted spleen preserving pancreatic surgery in MEN1 patients

    Nell, Sjoerd; Brunaud, Laurent; Ayav, Ahmet; Bonsing, Bert A.; Koerkamp, Bas Groot; van Dijkum, Els J. Nieveen; Kazemier, Geert; de Kleine, Ruben H. J.; Hagendoorn, Jeroen; Molenaar, I. Quintus; Valk, Gerlof D.; Rinkes, Inne H. M. Borel; Vriens, Menno R.


    BackgroundMultiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. ObjectiveTo describe robot-assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. MethodsRobot-assisted

  15. Role of splenic stroma in the action of bacterial lipopolysaccharides on radiation mortality: a study in mice carrying the Slsup(j) allele

    Ploemacher, R.E.; Brons, N.H.C.


    Slsup(j)/+ mice display a slight macrocytic anemia due to a defect in their hamopoietic organ stroma. They have a deficient endogenous spleen colony (CFU-end) formation following sublethal doses of gamma-radiation compared with their normal +/+ littermates, which is likely to be due to the low pre-irradiation CFU-S content of the Slsup(j)/+ spleen. CFU-S in these congenic mice do not differ in their sensitivity to gamma-irradiation or stem cell-activating factor. While injection of +/+ mice with 10 of lipopolysaccharide-W (LPS) one day prior to irradiation led to a substantial increase in their survival, the survival of Slsup(j)/+ mice was only slightly increased. Irradiation induced a similar dose-related reduction in the numbers of CFU-S in the spleen and femora of LPS-injected Slsup(j)/+ mice compared to similarly treated +/+ mice when measured directly after irradiation. At Day 9 after irradiation injection of LPS led to a significantly higher CFU-end formation and higher numbers of CFU-S and nucleated cells in the Slsup(j)/+ spleens compared to LPS-injected +/+ mice. No such diff