Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous injection of BCG in rats induces protection against liver cell necrosis produced by CCl4. Impairment of hepatic mixed function oxidases by cytokines produced by activated Kupffer cells is the mechanism proposed to explain that protection. To verify the function of hepatic mixed function oxidases after Kupffer activation, the sleeping time after sodium pentobarbital anesthesia was evaluated in rats after intravenous injection of BCG. Male adult albino rats received BCG (50 micrograms, intravenous) and 48 h or 6 days after were anestethized with sodium pentobarbital (33 or 66 mg/g i.p.). The sleeping time was measured from the beginning of sleep until the animal started having spontaneous movement and stand up on the forepaws. The results showed that the animals treated with BCG presented a significative increase in the sleeping time, indicating reduced inactivation of the pentobarbital, an indirect evidence of inhibition of mixed function oxidase system. BCG treated rats showed hepatic and splenomegaly, both 48 and 6 days after treatment. Histology showed an increase in number of mononuclear cells in the sinusoids in the liver and in the red pulp of the spleen 48 h after injection. Small epitheliod granulomas scattered in the hepatic lobules and in the red pulp were observed in rats killed six days after the BCG injection. Hepatocyte injury, induced by activated macrophages, would be not responsible for the reduced pentobarbital inactivation, because at six days there were several granulomas scattered in lobules, but the increase of sleep time in this group was similar to that observed in rats 48 h after injection of BCG. These results demonstrate that activation of Kupffer cells with BCG induces impairment of mixed function oxidase system soon as 48 h after injection of activator, probably due to production of IL-1, IL-6 and TNF alpha by activated Kupffer cells and other mononuclear cells migrated to the liver.
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PMID:Increased sleeping time after pentobarbital anesthesia in rats treated with intravenous injection of BCG. 1075 4

Although large human populations have been safely immunized against tuberculosis with two live vaccines, Mycobacterium bovis BCG or Mycobacterium microti, the vole bacillus, the molecular basis for the avirulence of these vaccine strains remains unknown. Comparative genomics has identified a series of chromosomal deletions common to both virulent and avirulent species but only a single locus, RD1, that has been deleted from M. bovis BCG and M. microti. Restoration of RD1, by gene knock-in, resulted in a marked change in colonial morphology towards that of virulent tubercle bacilli. Three RD1-encoded proteins were localized in the cell wall, and two of them, the immunodominant T-cell antigens ESAT-6 and CFP-10, were also found in culture supernatants. The BCG::RD1 and M. microti::RD1 knock-ins grew more vigorously than controls in immunodeficient mice, inducing extensive splenomegaly and granuloma formation. Increased persistence and partial reversal of attenuation were observed when immunocompetent mice were infected with the BCG::RD1 knock-in, whereas BCG controls were cleared. Knocking-in five other RD loci did not affect the virulence of BCG. This study describes a genetic lesion that contributes to safety and opens new avenues for vaccine development.
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PMID:Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. 1241 Aug 28

Live mycobacteria have been reported to signal through several pattern recognition receptors (PRR), among them toll-like receptor 4 (TLR4) and TLR2 in vitro. Here, we investigated the role of TLR4 in host resistance to Mycobacterium bovis (BCG) infection in vivo. In vitro, macrophages of TLR4 mutant C3H/HeJ mice infected with BCG expressed lower levels of TNF than controls, and TNF release was further decreased, although not completely absent, in the absence of TLR2. In vivo, TLR4 mutant C3H/HeJ and control C3H/HeOUJ mice were infected with BCG (2 x 10(6) CFU i.v.). Both TLR4 mutant and wild-type mice were able to control the infection and survived 8 months post-BCG infection. Macrophage activation with abundant acid-fast bacilli and expression of inducible nitric oxide synthase (iNOS) and MHC class II antigens was seen in both groups of mice. However, TLR4 mutant mice experienced an arrest of body weight gain and showed signs of increased inflammation, with persistent splenomegaly, increase in granuloma number and augmented neutrophil infiltration. Infection of TLR4-deficient mice with higher doses of BCG (1 and 3 x 10(7) CFU, i.v.) increased the inflammation in spleen and liver, associated with a transient, higher bacterial load in the liver. In summary, TLR4 mutant mice show normal macrophage recruitment and activation, granuloma formation and control of the BCG infection, but this is associated with persistent inflammation. Therefore, TLR4 signaling is not essential for early control of BCG infection, but it may have a critical function in fine tuning of inflammation during chronic mycobacterial infection.
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PMID:Control of Mycobacterium bovis BCG infection with increased inflammation in TLR4-deficient mice. 1455 48

While studying the unique Nramp1 (Slc11a1)-independent susceptibility to Mycobacterium bovis (BCG) infection of BXH-2 mice, we noted that these mice develop important splenomegaly and enlargement of lymph nodes. Segregation analyses in several F2 crosses showed that splenomegaly segregates as a single recessive trait caused by a novel mutation in BXH-2, independent of the infection. Histologic and fluorescence-activated cell sorter (FACS) analyses indicated that splenomegaly is associated with a large increase in Mac1+/GR1+ (macrophage antigen-1+/granulocyte differentiation antigen 1+) granulocyte precursors in spleen, lymph nodes, and bone marrow, resembling a myeloproliferative syndrome. This is concomitant to extramedullary erythropoiesis in the spleen, as measured by proportion of Ter119+ erythroid cells. The locus controlling this myeloproliferative syndrome and splenomegaly was designated Myls and maps to an 18 centimorgan (cM) region of chromosome 8, which also contains an integrated copy of an N-ecotropic murine leukemia virus (MuLV) provirus (Emv2). The relationship between Myls, expansion of Mac1+/GR1+ cells, and Emv2 was investigated. Homozygosity at Myls is necessary but not sufficient for B-ecotropic virus replication in splenocytes, the extent of which appears to be under separate genetic control. Our results suggest a model in which Myls-dependent myeloproliferation in BXH-2 acts as a predisposing factor for the subsequent development of virally induced myeloid leukemia characteristic of this strain.
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PMID:Genetic control of myeloproliferation in BXH-2 mice. 1463 Aug 19

To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable Mycobacterium bovis BCG by the aerosol or intravenous route and then challenged six weeks later with virulent Mycobacterium tuberculosis. The day after immunization, the counts were 3.71 +/- 0.10 log(10) CFU in the lungs of aerosol-immunized mice and 3.65 +/- 0.11 and 4.93 +/- 0.07 log(10) CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 +/- 0.14 and 3.54 +/- 0.07 log(10) CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 +/- 0.28 and 5.12 +/- 0.23 log(10) CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with M. tuberculosis by implanting 2.37 +/- 0.13 log(10) CFU in the lungs. Six weeks after challenge, M. tuberculosis had multiplied so that the counts were 6.41 +/- 0.27 and 4.44 +/- 0.14 log(10) CFU in the lungs and spleens of control mice, respectively. Multiplication of M. tuberculosis was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 +/- 0.24 and 3.73 +/- 0.34 log(10) CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of M. tuberculosis resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.
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PMID:Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG. 1474 54

In this case report a rare adverse event (mild toxic epidermic necrolysis (Lyell)) was described. Incorrect a purified protein derivative (PPD) administration involves false negative tuberculin test (TT): BCG vaccine was injected even though high immunization to BCG. Mild, benign epidermic necrolysis, fever, mononucleosis-like syndrome, splenomegaly and lymphadenopathy were observed. Evaluation of white blood cells was done by automatic (simultaneously two analysers: Baker 900 plus and Technicon, Bayer) and by microscopic methods and revealed high lymphocyte activation (blastic transformation), lymphocytosis and high eosinophilia.. Wiener and coworkers describe interleukin-2-induced dermatotoxicity resembling toxic epidermal necrolysis. Further the most common side effects of IL-2 are skin eruptions and eosinophilia. Careful analysis yielded the conclusions that Lyell's syndrome may be fatal consequence of inappropriate revaccination, hyperergia--delayed type hypersensitivity and massive IL-2 release. Successful dexamethasone therapy confirms this observation.
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PMID:[Mild form of Lyell's syndrome as an consequence of inappropriate BCG revaccination--case report]. 1569 Jul 9

Tumor necrosis factor-alpha (TNF-alpha) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-alpha (rgpTNF-alpha). Using rgpTNF-alpha along with neutralizing anti-rgpTNF-alpha antiserum, we tested the effect of modulating the levels of TNF-alpha on antigen-specific T cell proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation. Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-alpha antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-alpha in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-alpha activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-alpha.
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PMID:Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig. 1595 60

Hemophagocytic syndrome (HS) is a life-threatening condition of hyperinflammation. Main symptoms are: prolonged fever, cytopenia, hepatosplenomegaly, hemophagocytosis, hyperferritinemia, hypertriglyceridemia and hypofibrinogenemia. Primary genetic form and secondary HS associated with infections, malignancies or autoimmune disorders can be distinguished. Untreated HS in most cases leads to death. We analyzed retrospectively 7 cases of HS in children (3 girls, 4 boys; aged 10 days -14 years) treated in 3 different pediatric centers from 2004 to 2009. In 3 cases HS was associated with infections (EBV, CMV, Bacillus Calmette Guerin - BCG), in 1 child with non-Hodgkin anaplastic large cell lymphoma (ALCL), in 1 patients probably with side effect of antiepileptic drug. In 2 cases cause of HS remained unknown. Fever, hepatomegaly, pan- or bicytopenia and hyperferritinemia were present in all children. In addition, splenomegaly was noted in 6 cases, hemophagocytosis in 6 children, impaired function or decreased number of NK cells in 4 cases, hypofibrino-genemia in 5 and hypotriglyceridemia in 4 patients. Among other symptoms and signs we observed: lymphadenopathy, hepatic failure, oedema, rash, neurological symptoms, increased level of LDH and inflammatory markers. In one child acute pancreatitis occurred. Among others, antibiotics, antiviral and immunosuppressive drugs were used in therapy. HLH-2004 protocol was applied in 4 cases. Patient with ALCL was treated with chemotherapy and allogeneic stem cell transplantation. Four patients are alive, 2 died because of HS, child with ALCL died because of generalized infection in peritrans-plantation period. In case of prolonged fever, splenomegaly and cytopenia diagnosis of HS should be considered. Following tests are recommended: complete blood count, ferritin, triglycerides, fibrinogen, bone marrow aspiration and NK cell assessment. Patients should be also screened for infections and malignancies. Early diagnosis of HS and underlying condition is crucial to start lifesaving therapy.
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PMID:[Hemophagocytic syndrome in children with different underlying conditions]. 2134 76

There are many strategies to control leishmaniasis, but majority of them are inadequate. Killed Leishmania vaccine (KLV) has been applied for its immunogenicity in human and mouse model. Bacillus Calmette-Guerin (BCG) as adjuvant is an immune-modulator inducing humoral and cellular immune responses during zoonotic cutaneous leishmaniasis (ZCL). Both KLV and BCG have been applied for their immune responses in hosts for controlling leishmaniasis. In this study, KLV and BCG were applied to inhibit replication and visceralization of Leishmania major in BALB/c mice. Mice were injected with KLV and BCG, followed by infection with promastigotes of L. major. Six weeks after infection, a small nodule appeared, which was followed by development of a large lesion and visceralization. Effects of KLV and BCG, physiopathological changes, lesion size, delay of lesion formation, proliferation of amastigotes inside macrophages and detection of amastigotes in target organs were studied. Results showed that the KLV had anti-leishmanial activity by reducing lesion size on late infection. In KLV and BCG group, the average number of amastigotes in macrophages was lower than in other groups. Significant reductions in number of amastigotes in both spleen and lymph node were observed, indicating lower visceralization of Leishmania parasites in these target organs. No significant changes were presented in body weights, survival rates and degrees of splenomegaly in test group. It can be concluded that application of KLV and BCG had acceptable efficacy in reduction of skin lesions size and proliferation of parasites, even though a few side-effects were observed. It is indicated that KLV/BSG may have ability to modulate host immune responses against Leishmania parasites and to reduce pathophysiology of the disease during infection.
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PMID:Evaluation of anti-leishmanial effects of killed Leishmania vaccine with BCG adjuvant in BALB/c mice infected with Leishmania major MRHO/IR/75/ER. 2353 46


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