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)

An eight-month-old female German shepherd dog had pathological fractures affecting the distal radius and ulna and ribs. Radiographically, there were bilaterally symmetrical osteolytic lesions affecting the metaphyses of multiple long bones, ribs and skull and the dog had splenomegaly. Histologically, the spleen, thymus and bones were infiltrated with large lymphoblastic cells with a high mitotic rate; the diagnosis was lymphoma. Lymphoma primarily affecting bone is an uncommon diagnosis in the dog but it should be considered in young animals with osteolytic lesions affecting multiple bones.
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PMID:Polyostotic lymphoma in a young dog: a case report and literature review. 932 81

We studied the effect of exposure to hyperbaric oxygen (HBO): 2.8 atm absolute 100% oxygen for 4 h daily over 3-7 days, on the immune system of normal (BALB/c and MRL- +/+) and autoimmune MRL-lpr/lpr) mice. In HBO exposed BALB/c mice, we observed a remarkable decrease in the cell population of the spleen and thymus. We found that the sensitivity to HBO varied among subpopulations of lymphocytes. For example, CD4+ CD8+ double positive cells in the thymus and B220+ B cells in the spleen were more sensitive than CD4+ or CD8+ single positive T cells in the thymus, and Thy-1+ T cells in the spleen, respectively. Accordingly, despite the decrease in total cell number in the spleen, the proliferative response of T cells from the spleen to Con A was not impaired in the HBO exposed mice. Exposure of MRL-lpr/lpr mice to HBO caused a marked reduction of weight and cell population of the otherwise enlarged spleen and lymph nodes, and amongst others of percentages of B220+Thy-1+ double positive abnormal cells. These results suggest the HBO therapy may be applicable for the treatment of some autoimmune diseases.
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PMID:Differential sensitivities to hyperbaric oxygen of lymphocyte subpopulations of normal and autoimmune mice. 937 15

The polypeptide (p)50 molecule, a subunit of nuclear factor (NF)-kappaB, is produced after proteolytic processing of the p105 precursor (NF-kappaB1). Although the p105 precursor has been postulated to play a role in the regulation of the Rel/NF-kappaB activity, its physiological relevance remains unclear. To investigate that, we generated mutant mice lacking the COOH terminal half of the p105 precursor, but expressing the p50 product (p105-/-). These mutant mice displayed an inflammatory phenotype composed of lymphocytic infiltration in lungs and liver, and an increased susceptibility to opportunistic infections. Enlargement of multiple lymph nodes, splenomegaly due to erythrocytic extramedullary hematopoiesis, and lymphoid hyperplasia were also observed in p105-/- mice. Cytokine production in p105-/- macrophages was severely impaired, whereas proliferative responses of p105-/- B cells were increased. T cell functions were only moderately impaired in mutant mice. Loss of p105 also led to enhanced constitutive p50 homodimer and inducible NF-kappaB activities in unstimulated and stimulated cells, respectively. As several genes regulated by Rel/NF-kappaB were upregulated in p105-/- thymus but downregulated in p105-/- macrophages, the enhanced p50 homodimers appear to function as transcriptional activators or repressors, depending on the cell type. Thus, the p105 precursor is indispensable in the control of p50 activity, and lack of the precursor has distinct effects on different cells.
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PMID:Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50. 952 15

Lyn kinase-deficient (lyn-/-) mice show several abnormalities such as reduced numbers of circulating B cells, hyper-IgM, and low proliferative responses induced by CD40 ligand. Lyn-/- mice also develop splenomegaly, produce autoreactive Abs with age, and finally develop glomerulonephritis. Another abnormality observed in lyn-/- mice is that their disability to form germinal centers (GCs). It has been considered that GCs play an important role in affinity maturation and differentiation to B cell memory upon immunization with thymus-dependent Ag. Since Lyn kinase has been thought to be downstream of the signals from the B cell Ag receptor as well as CD40, we studied whether or not lyn-/- mice could exhibit normal Ag-specific class switching and affinity maturation following somatic hypermutation. The mice were immunized with (4-hydroxy-3-nitrophenyl)acetyl-chicken gamma-globulin (NP-CG). Production of NP-specific IgG1 Abs was slightly reduced but clearly detectable. The affinity of Abs produced was comparable to that in wild-type mice. Furthermore, somatic hypermutation occurred in the heavy-chain variable region at the same level as that in wild-type mice. Therefore, we conclude that isotype switching and affinity maturation occur normally in lyn-/- mice without the formation of GCs. The results lead to a speculation that Lyn may not play a role in induction of isotype switching or affinity maturation, despite being downstream of the signals from the B cell Ag receptor complex and CD40, and that GC architecture may not be absolutely essential for affinity maturation.
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PMID:Affinity maturation in Lyn kinase-deficient mice with defective germinal center formation. 959 Feb 25

Naturally acquired immunity to Plasmodium falciparum may be linked to key features of the immune system that change during normal development and ageing. Evidence of this was seen in non-immune Javanese transmigrants taking up residence in hyperendemic Irian Jaya, Indonesia. After 1-2 years of residence, the adult migrants had less frequent and less intense parasitaemias than their children. Splenomegaly and malaria-like symptoms were also less common in the adults. These age-dependent patterns of relative resistance to P. falciparum mirrored those in lifelong residents. The Javanese adults acquired protective immunity against chronic exposure to infection relatively quickly compared with their children. However, during the initial exposure to infection, the incidence of emergency medical evacuation to hospital with a clinical diagnosis of malaria was 7-fold higher among the adults than in their children. The exaggerated susceptibility of adults to severe morbidity and mortality has been reported in other populations during initial exposure to infection. Thus, whereas adults acquired protection against chronic exposure more rapidly than the children, they were initially more susceptible to severe disease. One possible explanation for these findings is the changes in the immune system that normally occur during ageing. Such changes may establish differences between children and adults that profoundly affect the course of infection by P. falciparum. The ratio of naive to memory T cells gradually diminishes during ageing, as a result of the cumulative effect of exposure to the myriad antigens encountered throughout the normal course of life. Moreover, the gradual involution of the thymus progressively limits the production of naive T cells. The likelihood of stimulating memory T cells with cross-reactive antigens may increase with age and this may bias the immune response to the relative benefits of the host under chronic exposure, or to the detriment of the host under acute exposure. Intrinsic features of the immune system that change with age may determine key characteristics of the immune response to infection by P. falciparum, and whether that response is relatively harmful or beneficial may depend upon the conditions of exposure (i.e. acute or chronic).
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PMID:Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum. 968 90

Age-related changes in peripheral blood, spleen, and thymus of ad libitum (AL)-fed and dietary restricted (DR) C57BL/6J x CBA/CaH-T6/J F1 (B6CBAT6 F1) mice at young (3 mo), middle (16 mo), and old (30 mo) ages were studied to define how dietary restriction retards immune aging. Dietary restriction at 25% AL intake level initiated at weaning significantly reduced the rates of age-related declines in peripheral blood T helper cells, naive T helper cells, and naive cytotoxic T lymphocytes (CTLs). As a result, concentrations of these cell types in old DR mice were equivalent to 161%, 176%, and 250% of those in old AL controls. Dietary restriction also abolished age-related splenomegaly and decreased total splenocyte numbers in old DR mice. Dietary restriction did not prevent age-related decline in thymus size, but preserved thymus cellularity in old mice. Old DR mice had twice as many total thymocytes and 2.6 times as many CD4+CD8+ immature thymocytes as old AL controls. The correlations between total immature thymocytes and concentrations of circulating naive T helper cells and naive CTLs increase with age and become significant in old mice. Thus, dietary restriction preserves immature T-cell precursors in the thymus during aging to maintain higher concentrations of circulating T helper and naive T cells in peripheral blood.
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PMID:Delayed immune aging in diet-restricted B6CBAT6 F1 mice is associated with preservation of naive T cells. 975 30

PD-1, an Ig superfamily member, contains an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail. It is expressed in a minor fraction of CD4-CD8- normal thymocytes and induced in peripheral lymphocytes following activation. To assess the possible roles of PD-1 in the immune responses, PD-1-deficient (PD-1-/-) mice were generated by a gene-targeting strategy. PD-1-4- mice developed and grew normally. Although the thymus was apparently normal, PD-1-/- mice showed moderate but consistent splenomegaly, which reflected the increased cellularity of both lymphoid and myeloid cells. The proliferative response of B cells by anti-IgM antibodies, but not of T cells by an anti-CD3 (145-2C11) mAb in vitro, was augmented in PD-1-/- mice as compared with control littermates. PD-1-/- mice showed increased serum levels of IgG2b, IgA and most strikingly IgG3, while those of IgM and IgG1 were comparable with control mice. Furthermore, PD-1-/- mice exhibited significantly augmented IgG3 anti-DNP antibody response to a type 2 T-independent antigen, DNP-Ficoll, with comparable IgM and IgG1 antibody responses with littermate controls. In the peritoneal cavity, the B-1 cell population in PD-1-/- mice exhibited significantly reduced expression of CD5, a negative regulator of B-1 cell activation, despite a marginal increase in the number of B-1 cells. Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching.
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PMID:Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. 979 23

The SCID mouse represents a valuable tool for assessing growth characteristics and drug sensitivity of human leukemic cells. We have examined differences in the engraftment patterns in SCID mice of primary human leukemic cells isolated from children (< 21 years old) with either t(1;19)+/E2A-PBX1+ or t(9;22)+/BCR-ABL+ acute lymphoblastic leukemia. Leukemic cells from 13/24 t(1;19)+/E2A-PBX1+ patients caused overt leukemia in SCID mice. Macroscopic lesions were evident in 6/13 cases, with multiple sites involved in some mice: hepatomegaly,(3) splenomegaly(4), thymic enlargement; liver tumors(1), kidney tumors(1), abdominal tumors(1). Microscopic lesions in SCID mouse organs were present in all 13 cases and involved the bone marrow, brain, heart, gut, liver, kidney, lung, ovary, pancreas, skeletal muscle, spleen, and thymus. Leukemic cells from 5/20 t(9;22)+/BCR-ABL+ patients caused overt leukemia in SCID mice. Notably, macroscopic lesions (splenomegaly; leukemic bones; hepatic tumors) were observed in only 1 case. In all 5 cases, microscopic lesions were found in the mouse bone marrow. Additional microscopic lesions were restricted to skeletal muscle, spleen, and mesentery (1 case) or thymus (1 case). These findings differ markedly from those of t(1;19)+/E2A-PBX1+ leukemic cells due to the lack of involvement of major organs such as liver, pancreas, kidney, skin, or brain. These data illustrate the biological heterogeneity of childhood ALL and suggest that the differential risks associated with t(1;19)+/E2A-PBX1+ and t(9;22)+/BCR-ABL ALL might arise from unique engraftment and proliferation capabilities of the respective leukemic cell populations.
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PMID:Distinct in vivo engraftment and growth patterns of t(1;19)+/E2A-PBX1+ and t(9;22)+/BCR-ABL+ human leukemia cells in SCID mice. 1003 3

A model system of clonal triploid ginbuna and tetraploid ginbuna-goldfish hybrids was employed to demonstrate the presence of graft-versus-host reaction (GVHR) in a teleost fish. Tetraploid scale grafts on triploid clone members evoked an acute rejection, whereas the reverse transplants were accepted. When sensitized triploid cells were injected into tetraploid recipients, a typical GVHR was induced, leading to death of the recipients within one month. The onset of illness appeared about one week after cell injection as a loss of appetite and constipation, followed by a scale protrusion, severe haemorrhage, local destruction of the ventral skin and prominent splenomegaly. GVHR was most effectively induced by head-kidney cells and peripheral blood leukocytes (PBL), followed by spleen and thymus cells. Donors had to be sensitized at least twice by scale grafting to induce the reaction. A considerable number of recipients injected with cells from donors which had been sensitized by allogenetically different tetraploids died, suggesting a limited polymorphism or heavy cross-reactions between the alleles of the histocompatibility antigens. Ploidy analyses revealed that donor cells greatly increased in the host liver and spleen, constituting approximately 30% of total cells after 2 3 weeks. Most of these features of acute GVHR observed in this fish system are quite similar to those found in mammals and birds. thereby suggesting the presence of allo-reactive cytotoxic T lymphocytes in teleosts.
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PMID:The graft-versus-host reaction (GVHR) in the ginbuna crucian carp, Carassius auratus langsdorfii. 1022 65

Protection against infection with encapsulated bacteria is mediated by IgG antibodies against the capsular polysaccharides. Production of such antibodies is impaired during infancy, when susceptibility to bacterial meningitis is greatest. Recent studies have proposed the use of anti-CD40 antibody to increase responsivenesses to polysaccharide antigens. We show here that the IgG response to a model polysaccharide antigen is greatly increased, but retains thymus-independent characteristics--switching continues to be mainly to IgG3 and neither germinal centers nor memory B cells are formed. Furthermore, anti-CD40 causes striking splenomegaly in mice, which is accompanied by dramatic cellular redistribution and proliferation of dendritic cells, macrophages, T cells and endothelium, as well as B cells. These findings raise the possibility that the anti-CD40 effect is due mainly to increased activity of accessory cells that affect plasmablast growth and differentiation rather than mimicry of T cell help.
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PMID:Anti-CD40 antibody enhances responses to polysaccharide without mimicking T cell help. 1054 Mar 33


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