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)

In previous studies we demonstrated that an induced asialo-GM1 positive (ASGM1+) cell of donor origin that exerts natural killer cell-like activity (NK activity+) plays a crucial role in the development of graft-versus-host (GVH)-associated tissue damage and severe immunosuppression. This study examined whether the ASGM1+ (NK activity+) GVH effector cells were activated by non-specific signals or whether these cells were triggered by specific alloantigens and displayed antigenic specificity. C57B1/6 (B6) donor mice were treated with either B6 x AF1 (B6AF1) lymphoid cells and anti-asialo GM1 antibodies (anti-ASGM1) to induce and eliminate specifically activated B6-anti-B6AF1 ASGM1+ (NK activity+) cells or with polyinosinic: polycytidylic acid (poly I:C), and anti-ASGM1 to eliminate non-specifically activated ASGM1+ (NK activity+) cells. Donor spleen and lymph node cells depleted of the specific allo-induced ASGM1+ NK reactive cells showed near normal numbers of L3T4+ and Lyt-2+ cells and retained T- and B-cell functions as measured by mitogen responses (to PHA, Con A and LPS), mixed lymphocyte responses (MLR) (to B6AF1) and the generation of cytotoxic T cells (CTL) (to B6AF1 blasts). Anti-ASGM1 treatment almost completely abrogated NK activity in all donor inocula. GVH reactions were induced by injecting treated donor cells into B6AF1, B6 x C3HejF1 (B6C3HF1) and B6 x SJLF1 (B6SJLF1) hybrids and monitored by splenomegaly, suppression of T-cell mitogen responses and the development of histopathological lesions in the thymus, liver and pancreas. Cells from donors depleted of non-specifically (poly I:C) induced ASGM1+ cells induced severe histological lesions, marked immunosuppression and splenomegaly in all three F1 hybrid combinations. When the donor cells were depleted of specifically induced (B6-anti-B6AF1) ASGM1+ cells and injected into the three F1 combinations they induced splenomegaly in all three but caused severe tissue injury and intense immunosuppression only in B6C3HF1 and B6SJLF1 mice and not in B6AF1 mice. Genetic analysis suggests that the H-2D (or a closely related) region of the H-2 complex plays an important role in the activation of the specific GVH effector cells. These results suggest that the cell(s) responsible for splenomegaly are different from the ones that cause severe GVH-associated tissue damage and immunosuppression although there may be cells and/or lymphokines common to both processes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Induction, specificity and elimination of asialo-GM1+ graft-versus-host effector cells of donor origin. 183 14

Injection of B10.D2 cells into irradiated H-2d compatible (DBA/2xB10.D2)F1 recipients provokes a lethal GVH that can be abrogated by donor preimmunization against host-specific DBA/2 non-H-2 antigens. To study the possible relationship between the observed protection and restoration of immune responsiveness, we compared spleen cellularity, selected T and B cell functions, and NK activity in GVH and protected mice during the 1st month after grafting. Normal and isografted mice served as controls. GVH was found to be characterized by an early stimulation phase associated with splenomegaly and increased percentages (but not numbers) of Lyt-2+ and L3T4+ cells, followed by profound aplasia and abrogation of IL-2 production. Response to a B cell mitogen (LPS) is depressed, and cells from GVH mice exert a strong suppressive effect on the LPS and PHA responsiveness of normal cells. Suppression appears to be mediated by a radioresistant, nylon nonadherent, asialo GM1 negative cell expressing a low level of Thy-1 antigen. In contrast, protection correlates with progressive restoration of spleen cellularity and LPS responsiveness, with decreased but clearly detectable IL-2 production, and transient nonspecific suppressor activity. The immune status of protected mice resembles that of isografted controls. No correlation was found between mortality (or protection) and either PHA responsiveness, which remained depressed in all grafted mice throughout the observation period, or NK activity, which was strongly depressed in both GVH and protected mice. In conclusion, protection correlates with the disappearance of nonspecific suppressor cells and the restoration of cellularity and certain nonspecific immune functions. Donor immunization against host-specific non-H-2 antigens, which protects against mortality, also protects against GVH-associated immune deficiency.
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PMID:Lethal graft-versus-host reaction against non-H-2 antigens. I. Prevention of GVH-associated immunodeficiency by preimmunizing the donor against host-specific non-H-2 antigens. 252 8

Spleen cell blastogenesis to mitogens and antibody responses to sheep erythrocytes (sRBC) were tested in BALB/c mice with experimental E. cuniculi infections. Blastogenesis responses of spleen cells 1 week post-infection were significantly lower than normal to T-cell mitogens (Con A and PHA) and were unchanged in response to B-cell mitogens (LPS and PWM). After 2 weeks post-infection, the responses to T cell mitogens returned to normal. Mixing spleen cells from 1-week infected mice with cells from uninfected mice failed to reveal the presence of suppressor cells. Antibody responses to sRBC were significantly slower to develop in 1 week-infected mice compared with uninfected mice or mice infected 2 weeks earlier or at the same time as sRBC challenge. Infected mice displayed splenomegaly which was most pronounced 1 week post-infection and the differential spleen cell counts revealed the presence of lymphoblasts. Lymphohyperplasia appeared to cause the splenomegaly. No shifts in the proportion of Thy 1.2+ T cells, Ig+ B cells, or esterase-positive macrophages were detected. These results indicate that the immune system in BALB/c mice is depressed early during E. cuniculi infections.
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PMID:Modulated immune responsiveness associated with experimental Encephalitozoon cuniculi infection in BALB/c mice. 297 36

The clinical, morphological, immunological and molecular features of seven patients with a stable picture of chronic granular lymphocytosis, observed over a period of up to 4 years, were studied. Mild splenomegaly was detected in one patient, while lymphoadenopathy and hepatomegaly were absent. Surface marker analysis showed in five patients the common membrane phenotype of granular T-cell lymphocytosis (T3+, T4-, T8+, Leu-7+); of the remaining two, one presented an unusual phenotype (T3+, T4+, T8+) and the other showed a marked positivity with the Leu-11 and M1 monoclonal antibodies, but lacked the T3, T4, T8 antigens. Three cases had a low (less than 30%) expression of the T1 antigen. Functional studies showed that the proliferative response to PHA and the NK function were reduced in four of the seven cases. Molecular analysis, performed in six cases, revealed a monoclonal rearrangement of the T-cell receptor beta-chain gene in three, a polyclonal T-cell configuration in two and a germ-line arrangement in the last. All three monoclonal cases showed a depressed NK activity and two a reduced PHA response. The results of this study document the heterogeneity of granular lymphocyte expansions and suggest that the clonal or reactive nature of these often indolent proliferations, suspected on the basis of immunologic functional studies, may be recognized at the DNA level.
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PMID:Heterogeneity of large granular lymphocyte proliferations: morphological, immunological and molecular analysis in seven patients. 349 16

The authors have studied the case of a female patient with rheumatoid polyarthritis, who developed a lymphocytic proliferation in the blood, the marrow, and the liver, associated with a neutropenia. Several similar cases have been recently reported in the literature. The cellular proliferation is made of large granulous lymphocytes and the study of membrane markers enables to find the following homogeneous phenotype: E rosette+, CD8+, HNK-1+, FcR+, CD4-luminal diameter "divided by degrees - -, IgS-, HLA class II-. This lymphocytic sub-population produces little interleukin-2, responds weakly to mitogens (PHA, CON A, PWM), and inhibits the response of normal lymphocytes to the same mitogens. These lymphocytes have a weak natural killer activity but, on the contrary, develop a very strong cytotoxic activity which is antibody-dependent. Clinically, splenomegaly, anemia and infections are frequent and hepatomegaly or thrombopenia more rare. Adenopathies are never present. The evolution is chronic in nature and not very aggressive, although the lymphocytic proliferation is monoclonal in origin, as demonstrated in molecular biology studies. The neutropenia might be secondary to an inhibiting effect of lymphocytes on the granular precursors of the bone marrow. There is a definite association between this lympho-proliferative syndrome and rheumatoid polyarthritis, and this association appears to be different from the Felty's syndrome.
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PMID:[Characterization of chronic lymphocytic proliferation in a female patient having rheumatoid polyarthritis with neutropenia]. 361 55

Two homosexual men with the acquired immunodeficiency syndrome (AIDS) who developed a multicentric variant of angiofollicular lymph node hyperplasia (AFLNH) (Castleman's disease) and Kaposi's sarcoma are reported. Both had diffuse adenopathy, splenomegaly, and a systemic inflammatory state. Both had an absolute increase in Leu 1+ lymphocytes, which was associated with markedly decreased Leu 3+ lymphocytes, markedly increased Leu-2+ lymphocytes, and a very low Leu 3/2 ratio. The lymphocytes of both patients had a normal blastogenic response to PHA. The lymphocytes of patient 1 had a poor response to autologous or allogenic cells in the mixed lymphocyte culture reaction. AFLNH represents another lymphoreticular complication of AIDS. Given the interrelationships between AFLNH, the development of Kaposi's sarcoma, and the aggressive clinical course seen in our two patients and those in the literature, the aggressive use of lymph node biopsy may be an important prognostic tool for the patient with the acquired immunodeficiency syndrome.
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PMID:Multicentric angiofollicular lymph node hyperplasia (Castleman's disease) followed by Kaposi's sarcoma in two homosexual males with the acquired immunodeficiency syndrome (AIDS). 387 3

The results of immunological and purine enzyme investigations in an adult male patient with common variable immunodeficiency, recurrent lymph node granuloma and splenomegaly are presented. Serum immunoglobulins were present in trace amounts only and a progressive loss of Ig-bearing peripheral lymphocytes were demonstrated. Furthermore, the mitogenic responses to PHA. ConA and PWM were markedly reduced and the ratio of T.m/T.g cells was decreased. Finally, a combined deficiency of lymphocyte purine 5-nucleoside phosphorylase was demonstrated in the patient.
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PMID:Common variable immunodeficiency and purine nucleotidase and nucleoside phosphorylase deficiency. A case report. 626 34

Splenic responses of CBA/J mice infected with 250 embryonated ova of the nematode, Toxocara canis were characterized during the first month post-inoculation (P.I.). By the 6th day of infection, spleen to body weight ratios were over 3.5 times greater in infected mice than uninfected controls. This ratio peaked at 5.0 on day 14 and declined slightly by day 36 P.I. Lymphocyte transformation studies were carried out using the T cell mitogens, Con A and PHA and the B mitogen, LPS. The responses of infected mice to all of the mitogens were greater than or equal to the responses of uninfected mice at all times studied. Unstimulated lymphocytes from infected mice spontaneously incorporated approximately 10-fold more 3H-TdR than did uninfected control mice during the first 2 weeks of infection. Antigen-specific lymphocyte transformation was also performed using a crude extract of homogenized embryonated ova (TEE) as the antigen. Positive responses were obtained at all times examined but were greatest during the first 2 weeks of infection. The T cell basis of this response was demonstrated by Anti-Thy 1.2 plus complement treatment prior to the initiation of the lymphocyte transformation assay. Collectively, these results suggest that in mice, T. canis elicits a striking splenomegaly as early as 1 week after oral inoculation. The lymphocyte transformation studies suggest that the splenomegaly may be due in large part to proliferation of the white pulp based on the amount of spontaneous labelling observed. Increased mitogenic responses indicate that T. canis does not elicit nonspecific immunosuppression and the positive response to the TEE antigen suggests that at least some of the lymphoproliferation is antigen specific.
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PMID:Spleen cell responses in experimental murine toxocariasis. 633 50

In vivo and in vitro T lymphocyte function was studied in 64 patients with X-linked and common "variable" primary hypogammaglobulinaemia. Lymphopenia, splenomegaly, depressed in vitro lymphocyte transformation to mitogens and failure to manifest delayed hypersensitivity skin reactions occurred frequently in the common "variable" group, particularly those with adult onset disease. However, relative circulating T lymphocyte numbers and in vitro lymphocyte transformation in a mixed lymphocyte reaction with the CLA4 lymphoid cell line were normal. Antibody mediated and PHA induced lymphocytotoxicity were also normal. These findings indicate the presence of a generalised lymphocyte defect which is selective for certain T lymphocyte functions. Despite these apparent T lymphocyte defect, none of the patients suffered from the unusual opportunistic parasitic, viral or fungal infections which tend to occur in infants with severe primary defects of both T and B lymphocytes.
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PMID:Cellular immunity in primary hypogammaglobulinaemia: evidence for a generalised lymphocyte defect in some patients with "common" variable hypogammaglobulinaemia. 697 57

A 70-year-old woman was admitted to our hospital in November 1992 for evaluation of anemia. Physical examination revealed anemia, jaundice, swelling of axial and inguinal lymph nodes, and splenomegaly. Abnormal hematological findings were as follows: Hb of 3.9 g/dl, reticulocyte count of 58.2% (61.7 x 10(4)/microliters), hyperplasia of normal erythroblasts in bone marrow, and eosinophilia (21.0%, 2352/microliters) in peripheral blood. Routine laboratory examinations revealed polycolonal hypergammaglobulinemia 3.0 g/dl, a high level of serum LDH (797 IU/I) and a total bilirubin of 2.4 mg/dl (indirect, 1.6 mg/dl). The serum haptoglobin level was very low (< 5 mg/dl). Results of serological examinations were as follows: IgG of 3366 mg/dl, CH50 of 16.0 U/ml, positive Coombs test 2+, and positive tests for antinuclear antibody, rheumatoid factor, and cold agglutinin. CRP was negative. PHA-stimulated lymphocyte blast formation, NK activity, and ADCC activity were found to be suppressed, and the percentage of CD4-positive lymphocytes in peripheral blood was also low. An axillary lymph node biopsy revealed reactive lymphadenitis. No signs or history suggested allergy, collagen disease, or parasitic infection. Autoimmune hemolytic anemia (AIHA) complicated by immunologic abnormalities and eosinophilia was diagnosed. Oral prednisolone markedly reduced the hemolytic anemia, eosinophilia, lymph node swelling, and splenomegaly, but NK activity remained low.
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PMID:[Autoimmune hemolytic anemia with eosinophilia in elderly patient]. 892 99


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