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

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
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PMID:Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells. 168 36

Cell adhesion molecules (CAMs) are cell surface proteins with unique specificities that allow intercellular adhesion. The importance of CAMs for normal lymphocyte growth and differentiation is underscored by the association between neoplastic disease states and abnormal CAM expression. In the present study we analysed the cell surface expression of several CAMs on peripheral blood lymphocytes from patients with progressive chronic lymphocytic leukemia of B-cell type (B-CLL) (n = 21) and stable monoclonal B-lymphocytosis of undetermined significance (B-MLUS) (n = 20). The CAM expression was analysed on the B-cell clone and on normal T- and NK-cell populations separately using monoclonal antibodies (MAbs). A phorbol ester-induced lymphocyte aggregation assay and blocking MAbs were also used. The B-cell clone in B-CLL expressed ICAM-1 (CD54) more frequently and at a higher density than in B-MLUS. The brightest CD54 expression was noted in patients with prominent lymphadenopathy and/or splenomegaly. The beta 2 integrin CD11a (Leu-CAMa, LFA-1) was detected on some B-cell clones and seemed to relate to tissue localization of the disease. T and NK cells showed a low expression of CD11a in B-CLL patients, while in B-MLUS a high proportion of non-clonal cells coexpressed CD11a with a high staining intensity. The relative numbers of both CD18+ as well as CD2+ cells showed a positive correlation with phorbol ester induced cell aggregation in B-MLUS patients (p < 0.05). The aggregation was blocked by adding MAbs against CD18 in most cases but to a greater extent in B-CLL. These results extend and corroborate our earlier findings on surface phenotypic characteristics of clonal and non-clonal lymphocytes in different clinical subtypes of B-CLL. CAM expression on the monoclonal lymphocytes may play a role in their interaction with regulatory immune cells and their tissue localization.
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PMID:Expression of adhesion molecules CD11/CD18 (Leu-CAMs, beta 2-integrins), CD54 (ICAM-1) and CD58 (LFA-3) in B-chronic lymphocytic leukemia. 751 9

Expression of surface adhesion molecules of the Ig superfamily (CD54 and CD58), of the integrin family (beta 1, beta 2, and beta 3 chains), of the selectin family (L-selectin), and of the lymphocyte homing receptor (CD44) was analyzed on B-cell chronic lymphocytic leukemia (B-CLL) cells from 74 patients. The aim of the study was the definition of phenotypically distinct disease subsets and the correlation of adhesion molecule phenotypes with clinical parameters. Expression of CD58 on B-CLL cells defined more advanced disease stages. In comparison with beta chain-positive cases, patients whose cells did not express beta 1, beta 2, and beta 3 integrin chains fell into the most favorable prognostic group, with lower lymphocytosis and the absence of splenomegaly, diffuse bone marrow infiltration, and therapy requirement. A novel finding was the expression of beta 3 chains on cells from a minority (12 of 74) of B-CLL cases. beta 3 chains were always coexpressed with beta 1 and beta 2 chains. Two-color immunofluorescence analyses of adhesion molecules such as alpha x beta 2 integrin (LeuM5) and L-selectin (Leu8) showed that these markers were detectable on variable proportions of leukemic cells, thus confirming the intraclonal phenotypic heterogeneity of B-CLL. Differences in the intensity of CD44 expression were also shown among the various B-CLL clones. Finally, no major variations were shown by comparison of adhesion molecule phenotypes of leukemic cells simultaneously obtained from blood and bone marrow, and of CD5+ versus CD5- clones.
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PMID:Adhesion molecule expression on B-cell chronic lymphocytic leukemia cells: malignant cell phenotypes define distinct disease subsets. 768 26

In this study, we examined expressions of several adhesion molecules (AdMs), i.e. leukocyte function antigen-1 (LFA-1: CD11a/CD18), Hermes homing receptor (CD44) and intercellular adhesion molecule-1 (ICAM-1: CD54), on leukemia cells from 51 adult patients with newly diagnosed acute myeloid leukemias (AMLs) to elucidate clinical significance of these AdM expressions. Those expressions in lymphoid malignancies have been correlated with tumor evolutions, but CD44 was detected in all the AML cases examined and CD54 expression did not associate with their clinical characteristics or outcomes. However, we found that LFA-1 expressions significantly correlated with splenomegaly, resistance to induction chemotherapies and short survival periods in AML patients.
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PMID:Clinical significance of LEA-1 expression in adult acute myeloid leukemia. 864 44

To investigate whether expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in childhood acute lymphoblastic leukaemia (ALL) has an impact on the biological behaviour of the disease, we evaluated 751 children of the ALL-BFM 90 trial with B-cell precursor- (n = 677) or T-cell-ALL (n = 74) for CD54 expression within immunological subgroups, its correlation to certain clinical features, and therapy outcome. The highest percentage of patients expressing CD54 was found in common- and pre-B-ALL (76.1% and 61.4%, respectively). There was intermediate expression in pre-pre-B-ALL (47.8%), and the lowest expression was detected in T-ALL (12.2%). A significant positive correlation could be demonstrated between low CD54 expression (< 20% stained blasts) and high peripheral leucocyte counts, central nervous system (CNS) involvement, and splenomegaly at the time of diagnosis (P < 0.01). In addition, CD54 expression was a favourable but not independent prognostic factor. Event-free survival estimate at 4.5 years was 86% for CD54+ patients (n = 463), compared with 78% for CD54- patients (n = 241) (P < 0.01). These findings demonstrate that CD54 expression has an impact on dissemination patterns and outcome of childhood ALL, and emphasizes the potential relevance of adhesion mechanisms in influencing clinical characteristics and prognosis of haematological malignancies.
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PMID:Expression of intercellular adhesion molecule 1 (ICAM-1) in childhood acute lymphoblastic leukaemia: correlation with clinical features and outcome. 902 17

Mice with chronic graft-versus-host disease (GVHD), induced by injection of DBA/2 lymphocytes in (C57BL10*DBA/2) F1 hybrids, develop a syndrome resembling systemic lupus erythematosus (SLE) with immune complex glomerulonephritis. In this model we evaluated the role of interactions between CD11a (LFA-1alpha) and CD54 (intercellular adhesion molecule-1 (ICAM-1)) molecules on leucocytes in the development of renal disease in systemic autoimmunity. Two weeks after induction of GVHD, when anti-nuclear autoantibodies were detected in the circulation and immune complexes had formed in the glomeruli, mice were injected twice per week with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle PBS, or with control rat IgG. MoAb treatment significantly lowered albuminuria and increased survival compared with control mice with GVHD. In the glomeruli of MoAb-treated mice there was markedly less binding of immunoglobulin and C3, while anti-renal tubular epithelium autoantibodies, but not anti-glomerular basement membrane autoantibodies, were significantly lowered in the circulation 4 weeks after disease induction. In addition, MoAb treatment inhibited the glomerular influx of CD11a+ cells and decreased development of histological abnormalities in the kidneys. Both rat IgG- and MoAb-treated mice developed anti-rat immunoglobulin antibodies. Furthermore, a marked splenomegaly with an increase of the T cell compartment was observed in MoAb-treated mice with GVHD. These results show that CD11a/CD54 interactions are crucial for the full-blown development of lupus nephritis in this model. Treatment aimed at blocking the activity of these molecules profoundly attenuated the development of renal disease in chronic GVHD even if started when first symptoms of SLE (i.e. anti-nuclear autoantibodies in sera and glomerular binding of immunoglobulins) were already detectable.
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PMID:Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies. 915 6

The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice. ISIS 3082 was specifically designed to inhibit murine ICAM-1 and was included in this study to evaluate the effects of prolonged ICAM-1 inhibition. The oligonucleotides were administered by bolus i.v. injection (via tail vein) every other day for 27 days (14 doses) at dose levels of 0, 0.8, 4, 20, and 100 mg/kg per injection ISIS 2302 or 20 mg/kg per injection ISIS 3082. The basic group size consisted of 10 male and 10 female mice, which were sacrificed 2 days after the last dose and an additional 5 mice per sex in vehicle control and 100 mg/kg ISIS 2302 dose groups, which remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, and there were no effects of either oligonucleotide on body weight gain or food consumption. The most common changes observed in this study included a mixed mononuclear cell infiltrate seen in a number of organs or tissues, splenomegaly, and lymphoid hyperplasia at dose levels of > or = 20 mg/kg ISIS 2302. In the group that received the highest dose level of ISIS 2302 (100 mg/kg), there were alterations in serum chemistry parameters that appeared to be related to perturbations in the liver, including 3- to 4-fold increases in aspartate and alanine aminotransferase and smaller changes in bilirubin, alkaline phosphatase, cholesterol, triglycerides, and albumin levels. Treatment-related effects on hematologic parameters were limited to the 100 mg/kg ISIS 2302 dose group and included slight monocytosis and thrombocytopenia. None of the effects observed appeared to be life threatening. Complete or partial reversal of all effects was evident in the remaining high-dose ISIS 2302 animals at the end of the 4-week recovery period. Comparison of the effects produced by the same dose level (20 mg/kg) of ISIS 2302 and ISIS 3082 did not reveal any differences that could be attributed to exaggerated pharmacology. In conclusion, treatment-related alterations were observed primarily at the 100 mg/kg dose level, including immune stimulation and hepatic alterations, which were partially reversed following a 4-week treatment-free period.
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PMID:Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice. 936 6

CVID is immunologically characterized by defective antibody production. Various additional immunological abnormalities have been reported, but little is known of the role of adhesion molecules in CVID. In 31 CVID patients serum levels of L-selectin (CD62L), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54) were significantly elevated compared with controls. In 15 CVID patients investigated, the number of L-selectin-positive cells was significantly reduced in both CD4+ and CD8+ lymphocytes compared with controls, and these changes were observed in both CD45RA+ and CD45RO+ subsets. In CD19+ lymphocytes the percentage of ICAM-1+ cells was significantly increased compared with controls. Fifty percent of the patients had splenomegaly. These patients demonstrated even higher serum levels of adhesion molecules, a lower percentage of L-selectin-positive and a higher percentage of CD38+ cells in many T lymphocyte subsets compared with both other CVID patients and controls. Finally, in this patient group the percentage of L-selectin-positive CD19+ lymphocytes was significantly reduced compared with both other patients and controls. These findings indicate a state of ongoing T lymphocyte activation in CVID, especially in the subgroup of patients with splenomegaly, which may contribute to the impaired antimicrobial defence observed in these patients.
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PMID:Adhesion molecules in common variable immunodeficiency (CVID)--a decrease in L-selectin-positive T lymphocytes. 982 85

In B-chronic lymphoproliferative disorders (B-CLD) adhesion molecules (AM) have been investigated in order to explain the variable biologic behavior and dissemination patterns and to assess their contribution to the differential diagnosis and prognosis of these diseases. The main AM studied either by immunohistochemistry on lymph node sections or by flow cytometry in blood and bone marrow specimens are L-selectin, CD11a/CD18 (LFA-1), CD54 (ICAM-1), CD44 (HCAM), CD11c/CD18 (gp150/95), and CD49d/CD29 (VLA-4). Among B-CLD, hairy-cell leukemia (HCL) and follicular lymphoma (FL) show a uniform AM expression pattern. Thus, HCL is characterized by high CD54, CD44, VLA-4, CD11c, and CD18 and by low or absent CD11a and L-selectin, whereas FL confined to the lymph nodes is characterized by high CD11a, CD18, and CD54 expression. Diffuse growth and dissemination of FL is associated with alteration in the AM profile. Mantle-cell lymphoma (MCL) seems to be characterized by low or absent L-selectin and CD11c and high CD54 expression, especially compared with B-chronic lymphocytic leukemia (B-CLL). B-CLL is the most heterogeneous among all B-CLD with respect to AM expression. In general, low LFA-1 and CD54, high L-selectin and CD44, and variable CD11c characterize B-CLL. Cases with splenomegaly as their prominent feature bear high CD11a, CD18, CD29, and CD11c on the surface of the leukemic cells. Small lymphocytic lymphoma (SLL) shares the same AM phenotype with B-CLL, with the possible exception of LFA-1, which is strongly expressed on SLL cells. LFA-1 and CD54 are more frequently positive in lymphoplasmacytic lymphoma (LPL) as compared with B-CLL. Splenic lymphoma with villous lymphocytes differs from B-CLL by its high LFA-1, VLA-4, and CD54 and low L-selectin expression, whereas its high LFA-1 positivity can differentiate it from HCL. Surface and soluble AM have been investigated as possible prognostic markers in these diseases. Conflicting data exist concerning the prognostic significance of surface AM. However, high soluble (s)CD44 and CD54 levels in B-CLL and non-Hodgkin's lymphomas (NHL) are considered as adverse prognostic factors.
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PMID:Adhesion molecules in B-chronic lymphoproliferative disorders. 1031 87

Murine syngeneic pregnancy is characterized by the transient splenomegaly at mid gestation. Recent studies from our laboratory have indicated the initiation of T-cell dependent B-cell response in the spleen during early pregnancy (Hegde and Nainan 1998). Present studies were carried out to understand the role of cell adhesion and MHC class II (Ia) molecules in the induction of Th-2 type of response in the spleen of pregnant mouse. Immunochemical localization of ICAM-1, LFA-1, Mac-1 and Ia in spleen have been carried out at different stages of pregnancy and formation of cell clusters and natural cell adhesion assay with splenocytes were carried out on day 1 (D1) pregnancy and compared with control. Upregulation of ICAM-1, LFA-1, Mac-1 and Ia was observed during early pregnancy. This coincided with the formation of germinal centers (GC) and Th2 type of interleukins in spleen as reported earlier. Increased expression of cell adhesion and Ia molecules during early pregnancy provides additional evidence for the systemic shift to Th2 type of immune response in syngeneic murine pregnancy.
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PMID:The role of LFA-1, Mac-1, ICAM-1 and Ia in the induction of Th-2 type of immune response in spleen during murine syngeneic pregnancy. 1084 94


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