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)

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

The L-selectin mediated adhesion of freshly isolated peripheral blood mononuclear cells (PBMCs) to phosphonomonoester core polysaccharide (PPME) and fucoidin derivatized gels was investigated in seven cases of monoclonal lymphocytosis of undetermined significance (B-MLUS) and 12 cases of chronic lymphocytic leukaemia: B-CLL, patients with peripheral lymphocytosis (LY-patients), lymph node enlargement (LN-patients) and splenomegaly (SM-patients). PBMCs isolated from the peripheral blood of 10 healthy donors served as controls. The binding to PPME and fucoidin correlated well (n = 19, P = 0.01). Adhesion of PBMCs from B-MLUS and B-CLL showed a greater variability than controls. A higher number of cells, on average, bound to PPME and fucoidin derivatized polyacrylamide gels in B-MLUS than in B-CLL. However, the differences observed were not statistically significant. In four cases with B-CLL, the stimulatory effect of interferon-alpha on the function of L-selectin and some other accessory molecules was also studied. The increased binding of PBMCs to immobilized analogue molecules (PPME, fucoidin) and to high endothelial venules (HEVs) in the in vitro HEV-binding assay supports the notion that interferon-alpha not only increases the expression of the adhesion molecules, but also results in an enhanced adhesive function.
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PMID:Expression of an adhesion molecule and homing in B-cell chronic lymphocytic leukaemia: II. L-selectin expression mediated cell adhesion revealed by immobilized analogue carbohydrates in B-cell chronic lymphocytic leukaemia and monoclonal lymphocytosis of undetermined significance. 816 54

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), "normal" sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58; P = .03). Moreover, patients with "increased" sL-selectin levels (>/=3.12 microgram/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 microgram/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis.
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PMID:Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia. 978 46

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

Lymphocyte trafficking in the gastrointestinal tract is primarily mediated by interactions with the mucosal addressin cell adhesion molecule 1 and its lymphocyte ligand, alpha(4)beta(7), and partly by L-selectin (L-Sel) interactions with peripheral node addressin coexpressed on some mucosal addressin cell adhesion molecule 1. We inquired whether intestinal responses in mice lacking L-Sel would be enhanced. L-Sel-deficient (L-Sel(-/-)) mice were orally immunized with either Salmonella vaccine vector or Salmonella vector-expressing colonization factor Ag I (CFA/I) from enterotoxigenic Escherichia coli. In L-Sel(-/-) mice, mucosal IgA anti-CFA/I fimbrial responses were greatly reduced, and systemic IgG2a anti-CFA/I fimbrial responses were 26-fold greater compared with C57BL/6 (L-Sel(+/+)) mice. L-Sel(-/-) Peyer's patch (PP) CD4(+) Th cells revealed IFN-gamma-dominated responses and an unprecedented absence of IL-4, whereas the expected mixed Th cell phenotype developed in L-Sel(+/+) mice. PP CD4(+) Th cell anti-Salmonella responses were nearly nonexistent in L-Sel(-/-) mice immunized with either Salmonella vaccine. Splenic CD4(+) Th cell anti-Salmonella responses were reduced but did show cytokine production in Ag restimulation assays. Increased colonization of PP and spleen was noted only with the Salmonella vector in L-Sel(-/-) mice, resulting in increased splenomegaly, suggesting that the Salmonella-CFA/I vaccine was not as infectious or that the presence of the fimbriae improved clearance, possibly because of reduced neutrophil recruitment. However, sufficient anti-Salmonella immunity was induced, because Salmonella vector-immunized L-Sel(-/-) mice showed complete protection against wild-type Salmonella challenge, unlike L-Sel(+/+) mice. This evidence shows that L-Sel is important for development of mucosal immunity, and absence of L-Sel is protective against salmonellosis.
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PMID:Impaired mucosal immunity in L-selectin-deficient mice orally immunized with a Salmonella vaccine vector. 1141 77

To study the relationship between the level of the soluble L-selectin (sL-selectin) in plasma and surface L-selectin expression on leukemic cells and episode and state of illness in acute leukemia patients, the plasma level of sL-selectin was measured by a sandwich enzyme-linked immunosorbent assay, and the expressions of surface L-selectin and its gene (lyam-1) were detected by immunohistochemistry and RT-PCR. The results showed that the levels of sL-selectin were significantly higher in untreated and therapy-resistant acute leukemia patients, and expression of L-selectin mRNA and cell surface L-selectinin in untreated and NR patients were significantly lower than that in CR patients and control group (P < 0.05). The plasma levels of sL-selectin were significantly increased in patients with splenomegaly and hepatomegaly (extramedullary infiltration). The levels of sL-selectin were related to the clinical course of the acute leukemia patients. A significant correalation existed between expressions of L-selectin mRNA and surface L-selectin in acute leukemia patients (gamma = 0.782, P < 0.05). It is concluded that expression of L-selectin gene was down-regulated in level of mRNA and protein in acute leukemia patients and both changes were highly correlated. Monitoring of the plasma level of sL-selectin is possibly useful for early diagnosis of relapse and extramedullary infiltration in acute leukemia.
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PMID:[Study on expression of cell surface L-selectin and soluble L-selectin in patients with acute leukemia]. 1284 6