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)

A 24 year old male with a history of eczema, recurrent mild infections, and thrombocytopenia consistent with the Wiskott-Aldrich syndrome (WAS) presented with a mediastinal mass, generalized lymphadenopathy, splenomegaly, and severe thrombocytopenia. Studies of immune function including immunoglobulin levels and T-cell subsets were normal. Furthermore, his T lymphocytes proliferated normally in response to phytohemagglutinin, concanavalin A, and the combination of neuraminidase/galactose oxidase. However, their proliferative responses to anti-CD43 antibody and periodate were diminished, consistent with the clinical diagnosis of WAS. An initial inguinal lymph node biopsy surprisingly revealed Kaposi sarcoma. However, following splenectomy to increase the platelet count, biopsy of the mediastinal mass revealed T-cell large cell lymphoma. Studies of biopsied tissue for the presence of Epstein-Barr virus and cytomegalovirus were negative, as were studies of blood, including the polymerase chain reaction, for the presence of the human immunodeficiency virus (HIV). This is the first report of Kaposi sarcoma arising in a patient with a congenital immunodeficiency syndrome. Although Kaposi sarcoma can arise in the face of the severe immunosuppression that follows allograft transplantation and in patients infected with HIV, we postulate that longevity in the face of mild immunosuppression was the major factor in the development of Kaposi sarcoma in this patient.
 ...
PMID:Coincident Kaposi sarcoma and T-cell lymphoma in a patient with the Wiskott-Aldrich syndrome. 131 18

In this study, we compared small lymphocytic lymphomas with predominant lymphadenopathy with those with predominant splenomegaly and found differences in morphology and immunophenotype as well as clinical features. Cases with lymphadenopathy were characterized by widespread disease, CLL type morphology with proliferation centers, and a CD5, CD11c, CD23, CD43 positive, CD45Ro negative immunophenotype. Cases with predominant splenomegaly had more localized disease, a mantle zone pattern or a diffuse growth pattern without proliferation centers, and a CD5, CD11c, CD23, CD43 negative, and sometimes CD45Ro positive immunophenotype. CD45Ro (UCHL1) positivity and alkaline phosphatase staining were associated with a mantle zone growth pattern. Comparison with other small lymphocytic lymphoma subtypes indicated that each has its own specific immunophenotype.
 ...
PMID:Small lymphocytic lymphomas with predominant splenomegaly: a comparison of immunophenotypes with cases of predominant lymphadenopathy. 172 85

The term "plasmacytoid T-zone cells" has been used to describe distinctive cells that occur in clusters in the paracortex of some reactive lymph nodes. Recently, tumorous proliferations of these cells have been described in several patients with myelomonocytic leukemias. Neither the nature of these cells nor their relationship to myeloid leukemia has been conclusively established. We report the case of a 64-year-old woman with chronic myelomonocytic leukemia who developed lymphadenopathy that proved to be due to tumorous accumulation of plasmacytoid T-zone cells in the interfollicular regions of the lymph nodes. She underwent splenectomy because of symptomatic splenomegaly; the resected spleen also contained aggregates of plasmacytoid T-zone cells, in addition to extramedullary hematopoiesis. On treatment with busulphan and prednisone, the lymphadenopathy resolved and did not recur. The patient died 7 years later with blast transformation of her myelomonocytic leukemia and no recurrence of lymphadenopathy. The aggregates of plasmacytoid T-zone cells were architecturally and cytologically distinct from the leukemic infiltrates of myeloid cells in the spleen, and there was no evidence of differentiation of these cells into myeloid or monocytic cells. A panel of monoclonal antibodies on paraffin sections revealed no lineage-specific T- or B-cell markers (UCHL1-, L26-), and the plasmacytoid cells were positive for CD68 (KP1) and L60 (CD43), as well as faintly positive for 4KB5 (CD45RA) and MB1 (CD45R). They did not stain with antibodies to myeloid lineage antigens CD15, lysozyme, or myeloperoxidase. The combination of clinical, morphologic, and immunologic features of plasmacytoid T-zone cells in this case suggests that these cells may be of monocytic lineage but are not direct precursors of mature monocytic or granulocytic cells, and may not be part of the neoplastic clone in patients with myelomonocytic leukemia.
 ...
PMID:Plasmacytoid T-zone cell proliferation in a patient with chronic myelomonocytic leukemia. Histologic and immunohistologic characterization. 184 25

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.
 ...
PMID:Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease. 753 57

Leukosialin (also known as Ly48, CD43, and sialophorin) is a major cell surface sialoglycoprotein found on a variety of hematopoietically derived cells. The precise function of this molecule is poorly understood but it has been implicated in cell proliferation and intercellular adhesion. We developed a transgenic mouse model to assess leukosialin's function in vivo. Our approach was to alter mouse CD43 (mCD43) expression in the B-cell lineage where it is tightly regulated, by expressing it in peripheral B cells where it is normally absent. To drive expression of leukosialin in mature B cells, the immunoglobulin heavy chain enhancer was fused to the mCD43 gene. mCD43-immunoglobulin heavy chain enhancer transgenic mice display splenomegaly due to increased numbers of B cells. Transgenic B cells show a striking increase in their ability to survive in vitro compared to B cells from nontransgenic control mice. This prolonged survival is reflected in a decreased susceptibility to apoptosis. These observations suggest that mCD43 plays an important role in the regulation of B-cell survival. The alteration of the temporal expression, or "disregulation," of a gene in transgenic mice provides a general strategy for elucidating the in vivo role of other molecules involved in cell signaling and adhesion.
 ...
PMID:Disregulation of leukosialin (CD43, Ly48, sialophorin) expression in the B-cell lineage of transgenic mice increases splenic B-cell number and survival. 783 40

An indolent variant of splenic marginal zone lymphoma (SMZL) lacking massive splenomegaly has been described as an incidental finding in spleens removed for rupture or hypersplenism. We studied traumatically ruptured spleens with expanded marginal zones (MZs) to assess the incidence of occult monoclonal B-cell populations in this setting. Ninety-one ruptured or lacerated spleens removed from 1984 to 1995 were classified as to whether they had expanded MZs (> 12 cell layers thick). When available, paraffin-embedded, formalin-fixed tissue from cases with expanded MZs was examined for immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) and stained for CD20, CD43, and kappa and lambda light chains. Splenectomies were performed for blunt (70 patients) and penetrating (7 patients) trauma, surgical misadventure (13 patients), or spontaneous rupture (1 patient). There were 58 men and 33 women in our study, ranging in age from 17 to 87 years (mean, 40 yr). Average spleen weight was 183 g (range, 44-505 g). Twenty-seven (30%) of 91 patients had expanded MZs. There were no significant differences in age, sex, spleen weight, or reason for excision between those cases with and without MZ expansion. Germinal centers varied from absent to inactive to floridly reactive. Paraffin blocks were available in 24 cases; the 20 with amplifiable DNA were polyclonal by PCR. Follow-up was available for 25 of the 27 patients with expanded MZs (range, 1-85 mo; median, 6 mo); lymphoma did not develop in anyone, although one patient's spleen was morphologically suspicious for lymphoma, showing involvement of red pulp by MZ-type B-cells; PCR revealed a polyclonal pattern. This patient's 3-year follow-up revealed no evidence of lymphoma. Traumatically ruptured spleens with expanded MZs do not seem to harbor occult B-cell clones, as detected by PCR. Although a few cases of incidentally removed spleens have been reported to contain low-stage SMZL, this seems to be an infrequent event.
 ...
PMID:Ruptured spleens with expanded marginal zones do not reveal occult B-cell clones. 943 66

A 72-year-old man was referred to our hospital because of lymphadenopathy, splenomegaly, and leukocytosis. His WBC count was 54,300/microliter, with 89.6% atypical lymphocytes two to three times the diameter of red blood cells, cleaved nuclei, and one or two nucleoli. A lymph node specimen revealed a vaguely nodular pattern, and the diagnosis of mantle cell lymphoma (MCL) was made. The lymphoma cells appeared smaller and more mature than the leukemic cells. The phenotype of the peripheral blood and the lymph node cells was CD5+ CD10- CD19+ CD20+ and the same rearranged JH bands were detected, suggesting that their lymphocytes were of the same origin. In addition, the phenotype of the leukemic cells was CD23+ CD38+ CD43- CD44+ FMC-7+ micro+ chi+. Cytogenetic analysis revealed complex anomalies but not t(11; 14). Cyclin D1 protein was not detected. Because the lymphocyte morphology of the peripheral blood and lymph nodes was discordant, we speculated that variant large cells had proliferated mainly in the peripheral blood. The patient achieved a partial response after 6 courses of CHOP regimen, and was then placed on a COP regimen. He seemed to have MCL, but the following findings were unusual: marked lymphocytosis at initial presentation, discordant morphology, CD5+ CD10- CD23+ CD43- phenotype with neither t(11; 14) or cyclin D1 over-expression.
 ...
PMID:[Mantle cell lymphoma with marked lymphocytosis at the presentation and with discordant morphology between the lymph node and peripheral blood]. 979 5

A 73-year-old woman presented with abdominal pain, weakness, and weight loss. Pertinent medical history included myelofibrosis, severe anemia, and lumpectomy for breast cancer. Computed tomography showed marked splenomegaly and numerous soft tissue masses in the mesentery. Excisional biopsy of the mass showed an encapsulated tumor with yellow-tan nodular growth pattern. Microscopically, the tumor was characterized by the presence of bizarre giant cells in background of prominent dense fibrous stroma. The atypical giant cells were positive for FVIII antibody staining. Many other cells were positive for CD43 antibody staining, indicating that the tumor was hematopoietic in nature, so-called sclerosing extramedullary hematopoietic tumor. Extramedullary hematopoiesis is a common phenomenon associated with severe anemia of any cause. When associated with myelofibrosis, however, it has different morphology from extramedullary hematopoiesis of the other causes. The significance of recognizing sclerosing extramedullary hematopoietic tumor is that it is often mistaken for sarcomas and other malignant neoplasms, especially when the clinical history is unknown.
 ...
PMID:Sclerosing extramedullary hematopoietic tumor. 1208 30

The discovery of an unusual T-cell subset characterized by the expression of the alpha/beta T-cell receptor without expression of either CD4 or CD8 [alpha/beta-double-negative T cells (alpha/beta-DNTCs)] provided critical insights in the evaluation of a "new" lymphoproliferative disorder known as autoimmune lymphoproliferative syndrome (ALPS). ALPS is a disorder of defective Fas-mediated lymphocyte apoptosis, manifested by accumulation of alpha/beta-DNTCs and other lymphocyte subsets, leading to lymphadenopathy and splenomegaly, autoimmunity, and an increased risk of lymphoma. The expanded population of alpha/beta-DNTCs from ALPS patients has a remarkable uniform phenotype that is for the most part similar to alpha/beta-DNTCs from mice with defective Fas (lpr) or Fas ligand (gld). This is in contrast to the minor alpha/beta-DNTC compartment in healthy individuals that contains multiple, immunophenotypically distinct subpopulations. Current data indicate that alpha/beta-DNTCs from ALPS patients are derived from cytotoxic CD8(+) T cells, chronically activated in vivo but anergic in vitro. Their anergic state may be related to persistent modifications of O-linked carbohydrates on cell surface molecules, such as CD43 and CD45, as well as to the increased presence of interleukin-10. Although largely consistent with a model of (linear) CD8(+) cytotoxic T-cell differentiation, the expression patterns of certain surface molecules, such as CD27 and CD28, are not consistent with this model. This may be the result of the perturbed homeostasis of lymphocytes in ALPS, thereby revealing pathways of differentiation and immunophenotypes, including phenotypes pertaining to cell surface glycosylation that are hidden from view in healthy individuals.
 ...
PMID:A composite picture of TcR alpha/beta(+) CD4(-)CD8(-) T Cells (alpha/beta-DNTCs) in humans with autoimmune lymphoproliferative syndrome. 1213 44

In the World Health Organization classification system, splenic marginal-zone lymphoma (splenic MZL) is described as an indolent B-cell lymphoma, which generally presents as splenomegaly with involvement of the bone marrow and peripheral blood. Presence of disease in peripheral lymph nodes and extranodal locations is uncommon. Splenic MZL is characterised by micronodular infiltration of the spleen with marginal-zone differentiation; the immunophenotype is usually IgM+ IgD+/- cytoplasmic-Ig-/+ pan B antigens+ CD5- CD10- CD23- CD43-/+ cyclin D1-; and the most common genetic abnormalities are deletions at 7q22-7q32. Most patients with splenic MZL live for a long time but classic prognostic factors cannot distinguish between patients who are likely to have good and poor outcomes. However, immunological events, such as haemolytic anaemia and immune thrombocytopenia, or the presence of a monoclonal component, are significantly associated with shorter survival. Splenectomy is considered the first-line treatment of choice for splenic MZL; it results in only partial remission, but responses are generally sufficient for correcting cytopenia, improving quality of life, and increasing survival.
 ...
PMID:Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. 1257 51


1 2 3 Next >>