Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the molecular mechanisms accounting for hemodialysis-induced neutropenia, the regulation of plasma membrane expression of leukocyte adhesion glycoproteins was investigated by both flow cytometry and immunoprecipitation techniques. The members of the LFA family of integrins, Mac-1/Mo1 (CD11/CD18) and gp150/95 (CD11c/CD18), involved in adhesion of myeloid cells to endothelia and other substrates, were found to be overexpressed on the plasma membrane of neutrophils from patients undergoing hemodialysis with a Cuprophane dialyzer, whereas no change was observed in the expression of LFA-1 (CD11a/CD18). By contrast, dialysis with Cuprophane membranes, as well as in vitro treatment with different activating agents, induced a downregulation on the expression of both the Leu-8/LAM-1 antigen, the human neutrophil peripheral lymph node homing receptor, and the CD43 major sialoglycoprotein involved in leukocyte homotypic adhesion. Kinetics studies showed that these up- and downregulatory processes of antigen expression occur very rapidly, correlating with maximal neutropenia. Recovery of initial levels of expression of CD11b/CD18 and Leu-8/LAM-1 adhesion molecules was observed after one hour of hemodialysis. However, the basal expression of CD43 was not restored by that time. The coordinated upregulation of CD11b and CD11c and downregulation of LAM-1 and CD43 adhesion receptors provide molecular mechanisms for understanding leukoaggregation, adherence to endothelia, and extravasation of neutrophils ultimately leading to the hemodialysis-induced neutropenia.
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PMID:Differentially regulated cell surface expression of leukocyte adhesion receptors on neutrophils. 176 94

Chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) are differentiated B-cell leukemias with well-described clinical, morphologic, and immunologic characteristics. We encountered two patients with indolent chronic B-cell leukemia showing overlapping features of these malignancies. The patients had progressive splenomegaly, minimal lymphadenopathy, and abnormal lymphoid cells with abundant cytoplasm and villi, which were strongly positive for surface antigens CD22 and CD11c, features associated with HCL. However, blood counts showed lymphocytosis without neutropenia and monocytopenia, and the bone marrow biopsies demonstrated tightly aggregated nodules of lymphocytes. In addition, the lymphoid cells were dual positive for CD19 and CD5, displaying weak-to-moderately positive monoclonal surface immunoglobulin, findings strongly suggestive of CLL. One patient failed to respond to therapy with chlorambucil and prednisone. The second patient showed a partial response to treatment with 2-chlorodeoxyadenosine. We compare our patients with similar variants of differentiated B-cell leukemias reported in the literature, including disorders described as hairy cell variant (HCL-V) or splenic lymphoma with villous lymphocytes (SLVL).
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PMID:CD5+ chronic B-cell leukemia with features intermediate to chronic lymphocytic leukemia and hairy cell leukemia. 752 21

In order to see whether leucocyte-derived adhesion molecules are involved in ischaemia and reperfusion, the total and differential leucocyte counts and expression of the LFA complex i.e. CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p 150,95) were monitored before and after standard cold and heat tests in 8 females with Raynaud's Disease and 8 matched controls. All patients suffered from vasoconstriction during the cold test which, compared with controls, was associated with fewer granulocytes expressing significantly more CD11b/CD18 (Mac-1) integrin and a significant degree of neutropenia persisting during reperfusion. Leucocyte-endothelial adhesive interactions may therefore occur during ischaemia and reperfusion.
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PMID:Neutrophil-derived adhesion molecules in human digital ischaemia and reperfusion. 779 48

This ex vivo study determined the expression of leucocyte adhesion receptors for endothelial adhesion molecules in 10 patients with peripheral arterial occlusive disease (PAOD) and in 10 healthy controls before and after treadmill exercise. Granulocytes from venous blood samples were separated on a Ficoll-Hypaque gradient and the phenotypical expression of CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) was observed by double indirect immunofluorescence using specific monoclonal antibodies. The total and differential white blood cell counts were monitored before and after exercise. In the PAOD patients a significant reduction in the number of granulocytes expressing CD11b/CD18 (Mac-1) and CD11c/CD18 (p150,95) associated with a significant neutropenia was observed after exercise, suggesting that leucocyte-endothelial interactions occur during ischaemia.
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PMID:Human leucocyte-endothelial interactions in peripheral arterial occlusive disease. 818 9

The purpose of this study was to compare two different in vitro culture conditions for the preservation of human granulocytes. These cells could be used in patients with severe neutropenia following cytotoxic chemotherapy if the functional capacity was retained, and autologous transfusions of granulocytes would circumvent the risk of alloimmunization. Granulocytes were obtained from the peripheral blood of healthy donors and patients with hematologic malignancies who received cytotoxic chemotherapy supported by recombinant human granulocyte colony-stimulating factor (R-metHuG-CSF, 300 micrograms/day, s.c.). Granulocytes were either cultured for 72 h at 4 degrees C in the presence of 100 ng/ml G-CSF or cryopreserved at -196 degrees C. The viability, surface antigen expression, and function of the granulocytes were assessed. Since effective microbial killing involves the attachment of granulocytes to blood vessel walls, transmigration into tissues, chemotaxis, and phagocytosis, the surface expression of the adhesion molecules LFA-1 (CD11a/CD18) and gp 150,95 (CD11c/CD18) was measured. In addition, the IgG receptors Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16), as well as the complement receptor CR3 (CD11b/CD18), were assessed. Dynamic superoxide anion release served as a measure of the metabolic pathway of the oxidative burst after f-Met-Leu-Phe (fMLP) and phorbol-12-myristate-13-acetate (PMA) stimulation. Substantial differences in the preservation of granulocyte integrity and function were observed between the two storage conditions. Cryopreservation abolished reactivity to extracellular stimuli and severely affected the cell phenotype. On the other hand, functional activity could be maintained for up to 72 h when in vivo primed granulocytes of patients were incubated at 4 degrees C in the presence of G-CSF. This storage modality may permit the use of granulocyte autotransfusion to reduce the risk of neutropenic fever.
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PMID:Granulocytes harvested following G-CSF-enhanced leukocyte recovery retain their functional capacity during in vitro culture for 72 hours. 887 10

Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.
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PMID:Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation. 919 Oct 1

The effects of intravenous injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on circulating neutrophil numbers, pulmonary vascular permeability, and morphologic changes in the lung were examined in rabbits. Intravenous injection of rhG-CSF caused a rapid, profound neutropenia due to neutrophil sequestration primarily within capillaries but also in larger microvessels of the lungs. Examination of neutrophil deformability using microfilters revealed that granulocyte colony-stimulating factor (G-CSF) treatment caused a rapid stiffening of neutrophils through the polymerization of F-actin but not microtubule assembly. The expression of CD11b, CD11c, and CD18 on human neutrophils after G-CSF treatment increased, but CD11a did not. Intravenous injection of rhG-CSF did not induce neutrophil emigration or albumin leakage into alveolar space, wet/dry lung weight ratios were unchanged, and no pathologic changes in lung histology were observed. These studies indicate that injection of rhG-CSF caused a rapid neutropenia and neutrophil sequestration in the lungs that is likely to be mediated through a G-CSF-induced decrease in neutrophil deformability, although neutrophil-endothelial cell adhesion may also play a role. However, this G-CSF-induced neutrophil sequestration did not induce a massive lung injury.
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PMID:Granulocyte colony-stimulating factor induces neutrophil sequestration in rabbit lungs. 965 Nov 93

The initiation of hemodialysis using cuprophane membranes is followed by a rapid fall in the circulating neutrophil count. This neutropenia is caused by a transient sequestration of neutrophils in the lung due to homotypic aggregation, largely in response to generation of C5a by contact of plasma with the dialyzer. The transient nature of hemodialysis neutropenia is due to desensitization of neutrophils to stimulation by C5a, thus demonstrating desensitization in vivo. To examine the in vivo effects on surface phenotype of continuous exposure of neutrophils to C5a over 3 h, the surface expression of 22 antigens was examined by flow cytometry in patients undergoing dialysis. Neutropenia was prominent at 15 min and absent at 60 and 180 min of dialysis. CD10, CD11b, CD11c, CD13, CD18, CD35, CD45, CD66acde, and CD66b were upregulated at 15 min and remained upregulated at 180 min. CD61 and CD63 increased slightly at 15 min and returned to baseline by 180 min. CD16 and CD62L were down regulated at 15 min and normalized by 180 min. CD15s, CDw17, CD32, and CD44 were slightly down regulated at 15 min and then returned to baseline by 180 min. CD11a, CD15, CD24, CD31, and CDw65 did not change during dialysis. This study demonstrates the changes in surface phenotype of neutrophils during prolonged in vivo exposure to C5a over 3 h, during which time neutrophils become desensitized to subsequent stimulation by similar concentrations of C5a but maintain responsiveness to other chemotactic stimuli.
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PMID:Changes in neutrophil surface phenotype during hemodialysis. 982 71

We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.
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PMID:Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin. 1211 71

Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobulin gene rearrangements and express monoclonal surface immunoglobulin of either IgG or multiple heavy-chain isotypes. Treatment of hairy cell leukemia should be considered for symptomatic patients. It is indicated in patients with significant neutropenia, anemia, thrombocytopenia, symptomatic splenomegaly, constitutional symptoms due to hairy cell leukemia, or recurrent serious infections. Many treatments exist, including cladribine, pentostatin, interferon-alpha, splenectomy, rituximab (mabthera), and BL-22 immunotoxin.
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PMID:Hairy cell leukemia: an update. 1279 30


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