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)

Thrombocytopenia is common in sick preterm babies. Despite this, platelet production in thrombocytopenic preterm babies has rarely been assessed. To address this problem we have developed miniaturized assays to study circulating megakaryocyte (MK) progenitors [burst-forming unit (BFU)-MK and colony-forming unit (CFU)-MK], total cultured MK precursors and mature MK, by culturing mononuclear cells purified from 0.5-1 mL of preterm peripheral blood. MK lineage colonies and cells are identified by an anti-IIb/IIIa antibody (CD61). We prospectively studied circulating BFU-MK/CFU-MK, total cultured MK precursors and mature MK in 63 preterm babies (gestational age 24-34 wk). Twenty-six developed early thrombocytopenia (platelets < 150 x 10(9)/L by 48 h), whereas the remaining 37 babies maintained normal platelet counts. Twenty-one of the 26 thrombocytopenic babies were born to mothers with pregnancy-induced hypertension or were growth retarded. At birth, thrombocytopenic babies had severely reduced numbers of all MK precursors compared with nonthrombocytopenic babies: BFU-MK 82 +/- 50 versus 663 +/- 174 colonies/mL, mean +/- SEM; CFU-MK 596 +/- 196 versus 3267 +/- 530 colonies/mL; total MK precursors 97 +/- 30 versus 301 +/- 49 x 10(3) cells/mL and mature MK 8 +/- 2 versus 37 +/- 8 x 10(3) cells/mL, respectively. Thrombocytopenia resolved by d 10 in all babies accompanied or preceded by a recovery to normal numbers of circulating MK progenitors. Eighteen (69%) of the thrombocytopenic babies were also neutropenic (neutrophils < 2 x 10(9)/L); in these babies neutrophil progenitor cells (CFU-granulocyte/monocyte) were also severely reduced compared with the nonthrombocytopenic babies (539 +/- 280 versus 1937 +/- 348 colonies/mL, mean +/- SEM). This indicates that the principal cause of the thrombocytopenia and neutropenia is reduced platelet and neutrophil production occurring as a consequence of reduced numbers of MK and CFU-granulocyte/monocyte progenitors, respectively. Taken together these data suggest the hematologic abnormalities characteristic of newborns born to mothers with pregnancy-induced hypertension or with intrauterine growth retardation are a consequence of dysregulation of fetal hemopoiesis occurring proximal to committed MK and neutrophil progenitors, most likely at the level of the primitive multipotent hemopoietic stem cell.
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PMID:Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. 879 56

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

Complement activation, neutrophil stimulation, increased cellular adhesiveness, transient leukocyte margination and pulmonary leukostasis take place during hemodialysis with cellulosic dialysis membranes. Several investigators have hypothesized that complement activation is primarily responsible for the acute neutropenia occurring during the early phase of bio-incompatible hemodialysis. We have investigated the relationship between complement activation, levels of expression of CD11b and CD61 integrins on neutrophils and platelets, neutrophil counts and blood gas measurements in patients dialyzed with three types of membranes, known to activate the complement system to a different extent. Polysulfone, cellulose acetate and cuprophane membranes were used subsequently in six patients in a prospective cross-over trial design to reduce inter-individual variability. Increased levels of CD61 and CD11b, as well as neutropenia, were detected regardless of the type of membrane used. We observed a high inter-individual variation with regard to complement activation suggesting varying susceptibility to dialysis membranes. We also report that the kinetics of anaphylatoxin generation were dissociated from those of the upregulation of adhesion molecules, early neutrophil margination and decrease in PaO2 during the first 30 min of hemodialysis. Similar results were obtained with all three types of dialysis membranes. The data strengthen the hypothesis that factors other than complement are involved in the induction of dialysis-related neutropenia and hypoxemia.
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PMID:Dissociation between complement activation, integrin expression and neutropenia during hemodialysis. 1051 74

A new megathrombocytopenic syndrome with giant platelets in peripheral blood and severe thrombocytopenia was diagnosed in a 4-month-old boy. His clinical course included repeated hemorrhagic incidents leading to death at age 37 months. Bone marrow ultrastructural analysis revealed numerous dystrophic megakaryocytes with giant membrane complexes. Although these features were similar to those described for megakaryocytes in mice lacking the gene for transcription factor p45-NF-E2, no abnormalities in the p45-NF-E2 gene could be documented. Platelet membrane analysis showed a reduction in glycoprotein (GP) Ib, but normal content of GPIIb and GPIIIa. Analysis of genes encoding for GPIb alpha and beta, GPV, and GPIX ruled out the possibility that the observed platelet abnormality is a variant of Bernard-Soulier syndrome. A moderate neutropenia was associated with a complete lack of expression of sialyl-Lewis-X on the surface of polymorphonuclear neutrophils. A common defect in posttranslational modification of glycoproteins could account for the diverse cellular abnormalities.
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PMID:Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes--a new syndrome? 1115 7

A clinical goal for ex vivo expansion of cord blood (CB) CD34(+) cells is to shorten the period of neutropenia and thrombocytopenia following myeloablative therapy and transplantation. Prolongation of cytokine expansion leads to the production of greater numbers of cells, and should have an impact on neutrophil and platelet recovery. Furthermore, expansion of CD34(+) cells should support the continued production of neutrophils and platelets in the 6-week period following transplantation. We tested these hypotheses by characterization of the kinetics (human CD45(+) cells in the blood) and phenotype (CD45, CD34, CD61, CD33, CD19 and CD3) of human engraftment in the non-obese diabetic severe combined immunodeficient mouse (NOD-SCID) following 7 or 14 d of ex vivo expansion of CB CD34(+) cells. Mice transplanted with 14 d cells showed greater percentages of human CD45(+) cells in the blood, bone marrow and spleen than mice transplanted with unexpanded cells or 7 d cells. Prolonging cytokine exposure of CD34(+) cells and transplantation with increasing numbers of input cells facilitated the production of absolute numbers of CD34(+), CD33(+), CD61(+) and CD19(+) cells in vivo. Furthermore, analysis of SCID engrafting potential showed that prolongation of culture duration facilitates in vivo expansion of CD45(+), CD34(+) and CD19(+) cells after transplantation. It is anticipated that prolonged (2 weeks) ex vivo culture of CB will have a beneficial clinical effect.
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PMID:Prolonged ex vivo culture of cord blood CD34(+) cells facilitates myeloid and megakaryocytic engraftment in the non-obese diabetic severe combined immunodeficient mouse model. 1152 68

Patients with chronic idiopathic neutropenia (CIN) display relatively low peripheral blood platelet counts and hypo-lobulated megakaryocytes in the bone marrow (BM). The underlying pathogenetic mechanismswere probed by studying the reserves and clonogenic potential of BM megakaryocytic progenitor cells using flow-cytometry and a collagen-based clonogenic assay for the identification of megakaryocyte colony-forming units (CFU-Meg). Thrombopoietin (TPO) and transforming growth factor-beta1 (TGFbeta1) levels were also evaluated in long-term BM culture supernatants using an enzyme-linked immunosorbent assay. CIN patients (n = 39) showed a low proportion of BM CD34(+)/CD61(+) megakaryocytic progenitor cells and low frequency of early and mixed CFU-Meg in the BM mononuclear, but not CD34(+), cell fraction, compared with healthy controls (n = 20). TPO and TGFbeta1 levels were significantly higher in patients compared with controls. TPO levels inversely correlated with platelet counts whereas TGFbeta1 values correlated inversely with CD34(+)/CD61(+) and CFU-Meg megakaryocytic progenitor cell numbers and positively with TPO levels. The addition of an anti-TGFbeta1 neutralising antibody significantly increased the numbers of CFU-Meg in CIN patients but not in controls, compared with baseline. These data suggest that increased local production of TGFbeta1 probably affects the BM megakaryocytic progenitor cell growth in CIN whereas the compensatory production of TPO finally balances the TGFbeta1-induced inhibitory effect.
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PMID:Impaired megakaryopoiesis in patients with chronic idiopathic neutropenia is associated with increased transforming growth factor beta1 production in the bone marrow. 1693 19