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)

A major limitation to the treatment of multiple myeloma by the thalidomide analogue CC-4047 (Actimid) is the development of a severe neutropenia. We investigated the hypothesis that this effect may have been due to CC-4047 enhancing the removal of neutrophils from the circulation by altering the expression of surface adhesion molecules required for endothelial binding, by binding to platelets, or by enhancing apoptosis. Flow cytometric analysis was used to examine the expression of neutrophil surface molecules, platelet binding and apoptosis in whole blood samples from 19 patients with multiple myeloma who were assigned to receive either 1, 2, 5 or 10 mg of CC-4047 every other day (e.o.d.) for 28 days. CC-4047 induced dose-related decreases in neutrophil numbers and increases in the percentage of CD64-positive neutrophils, but had little, or no effect on the expression of CD11b, CD62L or CD162, neutrophil-platelet binding, or apoptosis. Relative decreases in the neutrophil count were inversely associated with relative increases in the intensity of CD64 expression on neutrophils (r=- 0.307; p=0.028). Although seven patients developed severe neutropenia, none suffered severe or recurrent bacterial infections. The percentage of CD64-positive neutrophils was still increased in eight patients who continued receiving 1-5 mg CC-4047 e.o.d. for several months afterwards, but neutrophil counts were similar to pre-treatment values.
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PMID:The neutropenia induced by the thalidomide analogue CC-4047 in patients with multiple myeloma is associated with an increased percentage of neutrophils bearing CD64. 1671 24

Both leukocytes and platelets accumulate in the colonic microvasculature during experimental colitis, leading to microvascular dysfunction and tissue injury. The objective of this study was to determine whether the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes. The rolling and adherence of leukocytes and platelets in colonic venules of mice with dextran sodium sulfate (DSS)-induced colitis were monitored by intravital videomicroscopy. DSS elicited an increased recruitment of both rolling and adherent leukocytes and platelets. DSS-colitic mice rendered thrombocytopenic with anti-platelet serum exhibited profound reductions in leukocyte adhesion. Neutropenia, induced with anti-neutrophil serum, significantly reduced the adhesion of leukocytes and the accumulation of platelet-leukocyte aggregates while greatly enhancing the number of platelets that roll and adhere directly to venular endothelial cells. The enhanced platelet adhesion associated with neutropenia was mediated by platelet P-selectin interactions with endothelial cell P-selectin glycoprotein ligand (PSGL-1). DSS colitis was also associated with an increased expression of PSGL-1 in the colonic vasculature. These findings indicate that the recruitment of leukocytes and platelets in inflamed colonic venules are co-dependent processes.
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PMID:Mechanisms of platelet and leukocyte recruitment in experimental colitis. 1788 75