Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bleeding is a prominent feature of uremia and remains a significant cause of morbidity in hemodialysis (HD)-dependent patients. To measure the impact of the HD procedure, we performed a prospective cross-over study in eight patients placed consecutively for 2-week periods each on low-flux biocompatible polymethylmethacrylate, low-flux complement-activating cuprophane, and high-flux biocompatible polysulfone membranes. The primary measure of platelet function studied was shear-induced platelet aggregation (SIPA), which has been shown to be a physiologically relevant marker of platelet function and involves the interaction of von Willebrand factor (vWf) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa. Flow-cytometric analysis of the surface expression of platelet membrane GP Ib and GP IIb-IIIa was performed using fluorescein isothiocyanate (FITC)-conjugated monoclonal antibodies CD42b and CD41a, respectively. Multivariate analysis did not demonstrate a statistically significant effect of the type of dialysis membrane on platelet aggregation, calcium flux, or thromboxane B2 production. There was a marked decrease of SIPA in HD patients (pre-HD, mean +/- SEM, 19% +/- 3%) compared with normal controls (43% +/- 3%, P < 0.001), with a further decrease after the HD procedure (post-HD, 12% +/- 2%, P = 0.015 compared with pre-HD). This intradialytic decrease in SIPA correlated with a decrease in GP Ib (pre-HD, 385 +/- 21 mean fluorescence intensity [MFI]; post-HD, 285 +/- 21 MFI, P = 0.0001). GP IIb-IIIa was also significantly decreased post-HD (pre-HD, 1,022 +/- 70 MFI; post-HD, 881 +/- 64 MFI, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective platelet aggregation in uremia is transiently worsened by hemodialysis. 770 50

Bleeding and platelet dysfunction are prominent features of uremia. Sh ear-induced platelet aggregation (SIPA) involves the interaction of von Willebrand factor (vWF) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa, the same receptor-ligand pair involved in in vivo adhesion and aggregation of platelets in the arterial circulation. We have used a modified rotational cone-plate viscometer to measure SIPA and calcium flux in platelets. Flow cytometric analysis of the surface expression of GP Ib and IIb-IIIa was performed using flourescein isothiocyanate-conjugated monoclonal antibodies CD42b and CD41a, respectively. Uremic patients showed decreased SIPA (controls, 43% +/- 2% [mean +/- SEM]; chronic renal failure patients, 36% +/- 3%; chronic hemodialysis patients, 26% +/- 2%; P < 0.001) along with a decrease in GP IIb-IIIa (controls, chronic renal failure patients, and chronic hemodialysis patients, 840 +/- 25, 649 +/- 42, 661 +/- 38 mean flourescence intensity, respectively; P < 0.0001). Glycoprotein Ib in uremic patients was not significantly different from normal. Chronic hemodialysis patients also demonstrated increased platelet-bound fibrinogen (P < 0.001) and platelet-bound vWF (p < 0.01). Calcium flux and thromboxane B(2) generation during SIPA of uremic platelets was normal. However, uremic plasma showed twice the normal concentration of vWF (P < 0.001) and sodium dodecyl sulfate agarose gel electrophoresis revealed the presence of fibrinogen fragments. Mixing experiments demonstrated an inhibitory effect of uremic plasma on SIPA of normal platelets (decreased from 39% +/- 3% at baseline to 31% +/- 3% after incubation in uremic plasma) along with an activation-independent increase in platelet-bound fibrinogen and platelet-bound vWF. When uremic platelets were incubated in normal plasma, their SIPA increased from 12% +/- 5% at baseline to 18% +/- 4% after incubation in normal plasma; (P = 0.002), although it did not return to normal. These results suggest that the uremic platelet dysfunction results from decreased GP IIb-IIa availability due to receptor occupancy by fibrinogen fragments (and possibly vWF fragments).
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PMID:Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors. 860 4

Megakaryocytic differentiation of progenitor cells was investigated in nine patients with low-risk myelodysplastic syndromes (MDS) (eight refractor anemia [RA] and one RA with ringed sideroblasts [RARS] and five patients with high-risk MDS (two RA with excess of blasts [RAEB] and three RAEB in transformation [RAEB-T]). Bone marrow-derived CD34+ cells were enriched to a purity of 87% +/- 2% (mean +/- SEM) and assayed in short-term suspension cultures in the presence of 10 ng/mL of PEGylated recombinant human megakaryocyte (MK) growth and development factor (PEG-rHuMGDF) and in addition to 50 ng/mL stem cell factor and 10 ng/mL interleukin-3. Cells of the megakaryocytic lineage were identified by flow cytometric analysis of CD42b (GP1b) and mature MKs by morphologic criteria. Transcription of c-mpl receptor-specific mRNA in the CD34+ cells of these patients was investigated by full-length reverse transcriptase polymerase chain reaction of the p form of c-mpl as well as of the alternative splice product c-mpl k. CD34+ cells from seven healthy bone marrow donors served as controls. Differentiation along the MK pathway was stimulated in five patients with RA. C-mpl mRNA was expressed in the CD34+ cells in all cases. In three low-risk patients the capacity for in vitro MK growth was absent or minimal even though mRNA for c-mpl receptor was detected in the CD34+ cells of this group as well. In patients with high-risk MDS, PEG-rHuMGDF stimulated in vitro MK growth from CD34+ cells in only one of five cases. As in the patients with low-risk MDS, c-mpl mRNA for both c-mpl p and c-mpl k splicing products was detected. These results indicate that the in vitro response to stimulation with c-mpl ligand discriminates between two groups of patients with low-risk MDS and that the observed defect in megakaryocytic development is unrelated to the level of c-mpl expression in both low-risk and high-risk MDS.
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PMID:Characterization of defective megakaryocytic development in patients with myelodysplastic syndromes. 1008