Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pf4”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources
PubMed1985

Platelet behavior in patients with TIA: responsiveness to small doses of aspirin.

To study platelet role in cerebrovascular disease, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in a group of patients affected by cerebral ischemic attack (transient ischemic attack; TIA). Determinations were carried out within 1 month from the ischemic event and following short-term (1 month) and long-term (1 year) daily administration of low doses (50 mg) of aspirin (ASA). After the cerebral ischemic event, beta-TG and PF4 plasma levels were elevated. beta-TG and PF4 plasma levels did not decrease after 1 month of treatment with ASA and significantly increased in all the patients after 1 year. Such a trend can perhaps be related to the natural course of the disease and associated with the possible occurrence of collagen-induced platelet activation in cerebrovascular patients. Data suggest that although platelet activation occurs in TIA-affected patients, the high levels of beta-TG and PF4 may not be adequate parameters for evaluation of TIA relapses and ASA efficacy.

Adult↗
PubMed1995

A mapping study of 13 genes on human chromosome bands 4q11-->q25.

A chromosome band 4q21 gene (MLLT2, formerly called AF-4/FEL) involved in a reciprocal translocation with chromosome band 11q23 in t(4;11) acute leukemia has been cloned. To provide better definition of gene order and relationships in this region where MLLT2 resides, we used pulsed field gel electrophoresis (PFGE) to investigate 13 genes (including MLLT2) with physical locations in bands 4q11-->q25. Somatic cell hybrids derived from RS4;11, a leukemic cell line carrying the t(4;11)(q21;q23), were also used to localize genes in relation to MLLT2. Linkage of the interleukin 8 (IL8), albumin (ALB), and platelet factor 4 (PF4) genes was confirmed by NotI, SalI and SacII digests. The maximum distance between PF4 and ALB is 210 kb and between ALB and IL8 is 420 kb. The alcohol dehydrogenase, class I (ADH2, ADH3) gene cluster can be linked to the alcohol dehydrogenase, class III gene (ADH5) by SacII, NruI, and EagI digests. The maximum distance between them is 590 kb. Our study indicated that ALB, alpha-fetoprotein (AFP), PF4, beta-thromboglobulin (PPBP), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and IL8 genes can be physically linked. In this study the gamma-interferon induced protein 10 (INP10), bone morphogenetic protein 3 (BMP3), annexin III (ANX3), KIT, amphiregulin (AREG), immunoglobulin J polypeptide (IGJ), deoxycytidine kinase (DCK) and MLLT2 genes were not linked to one another or to the above two groups of genes. Our analysis using somatic cell hybrids combined with previous reports demonstrated that the ADH gene cluster is telomeric to MLLT2 and KIT, ALB, AFP, PF4, beta TG, GRO1, IL8, ANX3, AREG and DCK are centromeric to MLLT2.

Animals↗
PubMed1982

Enhanced platelet release reaction in insulin-dependent and insulin-independent diabetic patients.

Plasma beta thromboglobulin (BTG) and platelet factor 4 (PF4) levels were measured and correlated with plasma lipid and lipoprotein patterns in 20 insulin-independent diabetics, in 10 insulin-dependent diabetics and in 30 healthy controls matched to patients as to age, sex and weight. Increased plasma BTG and PF4 levels both in insulin-dependent and in insulin-independent diabetics indicate enhanced in vivo platelet activation and release reaction in these patients. No difference in BTG and PF4 values between these two groups of diabetic patients was observed in our study. A marked correlation between plasma PF4 values and plasma glucose levels was shown in insulin-dependent diabetics only whereas a significant positive correlation with plasma triglycerides and plasma triglyceride VLDL and a negative correlation with cholesterol-HDL was shown in insulin-independent diabetics.

Adult↗
PubMed1985

Do malfunctioning bioprosthetic heart valves represent a potential thrombogenic focus?

In vivo platelet reactivity, expressed by plasma concentration of beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), was determined in 57 patients with bioprosthetic heart valves: 35 had well-functioning bioprostheses (WFBP), while 22 had documented malfunctioning bioprostheses (MFBP). beta TG and PF4 values in patients with WFBP were not significantly different from controls, even when these determinations were repeated at monthly intervals, whereas beta TG and PF4 concentration was significantly higher in patients with MFBP compared to both groups. There was a strong positive correlation between beta TG and PF4 in all subjects studied. Serum lactic dehydrogenase, indirect bilirubin level and reticulocyte count were significantly higher in patients with MFBP than in those with WFBP, but no correlation was found between platelet reactivity and rate of intravascular hemolysis. Our results suggest that there is an increased platelet release in vivo of the platelet-specific proteins in patients with MFBP not related to mechanical damage, and that bioprostheses, at least in a degenerative state, may represent a potential thrombogenic focus.

Adult↗
PubMedDate not supplied

Neutralization of DHG, a new depolymerized holothurian glycosaminoglycan, by protamine sulfate and platelet factor 4.

The neutralization of depolymerized holothurian glycosaminoglycan (DHG), unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) by protamine sulfate (PS) or platelet factor 4 (PF4) was studied. In in vitro studies, the prolongation of thrombin clotting time (TCT) by these glycosaminoglycans was completely neutralized by PS, whereas activated partial thromboplastin time (APTT) was relatively resistant to neutralization. In rats, prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT ex vivo. Heparin-cofactor-II-dependent antithrombin activity of DHG or UFH was neutralized by PF4 at a high concentration to the same extent; however, prolongation of the APTT by DHG was more resistant to neutralization by PF4 at a physiological plasma level than that by UFH. In conclusion, since the prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT, and since PF4 neutralized the antithrombin activity of DHG, these proteins may be useful as antidotes for DHG to prevent bleeding in case of an overdose.

Animals↗
PubMed1994

Influence of Pall Pl-50 platelet filters on lactate dehydrogenase, platelet factor 4, and complement factor 3 in stored platelet concentrates.

BACKGROUND: The study examines Pall Pl-50 platelet filters with respect to their influence on some biochemical properties of platelet concentrates. MATERIAL AND METHODS: Ten pairs of pooled platelet preparations, each consisting of 3 platelet concentrates, were studied. On day 1, one of the preparations was filtered and the other served as an identical non-filtered control. Immediately after filtration platelet counts, the levels of desarginated activated complement factor 3 (C3a), extracellular levels of lactate dehydrogenase (LDH) and extracellular and total concentrations of platelet factor 4 (PF4) were determined in both concentrates. After 5 days sterility testing and determination of extracellular levels of PF4 and LDH were performed. RESULTS: Extracellular concentrations of PF4 and C3a decreased immediately after filtration (p < 0.01). Furthermore, Pall Pl-50 filters caused cellular instability reflected by an increased release of PF4 (p < 0.01) during subsequent storage. CONCLUSION: Platelet concentrates filtered with Pall Pl-50 would not appear suitable for storage.

Blood Preservation↗
PubMedDate not supplied

Amniotic fluid platelet factor 4 and beta-thromboglobulin as markers of structural abnormalities.

Platelet factor 4 (PF4) and beta-thromboglobulin (BTG) are unique markers of irreversible platelet activation. We measured PF4 and BTG in amniotic fluid from 102 genetic amniocenteses, in which 78 had normal amniotic fluid alpha-fetoprotein (AFP) levels with normal pregnancies, and 24 had high amniotic fluid AFP levels with abnormal pregnancies. PF4 and BTG were significantly higher in the abnormal pregnancy/elevated amniotic fluid AFP group (p < 0.002 in each case) and correlated with AFP expressed as multiples of the median (p < 0.05 and p < 0.0001, respectively). Our results are compatible with passage of PF4 and BTG across fetal membranes and/or enhanced fetal platelet activation in fetuses with structural anomalies and elevated AFP.

Amniocentesis↗
PubMed1984

Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.

Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), beta-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet alpha-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation.

Adolescent↗
PubMed1994

Different effects of strenuous exercise and moderate exercise on platelet function in men.

BACKGROUND: Platelets play an important role in the pathogenesis of cardiovascular diseases. It is also noticed that on one hand, regular exercise can reduce the risk of cardiovascular diseases, and on the other hand, vigorous exercise provokes sudden cardiac death. We therefore hypothesize that various intensities of exercise may affect platelet function differently. METHODS AND RESULTS: Strenuous and moderate exercise (about 50% to 55% of peak oxygen consumption, VO2peak) on a bicycle ergometer in 10 sedentary and 10 physically active healthy young men was executed on two separate occasions. Blood samples were collected before and immediately after exercise. A newly designed tapered parallel plate chamber was used to assess platelet adhesiveness. Platelet aggregation induced by ADP was evaluated by the percentage of reduction in single platelet count. beta-Thromboglobulin (beta-TG) and platelet factor 4 (PF4) were measured by ELISA. In addition, a similar study on 5 patients with stable angina were also conducted. Our results showed that (1) in the sedentary healthy group, platelet adhesiveness and aggregation were increased by strenuous exercise and depressed by moderate exercise; (2) in the active healthy group, platelet adhesiveness and aggregation were enhanced by severe exercise, whereas only aggregation was decreased by moderate exercise; (3) in the patients with stable angina, platelet adhesiveness and aggregation were enhanced by strenuous exercise and adhesiveness was suppressed by moderate exercise; (4) the degree of hemoconcentration induced by acute exercise tended to be related to the severity of exercise in all subjects; and (5) although severe exercise elevated beta-TG and PF4, there were no significant changes in beta-TG, PF4, and the ratio of beta-TG to PF4 in healthy subjects after exercise. CONCLUSIONS: It is concluded that platelet adhesiveness and aggregability may be sensitized by strenuous exercise in both healthy subjects and patients with stable angina. In contrast, platelet function can be suppressed significantly by moderate exercise in the healthy and tends to be depressed in patients with stable angina. The former may increase the risk of cardiac arrest and the latter may protect us from cardiovascular diseases. In addition, the effects of acute exercise tend to be more pronounced in the sedentary than in the active.

Adult↗
PubMedDate not supplied

No effect of acetylsalicylic acid on B-thromboglobulin and platelet factor 4 plasma levels in patients with transient ischaemic attacks.

We studied the effect of acetylsalicylic acid (ASA) versus placebo on B-thromboglobulin (B-TG) and platelet factor 4 (PF4) plasma levels and ADP-induced platelet aggregation in 25 male patients with transient ischaemic attacks (TIA). The patients were allocated randomly to two groups: 14 patients received oral treatment with ASA 500 mg b.i.d. for 14 days, 11 patients placebo b.i.d. for the same period. B-TG and PF4 plasma levels and ADP-induced platelet aggregation were determined in basal conditions, and two hours, and seven and fourteen days after starting with ASA or placebo. In addition, the same parameters were studied in a group of 20 healthy males of matched age. Basal levels of plasma B-TG and PF4 and the maximal amplitude of ADP-induced platelet aggregation were abnormally high in TIA patients. ASA caused a significant reduction of B-TG plasma levels in TIA patients 2 hours after the first administration, but no effect was observed at the 7th and 14th day of treatment. PF4 plasma levels were unaffected by ASA treatment. It is concluded that ASA, at the dose conventionally used in clinical trials, does not affect the release of two alpha-granule proteins.

Aged↗
PubMed2005

Neutrophil adhesion to endothelial cells induced by platelet factor 4 requires sequential activation of Ras, Syk, and JNK MAP kinases.

Signal transduction mechanisms associated with neutrophil activation by platelet factor 4 (PF4; CXCL4) are as yet poorly characterized. In a recent report, we showed that PF4-induced neutrophil functions (such as adhesion and secondary granule exocytosis) involve the activation of Src-kinases. By analyzing intracellular signals leading to adherence, we here demonstrate by several lines of evidence that in addition to Src-kinases, PF4 signaling involves the monomeric GTPase Ras, the tyrosine kinase Syk, and the MAP kinase JNK. Furthermore, on stimulation, GTPases Rac2 and RhoA were activated, and each was translocated to a different membrane compartment. As shown by inhibitor studies, Rac2 and JNK are located downstream of Syk and Ras. Most intriguingly, the latter 2 elements appear to control the activity of Rac2 and JNK independently of each other at different phases of the activation process. Although a first phase of Rac2 and JNK activation of up to 5 minutes is initiated by Ras, the second phase (5-30 minutes) depends predominantly on the activity of Syk. In summary, we describe that coordinated activity of Syk, Ras, and JNK mediates neutrophil adhesion to endothelial cells and that PF4 induces sequential activation of these elements.

Cell Adhesion↗
PubMed2001

Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus.

The genes for the related human (h) chemokines, PBP (platelet basic protein) and PF4 (platelet factor 4), are within 5.3 kilobases (kb) of each other and form a megakaryocyte-specific gene locus. The hypothesis was considered that the PBP and PF4 genes share a common distal regulatory region(s) that leads to their high-level megakaryocyte-specific expression in vivo. This study examined PBP and PF4 expression in transgenic mice using 4 distinct human PBP/PF4 gene locus constructs. These studies showed that within the region studied there was sufficient information to regulate tissue-specific expression of both hPBP and hPF4. Indeed this region contained sufficient DNA information to lead to expression levels of PBP and PF4 comparable to the homologous mouse genes in a position-independent, copy number-dependent fashion. These studies also indicated that the DNA domains that led to this expression were distinct for the 2 genes; hPBP expression is regulated by a region that is 1.5 to 4.4 kb upstream of that gene. Expression of hPF4 is regulated by a region that is either intergenic between the 2 genes or immediately downstream of the hPF4 gene. Comparison of the available human and mouse sequences shows conserved flanking region domains containing potential megakaryocyte-related transcriptional factor DNA-binding sites. Further analysis of these regulatory regions may identify enhancer domains involved in megakaryopoiesis that may be useful in the selective expression of other genes in megakaryocytes and platelets as a strategy for regulating hemostasis, thrombosis, and inflammation. (Blood. 2001;98:610-617)

Animals↗
PubMed2005

Regulated expression of platelet factor 4 in human monocytes--role of PARs as a quantitatively important monocyte activation pathway.

Human mononuclear phagocytes have recently been shown to express constitutively and even more so, upon stimulation with bacteria, fungi, lipopolysaccharide (LPS), zymosan, or thrombin platelet basic protein (PBP). This CXC chemokine as well as platelet factor 4 (PF4), which is located genomically at a short distance from the PBP, were previously considered to be specific markers for the megakaryocyte cell lineage. Both chemokines have signaling and antimicrobial activity. In the present studies, transcriptional and expressional regulation of PF4 and related chemokines was studied in human monocytes. As shown by quantitative mRNA analysis, Western blots, radioimmunoprecipitation of cell extracts, and immunofluorescence and quantitatively with enzyme-linked immunosorbent assay, human monocytes express PF4 in the same order of magnitude as the known, regulated CXC chemokine interleukin (IL)-8. Expression of PF4 is up-regulated at the mRNA and protein level by thrombin and mediated by proteinase-activated receptors (PARs), resulting in a 32- to 128-fold higher mRNA level and leading to an up-to-sixfold increase of the peptide concentration in monocyte culture supernatants. Thrombin and the synthetic ligand of PAR-1 and PAR-2, SFLLRN, also induced comparable increases in the levels of mRNA for PBP, IL-8, regulated on activation, normal T expressed and secreted (RANTES), monocyte chemoattractant protein-1, and macrophage-inflammatory protein-1alpha and increased synthesis of these chemokines as shown by immunofluorescence or a quantitative immunobead-based method. The induction of increased mRNA levels for all chemokines by SFLLRN was unsurpassed by LPS, zymosan, interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-1. Activation of monocytes through PARs represents an alternate activation mechanism, independent from IFN-gamma, TNF-alpha, or other signaling pathways.

Cells, Cultured↗
PubMed1982

Migration of cultured vascular cells in response to plasma and platelet-derived factors.

Phagokinetic migration of cultured vascular cells was tested in response to human platelet-rich serum ('serum') and human platelet-poor plasma serum ('plasma'). The cell types tested included bovine aortic endothelial cells, human umbilical vein endothelial cells, human haemangiomal capillary endothelial cells, bovine adrenal microvascular pericytes, and bovine aortic smooth muscle cells. Human serum stimulated a significant increase in the rate of migration for all five cell types. Human plasma stimulated the endothelial cells to migrate but had no effect on the migration of pericytes or smooth muscle cells. Highly purified platelet-derived growth factor (PDGF) stimulated dose-dependent migration of smooth muscle cells causing a 50% increase in phagokinetic track area relative to controls. Neither pericyte nor endothelial cell migration was stimulated by PDGF. Rabbit antiserum to human PDGF completely blocked the smooth muscle cell migration induced by either 10% serum or 1 ng/ml pure PDGF. Purified platelet factor IV (PF4) stimulated migration of pericytes but not of smooth muscle cells nor endothelial cells. Sheep antiserum to human PF4 completely blocked the pericyte migration induced by either 10% serum or 1 microgram/ml pure PF4. These results indicate that PDGF is the primary factor in serum responsible for the migration of cultured aortic smooth muscle cells and that PF4 is a critical factor required to induce the migration of pericytes. Other factors present in both plasma and serum control the migration of vascular endothelial cells.

Animals↗
PubMed2005

[Transcription factors responsible for megakaryocyte-specific gene expression].

Megakaryocytes are the hematopoietic precursors of platelets, which play an essential role in thrombosis and hemostasis. Platelet factor 4 (PF4) is expressed exclusively in megakaryocytes and platelets and serves as a lineage-specific marker of megakaryocytic differentiation. We previously characterized a number of upstream enhancer and repressor elements and demonstrated that GATA-1 and ETS-1 are important for PF4 gene expression. Recently, we have determined the novel regulatory element termed "TME" in the PF4 promoter and identified a group of binding proteins from megakaryocytic HEL cells. Here we review the function of these proteins in PF4 gene expression and discuss megakaryocyte-specific gene expression and megakaryocytepoiesis.

Animals↗
PubMed2003

Frequency of heparin-induced thrombocytopenia in critical care patients.

The diagnosis of heparin-induced thrombocytopenia (HIT) in critically ill patients is complicated by lack of information on the frequency of HIT relative to thrombocytopenia from other causes. In addition, results from HIT diagnostic tests have not been clearly evaluated for clinical utility. In this prospective study, we estimated the frequency of HIT and the predictive performance of the heparin-platelet factor 4 enzyme-linked immunosorbent assay (heparin-PF4 ELISA) in 748 consecutive, heparin-treated patients in a combined intensive and coronary care unit. The criteria for diagnosis were as follows: two or more consecutive platelet counts below 150 x 10(3)/mm3 or a 33% or greater decrease in platelet count 5 or more days after beginning heparin, or any time after starting heparin for patients exposed to the agent within the previous 8 weeks; and a positive 14C-serotonin release assay (SRA), the reference standard. Specificity and predictive values for the heparin-PF4 ELISA were estimated in patients who met the clinical criteria for HIT. Of 748 patients, 267 were exposed to heparin for a sufficient length of time to be considered to be at risk for HIT. Forty of these patients (15.0%, 95% confidence interval [CI] 10.7%-19.3%) met the clinical criteria for HIT. Serum samples were available for 32 of these patients, one of whom tested positive by the SRA, yielding a HIT frequency of 0.39% (95% CI 0.01-2.1%). The specificity of the heparin-PF4 ELISA among thrombocytopenic patients with negative SRA results was 71%, and the positive (PPV) and negative (NPV) predictive values of this test were estimated to be 10% and 100%, respectively. The point estimate of the frequency of HIT in critically ill patients was less than 1% in this cohort. The low PPV and high NPV of the heparin-PF4 ELISA suggest that it can be used to exclude HIT as a cause of thrombocytopenia in this patient population.

APACHE↗
PubMed1986

Platelet alpha-granule release in chronic myeloproliferative disorders with thrombocytosis.

Platelet alpha-granule release in 22 patients affected by chronic myeloproliferative disorders with thrombocytosis and seven subjects with thrombocytosis secondary to splenectomy were studied. We found elevated beta-thromboglobulin (BTG) and platelet factor 4 (PF4) plasma levels in all patients. Intraplatelet content of BTG and PF4 was decreased in patients with idiopathic thrombocythaemia (IT) and idiopathic myelofibrosis (IMF). The BTG and PF4 results were also expressed as the ratio plasma BTG and PF4: whole blood platelet count. In patients with IT, BTG: whole blood platelet count ratio was low, conversely, the same ratio was high in patients with IMF. In conclusion, our results suggest the presence of an abnormal, BTG-deficient clone in IT and a peripheral platelet activation in IMF.

Beta-Globulins↗
PubMed1992

Megakaryocytic leukemia and platelet factor 4.

The de novo megakaryocytic leukemia fulfilling the FAB criteria is still an uncommonly recognized variant of acute leukemia. Many studies have shown that the megakaryocytic leukemic events may occur at a pluripotent stem cell level and clinical observations reveal that the megakaryocytic leukemias are diverse entities. The immunophenotyping using monoclonal antibodies against platelet specific surface antigens and the ultrastructural detection of platelet peroxidase reaction do not provide sufficiently useful information to determine whether a megakaryocytic leukemia is chronic, acute, therapy-responsive or therapy-unresponsive. More sophisticated techniques are required to further characterize megakaryocytic leukemic cells. In this review, we emphasize that megakaryocytic leukemic cells can be categorized into two groups; one with the PF4 mRNA, and the other without it, and that the expression of PF4 mRNA in the blasts could be a useful marker for the identification of mature megakaryoblasts. It seems that the patients with blasts expressing PF4 mRNA will have a longer survival and a better response to chemotherapy than those without PF4. We further discuss the fact that the detection of mRNAs of the IL-6 receptor, PDGF A- and B-chains, and TGF beta 1 in megakaryocytic leukemic cells will be useful to clarify the mechanisms involved in the proliferation of megakaryocytic leukemic cells and fibroblasts in the bone marrow. Furthermore, we reviewed data showing that megakaryocytic erythroid, and mast cell lineages share the nuclear transcription factor known as GF-1 (NF-E1 or Erf-1). We suggest that characterization of megakaryocytic leukemia should be performed using monoclonal antibodies against erythroid, megakaryocytic and mast cell lineages.

Base Sequence↗