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Biomedical subjects

J M Cesar

Publications and source records attributed to J M Cesar.

18 recordsLinked to original sources
PubMed2006

Phospholipase A2 activity in platelets of patients with primary thrombocythemia.

Patients with primary thrombocythemia (PT) have both, bleeding and thrombotic events. Although platelet aggregation tests are usually abnormal, synthesis of thromboxane B2 (TxB2) by platelets is increased. This feature could be the consequence of an increased phospholipase activity or a facilitated metabolism of arachidonate by prostaglandin synthetase pathway. We studied the activity of phospholipase A2 as well the arachidonate metabolism in platelets of patients suffering from PT. Eleven patients and 11 controls were included. Platelets were labelled with [14C]arachidonic acid ([14C]AA). Lost of radioactivity from phospholipids and new radioactive prostanoids were evaluated in calcium ionophore A23187 activated platelets, to explore phospholipase A2 activity. This assay was also carried out in aspirin-incubated platelets. We also studied the formation of prostanoids in platelets activated by radioactive free arachidonic acid. Platelet aggregation studies of patients were abnormal. [14C]AA incorporation in platelet phospholipids was normal. Ionophore activated platelets from patients and controls lost 26.1 +/- 8.3% and 24.1 +/- 10.5% of radioactivity, respectively, mainly from phosphatidylcholine. The main arachidonate metabolite was 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), which comprised 14.1 +/- 5.1% of the radioactivity released from phospholipids in patients, and a similar amount in the controls (14.4 +/- 7.5%). Formation of TxB2 was also similar in patients (5.5 +/- 1.2%) and controls (4.9 +/- 2.9%). Formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was also normal. Ionophore A23187 activation of aspirinized platelets of patients released 19.5 +/- 7.4% of radioactivity from phospholipids, which was completely metabolized to HETE. Formation of prostanoids HETE, HHT and TxB2 by arachidonic acid activated platelets of patients was normal. Phospholipase A2 activity as well both cyclooxygenase and lipoxygenase activities in platelets of patients with PT were found to be normal.

Adolescent↗
PubMed2000

Hereditary thrombocythaemia is a genetically heterogeneous disorder: exclusion of TPO and MPL in two families with hereditary thrombocythaemia.

Hereditary thrombocythaemia (HT) is an autosomal dominant disorder with clinical presentation and complications resembling sporadic essential thrombocythaemia (ET). Mutations in the thrombopoietin (TPO) gene causing overproduction of TPO and elevated TPO serum levels have been found previously in three families with HT. Here, we present evidence for genetic heterogeneity by demonstrating that HT in a Spanish and a US family is caused by genes other than TPO. Affected family members in both families had normal TPO serum levels. Genetic linkage analysis with TPO microsatellite markers excluded TPO as the disease gene in the Spanish HT family, and sequencing of the TPO gene revealed no mutations in the propositus of the US family. To test a role for MPL, the gene for the TPO receptor, we identified three single nucleotide polymorphisms (SNP) and a novel polymorphic CA microsatellite marker. By linkage analysis, we excluded MPL as the cause of HT in the Spanish family. Interestingly, mapping of the CA microsatellite marker to a region 40.5 kb upstream of MPL revealed the presence of sequences from the TIE gene, which encodes a tyrosine kinase receptor expressed on megakaryocytes and endothelial cells. Thus, MPL and TIE are in close physical proximity, and the CA microsatellite described here will be a useful genetic marker for both genes.

Adult↗
PubMed1999

Prevention of alphaII(b)beta3 activation by non-steroidal antiinflammatory drugs.

We have studied the effect of non-steroidal antiinflammatory drugs (NSAIDs) on alphaII(b)beta3 integrin activation and platelet aggregation. NSAIDs such as meloxicam, piroxicam, indomethacin and aspirin, but not aceclofenac or diclofenac interfered with the activation state of alphaII(b)beta3. NSAIDs that inhibited alphaII(b)beta3 activation were also able both to partially inhibit platelet primary aggregation and to accelerate platelet deaggregation. These effects of NSAIDs were not dependent on cyclooxygenase inhibition. The results obtained indicate that some NSAIDs exert a specific action on alphaII(b)beta3 activation, and provide an additional mechanism that accounts for their beneficial effects in diseases in which platelet activation is involved.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Plasma phospholipids and platelet function in uremic patients.

An increased activity of phospholipase A2 has been observed in the plasma of patients with uremia. This enzyme converts phosphatidylcholine to lysophosphatidylcholine (LPC), an inhibitor of platelet aggregation. We measured the levels of plasma phospholipids including LPC, and platelet aggregation in 7 patients with uremia. Platelet response to agonists was defective, mainly with collagen (p < 0.001). The patients' levels of LPC in plasma were similar to those of controls (109.7 +/- 41.6 vs. 80.4 +/- 16.8 nmol/ml) and did not correlate with the platelet response to adenosine diphosphate (r = -0.51). The amount of phosphatidylcholine was increased with respect to normal plasma (1,041.0 +/- 201.8 vs. 760.8 +/- 142.7 nmol/ml, p < 0.01), while the levels of other phospholipids were normal. These results do not suggest a participation of plasma LPC in the genesis of the platelet defect observed in patients with uremia.

Adolescent↗
PubMed1996

Platelets isolated by albumin gradient retain normal activation pathways.

Isolated platelets from samples with low counts produce technical problems. Albumin gradient (AG) has been shown to be useful for this purpose, preserving the aggregating response of these cells. The influence of this method in the enzymatic pathways that regulate the platelet activation is studied. Platelets were isolated by either AG or conventional centrifugation methods and labelled with C-14-arachidonic acid (C-14-AA). Isolated platelets were activated with thrombin (5 U/ml) and lipids were extracted according to Bligh and Dyer. Platelet phospholipids and prostanoids were resolved by TLC. The incorporation of C-14-AA by platelets was similar by both methods (31.7 +/- 18% versus 47.2 +/- 6.9%), as well as the distribution of C-14-AA in the five major platelet phospholipids. Formation of radioactive thromboxane B2, hydroxyheptadecatrienoic acid and hydroxyeicosatetraenoic acid by activated platelets was also similar by both methods. These findings suggest that platelet isolation by albumin gradient preserves the enzymatic pathways responsible for the activation of these cells.

Albumins↗
PubMed1995

Arachidonic acid metabolism in platelets of patients with essential thrombocythaemia.

Platelet aggregation tests and studies comprising [14C] arachidonic acid [14C]AA incorporation, release and metabolism were performed in resting and thrombinstimulated platelets of 11 patients with essential thrombocythaemia (ET) and 11 normal subjects. Nine patients had abnormal aggregation tests. Incorporation and distribution of [14C]AA in main platelet phospholipids (PLs) was similar in both groups. Activated platelets of patients with ET released more radioactivity from PLs that controls (13.7 +/- 5.4% versus 8.2 +/- 1.9%, p < 0.01). The formation of 12-L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) was also increased (3.3 +/- 1.4% of total radioactivity versus 1.6 +/- 0.4% in controls (p < 0.0001). The same results were obtained for the generation of thromboxane B2 (p < 0.01). We did not detect differences in the formation of 12-L-hydroxy- 5,8,10,14-eicosatetraenoic acid (3.3 +/- 1.7% in patents versus 2.0 +/- 0.5% in controls). These results indicate that platelets of patients with ET have an increased activity of phospholipases and suggest a facilitated metabolism of arachidonate by the prostaglandinsynthetase pathway. Our results also demonstrate that impairment of aggregation tests in these patients was not due to a defective activity of the enzymes involved in the release and metabolism of AA by platelets.

Adult↗
PubMed1995

Increased levels of plasma von Willebrand factor in migraine crisis.

INTRODUCTION: To evaluate the participation of the vessel wall in the pathogenesis of migraine attack, we measured the plasma levels of von Willebrand factor (vWF), a protein secreted from the endothelial cells. MATERIAL & METHODS: 17 patients suffering from migraine without aura and 25 healthy volunteers were studied. von Willebrand factor and platelet aggregation tests were studied by conventional methods. RESULTS: The levels of vWF:antigen increased from 72.4 +/- 29 U/dl in the intercrisis to 130.2 +/- 75 U/dl during the attack (p < 0.01). We did not detect difference in the platelet aggregability in both phases. Plasma vWF activity measured as ristocetin cofactor (vWF:RCo) was similar in intercrisis and crisis (100.6 +/- 31 U/dl vs 94.5 +/- 44 U/dl). CONCLUSIONS: There is a plasma release of vWF molecules during the migraine crisis. This feature is not platelet dependent and is probably a consequence of endothelial stress.

Adolescent↗
PubMed1994

Von Willebrand factor availability in platelet concentrates stored for 5 days.

Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage.

Blood Platelets↗
PubMed1994

Red cell lipid abnormalities in acquired acanthocytosis are extended to platelets.

Acquired acanthocytosis (AA) is an uncommon disease characterized by the presence of abnormal red cells (acanthocytes) in the blood smears of affected subjects. Acanthocyte membrane is enriched in cholesterol by an abnormal plasma lipoprotein. We studied the existence of similar changes in platelets of one patient with AA. Red cell cholesterol/phospholipid (Ch/PL) ratio in the patient was 1.6 (normal 1.1 +/- 0.1). Phosphatidylcholine (PC) comprised 36% of total phospholipid (30.7 +/- 1.8% in controls). Platelets showed aberrant morphology in the blood smears, and the ratio Ch/PL was high in comparison with normal platelets (1.4 v 0.6 +/- 0.1). PC comprised 52% of total PL (39.6 +/- 1.9% in normal platelets). Normal platelets incubated with autologous plasma for 24 h maintained a Ch/PL ratio of 0.7, whereas this value changed to 1.4 when these cells were incubated with plasma from the patient. These results suggest that platelets of patients affected by AA acquire the same biochemical abnormality as red cells.

Acanthocytes↗
PubMed1993

Lactate dehydrogenase isoenzymes in patients with essential thrombocythemia.

Various abnormalities have been described in platelets of patients with Essential Thrombocythemia (ET), including alteration in the glycolytic pathway and increased lactate production. Lactate dehydrogenase (LDH) isoenzymes were studied in 15 of these patients. Relative activity of LDH-5 isoenzyme was higher comparing with normal platelets (p < 0.05), while LDH-3 activity was diminished (p < 0.05). LDH-1, LDH-2 and LDH-4 isoenzymes were unchanged. We also found an altered profile of LDH isoenzymes in serum. These findings can contribute to improve the knowledge of platelet defects in ET and be useful in the diagnosis of these patients.

Blood Platelets↗
PubMed1993

Phospholipid determination in platelets, plasma and red cells of patients with chronic myeloproliferative disorders.

Red cell phospholipids (PLs) were assessed in 11 patients with essential thrombocythemia and 5 patients with polycythemia vera. Platelet and plasma PLs were also determined in 10 of these patients, and the results were compared with studies performed in 16 healthy volunteers. The amount of platelet PLs in patients was similar to controls (556 +/- 90 mmol/10(9) cells, versus 481 +/- 91 mmol/10(9) cells), as was the percentage of the main specimens of these compounds, including phosphatidylserine (11.1 +/- 0.8%), which is relevant for platelet procoagulant activity. We did not find differences between red cell PLs of patients (300 +/- 60 nmol/10(9) cells), versus controls (289 +/- 71 nmol/10(9) cells), and the sphingomyelin/phosphatidylcholine ratio in these cells was the same in both groups (0.75 +/- 0.1). Finally, we did not detect any alteration in the amount of plasma PLs specimens.

Blood Platelets↗
PubMed1993

[Platelet function after allogeneic bone marrow transplantation in Wiskott-Aldrich syndrome].

PURPOSE: To assess the platelet characteristics and functionalism in the Wiskott-Aldrich syndrome (WAS) after allogeneic BMT using cyclophosphamide and busulphan for conditioning. MATERIAL AND METHODS: Two WAS patients underwent allogeneic BMT. Platelet aggregation was studied prior to and after BMT, along with the intraplatelet amount of ADP and ATP. RESULTS: Platelet count, size and aggregation wholly recovered after BMT. The post-transplant content of platelet nucleotides was normal. CONCLUSIONS: Platelet function can be totally restored with cyclophosphamide/busulphan conditioned BMT in WAS. Platelet defects in this disease are due to defective thrombopoiesis.

Blood Platelets↗
PubMed1990

Arachidonic acid metabolism in platelets stored for 5 days.

(C-14)-Arachidonic acid [(C-14)-AA] metabolism was studied in platelet concentrates (PCs) stored for 5 d. There was a gradual decrease in uptake of radioactivity from day 0 to 3 (P less than 0.01). On day 0, distribution of radioactivity in platelet phospholipids (PLs), and formation of phosphatidic acid, HETE and cyclooxygenase products, when platelets were exposed to thrombin (5 U/ml), were similar to that reported for fresh platelets. On day 3 there was a change in the distribution of (C-14)-AA in platelet PLs which consisted of an increase in the percentage of radioactivity bound to phosphatidylserine, from 5.3 +/- 0.9% on day 0 to 8.8 +/- 1.5% on day 3 (P less than 0.001), and a decrease in (C-14)-AA in phosphatidylinositol (PI), from 12.4 +/- 1.5% on day 0, to 7.9 +/- 0.9% on day 3 (P less than 0.001). Phosphatidic acid generated by thrombin-stimulated platelets on day 0, comprised 2.6 +/- 0.5% of total radioactivity, but dropped to 1.4 +/- 0.3% on day 3 (P less than 0.001), and 0.9 +/- 0.2% on day 5 (P less than 0.01). These values showed a good correlation with the percentage of (C-14)-AA released from PI on the same days (r = 0.9). On day 0, 13.4 +/- 4.4% of platelet radioactivity was released from phosphatidylcholine by thrombin, but this amount was reduced to 6.8 +/- 3.4% on day 5 (P less than 0.05). Generation of radioactive 12-hydroxy-5,8,10,14-eicosatetraynoic acid (HETE) also dropped from 7.2 +/- 2.9 on day 0, to 2.1 +/- 1 on day 5 (P less than 0.01). We could not detect changes in cyclooxygenase metabolites. In conclusion, we suggest that various enzymatic pathways implicated in AA metabolism by platelets are impaired by storage.

Arachidonic Acid↗
PubMedDate not supplied

Lipid composition of platelets in patients suffering from migraine without aura.

Patients with migraine have a platelet hyperaggregability. As this alteration could be the consequence of an abnormal lipid composition of platelet membranes, we studied the phospholipid specimens and the cholesterol/phospholipid ratio in platelet of neuron patients suffering from migraine. The cholesterol/phospholipid ratio was 0.7 +/- 0.1 (normal 0.6 +/- 0.1, molar ratio). The proportion of five main platelet phospholipids components including phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, phosphatidylserine, and phosphatidylinositol, were also normal. These data suggest that platelet hyperactivity in patients with migraine is not due to an altered lipid content of those cells.

Adult↗