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D Mezzano

Publications and source records attributed to D Mezzano.

At least 19 recordsLinked to original sources
PubMed1992

Total sialic acid in human and canine platelets does not change with the platelet age.

Total platelet sialic acid (SA) was measured in three experimental conditions: (1) human and canine platelet density subpopulations obtained by centrifugation in arabinogalactan gradients, (2) circulating canine platelets during recovery from experimental immune and mechanical thrombocytopenias, and (3) platelets obtained from a patient with chronic immune thrombocytopenic purpura before and after splenectomy. The density of human and canine platelets is, in part, determined by their age. We found no significant differences in total SA between high-density (HD) and low-density (LD) platelets (9.32 +/- 2.0 vs. 9.55 +/- 1.3 micrograms/mg of platelet protein in dogs and 9.02 +/- 2.3 vs. 9.10 +/- 2.9 micrograms/mg in humans). In the human and canine thrombocytopenic models, the entrance of new platelets from the bone marrow is followed by their aging in the circulation. In these models, no significant changes in total SA content were detected in sequential measurements during the recovery of the thrombocytopenia. Accordingly, we conclude that total SA in human and canine platelets is unrelated to their age in circulation. These results do not support the notion that the loss of SA from membrane glycoproteins determines the recognition and removal of platelets from the circulation.

Animals↗
PubMed1992

Glomerular localization of platelet factor 4 in streptococcal nephritis.

Since platelet factor 4 (PF4), a cationic (pI 7.6) platelet secretory protein, binds avidly to glomerular polyanions both in vitro and in vivo, and is implicated in neutrophil chemotaxis, we studied by indirect immunofluorescence microscopy the presence of PF4 deposits in glomeruli of patients with poststreptococcal nephritis (APSGN). Goat antihuman PF4 serum was used as primary antibody and fluorescein-conjugated IgG fraction of rabbit antigoat IgG as second antibody. Controls consisted of nonimmune goat serum or anti-PF4 serum preabsorbed with human PF4, as primary antibodies. Glomerular deposits of PF4 were demonstrated in renal tissues obtained by biopsy in 14 of 20 patients studied; the deposits were particularly intense in 9 patients. PF4 was bound to the mesangium and to the capillary walls. There was a significant positive correlation between intraglomerular deposits of PF4 and the levels of proteinuria (p = 0.024). These findings provide further evidence for a role of platelets in the pathogenesis of APSGN and suggest that PF4 may contribute to alter the glomerular permeability in this disease.

Adult↗
PubMed1992

[Frequency of platelet specific alloantigens HPA-1a (P1A1) and HPA-4a (Pen(a)) expression in Chilean population].

The phenotype frequency of platelet-specific alloantigens has been reported to vary with the ethnic composition of the population under study and the only two HPA-4a negative individuals found in the United States were of Hispanic origin; therefore, the aim of this work was to define the frequency of expression of these systems in the Chilean population. Using an ELISA with captured antigen by monoclonal antibodies, 604 blood donors were typed for the platelet-specific antigen systems HPA-1 and HPA-4. Eight samples typed negative for HPA-1a (1.32%) and 596 typed positive (98.68%). The calculated gene frequencies were 0.88 for HPA-1a (gene frequency > 0.99). Since these antigens are involved in thrombocytopenic disorders such as neonatal alloimmune thrombocytopenia and post-transfusion purpura, their frequency in a population is of clinical relevance. The gene frequency found for HPA-1a is higher than in Europeans (0.85) and lower than in Mapuche Indians (0.99), which is to be expected from the ethnic origin of our population. The absence of HPA-4a negatives in this study does not support our original hypothesis of a higher polymorphism of this system among hispanics.

Antigens, Human Platelet↗
PubMed1992

[Neonatal autoimmune purpura: laboratory study of 5 cases].

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia. We report our experience in the study of five cases with severe neonatal-thrombocytopenia. Using an ELISA with antigen capture and other serologic tests on platelets, we investigated the sera of the five mothers. Sera from four mothers contained a platelet-specific alloantibody, anti-HPA-1a (PlA1) whereas the platelets typed as HPA-1b/b. In one case despite extensive serological investigation and clinically unequivocal diagnosis of AINT, no antibodies were demonstrated. The use of monoclonal antibodies for antigen immobilization, showed to be a reliable and sensitive test for the detection and identification of platelet antibodies in AINT. These techniques could also be used in the follow-up of patients at risk (e.g. pregnant HPA-1b/b women) and in the screening of blood donors lacking of certain antigens, whose platelets are collected to be transfused in patients with platelet-specific antibodies.

Antigens, Human Platelet↗
PubMed1991

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.

Animals↗
PubMed1990

Palmitoyl-CoA and the acyl-CoA thioester of the carcinogenic peroxisome-proliferator ciprofibrate potentiate diacylglycerol-activated protein kinase C by decreasing the phosphatidylserine requirement of the enzyme.

To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglycerol-activated protein kinase C, the cofactor dependence of this activating effect was studied with purified rat brain enzyme and histone H1 as substrate. Using two different assay systems, palmitoyl-CoA was found to decrease greatly the amount of phosphatidylserine required to activate the kinase. No relative changes were observed in the dependence of the enzyme for other cofactors (diacylglycerol, ATP, and Ca2+) in the presence of palmitoyl-CoA. The potentiating effect of palmitoyl-CoA and the decrease in phosphatidylserine requirement of the kinase was also demonstrated using the 47-kDa protein of human platelets as substrate and platelet protein kinase C as source of enzyme. The acyl-CoA thioester of the carcinogenic peroxisome-proliferator ciprofibrate was also found to decrease the phosphatidylserine requirement of protein kinase C. The data suggest that acyl-CoAs may play a role in the regulation of protein kinase C activity.

Acyl Coenzyme A↗
PubMed1990

[von Willebrand's disease].

von Willebrand's disease is the most frequent congenital disorder of primary hemostasis; it is transmitted in an autosomal manner and according to type there is an alteration in structure, function and/or synthesis or release of von Willebrand's factor. Patients present with muco-cutaneous hemorrhages of varying severity. Significant advances in the understanding of the molecular defect and laboratory diagnosis of the different subtypes of the disease have been made in the last years, but we still face the emergence of new subtypes and the difficulties posed by the genetic, clinical and laboratory variability of the disorder.

Humans↗
PubMed1990

Decrease in mean platelet survival time in acute poststreptococcal glomerulonephritis (APSGN).

In an attempt to study further the possible participation of platelets in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), we studied the platelet survival time, as an index of platelet activation, in 22 patients with APSGN. Mean platelet survival time was computed from the disappearance of radioactivity from blood, sampled serially after injection of autologous 51Cr-labelled platelets. C1q solid phase ELISA and conglutinin (K) solid phase ELISA were used to measure the serum levels of immune complexes. The platelet survival time in APSGN patients was 113 +/- 10 h vs 197 +/- 10 h in the control group (p less than 0.001); 68% of the patients had a shortened platelet survival, lower than 95% confidence limit. There was a significant increase in the platelet survival in the six patients that were studied after recovery from acute nephritic syndrome. There was no significant association between the mean platelet times survival and CICs (circulating immune complexes). Similarly, no significant correlation was found between the mean platelet lifespan and the severity of the glomerular disease, as assessed by the serum creatinine level and the proteinuria. These results support evidence of platelet activation and consumption in APSGN and we suggest that this activation occurs in the glomeruli capillary wall, due to platelet-vascular wall interaction.

Acute Disease↗
PubMed1986

Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelet density subpopulations.

The size, total protein, fibrinogen and 5-HT content were evaluated in density subpopulations of human and canine platelets fractionated in linear arabinogalactan gradients. The methodology was assessed to ascertain that platelet separation was by density and to discard artifactual changes and platelet release during the procedure. EDTA or PGE1 increased the size of human PRP-platelets, but not of dog platelets. In humans, high density (HD) platelets were 1.26 times larger and contained 1.88 times more fibrinogen, 2.23 times more 5-HT and 1.37 times more protein than low density (LD) platelets; in dogs, these density cohorts did not differ in protein content, but LD platelets were 1.29 times larger and had 1.33 times more fibrinogen and 5-HT than HD platelets. These findings suggest that cell density is mostly dependent on the protein content per unit volume of platelets (and not on dense bodies). The differences in fibrinogen and 5-HT content between HD and LD cohorts in humans and dogs may be related to platelet age. The difference in volume between HD and LD platelets in dogs is of uncertain interpretation.

Aging↗
PubMed1986

Changes in platelet beta-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptamine, ATP, and ADP during and after surgery with extracorporeal circulation in man.

Surgery with extracorporeal circulation (ECC) is associated with transient alterations of platelet function whose pathogenic mechanisms are not completely understood. To define further the platelet abnormalities, we determined the changes in platelet content of several granule-associated substances during and after ECC in patients subjected to aortocoronary bypass surgery. Platelet beta-thromboglobulin (beta-TG) decreased to 79.8% of the preoperative level at the end of ECC (p less than 0.01) and, as expected, did not recover 1 hr after the end of surgery. Platelet fibrinogen and albumin decreased to 67.9% (p less than 0.01) and to 29.8% (p less than 0.01) of baseline, respectively. However, 1 hr after surgery, platelet fibrinogen rose to 92% and albumin to 55.5% of baseline, denoting that during the recovery from ECC, platelets incorporate some plasma proteins. During ECC, platelet 5-hydroxytryptamine (5-HT) and total ATP and ADP decreased to 50.8% (p less than 0.01), 63.2% (p less than 0.01), and 69.9% (p less than 0.01) of their respective preoperative values, indicating dense body release. One hour after surgery, ATP recovered to 83.8%, suggesting that previous depletion compromised also the metabolic pool of adenine nucleotides. In summary, Our results confirm and extend previous observations demonstrating alpha-granule release during ECC. Platelets undergoing ECC can incorporate plasma proteins as evidenced by the rapid increase of platelet fibrinogen and albumin after bypass. Although the mechanisms of this increase and site of storage of the exogenous substances are unknown, this observation justifies further studies to determine if internalization of plasma proteins, especially fibrinogen, may take place in physiological conditions. Dense body depletion with transient storage pool deficiency appears to be a component of the reduced platelet function during ECC. Consumption of metabolic ATP with alteration of platelet energy metabolism may further impair platelet function, contributing to the bleeding episodes observed during surgery with ECC.

Adenosine Diphosphate↗