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Biomedical subjects

V Vicente

Publications and source records attributed to V Vicente.

At least 37 records · Page 2Linked to original sources
PubMed2001

Role of factor XIII Val 34 Leu polymorphism in patients with migraine.

At present, it is contradictory to determine if the combination of certain prothrombotic polymorphisms and migraine increases the risk to develop ischaemic cerebrovascular disease. Recently, the common Val34Leu polymorphism of the A-chain factor XIII gene, associated with variations in factor XIII activity, has been suggested to play a significant role in the development of arterial and venous thrombotic disorders. We analysed the prevalence of this polymorphism in 17 patients with coexisting ischaemic cerebrovascular disease and migraine (5 with aura, and 12 without aura), 89 patients with migraine (43 with aura, and 46 without aura), 116 patients with ischaemic cerebrovascular disease, and 467 healthy Caucasian controls from the South of Spain. Genomic PCR amplification, using a mutated oligonucleotide, and allele-specific restriction assays were used for genotyping. The factor XIII Leu 34 variant was present in 47.1; 40.5; 34.9; and 35.1% of patients with coexisting ischaemic cerebrovascular disease and migraine, ischaemic cerebrovascular disease, migraine, and control subjects, respectively. These data suggest that the factor XIII Leu 34 allele does not play a protective role against these disorders in our population.

Adult↗
PubMed2001

Polymorphisms of P-selectin glycoprotein ligand-1 are associated with neutrophil-platelet adhesion and with ischaemic cerebrovascular disease.

P-selectin glycoprotein ligand (PSGL-1) shares common features with platelet glycoprotein Ibalpha. A recently described polymorphism in this receptor that results in a variable number of tandem repeats (VNTR) sequence present either 16, 15 or 14 times (alleles A, B or C) could, similar to GPIbalpha, be functionally relevant. The allelic frequency of this polymorphism was investigated in 469 individuals from the south of Spain, and was similar to that previously described in other Caucasian populations: 85% A, 14% B and 1% C alleles. We identified two new polymorphisms genetically linked to the C isoform, resulting in the Ser273Phe and Met274Val changes. To assess the functional consequence of the polymorphisms in the receptor, we performed flow cytometric analysis of P-selectin dependent neutrophil-platelet interaction. Neutrophils carrying the shortest C allele and the amino acid variations in residues 273 and 274 exhibited a significantly lower capacity to bind activated platelets than A/B and A/A samples (mean fluorescence intensity of CD42b+ neutrophils 262 versus 303 and 319 respectively, P < 0.05). The distribution of the VNTR was analysed in three case-control studies including 104 cerebrovascular (CVD), 101 coronary heart disease (CHD) and 150 deep venous thrombosis (DVT) patients. The results showed that smaller (B and C) alleles seem to be associated with a lower risk of developing CVD (P = 0.008) but not to be related to CHD or DVT. In conclusion, polymorphisms of the PSGL-1 receptor may influence the neutrophil-platelet binding, and represent a risk factor for CVD.

Adolescent↗
PubMed2001

Binding of recombinant apolipoprotein(a) to human platelets and effect on platelet aggregation.

The interaction of lipoprotein(a) [Lp(a)] with platelets is not well defined, particularly with regards to the individual contribution of the protein components of Lp(a), the apo B-100 and the apolipoprotein apo(a). This study investigated the binding of different recombinant apo(a) [r-apo(a)] isoforms, to human platelets and its effect on platelet aggregation. Scatchard analysis of saturation binding experiments demonstrated that human platelets display a single class of high affinity r-apo(a) binding sites (71 +/- 46 molec./platelet, Kd = 5.6 +/- 2.0 nmol/L). Platelet activation with strong agonists (thrombin, arachidonic acid) increased 2- to 10-fold the r-apo(a) binding, without affecting the affinity. Competition assays showed that the binding sites are highly specific for r-apo(a) and Lp(a). At high concentration t-PA could also bind to the r-apo(a) binding sites. By contrast, neither fibrinogen nor plasminogen inhibited to the r-apo(a) binding. The lysine analogue EACA inhibits the binding of r-apo(a) to platelets, thus suggesting the involvement of lysine residues in that interaction. Moreover, the r-apo(a) binding to platelets is unlikely mediated by GPIIb/IIIa-attached fibrin since it is not affected by platelet treatment with either LJ-CP8, a monoclonal antibody that specifically blocks fibrinogen binding to GPIIb/IIIa, nor GPRP, an inhibitor of fibrin polymerisation. Finally, we show that the distinct recombinant apo(a) proteins, as well as native Lp(a), promote an aggregation response of platelets to otherwise subaggregant doses of arachidonic acid. This proaggregant effect of r-apo(a) is dependent on its binding to platelets since it requires a minimum incubation time, and it is prevented by EACA at concentration inhibiting the r-apo(a)-platelet interaction. These results suggest that the prothrombotic action of Lp(a) may be in part mediated by modulating the platelet function through the interaction of its apo(a) subunit with a specific receptor at the platelet surface.

Adenosine Diphosphate↗
PubMed2000

Platelet GP Ib/IX/V complex: physiological role.

Platelets play an essential role in primary hemostasis and in thrombotic events, particularly in arterial vessels, as rheological conditions originate closer interactions between platelets and endothelium than lower shear rates. In response to vascular injury, platelets adhere to the subendothelial matrix by membrane receptors potentiating the generation of thrombin, become activated, and a series of biochemical processes induce platelet aggregation and liberation of intracellular metabolic products to the extracelular medium. Among platelet receptors, glycoprotein (GP) Ib/IX/V complex is peculiar, as it binds adhesive proteins, mainly von Willebrand factor (vWF), and thrombin, the main platelet agonist. Platelet adhesion and subsequent aggregation under conditions of high shear flow, essentially relies upon this receptor's capacity of binding to the subendothelial matrix, initiating signal transduction. Two proteins associated to GP Ib/IX/V, actin-binding protein (ABP) 280 and 14-3-3zeta, are potential mediators of signal transduction by the complex, but their specific contribution in this process is not yet fully understood. Additionally, two proteins implicated in signal transduction by immune stimuli, FcgammaRIIA and FcR gamma-chain, associate with GPIb/IX/V complex, and increasing data indicate a potential role in GPIbalpha mediated signal transduction.

14-3-3 Proteins↗
PubMed2000

Mobilization of hematopoietic progenitor cells with paclitaxel (taxol) as a single chemotheraupetic agent, associated with rhG-CSF.

We assessed the mobilization capacity of taxol with rhG-CSF, both as a single chemotherapeutic agent and in the presence of cyclophosphamide (CY), and compared the effect with yields achieved when mobilization was performed solely with rhG-CSF. Fifteen patients with breast cancer received taxol 170 mg/m2 (continuous infusion, day 1) and rhG-CSF (8 microg/kg/day, from day 2 until the end of apheresis) (T-G group), while seven breast cancer patients were additionally treated with CY (4 g/m2) on day 2, followed by rhG-CSF starting at similar doses on day 3 (T-CY-G group). The PBSC collections after taxol with/without CY were compared with those of 30 breast cancer patients who had received rhG-CSF (8 microg/kg/day) for mobilization. No differences were found in the characteristics of patients included in any of the three mobilization groups. The median yield of CD34+ cells from all patients included in taxol containing schedules was 9 x 106/kg (range 2-26) collected with a median of one apheresis procedure (range 1-4). Leukaphereses began earlier in the T-G group (median day 8, range 7-10) than in the T-CY-G group (median day 13, range 11-17). In most patients (20 out of 22) who received taxol containing regimens, more than 2.5 x 106 CD34+ cells/kg, a threshold considered to be sufficient for hematopoietic reconstitution, were collected with a single apheresis. Those patients in the T-G group experienced less neutropenic and thrombocytopenic days, with all neutropenic fever episodes developing in patients treated with the T-CY-G schedule (43%). When considering priming with rhG-CSF alone in our historical cohort of 30 breast cancer patients, a significant detrimental effect was observed in comparison with taxol mobilizing schedules, in the number of aphereses performed, in the total yield CD34+cells and in the number of patients who achieved the target dose of 2.5 x 106/kg CD34+ cells within the first collection procedure. We conclude that taxol containing schedules are effective in mobilizing PBSC and facilitate the collection of high yields of CD34+ cells (usually more than 5 x 106/kg recipient body weight) with a reduced number of apheresis procedures. Taxol, as a single agent with rhG-CSF, exhibits less hematological toxicity than the combination chemotherapy mobilization regimen including CY. Bone Marrow Transplantation (2000) 25, 231-235.

Adult↗
PubMed2000

Re-mobilization of peripheral blood progenitor cells within a short time interval fails to achieve effective progenitor cell yields.

We report the case of a healthy donor who was mobilized for the purpose of performing an unrelated donor transplantation with subcutaneous injections of rhG-CSF. Because of accidental loss of progenitors, 3 days after completing the first collection, the donor was mobilized again with rhG-CSF, and progenitors were collected. While a similar increase in the pre-apheresis leukocyte count was observed in both procedures, fewer mononuclear cells were mobilized during the second rhG-CSF course, resulting in a poor CD34+ yield. These data suggest that an 8-day interval between commencement of rhG-CSF mobilizations is insufficient to predict an efficient collection of hematopoietic progenitors to ensure engraftment after bone marrow transplantation.

Female↗
PubMed2000

Factor XIII Val34Leu polymorphism in primary intracerebral haemorrhage.

INTRODUCTION: Recently, the common Val34Leu polymorphism of the A-chain factor XIII gene, associated with high factor XIII activity, has been identified as a protective genetic factor against occlusive arterial and venous diseases. Moreover, this polymorphism has been suggested to be the first one to increase the risk of cerebral haemorrhage in a small number of Caucasian patients. The aim of our study was to investigate the role of this polymorphism in patients with primary intracerebral haemorrhage from a distinct population. MATERIAL AND METHODS: Patients with non-traumatic primary intracerebral haemorrhage (n=116), age-, race-, sex- and risk factor-matched controls (n=116), and individuals from the general population (n=465) were genotyped for the factor XIII Val34Leu polymorphism by polymerase chain reaction and allele specific restriction assay. The relationships of the Val/Leu genotype with distinct intracerebral haemorrhagic risk factors and with early mortality associated with the haemorrhagic episode were also analysed. RESULTS: No statistical difference in terms of prevalence was detected between patients (P=0.190) and controls (P=0.181). The frequency of the FXIII Leu34 allele was similar in the general population (P=0.191). CONCLUSION: The results suggest that the Leu 34 allele of the A-chain factor XIII gene has a minor role in the development of non-traumatic primary intracerebral haemorrhage. Moreover, the simultaneous presence of the Leu 34 allele with selected risk factors for this disease does not increase the risk of developing this disease.

Aged↗
PubMed2000

Evaluation of pooled platelet concentrates using prestorage versus poststorage WBC reduction: impact of filtration timing.

BACKGROUND: Concern for the undesirable consequences of transfusing passenger WBCs is leading to the general use of WBC-reduced platelet concentrates (PCs). However, the impact of prestorage versus poststorage WBC reduction on the quality of platelet products has not been clearly defined. STUDY DESIGN AND METHODS: Pooled PCs were WBC reduced before or after 5-day storage, by use of a WBC filter (PXL-8, Pall Corp.). Samples from pools were taken on days 1 and 5, before and after filtration, and on Day 9 of storage and assessed for cell counts, biochemical values, expression of platelet glycoproteins, thrombin generation, and content of IL-6, IL-8, TNFalpha, transforming growth factor beta1 (TGFbeta1), and anaphylatoxins C3a and C4a. RESULTS: Filtration of fresh and 5-day-stored pooled PCs via a PXL-8 filter was similarly efficient, rendering pools with low WBC counts (<1 x 10(6) cells) and high platelet recovery (>95%). No major changes were found in the metabolic behavior or the expression of platelet GPIb, GPIIb/IIIa, CD62, and CD63 in PCs filtered before or after storage. Filtration, either before or after storage, increased by less than 5 percent the proportion of CD62+ platelets. Moreover, no changes were found in the concentration of prothrombin fragments 1 and 2 and thrombin-antithrombin complexes in the pooled PCs derived from the time of filtration. Finally, prestorage WBC reduction abrogated the accumulation of IL-6 and IL-8, but it did not prevent that of anaphylatoxins C3a and C4a nor of TGFbeta1. However, filtration through a PXL-8 filter significantly reduced (40-90%) the amount of IL-8, C3a, and C4a in the filtrate. CONCLUSIONS: The timing of PXL-8 filtration of PCs has little impact on the efficiency of WBC reduction and on platelet recovery, and it does not seem to affect the quality of platelets or the generation of thrombin in the PCs. As regards the goal of reducing the amount of bioactive products in PCs, it remains uncertain as to whether prestorage WBC reduction fully eliminates the need for poststorage filtration. Prestorage filtration leads to low levels of IL-6 and IL-8 in PCs, but it does not impair the poststorage content of TGFbeta1 or anaphyla-toxins. By contrast, poststorage PXL-8 filtration removes significant amounts of C3a and C4a, and thus it might provide clinical benefits beyond those of prestorage WBC reduction.

Blood Preservation↗
PubMed2000

Evaluation of leukocyte-depleted platelet concentrates obtained by in-line filtration.

BACKGROUND AND OBJECTIVES: The use of leukocyte-depleted platelet concentrates (PCs) is justified, yet questions remain regarding their properties. We have assessed the in vitro quality of WBC-reduced PCs obtained by using a new in-line filter. MATERIALS AND METHODS: Twenty blood units were randomized for standard component preparation, or for processing including in-line leukodepletion of platelet-rich plasma using an ATS(TM) PL Pall filter. The resultant PCs were compared during storage for several in vitro platelet quality parameters, content of cytokines and anaphylatoxins, and coagulation markers. RESULTS: In-line filtration of platelet-rich plasma through ATS PL was highly efficient rendering PCs with 99.93% less white blood cells (WBCs) than standard PCs. During storage for up to 9 days, leukocyte-depleted units displayed platelet content, biochemical parameters, and platelet surface expression of glycoproteins Ibalpha, IIb/IIa, CD62 and CD63, similar to those of standard units. However, in-line leukocyte-reduced PCs displayed no significant accumulation of IL-6 and IL-8 during storage in contrast to standard units. Moreover, while storage promoted complement activation with C3a and C4a liberation in both WBC-reduced PCs and standard units, the concentration of these anaphylatoxins after the 9-day storage period was higher in the former group. Finally, all units, standard and leukocyte-reduced, displayed a similar storage-promoted rise in TGF-beta(1), and a mild prolongation of activated partial thromboplastin and prothrombin times. CONCLUSION: In-line filtration during component preparation appears as an easy and effective procedure for obtaining prestorage leukocyte-depleted PCs. During subsequent blood bank storage, these WBC-reduced PCs display, in comparison with standard PCs, normal in vitro platelet properties, decreased accumulation of cytokines IL-6 and IL-8, and increased complement activation.

Anaphylatoxins↗
PubMed2000

A common polymorphism flanking the ATG initiator codon of GPIb alpha does not affect expression and is not a major risk factor for arterial thrombosis.

The platelet membrane glycoprotein (GP) Ib alpha plays a key role in the initial formation of thrombi. Polymorphisms (VNTR and HPA-2) in this receptor are associated with increased risk of coronary heart disease (CHD) and cerebral vascular disease (CVD). We investigated whether a recently described polymorphism (S/R), due to a single base change (T-->C) five nucleotides upstream the initiator codon of GPIb alpha, might influence the expression of the protein, and be implicated in the development of arterial thrombosis. One hundred and thirty nine healthy individuals provided blood samples for DNA analysis of platelet GPIb alpha polymorphisms, and for flow cytometric analysis of the surface expression of the receptor. A group of 20 S/R normal individuals and an identical number of S/S participants, age and sex matched, was investigated for the analysis of the density of various platelet receptors. The distribution of the S/R polymorphism was also analyzed in two case/control studies including 104 CVD patients, 101 CHD patients, and one control age, sex, and environmental risk factors matched for each case patient. Surface density of GPIb alpha showed no wide variations between individuals, was not influenced by the presence of S or R alleles, nor associated with the VNTR or HPA-2 polymorphisms. The prevalence of the S/R genotype among CVD and CHD patients was not distinct from that in the control groups. We conclude that the S/R polymorphism of GPIb alpha, flanking the initiator codon of the receptor, does not seem to be associated with surface levels of the protein, and is not an independent risk factor for arterial thrombosis.

Adult↗
PubMed2000

The FXIII Val34Leu polymorphism in venous and arterial thromboembolism.

BACKGROUND AND OBJECTIVE: Several hereditary disorders affecting coagulation factors have been identified as prothrombotic risk factors. Recently, the common Val34Leu polymorphism of the A-chain factor XIII gene, associated with high factor XIII activity, has been identified as a protective genetic factor against occlusive arterial and venous diseases in British and Finnish populations. The aim of our study was to investigate the role of this polymorphism in arterial and venous thromboembolic disorders in a distinct population. DESIGN AND METHODS: We analyzed the prevalence of this polymorphism in three case/control studies of consecutive patients from the south of Spain diagnosed as having acute coronary syndromes (101), acute cerebrovascular events (104), and deep venous thrombosis (97). RESULTS: No significant differences were detected in the prevalence of genotypes or alleles between patients and controls. INTERPRETATION AND CONCLUSIONS: The Leu 34 allele does not play an important role in the development of thromboembolic episodes in the Spanish population.

Adult↗
PubMed2000

Black fungi: clinical and pathogenic approaches.

Data are presented on the clinically relevant black yeasts and their relatives, i.e., members of the Ascomycete order Chaetothyriales. In order to understand the pathology of these fungi it is essential to know their natural ecological niche. From a relatively low degree of molecular variability of the black yeast Exophiala dermatitidis, potential agent of brain infections in patients from East Asia, it is concluded that this species is an emerging pathogen, currently going through a process of active speciation. It is found to be an oligotrophic fungus in hot, moist environments, such as steambaths. Cladophialophora-, Fonsecaea- and Ramichloridium-like strains, known in humans as agents of chromoblastomycosis, are frequently found on rotten plant material, but the fungal molecular diversity in the environment is much higher than that on the human patient, so that it is difficult to trace the etiological agents of the disease with precision. This approach has been successful with Cladophialophora carrionii, of which cells resembling muriform cells, the tissue form of chromoblastomycosis, were found to occur in drying spines of cacti. Phagocytosis assays provide a method to distinguish between pathogens and non-pathogens, as the killing rates of strict saprobes proved to be consistently higher than of those species frequently known as agents of disease. The therapeutic possibilities for patients with chromoblastomycosis are reviewed.

Antifungal Agents↗
PubMed1999

Platelet cryopreservation using a reduced dimethyl sulfoxide concentration and second-messenger effectors as cryopreserving solution.

Cryopreservation of platelets is of great interest since it could extend to years the shelf life of therapeutic platelet concentrates (PCs) and facilitate stockpiling and inventory control in blood banking. We have compared the cryopreservation of PCs by the standard method using 6% Me(2)SO as cryoprotectant with the method of freezing employing low concentrations of Me(2)SO (2%) plus ThromboSol, a mixture of second-messenger effectors that protect platelets from cold damage. PC pools were treated either with 6% Me(2)SO or with ThromboSol and 2% Me(2)SO and then placed directly in a -80 degrees C freezer or in the vapor phase of a liquid nitrogen freezer (-120 degrees C). After storage for 1 week or for 3 months, samples were removed, thawed, and analyzed. Measurements included cell recovery, biochemical parameters, membrane glycoproteins (GPs), platelet aggregation, and binding of radiolabeled von Willebrand factor (vWF) and fibrinogen. PCs cryopreserved with ThromboSol and 2% Me(2)SO displayed a platelet recovery (90%) equivalent to those frozen with 6% Me(2)SO. Following either cryopreservation procedure, platelets showed increased surface expression of P-selectin and moderate loss of GP Ibalpha in comparison to fresh platelets. The aggregatory response to ristocetin and the binding of vWF were similar in platelets frozen by either procedure. Finally, both methods promoted comparable impairment of the reactivity of platelets to thrombin, aggregation and binding of fibrinogen and vWF, compared to that of fresh platelets. In summary, cryopreservation of PCs using reduced Me(2)SO concentration and ThromboSol yields platelets with in vitro functional characteristics equivalent to those of cells frozen with the conventional method using 6% Me(2)SO.

Blood Platelets↗