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Biomedical subjects

V Vila

Publications and source records attributed to V Vila.

At least 19 recordsLinked to original sources
PubMed2006

Diagnostic usefulness of inflammatory markers in acute cellular rejection after heart transplantation.

BACKGROUND: Acute cellular rejection (ACR) affects early morbidity and mortality after heart transplantation. The diagnostic technique of choice is endomyocardial biopsy. Our aim was to evaluate the diagnostic usefulness of inflammatory markers as a noninvasive method to monitor cellular rejection. MATERIAL AND METHODS: We prospectively analyzed 73 cardiac transplant patients by determining the serum levels of protein fibrinogen (fgpro), functional fibrinogen (fgfun), C-reactive protein (CRP), and sialic acid (SA) coinciding with an endomyocardial biopsy (5.1 revisions/patient). The statistical methods were chi(2), Student's t-test, and ROC curves. RESULTS: Of the 373 controls, significant rejection was detected in 19%. Analysis of the relationship between ACR and the markers showed significantly elevated levels of fgpro (345 +/- 90 versus 307 +/- 74 mg/dL; P = .03), fgfun (361 +/- 101 versus 318 +/- 89 mg/dL; P = .04), and SA (74 +/- 22 versus 66 +/- 15 mg/dL; P = .02), but not CRP (19 +/- 29 versus 10 +/- 21 mg/dL; P = .07). SA displayed a better diagnostic utility (area under the curve 0.7; P < .01), 35% sensitivity, 85% specificity, and 82% negative predictive value for a cutoff point of 80 mg/dL. CONCLUSIONS: Among the inflammatory markers increased in ACR, SA was the most useful noninvasive tool for screening.

Acute Disease↗
PubMed2001

Relationship between fibrinogen protein and fibrinogen function in postmyocardial infarction patients.

The present study investigates the association between increases in the concentration and function of plasma fibrinogen in two groups of patients with chronic ischemic heart disease (11 with recurrent ischemic events and 19 free of these episodes) and in 34 healthy controls. The fibrinogen function index (fibrinogen function per unit of fibrinogen protein) (FgFI) was used as a measure of the fibrinogen clotting potential. The prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) were used as procoagulant markers. Plasma sialic acid (SA) was also evaluated as an inflammatory marker. No differences were found between FgFI (1.06+/-0.13 vs. 1.02+/-0.13), F1+2 (1.2+/-0.5 vs. 1.1+/-0.4 nmol/l) and TAT (2.5+/-1.3 vs. 2.5+/-0.7 microg/ml) in postinfarction patients without recurrent coronary ischemic events and the control group. However, postinfarction patients who suffered recurrent coronary ischemic events had significantly higher FgFI than patients without these symptoms (1.19+/-0.09 vs. 1.06+/-0.13), P<.01) and than the control group (1.19+/-0.09 vs. 1.02+/-0.13, P<.001). Moreover, the F1+2 (1.4+/-0.5 vs. 1.1+/-0.4 nmol/l, P<.05) and TAT (3.6+/-3.3 vs. 2.5+/-0.7 microg/ml, P<.05) were significantly higher in patients who suffered recurrent coronary ischemic events than in the control group. However, F1+2 and TAT were not different between patients with and without these symptoms. The fibrinogen protein (Fg-protein) concentration and high molecular weight fibrinogen (HMW-Fg) levels were significantly higher in both postinfarction patient groups than in the control group and in postinfarction patients with recurrent coronary ischemic events than in postinfarction patients without these symptoms. The plasma SA levels were significantly increased in postinfarction patients with and without recurrent coronary ischemia as compared with the control group. A positive correlation was found between fibrinogen and SA levels (r=.5, P<.01). In conclusion, our study indicates that the procoagulant factors, among which we include fibrinogen, F1+2 and TAT play a very active role in recurrent ischemic events in postmyocardial infarction patients. High plasma concentrations of both fibrinogen and SA suggests that fibrinogen becomes elevated as a consequence of inflammatory processes. The FgFI as an indicator of clotting potential of fibrinogen appears to be associated with ischemic events in chronic coronary artery disease.

Adult↗
PubMed2001

Changes in osteocalcin response to 1,25-dihydroxyvitamin D(3) stimulation and basal vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin.

Age-related osteopenia is known to occur differently throughout the skeleton. In the present study, we examine the influence of donor age (<50 and >50 years), and bone structure (cortical vs. trabecular) on osteocalcin and vitamin D receptor (VDR) expression in primary cultures of human osteoblastic cells (hOB) cells. Cells were isolated from trabecular bone samples obtained from donors undergoing either knee (mainly trabecular) (n = 22; 4 <50 years, 18 >50 years) or hip (mainly cortical) (n = 16; 6 <50 years, 10 >50 years) arthroplasty. Pooling the results from knee and hip hOB cell cultures, we found that secreted osteocalcin was higher in hOB cells from the younger donors, compared with that in older donors, and peaked after stimulation with 10(-6)--10(-8) mol/L 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. In cells from the latter donors, this secretion was maximal after 10(-6) mol/L 1,25(OH)(2)D(3) treatment. On the other hand, using reverse transcription followed by polymerase chain reaction, baseline osteocalcin mRNA was found to be lower in hOB cells from the older donors than in those from younger donors. After treatment with 10(-6)--10(-8) mol/L 1,25(OH)(2)D(3), osteocalcin mRNA increased over baseline in all groups of hOB cells studied. In age-matched cultures, both basal and 10(-6)--10(-8) mol/L 1,25(OH)(2)D(3)-stimulated osteocalcin mRNA showed similar values in hOB cells from both skeletal sites in younger donors. However, in the older donors, baseline as well as 10(-8) mol/L 1,25(OH)(2)D(3)-stimulated osteocalcin mRNA were higher in knee hOB cells than in hip hOB cells. Furthermore, baseline VDR mRNA expression was also higher in the former cells than in the latter cells in the older group. Considering the influence of donor age at each skeletal site of origin, we found lower baseline osteocalcin and VDR mRNA levels in hip hOB cells in the older group than in the younger group. Our findings indicate that the response of osteocalcin secretion and its mRNA to physiological doses of 1,25(OH)(2)D(3) decreases with aging and is associated with decreased VDR mRNA expression in hOB cells from mainly cortical bone.

Adult↗
PubMed2001

Effects of unfractionated and low molecular weight heparins on plasma levels of hemostatic factors in patients with acute coronary syndromes.

BACKGROUND AND OBJECTIVES: Unfractionated heparin (UFH) and enoxaparin (low molecular weight heparin) constitute fundamental therapies in the treatment of patients with acute coronary syndrome (ACS). Since enoxaparin appears to offer clinical advantages over UFH in managing ACS, markers of thrombin generation, endothelial function and acute phase response could manifest different responses to UFH or enoxaparin. The purpose of the present study was to investigate the effect that treatment with either UFH or enoxaparin has on plasma hemostatic markers in 24 patients with ACS. DESIGN AND METHODS: The patients were randomized to receive 5,000 IU intravenous bolus and continuous infusion of 18 IU/Kg/h UFH (n=11) or 1 mg/kg/12h subcutaneous enoxaparin (n=13). The plasma levels of fibrinogen (Fg), prothrombin fragment 1+2 (F1+2), thrombin antithrombin complex (TAT), von Willebrand factor (vWF), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were assayed at admission and 6, 12, 24 and 48 hours after heparin treatment. RESULTS: Upon admission, UFH and enoxaparin patients showed a significant increase in all the hemostatic parameters measured with respect to the levels in the control subjects. In comparison with the baseline levels of the UFH- and enoxaparin-treated patients, Fg showed a significant increase at 48 h and TFPI at 6, 12 and 24 hours. However, at 48 hours TFPI levels were not significantly higher than the basal values. There were no significant changes in F1+2, TAT, vWF or TF. INTERPRETATION AND CONCLUSIONS: Markers of thrombin generation, endothelial function and acute-phase reactants manifest a similar response to UFH and enoxaparin. An increase in thrombin generation may be a result of persistently activated inflammatory and endothelial processes, despite UFH and enoxaparin treatment.

Acute Disease↗
PubMed1999

Elevated high molecular weight fibrinogen in plasma is predictive of coronary ischemic events after acute myocardial infarction.

This study investigates the association between the concentration and function of plasma fibrinogen molecules measured at the time of hospital admission in patients with acute myocardial infarction (AMI), with reference to the risk of new coronary ischemic events during a three-day follow-up period of. Before starting fibrinolytic and anticoagulant treatment plasma fibrinogen, high molecular weight fibrinogen (HMW-fibrinogen), fibrin formation rate (FbFR) and phosphorous content in fibrinogen were determined in 90 AMI patients. During a three-day follow-up period 12 patients suffered new ischemic events. The 12 patients with coronary ischemia had higher concentrations of plasma fibrinogen (312+/-23 vs. 270+/-73 mg/dl, p<0.05) and HMW-fibrinogen (246+/-35 vs. 189+/-23 mg/dl, p<0.001) and a higher FbFR (65+/-30 vs. 40+/-25, p<0.001) than patients without these events. No association was found between the phosphorous content in fibrinogen and new coronary ischemic events. We conclude that after myocardial infarction an elevated plasma level of HMW-fibrinogen and a high FbFR value at the time of hospital admission are associated with new coronary ischemic events during a three-day follow-up period.

Aged↗
PubMed1998

Anterior pituitary development and Pit-1/GHF-1 transcription factor.

Anterior pituitary differentiation is a well-established paradigm in mammalian organogenesis. PIT1/GHF1, a homoeotic gene, plays a key role in terminal pituitary differentiation. Recently, a new set of transcription factors involved in early pituitary differentiation have been identified: Lhx-3, Lhx-4, P-OTX and Prop1. A pituitary-specific transcriptional cascade regulating a developmental programme leads to the determination of the mature cell types.

Animals↗
PubMed1997

Molecular cloning of gilthead seabream (Sparus aurata) pituitary transcription factor GHF-1/Pit-1.

We report here the complete nucleotide sequence of a cDNA clone encoding Sparus aurata GHF-1/Pit-1 isolated from an expression library prepared from gilthead seabream pituitary gland poly(A)+ RNA. The cDNA sequence (saGHF-1/Pit-1) encodes a protein of 371 amino acids (aa) containing a POU domain (aa 194-343) and a transactivation, STA domain (aa 1-128). Northern blot hybridization of pituitary RNA detected a single 3.0 kb band and a rat GHF-1/Pit-1 antiserum was found to immunoreact with pituitary protein species of 42 kDa by Western blot analysis. When compared with mammalian GHF-1/Pit-1 aa sequence, the POU and STA domains of saGHF-1/Pit-1 protein show 83% and 48% aa identity, respectively. In spite of the low homology of the transactivation domain, saGHF-1/Pit-1 is able to activate the transcription of the human growth hormone promoter.

Amino Acid Sequence↗
PubMed1997

The effect of thrombin on the dynamic exchange between intraplatelet and extraplatelet fibrinogen.

We examined the distribution of platelet fibrinogen and the exchange between intra- and extra-platelet fibrinogen in unstimulated and thrombin-stimulated platelets. In unstimulated platelets 60% of platelet fibrinogen was found in the soluble platelet fraction and 40% in the insoluble one. In platelets activated with thrombin, changes took place in the distribution of intraplatelet fibrinogen but not in the total fibrinogen content. At > or = 0.5 U/ml of thrombin the fibrin(ogen) content of the insoluble and soluble fractions was approximately 80% and 20%, respectively. When we evaluated how extraplatelet fibrinogen affects the content and distribution of intraplatelet fibrinogen, we found that when unlabelled fibrinogen was added to unstimulated and thrombin-stimulated platelets the content and distribution of intraplatelet fibrinogen remained unaltered. However, when 125I-fibrinogen was added, it was incorporated into unstimulated and thrombin-stimulated platelets. In unstimulated platelets, 70% of the incorporated 125I-fibrinogen was in the soluble fraction and 30% in the insoluble. In thrombin-stimulated platelets the distribution of the incorporated 125I-fibrinogen was 62% and 38% in soluble and insoluble fractions respectively. MoAb to GPIIb-IIIa produced 80% and 60% inhibition of 125I-fibrinogen incorporation by unstimulated and thrombin-stimulated platelets. Our data showed dynamic exchange between intraplatelet and extraplatelet fibrinogen both in unstimulated and thrombin-stimulated platelets mediated mainly by GPIIb-IIIa.

Blood Platelets↗
PubMed1994

Prevalence of mental disorders among children in Valencia, Spain.

A 2-stage survey was carried out to establish the point-prevalence of mental disorders and help-seeking behaviour in children aged 8, 11 and 15 living in the city of Valencia. Global prevalence rates, rates by age and rates by sex, as well as rates of specific diagnosis according to DSM-III-R criteria are described. Help-seeking behaviour was found to be related to an interaction between internalizing and externalizing symptoms and sex.

Adolescent↗
PubMed1993

Studies on the functionality of newly synthesized fibrinogen after treatment of acute myocardial infarction with streptokinase, increase in the rate of fibrinopeptide release.

In 15 patients with acute myocardial infarction who received 1,500,000 U of streptokinase, the gradual appearance of newly synthesized fibrinogen and the fibrinopeptide release during the first 35 h after SK treatment were evaluated. At 5 h the fibrinogen circulating in plasma was observed as the high molecular weight fraction (HMW-Fg). The concentration of HMW-Fg increased continuously, and at 20 h reached values higher than those obtained from normal plasma. HMW-Fg represented about 95% of the total fibrinogen during the first 35 h. The degree of phosphorylation of patient fibrinogen increased from 30% before treatment to 65% during the first 5 h, and then slowly declined to 50% at 35 h. The early rates of fibrinopeptide A (FPA) and phosphorylated fibrinopeptide A (FPAp) release are higher in patient fibrinogen than in isolated normal HMW-Fg and normal fibrinogen after thrombin addition. The early rate of fibrinopeptide B (FPB) release is the same for the three fibrinogen groups. However, the late rate of FPB release is higher in patient fibrinogen than in normal HMW-Fg and normal fibrinogen. Therefore, the newly synthesized fibrinogen clots faster than fibrinogen in the normal steady state. In two of the 15 patients who had occluded coronary arteries after SK treatment the HMW-Fg and FPAp levels increased as compared with the 13 patients who had patent coronary arteries. These results provide some support for the idea that an increased synthesis of fibrinogen in circulation may result in a procoagulant tendency. If this is so, the HMW-Fg and FPAp content may serve as a risk index for thrombosis.

Adult↗
PubMed1990

Insulin-like growth factor-I supports proliferation of autocrine thymic lymphoma cells with a pre-T cell phenotype.

We have studied the phenotypic characteristics and growth properties of murine T lymphoma cell lines derived from primary x-ray-induced thymic lymphomas at the earliest stage at which they can be detected, and well before spreading to other organs has occurred. These cell lines serve as model systems for the earliest events in T cell lymphoma induction, before tumor cell progression and spreading to other organs. We find that primary x-ray-induced T cell lymphoma lines have phenotypic characteristics of thymic pre-T cells and show no proliferative response to any of the IL tested nor to other hematopoietic growth factors. However, they do proliferate in response to insulin-like growth factor I (IGF-I) and to a small autocrine peptide distinct from IGF-I, which we term lymphoma growth factor. One of the earliest lesions in T cell lymphoma induction may therefore be an inhibition of differentiation at one of several specific points. In its early stages, T lymphoma cell growth may be restricted to an environment where local concentrations of specific growth factors such as IGF-I or lymphoma growth factor are sufficiently high.

Animals↗
PubMed1990

Hypercoagulable state after thrombolytic therapy in patients with acute myocardial infarction (AMI) treated with streptokinase.

Fibrinogen activity was studied in 70 patients with AMI who were treated with an intravenous infusion of SK (800,000 U/30 min or 1.5 mill U/60 min). Patients received a continuous infusion of heparin after thrombolytic therapy was completed. 800,000 U and 1.5 mill U SK recanalized infarct-related arteries at a rate of 78%. Early re-infarction occurred in 6% in each group. Upon admission to the hospital patients showed a hypercoagulable state that may be related to an elevated level of fibrinogen and HMW fibrinogen (70.5 +/- 2 vs 65 +/- 2% in patient and normal plasmas, respectively) that changed to a transitory hypercoagulable state indicated by decreased fibrinogen levels after SK treatment. Forty-eight hours after SK, a new fibrinogen hyperfunction, related to an increase in fibrinogen level and especially HMW synthesized fibrinogen (82 +/- 1 or 81 +/- 1%, 800,000 and 1.5 mill U SK, respectively) was observed, which was neutralized by heparin therapy (1,660 U/h with continuous infusion). The elevated levels of fibrinogen (363 +/- 21 vs 240 +/- 8 mg/dl in patient and normal plasmas, respectively) and HMW fibrinogen (70 +/- 3% with both SK hypercoagulable state that is not neutralized by the heparin dose were compared with those whose arteries recanalized. The former group had a higher concentration of fibrinogen (197 +/- 31 vs 147 +/- 18 mg/dl), HMW fibrinogen (78 +/- 0.5 vs 74 +/- 0.3%, respectively), and FPA (130 +/- 3 vs 6 +/- 4 pmol/ml) and more extensive fibrin gel formation kinetics (gelation rate 3.3 +/- 1.4 vs 1.1 +/- 0.2 OD/s x 10(-4), respectively) than the second group. The hypercoagulable state found in patients with acute myocardial infarction undergoing thrombolytic therapy may be related mainly to the progression of HMW fibrinogen and fibrinogen levels.

Adult↗
PubMed1990

Homozygous deletion of the retinoblastoma gene in an acute lymphoblastic leukemia (T) cell line.

Human leukemia cell lines were examined for the status of the retinoblastoma (RB) protein by immunoblotting analysis using antibodies raised against the TrpE-RB fusion protein. One of 16 cell lines examined, the T-cell acute lymphoblastic leukemia (ALL) line HSB-2, lacked the 110-Kd RB protein. Southern blot analysis of genomic DNA extracted from HSB-2 cells showed a large homozygous deletion of the RB gene, stretching from exon 18 beyond exon 27. Northern blot analysis showed multiple, abnormal RB transcripts in HSB-2. A truncated protein (72 Kd) was detected with 35S-methionine labeling but not with 32P-orthophosphate labeling of the HSB-2 cells. The genomic deletion of greater than 85 kb DNA at the RB locus (13q14) was not detectable in the karyotype of the HSB-2 cells. Among the 16 human leukemia cell lines examined for the status of the RB gene, only one, the HSB-2 line, showed an abnormal RB protein. Further study of primary leukemia and lymphoma samples appears to be warranted.

Blotting, Northern↗
PubMed1989

Human fibrinogen heterogeneity. A study of limited fibrinogen degradation.

Different fibrinogen species were examined in normal plasma following urokinase treatment, in isolated high molecular weight fibrinogen treated with plasmin and in plasma samples from patients with acute myocardial infarction receiving thrombolytic therapy. In normal plasmas two main fibrinogen species (Mr = 340,000 and Mr = 320,000) and an intermediate fragment (Mr = 330,000) were observed. The 340,000 fibrinogen was the most sensitive to degradation; it gave rise to 330,000 and 320,000 species. Degradation of isolated 340,000 fibrinogen was similar to plasma fibrinogen degradation. After thrombolytic therapy in acute myocardial infarction patients, when the plasma fibrinogen decreased near to zero, the new synthesized fibrinogen was 340,000 form. 'In vivo' conversion of 340,000 to 320,000 fibrinogen, associated with the transitory 330,000 form, was observed. The coagulation study of plasma fibrinogen showed that when Mr 340,000 fibrinogen decreased (40%), the gelation rate decreased and lag time increased drastically. The high 340,000 fibrinogen content found in acute myocardial infarction patients gave rise to the hypercoagulable state.

Blood Coagulation↗
PubMed1988

The role of protein kinase C in T lymphocyte proliferation. Existence of protein kinase C-dependent and -independent pathways.

The mouse cytotoxic T cell clone (CTLL-2) was able to grow in the presence of culture medium supplemented only with transferrin, 2-mercaptoethanol, and recombinant interleukin 2 (IL-2). This lymphokine stimulated the synthesis of DNA in these cells. Similarly, phorbol esters, which activate protein kinase C, induced DNA synthesis in this clone. Furthermore, this later proliferation was not blocked by anti-IL-2 receptor antibodies, which inhibited IL-2-induced proliferation, suggesting that it was not indirectly due to the secretion of IL-2 by the cells. CTLL-2 cells pretreated with high doses of phorbol esters for 48 h down regulated protein kinase C and were depleted of this enzyme. This was shown by: 1) purification and in vitro assay of protein kinase C; 2) the lack of effect of phorbol esters in the stimulation of the Na+/H+ anti-porter which has been directly linked to the activation of protein kinase C. As expected, those protein kinase C-depleted cells no longer synthesized DNA and proliferated in response to phorbol esters. However, they proliferated identically to control cells in response to IL-2. Therefore, our results suggest two different pathways for T cell proliferation, one which involves protein kinase C and the other which does not.

Animals↗