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C Sanz

Publications and source records attributed to C Sanz.

At least 55 records · Page 3Linked to original sources
PubMed1998

Endothelin mediated nitric oxide effects in ischemia--reperfusion associated with pancreas transplantation.

Formation of nitric oxide (NO) in ischemia-reperfusion (I-R) associated with pancreas transplantation could modulate the inflammatory response. In this sense, previous studies have demonstrated the action of NO on vasoactive substances like prostacyclin or endothelin. The present study was designed to evaluate the contribution of endothelin to the inflammatory events induced by NO in the I-R process associated with pancreas transplantation. For this purpose, pancreatic levels of endothelin, neutrophil infiltration, and prostacyclin were evaluated in an experimental model of pancreas transplantation after inhibition of NO synthesis or after NO inhibition plus addition of endothelin. Results show significant posttransplantation increases in endothelin, neutrophil infiltration, and prostacyclin production. These increases were prevented by NO inhibition. Endothelin administration plus nitric oxide inhibition reversed this effect, resulting in an increase in myeloperoxidase and 6-keto-prostaglandin F1alpha. These results suggest that the proinflammatory effects of NO in I-R associated with pancreas transplantation are mediated by the induction of endothelin generation.

Animals↗
PubMed1998

Pathogenesis of polycythemia vera.

BACKGROUND AND OBJECTIVE: Polycythemia vera (PV) is an acquired clonal myeloproliferative disorder characterized by increased production of mature red cells. We still lack a molecular target responsible for this disorder; however, recent investigations have focused on a number of molecules involved in signal transduction pathways mediated by erythropoietin (Epo) and other growth factors. Here we review the implication of these molecules in the pathogenesis of PV. INFORMATION SOURCES: The material reviewed in this work includes articles published in journals covered by Medline. We also include data obtained in our laboratory regarding to the significance of apoptosis inhibitory proteins in erythroid development. STATE OF THE ART AND PERSPECTIVES: Overproduction of erythroid cells in PV is particular in that it occurs in the absence of a recognizable physiologic stimulus, since circulating serum levels of Epo are normal or lower than normal. Genetic analysis as well as in vitro studies, have established an essential role for Epo in the survival and maturation of committed erythroid progenitors. Epo initiates its cellular response by binding to the Epo receptor (EpoR) expressed on the surface of immature erythroblasts. Following ligand binding, EpoR is known to activate a cytoplasmic protein tyrosine kinase, Jak2 which triggers a signal transduction cascade that leads to the development of early erythroid progenitors into mature erythroblast cells. Although the mechanism underlying the increased erythroid production in PV is not well understood, a number of causes have recently came for which may provide insights not only for the pathogenesis of PV but also for a fundamental biological process: the mechanism whereby a multipotential stem cell gives rise to a particular cell lineage.

Animals↗
PubMed1998

[Correlation of flow and static cytometry; their application to the study of anaplastic lymphomas].

PURPOSE: DNA study by cytometric methods is one of the prognosis factors considered in malignant tumours. Flow cytometry (FCM) was the most frequently used techniques in cell suspensions. Image cytometry (ICM) was also applied in cellular smears and it is possible to measure the results with an Image Analyzer, which supposes a substancial advantage over DNA studies. To confirm the results and correlation of the two techniques a controversial subtype of lymphoid tumour was selected: Anaplastic large cell lymphoma (ALCL). MATERIAL AND METHODS: Fifty four cases of ALCL (23 classical type and 31 ACL-Hodgkin related) were studied. Cytometry was performed in paraffin-embedded tissues previously dewaxed, rehydrated and minced. FCM was done in suspensions incubated with ribonuclease A and stained with propidium iodide in an EPICS-C flow cytometer. ICM study was performed in Feulgen-stained smears and measured by an Image Analyzer CAS-200. RESULTS: All cases were aneuploid. ALCL were 30.5% hypodiploid (HpD) and 69.5% hyperdiploid (HrD) by FCM; 43.5% HpD and 56.5% HrD by ICM. ALCL-HR were 58% HpD and 42% HrD by FCM; 68% HpD and 32% HrD by ICM. There was a lack of correlation of 22% between both methods but it was not statistically significant. CONCLUSIONS: We can conclude the obtained results by FCM and ICM are almost similar.

Aneuploidy↗
PubMed1997

The expression of Bcl-x is downregulated during differentiation of human hematopoietic progenitor cells along the granulocyte but not the monocyte/macrophage lineage.

Expression of the apoptosis inhibitory protein Bcl-x was studied in CD34+ hematopoietic precursor cells and in the promyelocytic leukemia cell line HL-60. The enriched population of CD34+ cells (more than 95%) was cultured in the presence of stem cell factor, interleukin-3 (IL-3), IL-6, and either granulocyte colony-stimulating factor or macrophage colony-stimulating factor to achieve granulocyte or monocyte/macrophage differentiation, respectively. The expression of Bcl-x increased in the early stages of both differentiation pathways. However, by day 21 of culture mature granulocytes were Bcl-x-negative, whereas monocytes/macrophages either maintained or increased the expression of Bcl-x. The pattern of Bcl-x expression in the differentiated CD34+ cells was similar to that observed in HL-60 cells differentiated along the granulocyte lineage (induced by incubation with retinoic acid), or along the monocyte/macrophage lineage (induced by incubation with phorbol diester). The bcl-x transcript predominant in HL-60 and CD34+ cells differentiated into monocytes/macrophages was bcl-xL. Although little is yet known regarding the functional significance of Bcl-x within the granulomonocytic compartment, marked changes in the pattern of its expression, as observed during granulomonocytic differentiation of HL-60 and CD34+ cells, are likely to alter the life span of mature granulocytes and monocytes/macrophages.

Antigens, CD↗
PubMed1997

Glycosyl-phosphatidylinositol-phospholipase type D: a possible candidate for the generation of second messengers.

Membrane associated glycosyl-phosphatidylinositols have been shown to be the precursors of inositol phosphoglycan second messengers. Extraction of human liver membranes and purification by serial thin layer chromatography revealed three glycolipids which co-migrated with glycosyl-phosphatidylinositol from rat liver. These lipidic fractions were partially sensitive to treatment with nitrous acid and to hydrolysis by glycosyl-phosphatidylinositol-specific phospholipase D from bovine serum. In parallel, glycosyl-phosphatidylinositol isolated from rat liver was found to be a substrate for the enzyme generating a biologically active inositol phosphoglycan species (determined by measuring inhibition of protein kinase A activity and stimulation of cell proliferation within the chicken embryo cochleovestibular ganglion). This molecule was recognised by an anti-inositol phosphoglycan antibody. Hence, we propose that glycosyl-phosphatidylinositol-specific phospholipase D could be implicated in cellular signalling.

Animals↗
PubMed1997

Correlation between mutations in p53 gene and protein expression in human lymphomas.

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5-9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.5%) anaplastic large cell lymphoma (ALCL), and in 1 of 24 (4%) T-cell NHLs. Immunostaining with anti-p53 antibody DO-7 was possible in 87 lymphomas, and overexpression of p53 protein was observed in 16 cases (18%). A discrepancy between the results of SSCP and immunostaining was detected on 18 tumor samples. Two cases with mutations in the gene showed no altered protein expression and 16 cases overexpressed p53 protein had no point mutations. In these cases, the possibility that mutations occur outside the exons studied has been tested and the entire coding sequence analyzed. Only one case showed a mutation in exon 10, and we found two cases carrying a polymorphism in exon 4 and in intron 10. We conclude that mutations in p53 occur mainly in high-grade B-cell NHLs. Although not limited to a specific subtype of lymphoma, they may be rare in Hodgkin's disease and in low-grade lymphomas. The discrepancies between overexpression and presence of mutations suggest (1) the existence of another mechanism to stabilize the p53 protein, and (2) that the immunohistochemistry cannot be used to predict mutations in the gene.

Antibodies, Monoclonal↗
PubMed1997

Effects of erythromycin on chemoattractant-activated human polymorphonuclear leukocytes.

1. Erythromycin (2-100 micrograms ml-1) produced a concentration-related inhibition of superoxide generation and elastase release induced by in vitro exposure of human polymorphonuclear leukocytes (PMNs) to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP; 30 nM). 2. By contrast, erythromycin (100 micrograms ml-1) did not alter the leukotriene B4 production elicited by FMLP (30 nM; in the presence of thimerosal 20 microM) or the intracellular calcium changes promoted by FMLP (30 nM; in the absence or presence of thimerosal 20 microM). 3. These results indicate that by reducing chemoattractant-triggered release of oxidative and proteolytic mediators from human PMNs, erythromycin may have clinically useful antiinflammatory effects.

Anti-Inflammatory Agents↗
PubMed1997

Prolonged holding of whole blood at 22 degrees C does not increase activation in platelet concentrates.

OBJECTIVES: Platelets prepared after holding of whole blood overnight at 22 degrees C have a well-preserved metabolism. However, the possibility that such prolonged incubation with active granulocytes may increase platelet activation has not been fully tested. METHODS: We investigated this possibility by flow cytometric analysis of membrane glycoproteins (GPs) Ib and IIb/IIIa and the activation markers CD62P and CD63 in platelet concentrates (PCs) prepared from whole blood that was held for either 6 h without cooling plates (n = 20) or for 24 h on cooling plates of 1,4-butanediol (n = 20). PCs were prepared by the platelet-rich plasma method and analyzed on the second storage day. RESULTS: Platelet yield and aggregation response to ristocetin, collagen and epinephrine + ADP were similar in both types of PCs, as was the mean fluorescence intensity for GPs Ib and IIb/IIIa. PCs prepared by the overnight-hold method did not differ from those obtained 6 h after collection in the percentage of platelets expressing CD62P (12.3 +/- 6.2% vs. 14.1 +/- 4.0%; p > 0.1) or CD63 (9.8 +/- 6.4% vs. 8.8 +/- 3.6%; p > 0.1). CONCLUSION: Prolonged holding of whole blood at 22 degrees C prior to component preparation does not increase the level of platelet activation.

Adenosine Diphosphate↗
PubMed1997

Growth of bacteria in platelet concentrates obtained from whole blood stored for 16 hours at 22 degrees C before component preparation.

BACKGROUND: Previous studies have shown that cooling whole blood to 22 degrees C immediately after collection allows it to be held for up to 16 hours before component preparation (overnight-hold method) without a significant decrease in the quality of components obtained. A study was designated to evaluate the effect of the overnight-hold method on the growth of bacteria in experimentally contaminated blood units. STUDY DESIGN AND METHODS: Twenty whole-blood units were inoculated with Staphylococcus epidermidis (300 colony-forming units [CFU]/mL; n = 10) or Escherichia coli (50 CFU/mL; n = 10) immediately after collection. Half the units of each group were fractionated 6 hours after collection and the other half after storage for 16 hours at 22 degrees C. Twenty additional whole-blood units were divided in two equal parts, one of which was white cell reduced before inoculation. These 40 half-units were inoculated with S. epidermidis or E. coli and processed by the overnight-hold method. The growth of bacteria was assessed in platelet concentrates on the second and fifth days of storage, in packed red cells on Day 35, and in fresh-frozen plasma after 60 days. RESULTS: No bacteria growth was detected in plasma or red cell units. On the second day of storage, both bacteria strains grew more slowly in platelet concentrates obtained from blood processed by the overnight-hold method. This difference disappeared for S. epidermidis on the fifth day. When white cell-reduced and non-white cell-reduced whole-blood units were compared, platelet concentrates from the latter showed a delayed growth of both bacterial strains on the second and fifty days of storage. CONCLUSION: Prolonged storage of whole-blood units at 22 degrees C before component preparation delays bacteria growth. This effect seems to be mediated by white cells.

Blood↗
PubMed1997

Haemodiafiltration with sorbent-regenerated ultrafiltrate as replacement fluid: a multicenter study.

BACKGROUND: Uncoated adsorbent charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The objective of this study was to assess the safety and the long-term clinical results. METHODS: Thirty-three chronic uraemic patients were dialysed for 1 year using two haemodialysers in series in order to separate convection from diffusion. At the outflow of the convective haemofilter, a cartridge containing 130 g of uncoated charcoal was inserted. The regenerated ultrafiltrate was then infused at the entrance of the diffusive dialyser. Ex vivo and in vitro studies were performed to analyse the adsorption characteristics and the release of aluminium, other trace elements, and microparticles. RESULTS: Passage through the charcoal left urea, phosphate, potassium, calcium, and bicarbonate concentrations unchanged. Creatinine, uric acid and beta 2-microglobulin were almost completely absorbed by the charcoal. Aluminium release was dependent upon time of storage, as inferred from studies on inter-lot variability. Washing with bicarbonate buffer (pH 7.0) allowed reduction of aluminium levels to within the pharmacopoeia requirements for intravenous fluids. No significant pre- or post-charcoal differences were observed for several trace elements such as manganese, selenium, arsenic, cadmium, mercury, lead, chromium and zinc. Copper was completely retained in the charcoal. Regenerated ultrafiltrate infused at the entrance of the diffusive dialyser was free of microparticles, bacteria, and endotoxin. Clinical tolerance was excellent and blood pressure control satisfactory. A significant decrease in serum values of beta 2-microglobulin was observed at 6 and 12 months of treatment. CONCLUSIONS: Reinfusion of ultrafiltrate through an uncoated charcoal cartridge proved to be a safe, well-tolerated and simple technique. Further potential benefits of regenerated ultrafiltrate may also include the maintenance of acid-base balance with reinfusion of endogenous bicarbonate.

Adult↗
PubMed1997

In vivo evaluation of platelet activation by different cellulosic membranes.

This study was undertaken to evaluate platelet activation in vivo induced by different cellulosic membranes by measuring the expression of P-selectin on the platelet surface during hemodialysis in 9 uremic patients. Hollow fiber dialyzers of similar surface with different cellulosic membranes (Cuprophan, cellulose acetate, cellulose triacetate, and Hemophan) were evaluated and compared to a synthetic membrane (polysulfone). Blood samples were obtained before hemodialysis and from the efferent and afferent limbs 5 min after the beginning of dialysis. P-selectin exposure was evaluated by flow cytometry (FACScan) using a monoclonal antibody (RUU 2.17). The percentage of platelets expressing P-selectin before hemodialysis and the percentage from the arterial line during hemodialysis were similar. All membranes evaluated induced platelet activation (estimated as the increase in percentage of platelets expressing P-selectin in samples obtained from the venous line with respect to the arterial line). Cuprophan induced more platelet activation than any other membrane (p < 0.05). The activation induced by cellulose acetate and cellulose triacetate membranes was also higher than that observed with Hemophan (p < 0.05). Hemophan-induced platelet activation was similar to that of polysulfone. These results indicate that all cellulosic membranes induce platelet activation during hemodialysis although there are quantitative differences among them. While Cuprophan induced the highest degree of platelet activation, Hemophan was the only cellulosic membrane that showed a degree of platelet activation similar to the biocompatible membrane polysulfone.

Adult↗
PubMed1997

[The study of prognostic factors of spontaneous subarachnoid hemorrhage].

INTRODUCTION: The subarachnoid haemorrhage non traumatic assumes between the 6-8% of all acute cerebrovascular, besides is more frequent in young persons. The mortility and mortality is high and the predictive factors of the worse prognostic in unknown. MATERIAL AND METHODS: In the present work, we realized a study of the patients admitted to our intensive care unite (UCI) a cause of the subarachnoid haemorrhage during the last ten years. In the same time of admitted to the UCI we applied Glasgow coma scale. Apache II and Hunt-Hess scale. The clinic dates analyzed were sex, age, glycemia, rate heart, middle arterial pressure, intraventricular haemorrhage and arrhythmias. The number of patients was the 100 the 68% were female and the 32% were male. The middle age was 48,98 +/- 21,82 years-old. RESULTS: We obtained a worse prognostic in the 58%, versus in the 42% of the patients and the prognostic factors were Glasgow coma scales. Hunt-Hess scale, rate heart, middle arterial pressure, glycemia, intraventricular haemorrhage and arrhythmias.

Adult↗
PubMed1997

[Value of protein 53 expression in lymphoma. Its correlation with genetic mutations].

PURPOSE: p53 is a tumour suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. We have tried to establish the value of expression of the p53 protein in malignant lymphomas and its correlation with the presence of structural gene abnormalities. MATERIAL AND METHODS: 230 cases of lymphomas (11 Hodgkin's disease and 219 non-Hodgkin's) were studied by immunohistochemistry using an anti-p53 monoclonal antibody (DO-7, DAKO). Sections were heated by pressure cooker in 0.01 M sodium citrate buffer pH 6 as a method for antigen unmasking. The quantification of levels of nuclear p53 protein were measured with an Image Analyzer (CAS-200, Becton-Dickinson S.A.). We have also searched for mutations in a series of 94 lymphomas using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in exons 5 to 9 of the p53 gene and the sample showing abnormal pattern were sequenced. RESULTS: p53 immunoreactivity has been detected in 82.6% of cases. The percentage of positive cells varies in a wide range which was divided into 0% (17.39%), less than 5% (57.39%), between 5-10% (13.91%) and more than 10% (11.30%). In all lymphoma subtypes, we have found the majority of cases show levels less than 10% and few more than 10%. We found abnormal bands in 9 of 94 lymphomas with different diagnosis (1 ALCL, 1 T-LNH, 2 B-LNH, 2 centroblastic, 1 lymphoblastic and 2 MALT). Two cases resulted to be a silent base change which not alter the function of the p53 protein and represent a common polymorphism. Seven cases showed single base pair missense mutations in all of them. Mutations in codons 179, 248 and 273 correspond to some of the typical hotspots described in p53 gene. CONCLUSIONS: p53 expression, is a frequent finding in malignant lymphomas, is variable and relates to histological subtype. The results suggest that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53 because the existence of cases with discrepancies between overexpression of the protein and presence of mutations.

DNA Mutational Analysis↗
PubMed1996

Characterization of three potato lipoxygenases with distinct enzymatic activities and different organ-specific and wound-regulated expression patterns.

Lipoxygenases are ubiquitous enzymes in eukaryotes. In plants, lipoxygenases are involved in the synthesis of the hormone jasmonic acid that regulates plant responses to wounding and, in addition, is an inducer of tuberization in potato. We have isolated potato lipoxygenase cDNA clones. From their deduced amino acid sequences, three distinct classes are defined (Lox1, Lox2, and Lox3). They are encoded in gene families that display organ-specific expression, lox1 being expressed mostly in tubers and roots, lox2 in leaves, and lox3 in leaves and roots. Consistent with their organ-specific expression pattern, Lox1 expressed in bacteria preferentially uses as substrate linoleic acid, abundant in membrane lipids of tubers, whereas linolenic acid, prevalent in leaves, is the preferred substrate for the other two classes of lipoxygenase. Analyses on reaction products of the enzymes expressed in bacteria reveal that Lox1 primarily produces 9- hydroperoxides. In contrast, the jasmonic acid precursor, 13-hydroperoxylinolenic acid, is the major product of the action of Lox2 and Lox3 on linolenic acid. Upon wounding, the levels of Lox2 and Lox3 transcripts rise markedly in leaves. While Lox3 mRNA accumulation peaks as early as 30 min after wounding, Lox2 shows a steady increase over a 24-h time course, suggesting different roles for these lipoxygenase isoforms in the synthesis of the plant hormone jasmonic acid.

Amino Acid Sequence↗
PubMed1996

Influence of the red blood cell preparation method on the efficacy of a leukocyte reduction filter.

The performance of a leukocyte reduction bedside filter with different types of RBC concentrates was analyzed. Three types of RBCs were prepared: buffycoat-depleted RBCs suspended in saline-adenine-glucose-mannitol (SAGM)-additive solution (BC-RBCs; n = 20), RBCs suspended in SAGM-additive solution without buffy coat removal (SAGM-RBCs; n = 20), and RBCs drawn in CPDA-I conservative solution and processed for component preparation by the platelet-rich plasma method (CPDA-RBCs; n = 20). The units were filtered within 8 h of collection. One filter was used for every 2 units. High numbers of residual WBCs were found even in the units filtered first. Filtration of CPDA-RBCs resulted in a higher residual WBC content than SAGM-RBCs or BC-RBCs (p = 0.0032 and p = 0.0002, respectively). The filter performance strikingly decreased when the WBC load per filter exceeded 4 x 10(9) or the platelet load was less than 100 x 10(9). We conclude that filter performance varies with the WBC and platelet content of the RBC concentrates. Under the experimental conditions assayed in this study CPDA-RBCs are the least appropriate ones to be used for bedside leukocyte reduction.

Blood Transfusion↗
PubMed1996

Procoagulant effect of incompatible platelet transfusions in alloimmunized refractory patients.

The clinical effectiveness of platelet transfusion in refractory patients is still a subject of debate. We have evaluated the possible hemostatic effect of platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet counts were less than 20,000/microliters. Platelet concentrates were always obtained by apheresis procedures from incompatible donors. The posttransfusion platelet recovery was greater than 15% only in 3 cases. In the first 6 patients, measurements of bleeding time performed immediately before transfusion were in all cases longer than 30 min and did not change significantly 10 and 60 min after platelet transfusions. In all patients, ex vivo perfusion experiments with Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were performed immediately before and 10 and 60 min after transfusion. No difference in platelet deposition onto the subendothelial surface was observed after platelet transfusion. Unexpectedly, the deposition of fibrin on the subendothelial surface was statistically augmented in the posttransfusion studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed statistically significant elevations (p < 0.01) in the posttransfusion samples (31.9 +/- 12.6 vs. baseline 5.8 +/- 1.7 ng/ml), not justified by TAT levels in the transfused material (2.3 +/- 0.17 ng/ml). Transfusion of incompatible platelets to refractory patients may activate coagulation mechanisms in the absence of an increase in peripheral platelet count.

Blood Group Incompatibility↗