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Biomedical subjects

A Durántez

Publications and source records attributed to A Durántez.

At least 19 recordsLinked to original sources
PubMed2004

A sustained activation of PI3K/NF-kappaB pathway is critical for the survival of chronic lymphocytic leukemia B cells.

The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk-, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-kappaB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-kappaB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-kappaB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth.

Adult↗
PubMed2004

The dinucleotide repeat polymorphism in the 3'UTR of the CD154 gene has a functional role on protein expression and is associated with systemic lupus erythematosus.

OBJECTIVE: To investigate the association of the (CA)n dinucleotide repeat in the 3' untranslated region (3'UTR) of the CD154 gene with systemic lupus erythematosus (SLE), and its functional role in protein expression. METHODS: The allelic and genotypic distributions of the polymorphism were compared in 80 patients with SLE and 80 controls. A complete clinical and analytical database was recorded in each patient in order to correlate the clinical manifestations in SLE with different alleles. To investigate the functional role of the polymorphism, the CD154 protein expression on activated lymphocytes from healthy homozygous controls was evaluated by flow cytometry. RESULTS: The 24 CA allele was the most represented in controls (p = 0.029), whereas the alleles containing >24 CA repeats were found in patients (p = 0.0043). Furthermore, when only homozygous women were considered, most controls carried two 24 CA alleles (p = 0.041), whereas most patients carried two alleles containing >24 CA repeats (p = 0.032). Also, patients carrying at least one 24 CA allele had less neurological involvement (p = 0.034), and carriers of at least one allele with fewer than 24 CA repeats presented more livedo reticularis (p = 0.006) and anti-Sm (p = 0.01) and anti-RNP (p = 0.038) autoantibodies. CD154 maximum expression in activated lymphocytes from all controls was reached after 54 hours, but it was more prolonged in controls carrying two alleles with >24 CA repeats (p = 0.0068). CONCLUSION: The CD154 3'UTR microsatellite is associated with SLE, and the most represented alleles in patients were accompanied by a more prolonged protein expression in activated lymphocytes from controls.

3' Untranslated Regions↗
PubMed2003

Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL.

BACKGROUND: Recent evidence indicates that the slowly expanding population of CD5(+) B cells that characterizes B-cell chronic lymphocytic leukemia (B-CLL) could be related to defects in the response to cytokine produced by T cells that regulate apoptosis. We studied the intracellular expressions of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) in T-helper 1 cells (Th1 response) of B-CLL. METHODS: Peripheral blood mononuclear cells from 21 healthy individuals and purified T cells from 21 early-stage and 15 late-stage B-CLL patients were activated with phorbol myristate acetate and ionomycin. The Th1 cytoplasmic cytokines were evaluated in CD4(+) and CD8(+) T cells by flow cytometry. RESULTS: The percentages of CD4(+) and CD8(+) T cells positive for IL-2 were significantly lower in B-CLL patients than in healthy individuals (P = 0.030 and 0.049, respectively). No significant differences in TNF-alpha or IFN-gamma intracellular expressions were found between patients and healthy individuals. TNF-alpha- and IFN-gamma-expressing CD8 T cells were disease stage dependent, being significantly higher in late-stage patients (P < 0.001 for both cytokines). CONCLUSIONS: Our present observations suggested that Th1 cytokines may be of major importance in the pathogenesis of B-CLL.

Adult↗
PubMed2002

[Study of pulmonary lesions with (99m)Tc-Tetrafosmin and chest spect. Determination of uptake related factors, diagnostic value and prognosis].

One hundred fifteen patients with 119 pulmonary lesions in which malignancy was suspected underwent a SPECT study with 99mTc-Tetrofosmin (TTF) to assess the possible factors involved in the uptake of the radiopharmaceutical. The TTF uptake rate in the lung tumor with respect to that of healthy tissue (TTF index) was evaluated in terms of: benignity and malignancy, histological type, stage, cell differentiation, size, necrosis, survival and the influence of P-glycoprotein (Pgp), detected by immunohistochemistry, on the TTF uptake. The mean TTF index in the 18 benign lesions studied was 1.01 0.05, while that of the 101 malignant lesions was 1.59 0.45 (p < 0.001), with a positive predictive value of 97.7% and a negative predictive value of 50%. The comparison of the histological types, degree of cell differentiation, necrosis and stage revealed no statistically significant differences. With respect to size, those tumors measuring > 3 cm showed greater uptake than smaller lesions. In patients with non-small cell lung cancer, a positive relationship was observed between the TTF index and survival, a circumstance that did not occur in patients with small cell lung cancer. In the cases in which the presence of Pgp was assessed, there was an inverse relationship between the TTF ratio and Pgp expression. In conclusion, thoracic SPECT with 99mTc-TTF has a high positive predictive value for the presence of lung cancer, although a negative study does not rule out the existence of the disease. The reason for this is the inverse relationship between 99mTc-TTF uptake and the density of Pgp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

CD154 polymorphism in Spanish populations. Differences in the allelic distribution between Canary islanders and Peninsulars.

The CD154 gene contains a dinucleotide repeat (CA)n in the 3' untranslated region. Allelic distribution in Spanish populations from two areas with different genetic background, the Canary Islands and Peninsula, are described. Seven alleles with different allelic distribution between the two groups, were found. This represents a highly polymorphic marker, useful for genetic studies on a critical molecule in immunity.

3' Untranslated Regions↗
PubMed1999

Modulation of apoptosis by cytokines in B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the slow and progressive accumulation of monoclonal apparently mature, CD5(+) B lymphocytes. The majority of circulating cells appear to be nondividing, and it has been suggested that a prolonged life span is mainly responsible for the accumulation of the leukemic cells. However, spontaneous programmed cell death by apoptosis occurs when B chronic lymphocytic leukemia cells are cultured in vitro. This may be because of the lack of an unidentified essential cytokine present in vivo. Thus, we investigate interleukin-2 (IL-2), IL-4, IL-6 and IL-10 in vitro effects on apoptosis of B cells from 32 previously untreated patients with B-CLL in initial clinical stages. B cells were isolated from peripheral blood, and apoptosis was measured in these cells immediately after isolation and following incubation in vitro, without and with the different cytokines, for 24 and 48 h. Distribution of cellular DNA content and quantitative analysis of apoptosis were determined by standard propidium iodide staining and flow cytometry. Spontaneous apoptosis occurred in B-CLL cells incubated in vitro in the absence of cytokines. Our results indicate that both IL-2 and IL-4, but not IL-6, inhibit in vitro apoptosis in a large percentage of B-CLL patients. IL-10 increases in vitro apoptotic cell number in stage 0 patients, but not in stage I and II. These data support the hypothesis that IL-2 or IL-4, may be cell survival factors in vivo and that IL-10 might be a candidate for immune therapy of early B-CLL.

Adult↗
PubMed1999

Characterization of adrenal medullary chromaffin cells by flow cytometry.

BACKGROUND: Adrenomedullary chromaffin cells are neural crest derivatives widely used as a model system to study neurosecretory mechanisms. Morphological, immunohistochemical, and functional data indicate that chromaffin cells are heterogeneous and support the distinction between adrenaline (A)- and noradrenaline (NA)-producing and secreting cells. The aim of this study was to characterize by flow cytometry the two main chromaffin cell subtypes in suspensions of cultured bovine chromaffin cells. METHODS: An indirect immunofluorescence method was used for the specific labeling of two intracellular enzymes, dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), involved in the synthesis of NA and A, respectively. Flow cytometry analysis of fluorescence labeling was performed in two chromaffin cell fractions differentially enriched in A-containing cells by centrifugation through density gradients. PNMT and DBH-related fluorescence was also correlated with the A and NA content of the cells assayed by HPLC measurements. RESULTS: No significant differences were found in forward-side scatter plots between the two cell fractions (A-enriched cells and mixed cells); however, the degree of labeling of the enzymes and the corresponding PNMT/DBH-related fluorescence ratio was significantly greater in the A-enriched cell fraction. The existence of changes in DBH and PNMT content of chromaffin cells over time (1 week) in culture was also examined. No significant variation in enzyme related fluorescence values was detected in any of the two cell fractions, and this result correlated well with HPLC determinations of the catecholamine content (A and NA) of the cells. CONCLUSIONS: Flow cytometry appears to be a useful technique to characterize chromaffin cell subtypes and to follow their phenotypic changes in response to growth factors.

Adrenal Medulla↗
PubMed1999

[Preliminary study by flow cytometry of the cell cycle and DNA quantification in cytokeratin-positive cells in tumors of the head and neck].

DNA ploidy and cell-cycle distribution were determined by flow cytometry in fresh tumor tissue of 27 epithelial head and neck carcinomas. Epithelial cells were labeled with a fluorescein-isothiocyanate-conjugated cytokeratin antibody to study the possible influence of contaminating stromal and inflammatory cells on the results of cell-cycle analysis of tumor cells. The patient sample included 26 men and 1 women with a mean age of 60 years. Without cytokeratin gating, 11/27 tumors (40.74%) were aneuploid. After selecting the cytokeratin population, 10 more aneuploid tumors were found that had not been detected when considering the total population. Therefore, aneuploid tumors increased from 40.74% to 77.74%. The remaining 6/27 (22.26%) tumors were diploid. In the tumors that were either aneuploid without cytokeratin gating or diploid, the S-phase and G2M phase were significantly higher after cytokeratin staining, specially in diploid tumors (24.2% versus 10% and 6.8% versus 3.2%, respectively, p < 0.01). Therefore, in head and neck tumors cytokeratin staining optimizes both the determination of DNA ploidy and cell-cycle analysis, which is advantageous for tumor staging and prognosis assessment in these patients.

Adult↗
PubMed1998

Prognostic significance of natural killer cell activity in patients with laryngeal carcinoma.

BACKGROUND: For laryngeal carcinoma, the present TNM clinical staging system does not seem completely satisfactory as a guide for providing a prognosis for survival. We believe that natural killer cell activity would probably have a role in a more reliable system. Therefore, we analyzed the disease outcome with previously untreated epidermoid carcinoma of the larynx, evaluating classic clinical and pathologic factors, as well as natural killer cell activity in peripheral blood samples of the patients. OBJECTIVES: To determine the level of natural killer cell activity in patients with laryngeal carcinoma and to analyze the prognostic value of this finding when associated with other clinical and pathologic variables. DESIGN: Prospective cohort study of surveillance of laryngeal cancer. Mean follow-up of 42.8 months. SETTINGS: Tertiary care referral center and ambulatory and hospitalized care. PARTICIPANTS: We compared 81 men (mean age, 62.4 years; range, 35-89 years) with laryngeal carcinoma with 44 healthy men serving as control subjects (mean age, 57.6 years; range, 37-82 years). RESULTS: Natural killer cell activity was significantly reduced in patients who had died of cancer-related causes in comparison with tumor-free survivors. Overall actuarial survival differed significantly in histologically assessed nodal involvement and low natural killer cell activity. Use of the Cox proportional hazards regression model showed that the factors that seem to have a prognostic effect on survival are histologically determined nodal involvement and low natural killer cell activity. CONCLUSIONS: These results support the prognostic significance of the determination of pretreatment natural killer cell activity in peripheral blood samples from patients with laryngeal carcinoma and suggest that assessment of adding such a determination to the current tumor staging system is advisable.

Adult↗
PubMed1998

Physiological differences between professional and elite road cyclists.

The purpose of this study was to compare the physiological responses of professional and elite road cyclists during an incremental cycle ergometer test. Twenty-five elite cyclists (EC; 23+/-1 yr) and 25 professional cyclists (PC; 25+/-2yr) performed a ramp protocol (increases of 25 W x min(-1)) during which the following parameters were measured: oxygen consumption (VO2), pulmonary ventilation (VE), ventilatory equivalents for oxygen and carbon dioxide (VE x VO2(-1) and VE x VCO2(-1), respectively), respiratory exchange ratio (RER), ventilatory thresholds 1 and 2 (VT1 and VT2, respectively), blood lactate, and electromyographic activity (EMG) of the vastus lateralis. Significant differences existed between the two groups mainly at submaximal intensities, since both VT1 and VT2 occurred at a higher exercise intensity (p<0.001) in PC than in EC (VT2: 80.4+/-6.6 vs 87.0+/- 5.9% VO2max in EC and PC, respectively). Lactate levels showed a similar response in both groups at low-to-moderate intensities (< 300 W), and thereafter blood lactate was significantly higher in EC. Finally, the "electromyographic threshold" (EMGT) occurred at a significantly higher intensity (p < 0.05) in PC when compared to EC (64.7+/-14.2 vs 56.0+/-14.9% VO2max, respectively). It was concluded that, in comparison with EC, PC exhibit some remarkable physiological characteristics such as a high VT2, an important reliance on fat metabolism even at high power outputs, and several neuromuscular adaptations.

Adaptation, Physiological↗
PubMed1998

[Correlation between 99m Tc-tetrofosmin uptake and P-glycoprotein expression in non-small-cell lung cancer].

UNLABELLED: We used thoracic SPECT to study the 99mTc-tetrofosmin (TF) uptake in patients with non-small-cell-lung-carcinoma (NSCLC). The results were compared with the percentage of P-glycoprotein (Pgp) found in flow cytometric analysis (FC) of samples of surgically-resected tumor tissue. MATERIAL AND METHODS: A total of 21 patients with NSCLC were studied by means 99mTC-TF and thoracic SPECT. Image analysis included the determination of the TF uptake rate in the lung mass with respect to that of healthy tissue of the contralateral lung. These rates were compared with the percentage of Pgp expression according to FC. FC analysis was also carried out in 16 samples of healthy lung tissue obtained from the patients. RESULTS: In healthy lung tissue, the mean Pgp expression according to FC was 4.58 +/- 1.87%. The cutoff value used to differentiate between Pgp positive and Pgp negative tumors was considered to be the mean plus two standard deviations (8.32). The Pgp-positive tumors (> 8.32%) presented significantly lower uptake levels (1.28 +/- 0.39) than the Pgp-negative lesions (1.66 +/- 0.33) (p = 0.029). CONCLUSIONS: There is a inverse correlation between the Pgp expression as determined by FC analysis and 99mTc-TF in NSCLC. Thus, this radiopharmaceutical provides rapid and non-invasive information on Pgp expression in these lesions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Deficiency of naive T cells in patients with sudden deafness.

BACKGROUND: Although there are a number of reports concerned with the role of immunity in the sudden onset of progressive sensorineural hearing loss, there are few references dealing with the involvement of immune-mediated mechanisms in sudden deafness. OBJECTIVES: To study the phenotype of peripheral blood lymphocytes in a group of patients with sudden deafness by use of 3-color flow cytometry. DESIGN: The study was carried out prior to the start of steroid therapy. Fourteen patients underwent a follow-up study once steroid therapy had been completed. Prospective analysis, case-control. SETTING: Tertiary case referral center, ambulatory and hospitalized care. PATIENTS: Twenty-two patients (13 men and 9 women; mean age, 45.3 years) were compared with 14 healthy control subjects (9 men and 5 women; mean age, 36 years). Patients were divided in 2 groups according to their response to steroid therapy. RESULTS: Decreased numbers of both CD4+ helper cells (38.4% vs 45.5%; P = .04) and CD8+ cytotoxic cells (17.5% vs 22.3%; P = .02) were observed in patients and compared with those in the control subjects, as well as reduced numbers of CD4+CD45RA+ cells (14.4% vs 29.3%; P = .01) and CD8+CD45RA+ naive cells (18.2% vs 25.4%; P = .04). In the group of patients with a good response to steroid therapy (group 1), a tendency toward normalization of the CD4+ (pretreatment, 38.6%; posttreatment, 44.6%), CD4+CD45RA+ (pretreatment, 15.2%; posttreatment, 21.7%), and CD4+CD45RO+ (pretreatment, 21.1%; posttreatment, 18.2%) cell counts was observed, with a slight decrease in the CD8+ population (pretreatment, 18%; posttreatment, 15.7%). However, in patients with a poorer response (group 2), while there were increases in the CD4+ (pretreatment, 38%, posttreatment, 50%) and CD4+CD45RA+ (pretreatment, 12.8%; posttreatment, 16.7%) cell counts after steroid therapy, there was a significant increment in the CD4+CD45RO+ memory cell count (pretreatment, 14.1%; posttreatment, 28.5%) and low CD8+CD45RA+ counts (pretreatment, 14.6%; posttreatment, 15.5%). No differences were observed in the numbers of B or natural killer cells or in the presence of activation antigens CD25 and HLA-DR when pretreatment and posttreatment levels were compared. CONCLUSION: These results demonstrate significant abnormalities in the subpopulations of lymphocytes in patients with sudden hearing loss, suggesting the existence of immune-mediated responses in the inner ear as possible etiopathogenic factors in this entity.

Adolescent↗
PubMed1995

Natural killer cell activity in patients with pernicious anemia.

Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma that ranges from three- to fivefold greater than that of the general population. It has been reported that NK cells may be involved in immunosurveillance against tumor spread. The natural killer cell activity of peripheral blood mononuclear cells was analyzed in 22 patients with pernicious anemia and in 19 healthy controls. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of gastrin levels and time elapsed since diagnosis. According to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16+) were found in peripheral blood mononuclear cells from patients and healthy controls. Our results show that in pernicious anemia patients, the percentage of NK cells present in peripheral blood mononuclear cells and their lytic activity are normal.

Aged↗
PubMed1995

Functional defect of T cells in autoimmune gastritis.

The functional response and phenotypic characterisation of peripheral blood T cells were studied in 41 patients with autoimmune gastritis--nine patients with autoimmune gastritis alone, 11 with untreated pernicious anaemia, and 21 with resolved pernicious anaemia who were taking vitamin B-12. Phenotypic analysis showed no changes in the CD4/CD8 ratio in any group of patients. CD3+ cells were significantly decreased and CD16+ cells were significantly increased in patients with autoimmune gastritis alone. Phytohaemagglutinin induced T cell proliferation, with or without interleukin 2, was reduced in the three groups. T cell proliferation induced by phorbol myristate acetate was normal. Interleukin 2 production of phytohaemagglutinin-stimulated lymphocytes was normal in the three groups. Five patients with pernicious anaemia treated with vitamin B-12 were followed and persistent hypoproliferation of T cells in response to phytohaemagglutinin was observed. The follow up study of the phenotype of these patients showed a significant increase of the CD2+ CD3- lymphocyte population after six months' treatment. In conclusion, the three groups of autoimmune gastritis patients studied have a functional defect in T cells that is independent of B-12 treatment and of the presence of pernicious anaemia.

Aged↗
PubMed1995

Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease.

We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 +/- 15.9%), while in 32 euthyroid patients under antithyroid drug therapy. NK activity was similar to that of controls (46.9 +/- 17.3 and 49.9 +/- 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 +/- 17.9 to 48.1 +/- 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56+ and CD16+ cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 +/- 12.8 to 49.9 +/- 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗