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Biomedical subjects

C Gutiérrez

Publications and source records attributed to C Gutiérrez.

At least 19 recordsLinked to original sources
PubMed2006

Enrichment of CD4+ CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids.

OBJECTIVES: To characterise and quantify the CD4+ CD25+ T cell population in patients with systemic lupus erythematosus (SLE) and to detect the possible influence of treatments and clinical manifestations. METHODS: Characterisation of CD25(low) and CD25(high) CD4+ T cells from healthy controls and from patients with SLE was carried out using flow cytometry, analysing the expression of activation and differentiation markers. The percentage of both circulating cell subsets was determined in 56 controls and 110 unselected patients with SLE. Data were related to treatment during the past 3 months and to various clinical manifestations. RESULTS: CD4+ CD25(high) lymphocytes from controls expressed low levels of CD69, CD154 or CD30, but also expressed glucocorticoid-induced tumour necrosis factor receptor, high levels of intracellular cytotoxin T lymphocyte-associated antigen 4, CD45RO and diminished amounts of CD4, all of which are phenotypic characteristics of natural regulatory T cells. CD4+ CD25(low) cells, on the other hand, expressed the highest levels of activation markers, indicating that they represent recently activated effector cells. Similarly, analysis of cells from patients with SLE showed the same two phenotypically distinguishable CD4+ CD25(low) and CD4+ CD25(high) populations, although both expressed slightly increased levels of activation markers. Quantitative analysis showed a considerably raised percentage of CD25(low) and, especially, CD25(high) cells in patients with SLE compared with controls. This increment was unrelated to clinical manifestations, but correlated with glucocorticoid treatment. Patients treated with glucocorticoids presented raised levels of CD25(high) cells, whereas untreated patients and those with anti-malarial or immunosuppressive drugs had levels similar to those in controls. CONCLUSIONS: The percentage of CD4+ CD25(high) cells was not altered in non-steroid-treated patients, whereas glucocorticoid treatment increased their frequency in patients with SLE.

Adult↗
PubMed2006

Polyomavirus BK nephropathy: the effect of an early diagnosis on renal function or graft loss.

Polyomavirus BK nephropathy is a new complication among renal transplant patients. We studied 664 cadaver renal transplant recipients from February 1998 to February 2005, divided into two periods: 448 (group A, February 1998 to July 2003) and 176 (group B, August 2003 to February 2005). Twenty patients (3%) developed biopsy-confirmed polyomavirus BK nephropathy; 13 (2.9%) in group A after worsening renal function and 7 (3.9%) in group B after a prospective cytologic study in urine, examining for decoy cells, and a qualitative polymerase chain reaction (PCR) assay in urine and blood. The mean time to diagnosis was higher among group A (15.0 +/- 1.6 versus 7.2 +/- 4.0 months), as was the serum creatinine (2.5 +/- 0.7 versus 2.0 +/- 0.6 mg/dL). After 12 months the serum creatinine was 2.7 +/- 1.3 versus 1.7 +/- 0.2 mg/dL, respectively. Poor prognostic factors were a persistently positive PCR in blood and viral inclusions in the control biopsy.

Adult↗
PubMed2005

Differential effect of IL10 and TNF{alpha} genotypes on determining susceptibility to discoid and systemic lupus erythematosus.

OBJECTIVE: To ascertain the possible involvement of functional interleukin 10 (IL10) and tumour necrosis alpha (TNFalpha) cytokine promoter polymorphisms on the susceptibility to discoid and systemic lupus erythematosus (DLE, SLE), and their associations with immunological features. METHODS: Single nucleotide polymorphisms of the IL10 (-1082, -819, and -592) and TNFalpha (-308) genes were determined using allele specific probes in 248 lupus patients and 343 matched controls. To assess functional significance of genotypes, basal mRNA cytokine levels were quantified in 106 genotyped healthy controls by real time RT-PCR. Specific autoantibodies and cutaneous manifestations were analysed in SLE patients and associated with functional genotypes. RESULTS: After analysing the distribution of IL10 and TNFalpha transcript levels according to promoter genotypes in healthy individuals, patients and controls were classified into functional single and combined genotypes according to the expected high or low constitutive cytokine production. High TNFalpha genotypes (-308AA or AG) were associated with SLE independently of IL10 alleles, whereas the risk of developing DLE and the prevalence of discoid lesion in SLE were higher in the high IL10/low TNFalpha producer group (-1082GG/-308GG). Cytokine interaction also influences the appearance of autoantibodies. Antibodies against Sm are prevalent among low producer patients for both cytokines, a genotype not associated with lupus incidence, whereas low IL10/high TNFalpha patients have the highest frequency of antibodies to SSa and SSb. CONCLUSIONS: IL10/TNFalpha interaction influences susceptibility to DLE and the appearance of specific autoantibodies in SLE patients, whereas high TNFalpha producer genotypes represent a significant risk factor for SLE.

Adult↗
PubMed2005

Tumour necrosis factor receptors (TNFRs) in Type 2 diabetes. Analysis of soluble plasma fractions and genetic variations of TNFR2 gene in a case-control study.

AIMS: We have studied the relationships between soluble fractions of tumour necrosis factor receptors (sTNFR1 and sTNFR2) in Type 2 diabetes (DM2) and its chronic microvascular complications. Likewise, we have analysed the genetic susceptibility of 196T > G exon6/CA-repeat intron 4 mutations in the TNFR2 gene in this population. METHODS: A case-control study was conducted to examine the role of sTNFRs in 345 DM2 patients and 173 healthy subjects. The mutations were studied in all healthy subjects and in a subset of 232 patients. RESULTS: sTNFRs levels were similar in healthy and DM2 patients. A positive correlation between age and both sTNFRs was observed in healthy subjects. In DM2 patients, sTNFR1 showed a positive correlation with age, systolic blood pressure and leptin levels (r = 0.53, P < 0.0001; r = 0.28, P = 0.005; r = 0.46, P < 0.0001, respectively) and sTNFR2 was positively correlated with age, triglycerides and leptin levels (r = 0.34, P < 0.0001; r = 0.21, P < 0.0001; r = 0.28, P = 0.002, respectively). Patients with micro- or macroalbuminuria showed higher plasma levels of sTNFR1 and sTNFR2 than normoalbuminuric patients, after adjusting for confounding variables (B = 0.85, P = 0.022, 95% CI: 0.12-1.58 for sTNFR1 and B = 1.50, P < 0.001, 95% CI: 0.67-2.33 for sTNFR2). In DM2 patients, TT-exon 6 homozygous showed lower levels of sTNFR1 [2,4 (1.1) vs. 3.4 (1.2) ng/ml], and the CA273-allele tracked with elevated plasma HDL-cholesterol [1.8 (0.7), 1.4 (0.3) and 1.3 (0.3) mm, for CA273/273, CA273/- and CA-/-, respectively]. No association was seen with other analysed variables. CONCLUSIONS: Our findings suggest that chronic TNF activation may have some pathogenic role in diabetic nephropathy in DM2 patients. Genetic variations in exon 6/intron 4 of the TNFR2 gene do not predispose to a major risk for DM2 or its microvascular complications.

Adult↗
PubMed2005

Evaluation of the antitumor activity of interleukin-12 in an experimental murine model of colorectal cancer induced by 1,2 dimethyl-hydrazine (DMH).

OBJECTIVE: Interleukin 12 (IL-12) is a cytokine that may enhance the proliferation and cytotoxic activity of T lymphocytes and natural killer (NK) cells. A relationship between extensive intratumoral infiltration of NK cells and longer survival rates in colorectal cancer (CRC) patients was previously noted. Preliminary evidence suggests that the combined administration of IL-12 and IL-2 may produce additive immunomodulatory activity. The purpose of this study was to determine whether the systemic administration of IL-12 (+/- IL-2) may induce an immune response against CRC as induced by 1,2-dimethylhydrazine (DMH). METHODS: Sixty-five 6-week-old Wistar rats were treated with weekly subcutaneous injections of DMH for 26 weeks at a dose of 20 mg/kg of body weight. Once tumoral induction was over, the animals were randomly allocated to one of three groups: I, control; II, intraperitoneal injections of IL-12; III, intraperitoneal injections of IL-12 combined with IL-2. At 30 weeks, all surviving animals were sacrificed. We studied the following parameters in each rat--number of tumors, size of tumors, and total tumoral volume. Tumor samples were studied using the monoclonal antibody CD 57 for the detection of NK cells. The extent of NK infiltration was classified as small, less than 50 NK cells/50 high-power field (HPF); moderate, 50 to 150 NK cells/50 HPF, and extensive, more than 150 NK cells/50 HPF. RESULTS: Thirty-five rats died before completion of the carcinogen exposure, and 30 rats were randomized (10 each group). In group II, 2 animals died during treatment. All rats in groups I and III developed tumors, while in group II two rats (25%) were tumor-free. Moreover, only one rat in group II developed multiple neoplasms, in contrast with group I and group III, where six rats (60%) and seven rats (70%), respectively, had more than one tumor. We found statistically significant differences in the mean number of tumors found in group II when compared to group I (p = 0.028) and group III (p = 0.019). Other parameters measured, such as biggest tumor size and total tumoral volume were found to be lower in group II, although no statistical differences were found between groups. Only 10% of rats in group I showed moderated/extensive NK cell infiltration, vs. 60% of rats in group II (p = 0.077) and 70% in group III (p = 0.02). CONCLUSION: The administration of DMH to rodents provides a reliable and consistent means of inducing CRC that may be suitable for the evaluation of anti-cancer therapies. Our findings suggest that IL-12 is effective against the development of experimental CRC. Its antineoplastic effect could be attributed to the stimulus of this cytokine on the intratumoral infiltration of NK cells.

1,2-Dimethylhydrazine↗
PubMed2004

Analysis of a quantitative PCR assay for CMV infection in liver transplant recipients: an intent to find the optimal cut-off value.

BACKGROUND: Preemptive therapy required highly predictive tests for CMV disease. CMV antigenemia assay (pp65 Ag) has been commonly used for rapid diagnosis of CMV infection. Amplification methods for early detection of CMV DNA are under analysis. OBJECTIVES: To compare two diagnostic methods for CMV infection and disease in this population: quantitative PCR (qPCR) performed in two different samples, plasma and leukocytes (PMNs) and using a commercial diagnostic test (COBAS Amplicor Monitor Test) versus pp65 Ag. STUDY DESIGN: Prospective study conducted in liver transplant recipients from February 2000 to February 2001. RESULTS: Analyses were performed on 164 samples collected weekly during early post-transplant period from 33 patients. Agreements higher than 78% were observed between the three assays. Optimal qPCR cut-off values were calculated using ROC curves for two specific antigenemia values. For antigenemia >or=10 positive cells, the optimal cut-off value for qPCR in plasma was 1330 copies/ml, with a sensitivity (S) of 58% and a specificity (E) of 98% and the optimal cut-off value for qPCR-cells was 713 copies/5x10(6) cells (S:91.7% and E:86%). Using a threshold of antigenemia >or=20 positive cells, the optimal cut-off values were 1330 copies/ml for qPCR-plasma (S 87%; E 98%) and 4755 copies/5x10(6) cells for qPCR-cells (S 87.5%; E 98%). Prediction values for the three assays were calculated in patients with CMV disease (9 pts; 27%). Considering the assays in a qualitative way, the most sensitive was CMV PCR in cells (S: 100%, E: 54%, PPV: 40%; NPV: 100%). Using specific cut-off values for disease detection the sensitivity, specificity, PPV and NPV for antigenemia >or=10 positive cells were: 89%; 83%; 67%; 95%, respectively. For qPCR-cells >or=713 copies/5x10(6) cells: 100%; 54%; 33% and 100% and for plasma-qPCR>or=1330 copies/ml: 78%, 77%, 47%, 89% respectively. CONCLUSIONS: Optimal cut-off for viral load performed in plasma and cells can be obtained for the breakpoint antigenemia value recommended for initiating preemptive therapy with high specificities and sensitivities. Diagnostic assays like CMV pp65 Ag and quantitative PCR for CMV have similar efficiency and could be recommended as methods of choice for diagnosis and monitoring of active CMV infection after transplantation.

Antigens, Viral↗
PubMed2004

Patterns of hormonal response to the GnRH agonist leuprolide in brothers of women with polycystic ovary syndrome: a pilot study.

BACKGROUND: The aim of this study was to evaluate the effect of a single dose of leuprolide acetate on gonadotrophin and gonadal steroid secretion in brothers of women with polycystic ovary syndrome (PCOS), in order to assess P450c17alpha activity. An oral glucose tolerance test (OGTT) and a lipid profile were also performed. METHODS: Twenty-two unrelated brothers of women with PCOS (PCOS(b)) and 14 brothers of normal cycling women (C(b)), matched for age, underwent a leuprolide acetate test (10 microg/kg s.c.) and an OGTT with measurement of circulating concentrations of gonadotrophins, steroid hormones, glucose, insulin and lipids. RESULTS: Clinical and basal hormonal parameters were similar in both groups. After leuprolide administration, PCOS(b) exhibited a significant increase of 17alpha-hydroxyprogesterone (17-OHP) compared to C(b) (P<0.05). However, only 45% of PCOS(b) showed a supranormal increase of 17-OHP (2 SD above the respective control group mean values, P<0.003) with a normal gonadotrophin response (group 1). The other 55% of the PCOS(b) exhibited a normal 17-OHP response to the analogue (group 2). However, in group 2, basal steroid concentrations did not show a uniform pattern: six of the PCOS(b) exhibited high basal androstenedione (2 SD above the respective control group mean values), three were very similar to C(b), and the other three presented lower basal testosterone concentrations (2 SD below the respective control group mean values) than those observed in C(b). CONCLUSIONS: This study shows that different responses to leuprolide in PCOS brothers make evident the heterogeneity of this syndrome in which P450c17alpha activity could be involved.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes.

BACKGROUND: IL-10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL-10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL-10 production. OBJECTIVES: The aim was to define possible mechanisms by which steroids up-regulate IL-10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL-10 by lymphocytes and cells of myeloid origin. METHODS: Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL-10 levels were determined by ELISA and by Northern blot, respectively. RESULTS: Monocytes, but not T or B cells, up-regulated the constitutive production of IL-10 following pre-treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up-regulation of IL-10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose-related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL-10 were up-regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL-10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL-10 production after pre-treatment with Dex. CONCLUSION: Our results support the fact that steroids up-regulate constitutive IL-10 production by selectively triggering activation signals on monocytes.

Blotting, Northern↗
PubMed2004

Prognostic value of apoptosis in breast cancer (pT1-pT2). A TUNEL, p53, bcl-2, bag-1 and Bax immunohistochemical study.

Apoptosis or programmed cell death produces cells breaking into several fragments of nuclei, cytoplasm or both nuclei and cytoplasm, known as apoptotic bodies which can be visualized in haematoxylin-eosin staining. Some genes (promoters and suppressors) control this process and certain mutations may induce the expression of abnormal proteins, which can be detected by immunohistochemical staining. Apoptosis can be detected by the TUNEL method either identifying apoptotic bodies or cells at the initial stages of the fragmentation process. We have studied 186 cases of infiltrating ductal breast carcinoma, stages pT1-pT2, and analysed the prognostic significance of tumour recurrence and overall survival of apoptotic index (AI) through univariate and multivariate analysis. We have also studied the immunohistochemical protein expression of apoptosis promoter and suppressors gene (p53, nuclear expression; bcl-2 and Bax, cytoplasm expression; BAG-1, nuclear and cytoplasm expression). The results indicate prognostic significance of p53 and bcl-2 related to patient death and bcl-2 and tumour size to tumour recurrence, bcl-2 acting as a protector factor (apoptotic suppressor) in both situations. On the other hand, we have not found useful prognostic information of AI either to tumour recurrence or overall survival in univariate or multivariate studies. In this study, Bax expression does not provide a new prognostic role in breast carcinoma, although it contrasts to the bcl-2 action and accelerates death.

Apoptosis↗
PubMed2003

Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features.

The present work was planned to research epidemiological and immunological features of systemic lupus erythematosus (SLE) in a Caucasian population from the north of Spain (Asturias). There is only one specialized immunology laboratory in this region where samples from all patients with a plausible or a firm diagnosis of SLE are referred for immunological analysis. Since 1992 we have reviewed registered data from samples submitted to the immunology laboratory with a firm, definitive diagnosis of SLE, based on the fulfillment of the American College of Rheumatology (ACR) criteria. We have constructed a database, which included 367 SLE patients. The point prevalence was 34.12/ 100 000 (95% CI: 30.63-37.61/100 000), whereas the incidence rate calculated during the last five years was 2.15/100 000/year (95% CI: 1.76-2.54/100 000/year). The female/male ratio varied according to the age at diagnosis, being maximum (50 : 1) between 22 and 28 years. The median age at diagnosis was significantly lower in females than in males. Immunological features also yielded sex and age peculiarities. The percentage of patients with anti-SSa antibodies yielded significant differences between males (18.6%) and females (34.6%). Anti-RNP and anti-Sm antibodies were more frequently present in childhood-onset patients, the difference with the oldest-onset group being statistically significant. Other analyses did not show significant differences, although, as a whole, we observed a trend towards a higher presence of autoantibodies related to an early disease onset.

Adolescent↗
PubMed2002

Bone mineral mass is associated with interleukin 1 receptor autoantigen and TNF-alpha gene polymorphisms in post-menopausal Mediterranean women.

Bone mass is known to be under genetic control. Interleukin-1 (IL-1), interleukin-6 (IL-6) and TNF-alpha are strong inductors of bone resorption. The estrogenic deficiency that occurs during menopause leads to an increase in the production of these cytokines. We analyzed the genetic susceptibility of several polymorphisms of the interleukin-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha genes in lumbar spine and hip bone mass in a sample of post-menopausal Caucasian Mediterranean women with osteoporosis. 104 post-menopausal osteoporotic women (58.6+/-4.8 yr) and 51 post-menopausal women without osteoporosis as the control group (57.2+/-4.5 yr) were studied. The osteoporotic group was in turn sub-classified into severe and non-severe osteoporosis. The variable number of tandem repeats IL1-ra, IL-6 SfaNI and TNF-alpha NcoI genetic polymorphisms were studied. Biochemical markers of bone turnover were measured in blood and urine. Women carrying the A2 allele (A2+) of the IL-1ra gene showed greater BMD in the lumbar spine (p=0.02) and hip (p=0.006), compared to those not carrying the allele (A2-). The IL-6 polymorphism studied in its 5' flanking region did not show any association with BMD values. The TNF-alpha gene G allele was associated with a greater bone mass in the non-severe osteoporotic subgroup, both in the lumbar spine (p=0.0007) and in the hip (p=0.02). Likewise, genotype combination A2+GG was associated to a greater hip BMD at the femoral neck and Ward triangle levels (p=0.02). We conclude that both IL-1ra and TNF-alpha can be candidate loci to be studied in the susceptibility to develop post-menopausal osteoporosis.

Alleles↗
PubMed2002

Effects of haemolysis, lipaemia, bilirubinaemia and fibrinogen on protein electropherogram of canine samples analysed by capillary zone electrophoresis.

The possible interference of haemolysis, lipaemia, bilirubinaemia and fibrinogen on capillary zone electrophoresis of canine samples were studied. Solutions of haemoglobin, lipid and bilirubin were prepared and mixed with serum aliquots to make up samples containing different concentrations of the putative interferent substance. In addition, samples of serum and plasma were assayed to assess the influence of fibrinogen. Haemolysis and lipids produced a change in electropherogram morphology giving an interference peak located in the beta-2 region when haemoglobin was increased, and in the alpha-2 region when lipids were increased. A rise in concentration of these interferents caused an increase in the beta and alpha-2 fractions respectively, and a decrease in the other fractions. Bilirubin did not alter morphology but gave an increase in the albumin and alpha-1 and a decrease in the alpha-2 and beta-2 fractions. No differences were found between serum and plasma samples, and fibrinogen did not produce any additional peak.

Animals↗