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Biomedical subjects

M Herranz

Publications and source records attributed to M Herranz.

At least 19 recordsLinked to original sources
PubMed2006

Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer.

Colorectal cancer is a major cause of cancer death worldwide. A number of key oncogenes and tumor suppressor genes have been proposed to drive progression from healthy colonic epithelia to malignant tumors, including members of the Wnt/beta-catenin pathway. Recently, CpG island promoter hypermethylation was shown to cause inactivation of two extracellular Wnt inhibitors in colon cancer: secreted frizzled-related proteins (sFRPs) and Wnt inhibitory factor-1 (WIF-1). Here, we show for the first time that another extracellular Wnt inhibitor, the DICKKOPF-1 (DKK-1) gene, is transcriptionally silenced by CpG island promoter hypermethylation in colon cancer cell lines (n=9), whereas treatment with the DNA-demethylating agent 5-aza-2-deoxycytidine restored DKK-1 expression. Restoration of DKK-1 function in non-expressing cells bearing a truncated APC (Adenomatous Polyposis Coli) gene had no effect on beta-catenin/T-cell factor-dependent transcription, but induced tumor suppressor-like features such as reduced colony formation density and tumor growth inhibition in nude mice. These results suggest additional functions for DKK-1 other than inhibiting canonical Wnt signaling. In primary colorectal tumors, DKK-1 was found hypermethylated in 17% (nine of 54) of cases. Furthermore, while for both SFRP-1 and WIF-1 methylation-associated silencing occurred across the whole spectrum of colorectal tumorigenesis, DKK-1 promoter was selectively hypermethylated in advanced colorectal neoplasms (Duke's C and D tumors).

Adaptor Proteins, Signal Transducing↗
PubMed2006

Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma.

The cell cycle inhibitor p21Waf1/Cip1 is among the most important mediators of the tumor suppressor p53. However, there is increasing evidence indicating that p21 could favor tumorigenesis in specific cell types. In particular, the absence of p21 delays the development of thymic lymphomas induced either by ataxia-telangiectasia mutated deficiency or by ionizing irradiation. Here, we extend these observations to the context of p53-deficient mice. The absence of p21 results in a significant extension of the lifespan of p53-null and p53-haploinsufficient mice, and this effect can be attributed exclusively to a decrease in the incidence of spontaneous thymic lymphomas. Specifically, despite the occurrence of a variety of tumor types in the context of p53 deficiency, the only tumors that were significantly impaired by the absence of p21 were thymic lymphomas. Moreover, the absence of p21 also delays the incidence of radiation-induced thymic lymphomas in p53-deficient mice. Interestingly, p21-deficient lymphomas have a higher apoptotic rate than p21-proficient lymphomas, and this could be on the basis of the delayed incidence of thymic lymphomas in the absence of p21. Together, our results indicate that p21 plays an oncogenic role restricted to thymic lymphomas that is mechanistically independent of p53 and associated to a lower tumor apoptotic rate.

Animals↗
PubMed2006

The dioxin receptor is silenced by promoter hypermethylation in human acute lymphoblastic leukemia through inhibition of Sp1 binding.

The transcription factor aryl hydrocarbon receptor (AhR) has relevant functions in cell proliferation. Interestingly, the AhR can either promote or inhibit proliferation depending on the cell phenotype. Although recent data reveal potential pathways for AhR signaling in cell proliferation, the mechanisms that regulate its activity in tumor cells remain unknown. Here, we have analyzed promoter hypermethylation as a potential mechanism controlling AhR expression in human tumor cells. AhR promoter CpG methylation was sporadic in a panel of 19 tumor cell lines except for the chronic myeloid leukemia (CML) K562 and the acute lymphoblastic leukemia (ALL) REH. When compared with normal lymphocytes, REH had very low constitutive AhR expression that could be attributed to promoter hypermethylation since treatment with the DNA demethylating agent 5-aza-2'-deoxycitidine (AZA) significantly increased AhR mRNA and protein. These results in leukemia-derived cell lines were further confirmed in primary ALL, where 33% of the patients (7/21) had AhR promoter hypermethylation. Chromatin immunoprecipitation (ChIP) showed that methylation impaired binding of the transcription factor Sp1 to the AhR promoter, thus providing a mechanism for AhR downregulation in REH cells. Therefore, promoter hypermethylation represents a novel epigenetic mechanism downregulating AhR activity in hematological malignancies such as ALL.

Azacitidine↗
PubMed2006

Emergency visits for childhood poisoning: a 2-year prospective multicenter survey in Spain.

OBJECTIVES: To describe the characteristics of childhood poisoning leading to consultation to 17 pediatric emergency departments in Spain. METHODS: During a 2-year period (January 2001 to December 2002), accompanying people of 2157 children with acute intoxication who visited consecutively at the emergency room were prospectively surveyed. RESULTS: Childhood poisoning accounted for 0.28% of all emergency visits during the study period. The median (interquartile range, 25th-75th percentile) age was 24 months (22-60 months); 67% of children were younger than 4 years. Drug ingestion was involved in 54.7% of cases (paracetamol was the most frequent drug), domestic products in 28.9%, alcohol in 5.9%, carbon monoxide in 4.5%, and illicit drugs in 1.5%. A total of 61.3% of patients were admitted within 1 hour after exposure to the toxic substance, and 10.3% had been already treated before arrival; 29.1% of patients were referred for clinical manifestations which were mostly neurological symptoms. Laboratory tests and other investigations were performed in 40.7% of cases. Gastrointestinal decontamination was used in 51.7% of patients, with activated charcoal in 32.3%. Treatment varied significantly according to the individual hospitals. A total of 83.3% of patients were treated as outpatients, 15.2% were hospitalized, and 1.5% were admitted to the intensive care unit. One 11-month-old boy with carbon monoxide intoxication died. Six patients had permanent sequelae (esophageal stenosis in 5 and partial blindness in 1). CONCLUSIONS: Young children who accidentally ingested drugs and, less frequently, domestic products accounted for most cases of intoxication who presented at the pediatric emergency department.

Adolescent↗
PubMed2006

[Assessment of the immigrant child].

In the last twenty years Spain has turned into one of the principal countries recipients of foreign population. As consequence of this massive entry of people, our country is among the first ones of Europe for interannual increase of population. The concept of immigrant child is very wide and includes minors of very diverse characteristics, as the proceeding from international adoptions, the children coming from developing countries or those that come from other developed countries. The immigrant children do not represent health risk for the autochthonous population, on the contrary, they are in situation of defenselessness for their scanty vaccination coverages, their situation of marginality and the precarious sanitary systems of the countries of origin. At the moment of offering medical paediatric attention to foreign children, we must individualize our actions in conformity with the characteristics of each patient. It is not possible to simplify in one unique protocol the best studies to resolve a problem of health in an immigrant child. The attention of these children implies an overstrain for the pediatrician and the sanitary personnel that receives them, because it is necessary to conquer idiomatic, cultural and social barriers to optimize the level of health of these patients. The syndromic initial description can help to prioritize the studies in each case (according to the most probable diagnoses). The children who return to the native land of their parents meet in a special situation of risk, for not being prepared to resist the attack of pathogen that do not exist or are rare in Spain.

Child↗
PubMed2005

Epigenetic silencing of E- and N-cadherins in the stroma of mouse thymic lymphomas.

Aberrant expression of some tumour suppressor genes and oncogenes by thymocytes had been involved in the development of primary thymic lymphomas induced by gamma-irradiation, but genetic alterations affecting critical genes expressed by stromal cells have not been yet explored. This paper analyzes a series of such tumours induced in C57BL/6J and in F1 hybrids of BALB/c and C57BL/6J mouse strains. As expected, hystopathological analyses revealed profound disorganizations within the thymus with a poor demarcation of the cortical and medullar areas. Immunological and quantitative on-line RT-PCR analyses confirm that E-cadherin (Cdh1) is essentially expressed by stromal cells of the thymus, while evidencing that the expression of this gene is significantly reduced in all tumours. In addition, and contrary to what one would expect, N-cadherin (Cdh2) that is exclusively expressed by stromal cells is likewise down-regulated in most of the thymic lymphomas. Although hypermethylation of the promoter region appears to be involved in the inactivation of Cdh2 in all tumours, additional epigenetic mechanisms mediated by repressors such as Snai1 may also play a role in Cdh1 silencing. These results represent the first reported case for tumour-associated gene alterations occurring not in the tumour cells per se, but in the stromal cells of primary thymic lymphomas. Additionally, since the expression of both genes is significantly up-regulated after a single high dose of gamma-radiation, but remained unchanged in treated thymic-lymphoma-free-mice, epigenetic down-regulation of E- and N-cadherin appears to occur concomitantly with the progression towards the most advanced stages of gamma-radiation-induced thymic lymphomas.

Animals↗
PubMed2003

[Poisoning in children. Methaemoglobinaemia].

Poisonings during childhood account for 0.3-0.4% of consultations in the emergency pediatric services and constitute a pathology that must be born in mind, because of its frequency, its consumption of resources, its repercussion on the surrounding milieu and the possibility of its prevention. With respect to its epidemiology, the first cause of pediatric poisoning are medicines, with paracetamol outstanding as the most frequent cause of poisoning. In the second place in order of frequency we find products of household use, although their importance in pediatric toxicology rests basically on the fact that some of these products, such as cosmetics, can result in accidental ingestion, almost exclusively involving children. Hospital procedure concerning the poisoned child involves a first phase of life support and stabilization measures, followed by identification of the toxin and measures of detoxification where necessary. Given the broad scope of the issue and the impossibility of covering all of pediatric toxicology, this article describes its epidemiology in our milieu and some considerations are made with respect to dealing with the most frequent or characteristic poisonings involving children. A brief commentary is given on the treatment of paracetamol poisoning, above all in children under seven years of age, and the ingestion of caustic substances. Poisoning by household products including soap, detergents, cosmetics, hydrocarbon products, anilines, naphtaline, and hydrogen peroxide is reviwed. Finally, methaemoglobinaemia's physiopathology, aetiology, clinical picture, diagnosis and treatment is reviewed.

Acute Disease↗
PubMed2001

Evidence of a possible epigenetic inactivation mechanism operating on a region of mouse chromosome 19 in gamma-radiation-induced thymic lymphomas.

Loss of heterozygosity (LOH) analysis, performed in 68 gamma-radiation-induced primary thymic lymphomas of F1 hybrid mice, provided evidence of significant LOH on chromosome 19 in a region defined by the D19Mit106 (22 cM) and D19Mit100 (27 cM) markers (Thymic Lymphoma Suppressor Region 8, TLSR8). Cd95 and Pten, two genes mapped at this region, were inactivated in a vast majority of these tumors (85.3% for Cd95 and 61.8% for Pten). Moreover, altered expression of Cd95 and Pten occurred concomitantly in 34 of 68 (50%) thymic lymphomas suggesting a coordinated mechanism of inactivation of these genes. Surprisingly, we also found that Jak2, a proto-oncogene located between Cd95 and Pten, was simultaneously inactivated in a significant fraction of the tumors analysed (24 of 34, 70.6%). Taken together these findings and the lack of mutations in the coding sequences of the mentioned genes clearly suggest a possible regional epigenetic inactivation mechanism on mouse chromosome 19 operating during the development of these tumors.

Animals↗
PubMed2001

Patient satisfaction after biofeedback for constipation and pelvic floor dyssynergia.

BACKGROUND: Patients referred for chronic constipation frequently report symptoms of straining, feeling of incomplete evacuation, or the need to facilitate defecation digitally (dyschezia). When such patients show manometric evidence of inappropriate contraction or failure to relax the pelvic floor muscles during attempts to defecate, they are diagnosed as having pelvic floor dyssynergia (Rome I). AIMS: To evaluate long-term satisfaction of patients with pelvic floor dyssynergia after biofeedback. PATIENTS: Forty-one consecutive patients referred for chronic constipation at an outpatient gastrointestinal unit and diagnosed as having pelvic floor dyssynergia who completed a full course of biofeedback. METHODS: Data have been collected using a standardised questionnaire. A questionnaire survey of patients' satisfaction rate and requirement of aperients was undertaken. RESULTS: Mean age and symptom duration were respectively 41 and 20 years. Half of patients reported fewer than 3 bowel motions per week. Patients were treated with a mean of 5 biofeedback sessions. At the end of the therapy pelvic floor dyssynergia was alleviated in 85% of patients and 49% were able to stop all aperients. Satisfaction was maintained at follow-up telephone interviews undertaken after a mean period of 2 years, as biofeedback was helpful for 79% of patients and 47% still abstained from intake of aperients. CONCLUSIONS: Satisfaction after biofeedback is high for patients referred for chronic constipation and diagnosed with pelvic floor dyssynergia. Biofeedback improves symptoms related to dyschezia and reduces use of aperients.

Adult↗
PubMed2001

90Sr content of soils from Biscay (Spain).

The concentrations of 90Sr at different depth levels have been determined in 55 soils from 11 points at Biscay (Spain) by extracting this radionuclide from 30 g samples. It was measured by beta-counting after purification. The concentrations of 137Cs in the same soils are known from previous studies. Soils were also characterised by sampling depth, particle size analysis and the usual chemical parameters. The 91Sr activity concentrations in the studied soils ranged from 0.28 to 9.10 Bq/kg, with an average value of 2.85 Bq/kg. The more frequent behaviour in a depth profile is a continuous decrease of 90Sr. The dependence of 90Sr activities on soil parameters and 137Cs concentration are discussed by statistical methods, mainly by correlation coefficients, cluster analysis and non-linear regression of the accumulated radionuclide with depth. By this technique an estimation of fallout can be made. The ratio of the estimated deposition rate for both nuclides had values in the range from 0.72 to 5.82. This variation is related to soil constituents.

Journal Article↗
PubMed2000

Determination and analysis of distribution coefficients of 137Cs in soils from Biscay (Spain).

The distribution coefficient of (137)Cs has been determined in 58 soils from 12 sampling points from Biscay by treating 10 g with 25 ml of an aqueous solution with an activity of 1765 Bq in the radionuclide, by shaking during 64 h and measuring the residual activity with a suitable detector. Soils were characterised by sampling depth, particle size analysis and the usual chemical parameters. Soils were thereafter treated to fix the chemical forms of (137)Cs speciation by successive extractions in order to determine fractions due to exchangeable, associated with carbonates, iron oxide and organic matter fractions, obtaining by difference the amount taken by the rest of the soil constituents. For this research, 16 soils from four points were selected from the previous samples. The greatest mean percentages of (137)Cs sorption were with the rest (69.93), exchangeable (13.17) and organic matter (12.54%) fractions. This paper includes also the calculation of partial distribution coefficients for chemical species as well as relations of distribution coefficients both among them and with soil parameters.

Journal Article↗
PubMed2000

Measurement of 137Cs in dust from steel scrap smelting

This paper deals with the measurement of 137Cs content in dust produced during steel scrap smelting and in the material produced from recycling the dust to recover the zinc oxide component. The measured samples have different densities and chemical compositions. The addition of radioactive standards to this kind of material to prepare a calibration standard is rather difficult. A theoretical analysis of the attenuation coefficient for this material together with its experimental measurement, show a linear relationship between the coefficient and density independent of chemical composition that allows the use of a soil sample to prepare calibration standards. An analysis of the validity of the method, as well as the development of a density correction factor is detailed. This factor is calculated incorporating the linear relationship between attenuation coefficient and density to the integral representing detection efficiency, and evaluating the integral by means of a Monte-Carlo program.

Journal Article↗
PubMed1999

Mouse p73 gene maps to the distal part of chromosome 4 and might be involved in the progression of gamma-radiation-induced T-cell lymphomas.

We have isolated and sequenced a DNA fragment of about 12 kb that comprises exons 5-14 of the mouse p73 gene. We have identified four polymorphic markers, and one of them has been used to genetically map p73 to the distal part of chromosome 4. Previously, we have reported that gamma-radiation-induced T-cell lymphomas undergo frequent loss of heterozygosity around marker D4Mit205b at the distal part of chromosome 4. Based on this, we have performed loss of heterozygosity analysis in a set of T-cell lymphomas, and we have found allelic losses of p73 in 32.6% (16 of 49) of the tumors analyzed. Interestingly, allelic losses occur concurrently at both p73 and D4Mit205b, thus suggesting that p73 could be specifically inactivated in radiation-induced T-cell lymphomas.

Alleles↗
PubMed1999

Oral immunization with urease and Escherichia coli heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults.

BACKGROUND & AIMS: Oral immunization with Helicobacter pylori urease can cure Helicobacter infection in animals. As a step toward therapeutic immunization in humans, the safety and immunogenicity of oral immunization with recombinant H. pylori urease were tested in H. pylori-infected adults. METHODS: Twenty-six H. pylori-infected volunteers were randomized in a double-blind study to four weekly oral doses of 180, 60, or 20 mg of urease with 5 microg heat-labile enterotoxin of Escherichia coli (LT), LT alone, or placebo. Side effects and immune responses were evaluated weekly after immunization, and gastric biopsy specimens were obtained after 1 month and 6 months for histology and quantitative cultures. RESULTS: Diarrhea was noted in 16 of 24 (66%) of the volunteers who completed the study. Antiurease serum immunoglobulin A titers increased 1. 58-fold +/- 0.37-fold and 3.66-fold +/- 1.5-fold (mean +/- SEM) after immunization with 60 and 180 mg urease, respectively, whereas no change occurred in the placebo +/- LT groups (P = 0.005). Circulating antiurease immunoglobulin A-producing cells increased in volunteers exposed to urease compared with placebo (38.9 +/- 13. 6/10(6) vs. 5.4 +/- 3.1; P = 0.018). Eradication of H. pylori infection was not observed, but urease immunization induced a significant decrease in gastric H. pylori density. CONCLUSIONS: H. pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals. An improved vaccine formulation may induce curative immunity.

Administration, Oral↗
PubMed1999

Analysis of the INK4a/ARF locus in non-Hodgkin's lymphomas using two new internal microsatellite markers.

Inactivation of the INK4a/ARF locus is a frequent event in non-Hodgkin's lymphomas (NHLs), which may be attributed to deletion, point mutation, and 5' CpG methylation at its promoter region. In the present study we evaluated the occurrence of deletions and genetic instability of INK4a/ARF locus in 30 paired normal and tumor samples of B cell NHLs by conducting an allelotypic analysis with two new polymorphic markers, one located at the intron 1 of p16INK4a gene and the other one placed downstream exon 1beta of p19ARF. Comparison of these results with those obtained in a previous paper using flanking markers (D9S171, D9S942, D9S958 and IFNA) allowed us to detect two new cases of microsatellite instability (L-446 and L-442), and to confirm the occurrence of LOH at the INK4a/ARF locus in one tumor (M-3770). On the contrary, this locus is not affected in three different tumors (L-421, L-272 and L-159) which exhibited LOH at some of the flanking markers.

Chromosome Mapping↗
PubMed1999

Helicobacter pylori in the oral cavity reflects handling of contaminants but not gastric infection.

Helicobacter pylori colonises the gastric mucosa, but can also be found within the oral cavity. The presence of H. pylori was monitored in the oral cavity of 22 patients with duodenal ulcer, before and after antibiotic treatment and of 24 hospital employees who were or were not professionally exposed to H. pylori. Gastric infection was determined by breath test. Bacteria in the oral cavity were detected by nested PCR of samples containing saliva and dental plaque, using primers specific for 16S rRNA and ureC genes. Before treatment, 9 out of 22 infected ulcer patients harbored H. pylori in their oral cavity. Bacteria disappeared from the oral cavity of 3 of 7 cured patients. Twelve of 17 exposed subjects harbored H. pylori in their oral cavity, while no bacteria could be detected in the mouths of the 7 nonexposed subjects. Presence of bacteria in the oral cavity reflects handling of contaminants; it does not correlate with gastric infection and does not seem to promote it.

Adolescent↗