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Biomedical subjects

M de Miguel

Publications and source records attributed to M de Miguel.

At least 19 recordsLinked to original sources
PubMed2002

[Early detection of child abuse. Pilot work program in the net].

The abuse of children is a social problem and its resolution is an aim of public health. Fully conscious of this, we have started a multi-disciplinary program formed by professionals from the Social Services, Health, Mental health, Education and the Local Police, based on a network, constituted in Burlada, a municipality in Navarra. The aim of this program is to facilitate a process of organisation of the different institutional levels, the exchange of information and the optimisation of resources so that we can facilitate a better treatment for each child and its family.

English Abstract↗
PubMed2001

Contribution of the microvessel network to the clonal and kinetic profiles of adrenal cortical proliferative lesions.

Monoclonal adrenocortical lesions have been characterized by an inverse correlation between proliferation and apoptosis, and polyclonal lesions show a direct correlation. Their relationship with the vascular pattern remains unknown in adrenocortical nodular hyperplasias (ACNHs), adenomas (ACAs), and carcinomas (ACCs). We studied 20 ACNHs, 25 ACAs, and 10 ACCs (World Health Organization classification criteria) from 55 women. The analysis included X-chromosome inactivation assay (on microdissected samples), slide and flow cytometry, and in situ end labeling. Endothelial cells were stained with anti-CD31, and the blood vessel area and density were quantified by image analysis in the same areas. Appropriate tissue controls were run in every case. Regression analyses between kinetic and vascular features were performed in both polyclonal and monoclonal lesions. Polyclonal patterns were observed in 14 of 18 informative ACNHs and 3 of 22 informative ACAs, and monoclonal patterns were seen in 4 of 18 ACNHs, 19 of 22 ACAs, and 9 of 9 ACCs. A progressive increase in microvessel area was observed in the ACNH-ACA-ACC transition but was statistically significant between benign and malignant lesions only (191.36 +/- 168.32 v 958.07 +/- 1279.86 microm(2); P < .0001). In addition, case stratification by clonal pattern showed significant differences between polyclonal and monoclonal benign lesions; 6% of polyclonal and 57% of monoclonal lesions had microvessel area >186 microm(2) (P = .0000008). Monoclonal lesions showed parallel trends (but with opposite signs) for microvessel area and density in comparison with proliferation and apoptosis, whereas polyclonal lesions showed inverse trends. In conclusion, the kinetic advantage of monoclonal adrenal cortical lesions (increased proliferation, decreased apoptosis) is maintained by parallel increases in microvessel area and density.

Adrenal Cortex↗
PubMed2001

Germline RET 634 mutation positive MEN 2A-related C-cell hyperplasias have genetic features consistent with intraepithelial neoplasia.

C-cell hyperplasias are normally multifocal in multiple endocrine neoplasia type 2A. We compared clonality, microsatellite pattern of tumor suppressor genes, and cellular kinetics of C-cell hyperplasia foci in each thyroid lobe. We selected 11 females from multiple endocrine neoplasia type 2A kindred treated with thyroidectomy due to hypercalcitoninemia. C-cell hyperplasia foci were microdissected for DNA extraction to analyze the methylation pattern of androgen receptor alleles and microsatellite regions (TP53, RB1, WT1, and NF1). Consecutive sections were selected for MIB-1, pRB1, p53, Mdm-2, and p21WAF1 immunostaining, DNA content analysis, and in situ end labeling. Appropriate tissue controls were run. Only two patients had medullary thyroid carcinoma foci. Nine informative C-cell hyperplasia patients showed germline point mutation in RET, eight of them with the same androgen receptor allele preferentially methylated in both lobes. C-cell hyperplasia foci showed heterogeneous DNA deletions revealed by loss of heterozygosity of TP53 (12 of 20), RB1 (6 of 14), and WT1 (4 of 20) and hypodiploid G0/G1 cells (14 of 20), low cellular turnover (MIB-1 index 4.5%, in situ end labeling index 0.03%), and significantly high nuclear area to DNA index ratio. MEN 2A (germline point mutation in RET codon 634) C-cell hyperplasias are monoclonal and genetically heterogeneous and show down-regulated apoptosis, findings consistent with an intraepithelial neoplasia. Concordant X-chromosome inactivation and interstitial gene deletions suggest clone expansions of precursors occurring at a point in embryonic development before divergence of each thyroid lobe and may represent a paradigm for other germline mutations.

Amino Acid Substitution↗
PubMed2000

Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates.

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8+/-29.9) and ISEL (50.9+/-12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features.

Adrenal Gland Neoplasms↗
PubMed2000

Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression.

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly understood. Herein we report the kinetic pattern of PIN, both not associated (primary) and associated (secondary) with coexistent invasive carcinoma (PCa). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N = (n pi/4)2. Fifty high-power fields (HPF), or the complete lesion if smaller, were screened in each lesion, and both mean and standard deviation were recorded. Statistical differences were studied by means of Fisher's exact test. ISEL indices were significantly (P < 0.0001) lower in PCa (0.1 +/- 0.3) than in primary PIN (0.5 +/- 0.3), while the MIB-I indices were similar in both conditions (P = 0.56). Statistically significant differences were also detected for both MIB-1 and ISEL indices when secondary PIN (MIB-1 1.9 +/- 0.7, ISEL 3.7 +/- 3.3) was compared with primary PIN (MIB-1 2.5 +/- 2.1, ISEL 0.5 +/- 0.3) and PCa (P < 0.0001). In terms of cellularity, primary PIN (26.3 +/- 7.1) revealed scores significantly lower (P < 0.0001) than those recorded in PCa (39.0 +/- 8.8) and secondary PIN (32.9 +/- 14.3). In conclusion, early prostatic tumor is mainly defined by down-regulated apoptosis rather than by increased proliferation. Secondary PIN displays unique kinetic features suggesting an evolved stage of primary PIN.

Aged↗
PubMed2000

Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex.

Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G(0)/G(1) cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G(0)/G(1) apoptosis and in ACAs regardless of clonality pattern and presence of G(0)/G(1) apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL - 1.93), whereas the correlation was inverse for monoclonal lesions (PR = -9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs.

Adenoma↗
PubMed2000

Paired inhibitory and triggering NK cell receptors for HLA class I molecules.

Human natural killer (NK) cells specifically interact with major histocompatibility complex (MHC) class I molecules employing different receptor systems, shared with subsets of alphabeta and gammadelta T lymphocytes. Killer cell immunoglobulin-like receptors (KIRs) recognize groups of human leukocyte antigen (HLA) class Ia proteins displaying common structural features at the alpha-1 domain; among them, KIR2DL4 has been proposed to specifically interact with the class Ib molecule HLA-G1. Members of a related family of immunoglobulin (Ig)-like receptors (ILT2 or LIR-1 and ILT4 or LIR-2), expressed by other leukocyte lineages, interact with a broad spectrum of class Ia molecules and HLA-G1. On the other hand, CD94/NKG2-A(-C) and NKG2D lectin-like receptors, respectively, recognize the class Ib molecules HLA-E and MICA. A recurrent finding within the different receptor families is the existence of pairs of homologous molecules that often share the same ligands but display divergent functions. Inhibitory receptors tend to exhibit an affinity for HLA molecules higher than their activating counterparts. Recruitment of SH2 domain-bearing tyrosine phosphatases (SHP) by cytoplasmic phosphorylated immunoreceptor tyrosine-based inhibition motifs (ITIMs) is a crucial event for the inhibitory signalling pathway. By contrast, triggering receptors assemble with homodimers of immune tyrosine-based activation motif (ITAM)-bearing adaptor molecules (i.e., DAP12, CD3 xi) that engage tyrosine kinases (ZAP70 and syk).

Histocompatibility Antigens Class I↗
PubMed1998

[Primary septicemias in pediatric patients. Hospital Infantil de la Paz (1990-1993)].

BACKGROUND: Septicemias comprise more than one third of nosocomial infections in children. Their risk factors are related with the exposition time, therefore they are evaluated in relationship to it. PATIENTS AND METHODS: Prospective observational study along 4 years in surgical children and in those entered in the Internal Medicine Unit patients of a children Hospital, with stays higher than two days. Data were collected from admission to discharge. Bivariant analysis of stay time until infection with Wilcoxon-Gehan test, followed by Cox regression with time interaction terms for the risk factors that did not fulfill the requisite of proportional risks. RESULTS: 4,098 children were studied. 3.8% suffered primary septicemia and more than one half had coagulase-negative staphylococci. Cox regression showed the following risk factors: type of surgery, peripheral and central venous catheter, urinary catheterization, stay previous to surgery and duration of intervention. The protection factors were more than 3 days of antibiotherapy, age higher than 1 year and male sex. The factors with interaction with time were: stay previous to surgery, sex and duration of intervention. CONCLUSIONS: The stay previous to surgery, antibiotherapy reduction and duration of instrumentations are risk factors susceptible to be modified in order to reduce the incidence of infection in children. Protection by means of antibiotics requires to be evaluated through an ad hoc designed study.

Child, Preschool↗
PubMed1998

In vivo response of mouse liver to gamma-radiation assessed by the comet assay.

The alkaline comet assay was used to measure DNA damage induced in liver cells of mice irradiated with gamma-radiation, as well as the repair competency of these cells. A simplified procedure for the isolation of nuclei from cells in solid tissues was developed. This simplified method allows nuclei to be processed into lysis only 5 min after briefly chilling the tissue to depress any enzymatic activity. The nuclei were spontaneously released by a sharp cut of the tissue and exposure of the cut to a drop of 50 mM sodium-phosphate buffer at pH 7.2, immediately before adding the low melting agarose. Thus, the procedure minimizes time-dependent modification of the endogenous level of damage by reducing additional strand breaks or repair produced during processing. The induction of DNA damage by gamma-radiation behaved as a one-hit event in the liver cells, as there was a positive linear correlation between the radiation dose and the fraction of DNA migrated into the comet tails. The level of DNA damage produced by gamma-radiation was highly significant at doses of 0.5 and 1 Gy. Based on the mean extent of DNA migration, the level of damage was not reduced following only one hour of repair time however, after two hours, there was a significant reduction in DNA migration. To increase the resolution of the statistical analysis, the nuclei of each sample were distributed in five types of comets, according to the percentage of DNA in the tail. To compare the frequency distributions of these types of comets between different experimental situations, a Pearson chi-square statistical analysis was applied. It was found, by this analysis, that the DNA repair which occurred 1 h after 1 Gy of gamma-irradiation is significant and that, after 2 h, more DNA repair occurs, but a significant residual damage still persists when comparing this sample with the control.

Animals↗
PubMed1998

Primordial germ cells, stem cells and testicular cancer.

Primordial Germ Cells (PGCs) arise in the mouse embryo as a small population of cells some way from the gonad anlagen. In order for the embryo to develop into a fully fertile adult animal the PGCs must increase in number and reach the gonad. Mutations causing sterility in the mouse have identified some of the genes involved in regulating PGC development and some of these genes have been molecularly cloned. Similarly, mutations affecting the development and differentiation of PGC-derived tumors (teratomas and teratocarcinomas) have been identified in certain strains of mice and these identify genes involved in the normal growth and differentiation of PGCs. These studies should help to define the role of growth factors in PGC development and in the development of germ-cell-derived tumors.

Animals↗
PubMed1997

A fast comet assay variant for solid tissue cells. The assessment of DNA damage in higher plants.

The single-cell gel electrophoresis or comet assay, under high alkaline conditions, detects low levels of DNA damage. In it, broken DNA migrates from the nucleus to the anode providing images similar to comets. To adapt this assay to solid tissue cells, nuclei were directly obtained from Allium cepa L. roots. The surface of each single fresh sharply cut meristem was exposed to a small drop of 50 mM Sörensen buffer at pH 6.8, placed on a regular agarose-coated slide. By immediately adding low melting point agarose at 30 degrees C, nuclei resulted embedded in agarose. A final layer of this agarose ended the preparative steps. Conventionaly prepared leukocytes were used as a control. The treatment with detergent (lysis step of the conventional assay) proved to be unnecessary for the nude nuclei. A 20 min-long electrophoresis (at 0.65 V. cm-1, 230 mA and 10 degrees C) was more sensitive than a 10 min-long one for detecting the differential response of plant nuclei to 2 and 4 Gy of gamma-irradiation. A short fixation in methanol transformed the preparations into semi-permanent ones, without altering their later DNA staining by ethidium bromide. The use of instantaneously isolated nuclei simplifies and expands the use of this technique to any eukaryotic cell from solid tissues.

Allium↗
PubMed1997

Renal biopsy collagen I mRNA predicts scarring in rabbit anti-GBM disease: comparison with conventional measures.

Progressive loss of normal structure associated with scarring is the hallmark of chronic diseases of most organs. To test the hypothesis that measurement of interstitial collagen mRNA levels would be a useful index to predict future scarring, we developed an assay to quantitate alpha 1(I) procollagen mRNA factored for GAPDH mRNA using RT-PCR (the "CI:G ratio"). We first defined conditions under which the assay could be used for analysis of renal biopsy samples. The CI:G ratio was then used to determine whether mRNA measurements performed at an early stage of inflammation (day 7) in a model of anti-GBM disease in the rabbit would predict outcome at day 30 as measured by interstitial and glomerular scarring and renal cortical hydroxyproline accumulation. The predictive value of this assay was compared to functional (serum creatinine and urine protein:creatinine ratio) and histologic (glomerular and interstitial scoring) parameters also measured at day 7. We found that the CI:G ratio alone provided a sensitive and discriminating assay over a wide range of renal injury that predicted various parameters of scarring with an average coefficient of determination (r2) of 0.69. This predictive power was higher than that found for conventional measures, which tended to have good discriminatory capacity over limited ranges of renal injury. The CI:G ratio provided significant additional predictive power over and above that available from combinations of conventional functional or histologic parameters. We conclude that measurement of the CI:G ratio in biopsy samples deserves further assessment as a potentially useful quantitative predictor of outcome that could lead to improved clinical decision-making.

Amino Acid Sequence↗
PubMed1994

Does the frequency of paracolostomy hernias depend on the position of the colostomy in the abdominal wall?

The aim of this study was to determine the rate of paracolostomy hernia in relation to transrectal or pararectal position of a colostomy. Fifty-four consecutive patients who had undergone an abdomino-perineal excision for rectal neoplasia were studied. The location of the colostomy was assessed by physical examination. Computerised Tomography (CT) scanning was used in the cases where its anatomical position remained in doubt. The colostomy was in a pararectal position in 29 (54%), while in 25 (46%) it was transrectal. CT was necessary to determine the location of the colostomies in 9 cases (16%), eight of which had a parastomal hernia. The colostomy was pararectal in 15 (52%) of the 26 patients who had a paracolostomy hernia, and in 14 (48%) of the 28 patients without a paracolostomy hernia. No statistically significant correlation was found between the presence of a parastomal hernia and the position of the stoma in the abdominal wall.

Abdominal Muscles↗