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Biomedical subjects

F Domínguez

Publications and source records attributed to F Domínguez.

At least 19 recordsLinked to original sources
PubMed2006

Usefulness of duodenal biopsy during routine upper gastrointestinal endoscopy for diagnosis of celiac disease.

AIM: To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS: A 15 year-trend (1990 to 2004) in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS: Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies (7.6%); an increase in the use of such was observed over the study period (1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004). Celiac disease was diagnosed in 22 patients (2.2%), this being more frequent in women than in men (3% and 1% respectively). Fourteen out of 514 (2.7%) patients with anaemia, 12 out of 141 (8.5%) with chronic diarrhoea and 8 out of 42 (19%) with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION: Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.

Adult↗
PubMed2006

Effect of an intrauterine device on the gene expression profile of the endometrium.

CONTEXT: The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation. OBJECTIVE: The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation. DESIGN: We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the gene expression profile of endometrium obtained at LH+7 (window of receptivity) from the same women (n = 5) at the following time points: month 1, corresponding to the natural cycle before IUD insertion; month 3, just before IUD removal; and months 5 and 15. Data were validated by quantitative RT-PCR for IGF binding protein-3, peroxisome proliferative activated receptor-gamma, glycodelin, and leukemia inhibitory factor and immunohistochemistry for glycodelin. RESULTS: We identified 147 genes significantly dysregulated in the refractory endometrium (78 up- and 69 down-regulated). Interestingly, 52 of these genes have previously been reported to be regulated during window of implantation. Surprisingly, the majority of genes (96.6%) remained dysregulated 2 months after IUD removal, but 1 yr later most of them (80%) returned to normal. CONCLUSIONS: Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.

Adult↗
PubMed2006

Neuropharmacological effects of an ethanol extract of the Magnolia dealbata Zucc. leaves in mice.

Magnolia dealbata Zucc. is considered to have tranquilizer and anticonvulsant properties in Mexican traditional medicine. In the present study we report the effects of a crude extract of Magnolia dealbata (30, 100 and 300 mg/kg) on mouse central nervous system (CNS). Pharmacological effects were tested on ambulatory activity, anti-anxiety response, sodium pentobarbital-induced hypnosis and pentylenetetrazole (PTZ)-induced seizures in comparison to honokiol, buspirone, ethosuximide and diazepam as corresponding reference drugs. No changes in spontaneous locomotor activity were produced posterior to Magnolia dealbata administration; however, a significant and dose-dependent diminution in the anxiety response was observed in experimental models such as plus-maze, head-dipping and exploratory rearing tests. Magnolia dealbata not only prolonged the time of sodium pentobarbital-induced hypnosis and delayed the onset of PTZ-induced mioclonus and clonus, but also hindered the presence of tonic seizures and avoided mortality. The hypnotic, anxiolytic and anticonvulsant effects obtained in these experiments support the hypothesis that Magnolia dealbata possesses CNS activity and reinforces the popular use in Mexican traditional medicine.

Animals↗
PubMed2006

Development and characterization of a murine monoclonal antibody specific for the P1.15 PorA proteins from vaccine strain B:4,7:P1.19,15 of Neisseria meningitidis.

Neisseria meningitidis isolates are conventionally classified by serosubtyping, which characterizes the reactivities of the PorA outer membrane protein variable-region epitopes with monoclonal antibodies (MAbs). New murine hybridomas, secreting specific MAbs against PorA of N. meningitidis serogroup B, were generated using conventional hybridoma procedures. Using outer membrane protein as antigen, we obtained two positive clones, and one of them we characterized. This MAb reacted, on whole-cell enzyme-linked immunosorbent assay (ELISA) and immunoblotting, only with strain subtype P1.15 and its IgG2b isotype. This MAb demonstrated bactericidal activity against the homologous strain in the presence of human complement.

Animals↗
PubMed2005

Leptin system in embryo development and implantation: a protein in search of a function.

Implantation is a crucial moment in the reproduction process that requires perfect synchronization between the embryo and the maternal endometrium. The embryo must reach the blastocyst stage and the endometrium must be prepared to receive it. An appropriate and specific molecular dialogue must also take place between them. There is ample evidence to show that the leptin system is implicated in this cross-talk. Examples are described. Although there is some controversy surrounding the data, they are supported by the presence of leptin receptor mRNA in mouse and human oocytes and embryos throughout preimplantation development. Otherwise, the leptin mRNA is only detected at the blastocyst stage in both human and mouse. Furthermore, leptin is found at higher concentrations in the conditioned media from competent human blastocysts than in those from arrested embryos, suggesting that this molecule is a marker for blastocyst viability. Given that expression of the leptin receptor increases in the human endometrium during the luteal phase, the secreted leptin could trigger its activation. Finally, leptin and the leptin receptor have been detected in implantation sites. All these findings point to the involvement of the leptin system in the molecular mechanism of the implantation process and embryo development.

Embryo Implantation↗
PubMed2003

Phenotypic gender differences in subjects with familial partial lipodystrophy (Dunnigan variety) due to a nuclear lamin A/C R482W mutation.

Phenotypic features appeared after puberty in female, but not male subjects with familial partial lipodystrophy (FPLD). We have studied anthropometrical, clinical, and metabolic gender differences in a Spanish family with FPLD resulting from a lamin A/C gene mutation, R482W. Genetic studies were carried out on 14 members of the family. In eleven heterozygous mutation carriers (6 men, 5 women), body composition was evaluated by bioelectric impedance analysis, skin-fold measurements were taken, and lipid profiles were drawn. Moreover, plasma glucose, insulin, and leptin were determined, and insulin resistance and beta cell response were evaluated using HOMA. Ten healthy women and 10 healthy men matched for age and body mass index were used as control group. Body composition was similar in these patients to normal people. However, skin-folds of extremities were thinner in FPLD women compared with those of control subjects, but not in men. The affected women, but not men, showed hypoleptinaemia, insulin resistance, and beta-cell hyperresponse compared with unaffected women. The lipid profile was normal in the young patients, irrespective of sex. Type 2 diabetes mellitus and hypertriglyceridaemia were detected in old and overweight patients only. In conclusion, molecular diagnosis allows us to demonstrate that women with FPLD present both adipose tissue and biochemical abnormalities early in life, and this did not happen in affected men.

Adolescent↗
PubMed2002

Expression of E-cadherin in squamous cell carcinomas of the supraglottic larynx with correlations to clinicopathological features.

The aim of this study was to investigate the prognostic significance of E-cadherin expression in squamous cell carcinomas of the supraglottic larynx. 101 primary carcinomas were retrospectively studied. The level of E-cadherin expression was determined by immunohistochemistry. There was a significant correlation between decreased E-cadherin expression and the presence of nodal metastases (P=0.007). T-stage (P=0.025) and histological grade (P=0.043) were also associated with nodal metastases. Multivariate analysis confirmed that these three parameters were independent predictors of nodal metastases. Decreased E-cadherin expression also correlated with an increase in recurrence rates (P=0.019). However, in multivariate analysis only pathological N-stage was significantly associated with disease-specific survival. We conclude that E-cadherin is an independent predictor of nodal metastases in supraglottic squamous cell carcinomas. Determination of E-cadherin expression levels might be useful in identifying patients with clinically negative lymph nodes who are at risk of occult metastases, allowing more effective treatment strategies to be implemented.

Biomarkers, Tumor↗
PubMed2002

[Cervical epidural anesthesia with 0.75% ropivacaine in shoulder surgery].

We present the cases of three patients scheduled for shoulder surgery under cervical epidural anesthesia with 0.75% ropivacaine. The technique was successful and surgery proceeded uneventfully in all three cases. The total doses of ropivacaine infused were 67, 90 and 109 mg. Premedication with intravenous atropine is recommended. Cervical epidural anesthesia offers several advantages over general anesthesia and other regional techniques for shoulder surgery: postoperative analgesia, lower total dose of the local anesthetic and single needle insertion with no need to elicit paresthesias or muscle movements. This technique brings about hemodynamic and respiratory changes in function of the extension and intensity of the block. Extent of the blockade to the upper thoracic sensory segments causes a total or partial sympathetic block with decreased heart rate, blood pressure and cardiac output. Limiting the initial and subsequent doses to restrict the sensory blockade to the surgical area will reduce hemodynamic complications. Ropivacaine provides an effective sensory block and a restricted motor block, reducing the probability of the restrictive pulmonary syndrome associated with cervical epidural anesthesia.

Aged↗
PubMed2002

[Intestinal metaplasia at the esophagogastric junction. Prevelence and association in patients undergoing endoscopy].

AIM: Short segments of intestinal metaplasia (IM) at the esophagogastric junction is an unclear entity. Several studies have reported wide variations in its prevalence and in the factors associated with its development. Recently, this entity has been divided into esophageal IM and cardiac IM, as two different lesions in etiopathogenesis and prognosis. We studied the prevalence of these conditions and their association with gastroesophageal reflux disease (GERD) and Helicobacter pylori infection. METHODS: In 161 patients, biopsies were obtained from the distal esophagus (2), just below the Z line (3), and in the gastric antrum (4). IM was diagnosed on the basis of staining of goblet cells with Alcian blue and was classified as esophageal if ILZ < IEG or cardiac ILZ = IEG. H. pylori was determined by rapid urease (CLO-test) and histology. Diagnosis of GERD was based on typical symptoms, endoscopy, and histology. In 54 patients with IM (73%) esophageal manometry and 24-hour pH-metry was also performed. RESULTS: IM was detected in 74 patients (46%); IM was esophageal in 33 patients (20.5%) and cardiac in 41 patients (25.4%). Patients with IM were significantly older than those without (p = 0.007) and took proton pump inhibitors more frequently (p = 0.004). No correlation was found between reflux symptoms, esophageal lesions or histological changes with either type of IM. No differences between esophageal or cardiac IM were detected by esophageal pH-metry. H. pylori infection was unrelated to cardiac IM, but these patients had a lower frequency of endoscopic and histological changes in the distal esophagus. CONCLUSIONS: Intestinal metaplasia is a common finding in patients sent for gastroscopy and is probably an acquired lesion that increases in prevalence with age. We found no associations between esophageal IM and GERD, evaluated by typical symptoms, endoscopic and histological changes and pH-metry. H. pylori infection showed no relation to cardiac IM.

Adult↗
PubMed2001

Role of inhibitors of isoprenylation in proliferation, phenotype and apoptosis of human retinal pigment epithelium.

BACKGROUND: Isoprenoid biosynthesis is known to be essential for diverse cellular functions, including cell proliferation. The aim of this work was to study the effects caused by the addition of different inhibitors of isoprenylation (lovastatin, manumycin A, farnesyltransferase inhibitor III and N-acetyl-S-farnesyl-L-cysteine) to human retinal pigment epithelium (RPE) in culture, as potential coadjunctive-to-surgery treatments applicable to proliferative vitreoretinopathy. METHODS: Human RPE cell cultures were established from adult corneal donors. Proliferation levels were evaluated using the incorporation of 5-bromo-2'-deoxyuridine into the DNA. Cell viability was measured by tetrazolium bromide transformation. Apoptosis was determined by DNA fragmentation assay, TdT-mediated d-UTP-X nick-end labeling (TUNEL) and phosphatidylserine exposure assessment. Changes in cell morphology and actin cytoskeleton were evaluated using a phase-contrast microscope and by fluorescent staining of actin cables with TRITC-phalloidin. RESULTS: We found that lovastatin showed an important antiproliferative effect on human RPE cells in culture. This effect was clearly dose-dependent, and adding mevalonate could reverse it. We also found that lovastatin induced changes in the distribution of actin cytoskeleton and, finally, that it also induced RPE apoptosis. Manumycin A, farnesyltransferase inhibitor III and N-acetyl-S-farnesyl-L-cysteine also showed antiproliferative effects in RPE. However, they do not have any effect on cell morphology or induction of apoptosis. DISCUSSION: We identified various effects of lovastatin on human RPE cultures: inhibition of cell proliferation, modifications of the phenotype and induction of apoptosis. Interestingly, the addition of different inhibitors of protein isoprenylation only affected the proliferation of the cells. There was no evidence that isoprenylated proteins inhibition is related to lovastatin-induced RPE apoptosis.

Actins↗
PubMed2001

The nucellus degenerates by a process of programmed cell death during the early stages of wheat grain development.

The nucellus, which is the maternal tissue of the wheat grain, degenerates during the early stages of development. We have investigated whether or not this degenerative process may be considered as programmed cell death (PCD). The analysis of DNA of tissues dissected from developing wheat (Triticum aestivum L. cv Chinese Spring) grains at 5-20 days post anthesis (dpa) showed the presence of DNA laddering, which is indicative of internucleosomal fragmentation of nuclear DNA, in maternal tissues but not in the endosperm. The TUNEL assay showed in-situ internucleosomal fragmentation of DNA in nuclei of parenchymal and epidermal cells of the nucellus, as well as in the pericarp, during the early stages of grain development (5 dpa). Furthermore, internucleosomal fragmentation of nuclear DNA was observed in nucellar projection cells in the middle stages of grain development (13-18 dpa), thus showing a process of PCD in these maternal tissues. Electron-transmission microscopy analysis allowed the morphology of PCD to be characterized in this plant tissue. Initially, fragmentation of the cytoplasm was observed, the nuclear envelope appeared dilated and to be forming vacuoles, and the content of heterochromatin increased. A progressive degradation of the cytosolic contents and organelles was observed, and the plasma membrane was disrupted. However, the Golgi apparatus remained intact and apparently functional even in the final stages of cell death.

Animals↗
PubMed2001

Nodular regenerative hyperplasia of the liver in a patient with celiac disease.

We present the case of dual adult celiac disease and liver disease with portal hypertension (esophageal varices); a percutaneous liver biopsy was compatible with nonspecific reactive hepatitis. Clinically, celiac disease was characterised by poor response to a gluten-free diet, with the development of a biochemical cholestasis and marked malnutrition. Our patient died of cerebral hemorrhage, at the age of 50 years, without associated risk factors. The necropsy demonstrated the existence of a nodular regenerative hyperplasia of the liver, splenic atrophy, gelatinous transformation of the bone marrow, and lymphocytic colitis. We discuss the different types of liver disorders associated with celiac disease and the possible relation between nodular regenerative hyperplasia and celiac disease, based on immunologic mechanisms.

Autopsy↗
PubMed2001

Prothymosin alpha, a mammalian c-myc-regulated acidic nuclear protein, provokes the decondensation of human chromosomes in vitro.

Prothymosin (ProT alpha) is an acidic nuclear protein, widely distributed in mammalian cells, whose expression is regulated by c-myc and linked to cell proliferation. ProT alpha interacts with histone H1 via its acidic domain, and its overexpression provokes the unfolding of chromatin fibers. Here we show that incubation of human native metaphase chromosomes with ProT alpha induces their extensive unravelling suggesting a function of this protein in chromosome decondensation.

Chromosomes, Human↗
PubMed2001

[Use of aprotinin during pediatric heart surgery].

OBJECTIVE: To study the efficacy of high doses of aprotinin during cardiopulmonary bypass (CPBP) in pediatric patients with a tendency to intra- and postoperative bleeding: children undergoing repeated operations and those with cyanotic cardiopathy. PATIENTS AND METHODS: A simple retrospective, random sample of 71 pediatric patients with cyanogenic cardiopathy was studied. Group I (n = 36) received a test dose of 50,000 KIU in 2 min. The initial dose was 1,700,000 KIU (170 ml/m2 of body surface) i.v., at an infusion rate of 150 ml/h. CPBP circuit prime dose was 1,700,000 (170 ml/m2 of body surface), with replacement at a volume equivalent to the circuit prime. The maintenance dose was 400,000 KIU (40 ml/m2/h) i.v. Infusion was suspended 2 hours after a patient's arrival at the intensive care unit (ICU). We recorded red blood cell loss and blood product requirements in the first 24 hours in the ICU, duration of surgery, intra- and postoperative diuresis, and complications. RESULTS: Group I required 13.96 +/- 12.09 ml/kg/h of packed red cells whereas Group II required 22 +/- 16.22 ml/kg/h (p < 0.05). The volume lost was less in Group I than in Group II (0.77 +/- 0.48 ml/kg/h vs. 2.12 +/- 3.9 ml/kg/h; p < 0.05). The means for intra- and postoperative diuresis in the first 24 hours were not significantly different. CONCLUSIONS: Aprotinin significantly reduces red blood cell loss and homologous blood transfusion requirements. No complications attributable to aprotinin were observed.

Anticoagulants↗
PubMed1999

Complex regulation of prothymosin alpha in mammary tumors arising arising in transgenic mice.

Expression of prothymosin alpha (PTA) has been related to cell proliferation, both normal and pathological. PTA has also been proposed to be a target of the c-myc protooncogene. To study PTA mRNA levels during pathological cell growth, and especially the effect of the activation of specific oncogenes on PTA expression, we have studied its expression in tumors that arise in transgenic mice. We found high PTA levels in mammary tumors arising in c-myc, c-neu, and v-ras transgenic mice. Levels of this protein were variable between different tumors, and there is a differential regulation of PTA respect to other putative c-myc target genes, such as Ornithine Decarboxylase (ODC). Furthermore, expression of PTA is not absolutely dependent of c-myc expression, as shown by MYC depletion experiments performed with antisense oligonucleotides. We conclude that regulation of PTA in these tumors is complex and depends on more than a single activated oncogene.

Animals↗
PubMed1998

Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells.

Prothymosin alpha (ProTalpha) is an acidic nuclear protein the expression of which is related to the proliferation and differentiation processes in mammalian cells. In the present study we have stably transfected HL-60 cells, a biological system that allows the study of both proliferation and differentiation, with recombinant vectors encoding sense and antisense ProTalpha mRNA. In the HL-60 cell clones overexpressing ProTalpha we observed an acceleration in the growth rate, whereas expression of the antisense orientation showed the opposite effect. Moreover, cell-cycle analysis demonstrated that the G1-phase was shortened in the cells expressing the sense construct. Before studying how ProTalpha affects differentiation, we showed that the down-regulation of ProTalpha gene during differentiation occurs in all mammalian cell lines (HL-60, K562, U937, MEL C88, N2A and PC12) analysed. The biological effect evoked by the induction of the ProTalpha sense vector was the retardation of cell differentiation, although expression of the antisense construct showed no effect on differentiation. In conclusion, our findings provide evidence that ProTalpha is directly implicated in cellular proliferation and that the maintenance of high levels of ProTalpha inside HL-60 cells is incompatible with their ability to differentiate.

Cell Differentiation↗