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Biomedical subjects

F Vidal

Publications and source records attributed to F Vidal.

At least 37 records · Page 2Linked to original sources

The additive factor method in rat information processing.

Sternberg introduced the additive factor method as a tool for discovering and studying in choice reaction time situations in human subjects. Underlying the method is the notion that if information processing consists of successive stages, then different factors affecting different stages must have additive effects on reaction-time measurements. The additive factor method has been extensively used in humans but few attempts have been made to examine whether or not additive reaction time patterns were obtainable in rats. In the present work, the subjects (13 Long-Evans rats) had to press down a lever and to respond to a visual (right or left) stimulus by releasing the lever and introducing the head into a lateral (right or left) operandum. The present findings show an additive pattern of effects of signal luminance and foreperiod duration on the mean reaction time which suggests that we have successfully manipulated two stages of rat information processing - the preprocessing stage and the motor adjustment stage, respectively. Accordingly, the present study sets the basis for the basis for investigating the effects of invasive manipulations (pharmacological and/or lesional) on information processing stages.

Journal Article↗

Preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) includes a variety of techniques that have been developed to detect the transmission to the offspring of genetic diseases or of chromosome abnormalities by couples at risk before a pregnancy is established, to avoid these couples the risk of recurrent abortions and/or of repeated terminations of pregnancy. Candidate couples are carriers of gene mutations or of structural chromosome rearrangements, or with recurrent spontaneous abortions of unknown origin. Diagnostic procedures include different modalities of gene amplification using the polymerase chain reaction (PCR) or of fluorescent in situ hybridization (FISH). Embryo biopsies are carried out at the 6-8 cell stage. Healthy embryos are transferred on day 4 or at the blastocyst stage. By now, several hundred healthy children have been born using PGD, and only one diagnostic error has been reported.

Abortion, Habitual↗

Up-regulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1.

Vascular endothelial growth factor (VEGF) is highly expressed in vascular remodeling processes and accelerates reendothelialization after mechanical denudation. Two VEGF tyrosine kinase receptors have been reported-fms-like-tyrosine kinase-1 (Flt-1) and kinase domain region (KDR). Little is known about the regulation of the expression of these receptors after vascular injury. Herein, we have analyzed the expression of Flt-1 after mechanical denudation of primary cultures of endothelial cells, which has been considered a useful in vitro model to study endothelium responses to vascular injury. After denudation, the Flt-1 protein and mRNA levels are clearly up-regulated, and transient transfection experiments showed a strong induction of the flt-1 promoter-dependent transcription. Analysis of the flt-1 promoter sequence revealed the presence of a putative binding site for the early growth response factor-1 (Egr-1) at positions -24 to -16. Electrophoretic mobility shift and supershift assays showed that Egr-1 was able to bind to this DNA sequence, and cotransfection of the flt-1 promoter reporter plasmid with an Egr-1 expression vector resulted in enhancement of its transcriptional activity. Furthermore, the mutation of the Egr-1 binding site markedly reduced the denudation-induced flt-1 promoter activity. These data demonstrate that Flt-1 is up-regulated after endothelial denudation and that Egr-1 plays a relevant role in this process.

Binding Sites↗

First observation for a cuprate superconductor of fluctuation-induced diamagnetism well inside the finite-magnetic-field regime

For the first time for a cuprate superconductor, measurements performed above T(c) in high quality grain aligned La1.9Sr0.1CuO4 samples have allowed the observation of the thermal fluctuation induced diamagnetism well inside the finite-magnetic-field fluctuation regime. These results may be explained in terms of the Gaussian Ginzburg-Landau approach for layered superconductors, but only if the finite field contributions are estimated by taking off the short-wavelength fluctuations.

Journal Article↗

The decision to cancel a preimplantation genetic diagnosis cycle.

It has been suggested that a minimum number (six) of cumulus-oocyte complexes (COCs) should be retrieved for fertilization to offer enough chances to ensure a pregnancy after a preimplantation genetic diagnosis (PGD) procedure. Therefore a decision to cancel a PGD cycle should be adequately weighted to offer the patients the highest chances to obtain a pregnancy. We describe a case where, after retrieving only three COCs suitable for fertilization, a triplet pregnancy was obtained. This case suggests that, although low numbers of COCs can reduce the effectiveness of the PGD procedure, other factors are involved in its final result. Thus, the opportunity of routinely cancelling such cycles should be reconsidered. In addition, this is, to our knowledge, the first case where sex selection was carried out to prevent the birth of carriers of the abnormal gene, and not of affected offspring.

Adult↗

Interchromosomal effects for chromosome 21 in carriers of structural chromosome reorganizations determined by fluorescence in situ hybridization on sperm nuclei.

We have used dual color fluorescence in situ hybridization (FISH) on decondensed sperm heads from four carriers of structural chromosome reorganizations, viz. t(3;15), t(Y;7), t(13;22) and inv(9), to assess the possible existence of an interchromosomal effect (ICE) on the segregation of chromosome 21. In the carriers of t(Y;7), t(13;22) and inv(9), all results were within the limits described in controls. A highly significant increase (P<0.0001) of disomy 21 (1.90% v 0.37%), which could be considered as a positive ICE, was observed in the t(3;15) carrier. Significantly higher percentages (P<0.0001) of diploid sperm (5.71% v. 0.27%) were also observed in this patient. Our results suggests that the occurrence of an ICE may depend on the reorganization and on the chromosome and chromosome regions involved, resulting in a particular meiotic behaviour (presence of unsynapsed regions, preferential meiotic configurations) that could lead to the observed increase in chromosome 21 disomies. Further studies with this technical approach in a wide range of structural reorganizations could help to elucidate the actual occurrence of ICEs.

Adult↗

Small oxidative changes in atherogenic LDL concentrations irreversibly regulate adhesiveness of human endothelial cells: effect of the lazaroid U74500A.

The adherence of monocytes to the endothelium is an early event in atherogenesis which is modulated by low density lipoproteins (LDL). We analyzed the effect of atherogenic LDL levels (180 mg cholesterol/dl, for 24 h) with minimal oxidative modifications (thiobarbituric-acid-reactive-substances (TBARS) concentration between 1.2+/-0.1 and 2.5+/-0.3 nmol of malonaldehyde bis-diethyl acetal (MDA) per mg protein) on human umbilical vein endothelial cell (HUVEC) adhesive properties. We used native LDL (n-LDL), and LDL exposed to spontaneous oxidation without antioxidants (mox-LDL) or with 20 micromol/l of the antioxidant butylated hydroxytoluene (BHT-LDL) or 10 micromol/l U74500A (U74500A-LDL), a scavenger of free radicals. Thiobarbituric-acid-reactive-substances (TBARS) levels were significantly higher in mox-LDL (2.5+/-0.3 nmol MDA/mg protein) than in BHT-LDL (1.6+/-0.2), U74500A-LDL (1.2+/-0.1) or in n-LDL (1.3+/-0.1). mox-LDL induced the greatest adhesion of U937 cells to HUVEC (103+/-9% over controls) followed by BHT-LDL (75+/-10%), U74500A-LDL (36+/-9%) and n-LDL (35+/-3%). The lazaroid U74500A efficiently protected U74500A-LDL against oxidative damage and prevented endothelial adhesiveness associated with this LDL modification, inducing adhesion effects similar to those of n-LDL. However, U74500A could not reverse the adhesion induced by previously oxidized LDL (mox-LDL). LDL did not induce the expression of the intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) or E-selectin, but it produced a downregulation of endothelial nitric oxide synthase (NOS III) mRNA levels. Thus, adhesiveness of human endothelial cells (EC) exposed to atherogenic concentrations of LDL is closely modulated by minimal changes in LDL oxidative state, and could be related to a downregulation of NOS III.

Analysis of Variance↗

Is the 'error negativity' specific to errors?

When subjects make an erroneous response in a choice reaction time task, an error negativity, or error-related negativity (N(E)/ERN), peaking at about 100 ms after EMG onset, has been described. This wave is often considered to be absent on correct response trials. We report a small N(E)/ERN wave on correct response trials during a choice reaction time task in which surface Laplacians were estimated by the source derivation method. This wave is well focused at FCz, and its time course is the same for correct responses trials, incorrect sub-threshold EMG activation trials, and error trials. Current source density maps, also indicate a focus at FCz. A second experiment showed the existence of a N(E) at FCz on correct trials during a simple RT task. Rather than an error detection process per se, we propose that the N(E)/ERN reflects either a comparison process leading secondarily to error detection, or an emotional reaction.

Adult↗

Factor IX gene sequencing by a simple and sensitive 15-hour procedure for haemophilia B diagnosis: identification of two novel mutations.

We have developed a simple, sensitive and cost-effective direct DNA sequencing procedure for the molecular diagnosis of haemophilia B. All factor IX gene essential regions were amplified under identical thermocycling parameters allowing mutation identification in less than 15 h from blood sample collection. Identical results in terms of accuracy and speed were obtained when using a single hair as the source of DNA. Using this approach, we have found mutations in 10 out of 10 haemophilia B patients, two of which are novel (P287T and S123C). Very suitable for individual studies, this procedure can be easily scaled up for higher throughput.

Electronic Data Processing↗

Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

Adult↗

Is there a place for preimplantation genetic diagnosis screening in recurrent miscarriage patients?

Chromosomal abnormalities are one of the factors known to interfere with normal embryo development; thus preimplantation genetic diagnosis (PGD) for chromosome anomalies may be a new tool for improving the pregnancy rate in selected groups of patients. Embryos from three groups of patients (control, aged and recurrent miscarriage patients) were screened by PGD using specific DNA probes for chromosomes 13, 16, 18, 21, 22, X and Y. The control and aged groups were included in the PGD study because the women carried sex-linked genetic disease. The frequencies of chromosome anomalies observed in older women (46.3%) and in recurrent miscarriage patients (53%) were significantly higher (P < 0.05) than the frequency in the control group (19.3%). After PGD screening and transfer of normal embryos, pregnancies were obtained in women who had undergone repeated abortions (approximate 25% pregnancy rate per transfer) but not in older women. On the basis of these data, it seems that PGD screening of embryos can help some women undergoing repeated abortions, as these techniques allow successful pregnancies to be obtained or, if no pregnancy can be obtained, the results may help the couple to decide whether to enter an embryo or gamete donation programme.

Abortion, Habitual↗

A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene.

Inhibin, a member of the TGF-beta superfamily, is synthesized in the testis by Sertoli cells and exerts an endocrine regulatory function on pituitary hormone synthesis. A distinct local function has been proposed, negatively controlling cellular growth in the testis (tumor suppressor activity). A critical test for the identification of a tumor suppressor is the reversal of transformed growth properties upon re-expression of the gene in tumor-derived cell lines. Sertoli cell-derived tumoral lines were previously established from tumors that develop in elderly transgenic males which express in the testis the large T antigen of polyoma virus. Both the tumors and the cells in culture exhibited reduced levels of the inhibin alpha subunit mRNA. Stable transfectants were generated, in which this subunit was expressed from a heterologous promoter. All of them exhibited a strict inhibition of growth at confluency. On the other hand, in addition to an aging-related decrease in inhibin synthesis, the alpha subunit gene was down regulated in vivo in cells expressing the viral protein. The conjunction of these two factors accounts for the age-related occurrence of testicular cancers in the transgenic model, again pointing to inhibin as a potent cell growth regulator in the seminiferous epithelium.

Antigens, Viral, Tumor↗

EMK protein kinase-null mice: dwarfism and hypofertility associated with alterations in the somatotrope and prolactin pathways.

Gene trapping was used in embryonic stem (ES) cells in an attempt to inactivate genes involved in development. The Emk (ELKL motif kinase) gene has been disrupted and a mutant mouse line derived. Previous work had shown that EMK kinases, called MARK in the rat, exert a major control on microtubule stability by phosphorylating microtubule-associated proteins and that genes homologous to Emk in yeast or Caenorhabditis elegans are essential for cell and embryonic polarity. Although we found the Emk gene to be active in the preimplantation mouse embryo and then to show a widespread expression, Emk-null mice had no embryonic defect and were viable. They show an overall proportionate dwarfism and a peculiar hypofertility: homozygotes are not fertile when intercrossed, but are fertile in other types of crosses. Insulin-like growth factor I (IGF I) and IGF-binding protein 3 (IGFBP3) were reduced in the plasma of homozygotes of both sexes. A direct implication of the EMK kinase in IGF I plasmatic production is unlikely because the Emk gene does not seem to be expressed in hepatocytes. Nevertheless, GH assayed at arbitrary times in plasma did not show differences between genotypes and GH concentrations in pituitary extracts were not found to be altered in homozygotes. Our results, though, do not exclude the possibility that in the mutants the overall quantity of GH secreted daily is reduced. Our observation of a smaller size of the pituitaries of the mutants is in favor of this hypothesis. The prolactin concentration in the pituitaries was much lowered in homozygous females, but it was normal in males. The possible involvement of EMK protein kinase in hormone secretion in the pituitary and/or the hypothalamus, via the microtubule network, is discussed.

Animals↗

The supplementary motor area in motor and sensory timing: evidence from slow brain potential changes.

The present study investigated the processing of durations on the order of seconds with slow cortical potential changes. The question is whether trial-to-trial fluctuations in temporal productions or judgments correspond to variations in the amplitude of surface Laplacians computed over particular scalp regions. Topographical analyses were done using the source derivation method. Subjects performed three successive tasks: (1) time production, in which they produced a 2.5-s interval separated by two brief trigger presses; (2) time discrimination, in which they detected small differences in intervals delimited by two brief clicks in comparison with a memorized standard interval: and (3) intensity discrimination (control task, devoid of time judgments), in which they detected small differences between the intensity of clicks, in comparison with standard clicks initially memorized. In order to focus on subjective differences, in the two discrimination tasks most comparison stimuli were identical to the standard, without the subjects being aware of it. At FCz, reflecting activity from the mesial frontocentral cortex that mainly includes the supplementary motor area (SMA), larger negativities were found during the longer target intervals, whether these were produced (task 1) or judged so (task 2). Those performance-dependent trends were restricted to the target intervals of the temporal tasks; they appeared neither during the 2 s preceding the target, nor during the control task. The data therefore suggest that the SMA subserves important functions in timing both sensory and motor tasks. We propose that the SMA either provides the "pulse accumulation" process commonly postulated in models of time processing or that it receives output from this process through striatal efferent pathways.

Adult↗

Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1.

A prospective analysis of 43 episodes of Pseudomonas aeruginosa bacteremia in HIV-1-infected subjects was performed and the results compared with the incidence and outcome of Pseudomonas aeruginosa bacteremia in other high-risk patients, such as transplant recipients, leukemia patients, or patients hospitalized in the intensive care unit. The incidence of bacteremia/fungemia as a whole and of gram-negative and Pseudomonas aeruginosa bacteremia in particular was greater in HIV-1-infected subjects than in the unselected general population admitted. In contrast, the incidence of Pseudomonas aeruginosa bacteremia in HIV-1-infected patients did not differ from that in patients with other high-risk conditions. In patients with HIV-1 infection, independent risk factors for presenting Pseudomonas aeruginosa bacteremia were nosocomial origin (OR, 2.7; 95% CI, 1.3-5.7), neutropenia (OR, 2.7; 95% CI, 1.07-6.8), previous treatment with cephalosporins (OR, 3.6; 95% CI, 1.1-11.6), and a CD4+ cell count lower than 50 cells/mm3 (OR, 3.1; 95% CI, 1.7-8.6). Primary bacteremia and pneumonia were the most common forms of presentation. Fourteen (33%) patients died as a consequence of the bacteremia. The presence of severe sepsis (OR, 17.5; 95% CI, 3.2-68) and the institution of inappropriate definitive antibiotic therapy (OR, 2.7; 95% CI, 1.1-13) were independently associated with a poor outcome. One year after the development of bacteremia, only eight (19%) patients remained alive.

AIDS-Related Opportunistic Infections↗

In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage: an analysis of chromosome abnormalities in human preimplantation embryos.

OBJECTIVE: To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage (RM) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases. DESIGN: Prospective controlled study. SETTING: University laboratory of reproductive genetics and a tertiary referral center for infertility. PATIENT(S): Nine women with a mean (+/-SD) of 3.9 +/- 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis, and a control group of young (n = 10) and older (n = 6) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases. INTERVENTION(S): In vitro fertilization, embryo culture for 72 hours, blastomere biopsy, and analysis of chromosomes 13, 16, 18, 21, 22, X, and Y with the use of fluorescent in situ hybridization. Transfer of chromosomally normal embryos into the uterus. MAIN OUTCOME MEASURE(S): Numeric chromosomal abnormalities in human embryos. RESULT(S): Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients. There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls. Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group, especially those affecting chromosome 13. CONCLUSION(S): There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM. The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure.

Abortion, Habitual↗