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E Fernandez

Publications and source records attributed to E Fernandez.

At least 37 records · Page 2Linked to original sources
PubMed2002

Transcriptional and post-transcriptional regulation of tyrosine hydroxylase messenger RNA in PC12 cells during persistent stimulation by VIP and PACAP38: differential regulation by protein kinase A and protein kinase C-dependent pathways.

VIP and PACAP38 are closely related peptides that are released in the adrenal gland and sympathetic ganglia and regulate catecholamine synthesis and release. We used PC12 cells as a model system to examine receptor and second messenger pathways by which each peptide stimulates transcriptional and post-transcriptional mechanisms that regulate the level of the mRNA for tyrosine hydroxylase (TH), the rate-limiting enzymatic step in catecholamine synthesis. Concentration-response studies revealed that PACAP38 had both greater efficacy and potency than VIP. The specific PAC1 receptor antagonist PACAP[6-38] blocked the effects of each peptide on TH mRNA content while the PACAP/VIP type II receptor antagonist (N-AC-Tyr(1)-D-Phe(2))-GRF-(1-29)-NH(2) was without effect. At equipotent concentrations, each peptide stimulated a transient increase in TH gene transcription lasting less than 3h. Continuous VIP treatment stimulated a transient increase in TH mRNA lasting less than 24h. In contrast, continuous exposure to PACAP38 stimulated a stable increase in TH mRNA that persisted for 2 days in the absence of elevated transcription, pointing to different post-transcriptional effects of the two peptides. PACAP38 alone had no effect on the magnitude of TH gene transcription or TH mRNA in A126-1B2 PKA-deficient PC12 cells. However, when combined with dexamethasone, PACAP38 produced a synergistic increase in TH mRNA in the absence of PACAP38-stimulated TH gene transcription. In contrast, VIP had no effect on either TH mRNA content or TH gene transcription in this model. PACAP38, but not VIP, stimulated PKC activity. Calphostin C antagonized the effect of PACAP38 on the persistent post-transcriptional elevation in TH mRNA. Thus, the results support the conclusion that VIP and PACAP38 each stimulate PAC1 receptors to increase TH gene transcription through a PKA-controlled pathway, but their divergent post-transcriptional effects result at least partly from differing abilities to stimulate PKC.

Animals↗
PubMed2001

An unprecedented recyclable catalyst system for asymmetric hydroboration.

Immobilised preformed chiral homogeneous catalysts were subjected to catalytic hydroboration of styrene with catecholborane and the activity, regio- and enantioselectivity observed were similar to those found when the corresponding homogeneous catalyst was used, remaining constant for several consecutive runs.

Journal Article↗
PubMed2001

Oral contraceptives and colorectal cancer risk: a meta-analysis.

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69-0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72-0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74-0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30-0.71). A better understanding of this potential relation may help informed choice of contraception.

Case-Control Studies↗
PubMed2001

DIP: The Database of Interacting Proteins: 2001 update.

The Database of Interacting Proteins (DIP; http://dip.doe-mbi.ucla. edu) is a database that documents experimentally determined protein-protein interactions. Since January 2000 the number of protein-protein interactions in DIP has nearly tripled to 3472 and the number of proteins to 2659. New interactive tools have been developed to aid in the visualization, navigation and study of networks of protein interactions.

Databases, Factual↗
PubMed2001

Apoptosis and proliferation in the neonatal murine heart.

The spatial and temporal patterns of apoptosis and proliferation in timed fetal, neonatal, and adult murine hearts have been determined using an in situ end-labeling technique for detecting fragmented DNA, and bromodeoxyuridine immunofluorescence as a marker for DNA synthesis. Also, cardiac expression of apoptosis-related proteins was assessed by immunofluorescence. Prominent apoptotic labeling was found in the right ventricular subendocardium and the basal septum in the area of the developing conduction system. In the right ventricle, apoptotic labeling surged late in the first day postpartum, then declined to levels similar to the left ventricle by postpartum day 8.5. Apoptotic labeling at the basal septum was greatest peripartum and gradually declined to levels seen in the rest of the heart by postpartum day 8.5. Cessation of proliferation did not occur simultaneously throughout the neonatal heart. Through postpartum day 4.5, incorporation of BrdU was greater in the left ventricle than in the right ventricle, particularly in the subendocardium. Bax and Fas, proapoptotic proteins, were detected homogeneously throughout both ventricles in the neonate, while Bcl-2, an antiapoptotic protein, was not detectable. These data suggest that postnatal cardiac remodeling results from changes in both apoptosis and proliferation. Furthermore, the temporal and spatial pattern of these processes, coincident with the hemodynamic changes associated with parturition, suggests that both processes may be regulated by mechanical factors.

Animals↗
PubMed2001

Smoking initiation and cessation by gender and educational level in Catalonia, Spain.

BACKGROUND: The role of gender and socioeconomic status in smoking has been characterized in the United States and Northern European countries. However, there is scarce information of the dynamic of the tobacco epidemic in Southern European countries. The aim of this study was to analyze smoking initiation and cessation according to level of education and gender in Catalonia, Spain. METHODS: Data from the Catalan Health Survey (1994), a cross-sectional study based in a representative sample of the noninstitutionalized population of Catalonia, was used. The relative risks and 95% confidence interval of smoking initiation were computed by means of Cox's regression. The odds ratios and 95% confidence intervals of quitting smoking were derived from logistic regression models. Direct responses from 4,370 men and 5,213 women ages 25 years or over were included for analysis. RESULTS: Ever smoking was inversely related to level of education in men. Males with the highest educational level tended to have a lower probability of being a smoker at a given age than those with less than primary school (relative risk = 0.6; 95% confidence interval: 0.5-0.7). This pattern appeared with small variation across age groups. In women, a reverse trend was present: the higher the level of education the higher the relative risk of starting smoking (relative risk = 4.6; 95% confidence interval: 3.1-6.7). Quitting smoking was more likely among men and women with higher education as compared to men and women with less than primary school (men: odds ratio = 1.5; 95% confidence interval 1.1-2.1; women: odds ratio = 4.6; 95% confidence interval: 2.1-10.4). CONCLUSIONS: The differential effect of education according to gender may reflect different phases of the smoking epidemic. In Catalonia, the transition of smoking from upper and lower socioeconomic groups occurred recently among men, and women have currently begun to experience this transition.

Adolescent↗
PubMed2001

High-resolution spatio-temporal mapping of visual pathways using multi-electrode arrays.

The parallel processing of visual information was studied with penetrating microelectrode arrays. We studied the high-resolution visuotopic organization of cat primary visual cortex, and the encoding of simple visual stimuli by ensembles of ganglion cells in the isolated turtle retina. The high-resolution visuotopic organization of visual cortex is non-conformal. Regions of visual cortex separated by 400 mu may have receptive field centers that are separated by as much as 3 degrees, or they may superimpose. Ganglion cells are 'generalists', and are poor specifiers of the color of full field visual stimuli. Groups of 'luminosity' type ganglion cells can assist in the specification of stimulus color, but even individual 'chromatic' ganglion cells are not capable of quality color specification. These basic studies have relevance to the development of visual neuroprostheses based upon electrical stimulation of the retina and cortex.

Animals↗
PubMed2001

High-resolution two-dimensional spatial mapping of cat striate cortex using a 100-microelectrode array.

Much of our understanding of the visuotopic organization of striate cortex results from single-electrode penetrations and serial recording of receptive field properties. However, the quality of these maps is limited by imprecision in quantifying electrode position, combining data from multiple laminae, and eye drift during the measurement of the receptive field properties. We have addressed these concerns by using an array of 100 closely spaced microelectrodes to investigate the two-dimensional visuotopic organization of layer IV in cat striate cortex. This array allowed simultaneous measurement of the receptive field properties of multiple single units on a regularly spaced grid. We found the relationship between cortical and visual space to be locally non-conformal: the receptive field locations associated with a closely spaced line of electrodes appeared randomly scattered in visual space. To quantify the scatter, we fitted a linear transformation of electrode sites onto the associated receptive field locations. We found that the distribution of the difference between the predicted receptive field location and the measured location had standard deviations of 0.59 degrees and 0.45 degrees in the horizontal and the vertical axes, respectively. Although individual receptive field positions differed from the predicted locations in a non-conformal sense, the trend across multiple receptive fields followed the maps described elsewhere. We found, on average, that the 13 mm2 of cortex sampled by the array mapped onto a 5.8-degrees) region of visual space. From the scaling of this map and a combination of the statistics of the receptive field size (2.7+/-1.5 degrees) and scatter, we have explored the impact of electrode spacing on the completeness and redundancy in coverage of visual space sampled by an array. The simulation indicated an array with 1.2-mm spacing would completely sample the region of visual space addressed by the array. These results have implications for neuroprosthetic applications. Assuming phosphene organization resembles the visuotopic organization, remapping of visual space may be necessary to accommodate the scatter in phosphene locations.

Animals↗
PubMed2001

Recent decline in cancer mortality in Catalonia (Spain). A joinpoint regression analysis.

The aim of this paper was to analyse recent changes in cancer mortality in Catalonia (Spain) between 1975 and 1998 using joinpoint regression models. Mortality data were obtained from the Mortality Registry of Catalonia. For each sex, age-standardised (standard world population) mortality rates were computed by the direct method, and joinpoint analysis was used to identify the best fitting points where a statistically significant change in the rates had occurred. In men, the overall cancer mortality (except skin non-melanoma) was highest in 1991 and decreased thereafter. Lung cancer was the main cause of cancer mortality, with an increase until 1989, and a subsequent levelling off (-0.8% annual between 1989 and 1998). Colorectal cancer was the second cause of cancer death, both in men and women, with a levelling-off of the rates since 1991 and 1989, respectively. In women, the mortality rate decreased for total cancer (except skin non-melanoma) since 1991 (-0.9% annually). Breast cancer increased until 1975, levelled-off and begun to decline since 1992 (-3.8% annual). Lung cancer increased since 1988 (+2.1%) and became the third cancer cause of death among women in 1998. These changes are mainly due to the decline of smoking prevalence in males, but not in females, and to the introduction of new diagnostic techniques and improved therapies for female breast cancer.

Adult↗
PubMed2001

CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure.

Human herpesvirus-8 (HHV-8) is the infectious agent responsible for Kaposi's sarcoma and encodes a protein, macrophage inflammatory protein-II (vMIP-II), which shows sequence similarity to the human CC chemokines. vMIP-II has broad receptor specificity that crosses chemokine receptor subfamilies, and inhibits HIV-1 viral entry mediated by numerous chemokine receptors. In this study, the solution structure of chemically synthesized vMIP-II was determined by nuclear magnetic resonance. The protein is a monomer and possesses the chemokine fold consisting of a flexible N-terminus, three antiparallel beta strands, and a C-terminal alpha helix. Except for the N-terminal residues (residues 1-13) and the last two C-terminal residues (residues 73-74), the structure of vMIP-II is well-defined, exhibiting average rmsd of 0.35 and 0.90 A for the backbone heavy atoms and all heavy atoms of residues 14-72, respectively. Taking into account the sequence differences between the various CC chemokines and comparing their three-dimensional structures allows us to implicate residues that influence the quaternary structure and receptor binding and activation of these proteins in solution. The analysis of the sequence and three-dimensional structure of vMIP-II indicates the presence of epitopes involved in binding two receptors CCR2 and CCR5. We propose that vMIP-II was initially specific for CCR5 and acquired receptor-binding properties to CCR2 and other chemokine receptors.

Amino Acid Sequence↗
PubMed2001

Interaction of a glucocorticoid-responsive element with regulatory sequences in the promoter region of the mouse tyrosine hydroxylase gene.

The purpose of the work reported here was to determine whether the tyrosine hydroxylase glucocorticoid-responsive element (TH-GRE) interacts with the cyclic AMP pathway and the CRE in regulating mouse TH promoter activity, and whether an additional, previously identified downstream GRE-like element also participates in the function of the TH-GRE and CRE. To determine the role of the cAMP pathway on TH-GRE function, we compared the effects of forskolin and dexamethasone on TH mRNA, TH gene transcription and TH promoter activity in a mutant PC12 cell line (A126-1B2) deficient in cAMP-dependent protein kinase A (PKA) with their effects in the wild-type parental strain. Forskolin treatment increased TH mRNA content, transcriptional activity and the activity of a chimeric gene with 3.6 kb of the TH promoter in wild-type cells, but not in PKA-deficient cells. In contrast, dexamethasone treatment stimulated equivalent increases in TH mRNA, TH gene transcription and TH promoter activity in each cell type. Mutation of the CRE in chimeric constructs containing 3.6 kb of the 5' flanking sequence of the mouse TH gene or coexpression of a dominant-negative mutant of CREB prevented the stimulation of TH promoter activity by forskolin. However, neither the mutation of the CRE nor inhibition of CREB influenced basal or dexamethasone-stimulated promoter activity. Site-directed mutagenesis of the TH-GRE eliminated the response of the promoter to dexamethasone. However, the mutagenesis of a more proximal 15-bp region with a GRE-like sequence had no demonstrable effect on the ability of dexamethasone to stimulate TH promoter activity. Neither mutagenesis of the TH-GRE or the downstream GRE-like sequence had an effect on the ability of forskolin to activate this chimeric gene. Taken together, these results provide evidence that a single GRE is sufficient for maximal induction of transcriptional activity by glucocorticoids and that the CRE is not required for either partial or full activity of this upstream GRE sequence.

Animals↗
PubMed2001

Affective and evaluative descriptors of pain in the McGill Pain Questionnaire: reduction and reorganization.

Recent reports indicate that several descriptors of pain sensations in the McGill Pain Questionnaire (MPQ) are difficult to classify within MPQ sensory subcategories because of incomprehension, underuse, or ambiguity of usage. Adopting the same methodology of recent studies, the present investigation focused on the affective and evaluative subcategories of the MPQ. A decision rule revealed that only 6 of 18 words met criteria for the affective category and 5 of 11 words met criteria for the evaluative category, thus warranting a reduced list of words in these categories. This reduction, however, led to negligible loss of information transmitted. Despite notable changes in classification, the intensity ratings of the retained words correlated very highly with those originally reported for the MPQ. In conclusion, although the intensity ratings of MPQ affective and evaluative descriptors need no revision, selective reduction and reorganization of these descriptors can enhance the efficiency of this approach to pain assessment.

Journal Article↗
PubMed2001

Social class inequalities in the use of and access to health services in Catalonia, Spain: what is the influence of supplemental private health insurance?

OBJECTIVE: To analyse social class inequalities in the access to and utilization of health services in Catalonia (Spain), and the influence of having private health insurance supplementing the National Health System (NHS) coverage. DESIGN: 1994 Catalan Health Interview Survey, a cross-sectional survey conducted in 1994. SETTING: Catalonia (Spain). STUDY PARTICIPANTS: The participants were a representative sample of people aged over 14 years from the non-institutionalized population of Catalonia (n = 12,245). MAIN OUTCOME MEASURES: Health services utilization, perceived health, having only NHS or NHS plus a private health insurance, and social class. RESULTS: Although one-quarter of the population of Catalonia had a supplemental private health insurance, percentages were very different according to social class, ranging from almost 50% for classes I and II to 16% for classes IV and V in both sexes. No inequalities by social class were observed for the utilization of non-preventive health care services (consultation with a health professional in the last 2 weeks and hospitalization in the last year) among persons with poor self-perceived health status, i.e. those in most need. However, social inequalities still remain in the use of health services provided only partially by the NHS, and when characteristics of last consultation are taken into account. Subjects who paid for a private service waited an average of 18.8 minutes less than those attending the NHS. Within the NHS, social classes IV and V waited longer (35.5 minutes) than social classes I and II (28.4 minutes). CONCLUSION: The NHS in Catalonia, Spain, has reduced inequalities in the use of health services. Social inequalities remain in the use of those health services provided only partially by the NHS.

Adolescent↗
PubMed2001

Cofactor dependence and isotype distribution of anticardiolipin antibodies in viral infections.

BACKGROUND: Antibodies to cardiolipin (aCLs) are often detected in patients with autoimmune disorders or infectious diseases. OBJECTIVE: To investigate the distribution of aCL isotypes and requirement of protein cofactor in viral infections in order to establish the importance, if any, of these antibodies in these infectious diseases. PATIENTS AND METHODS: The isotype distribution of aCLs in the sera from 160 patients with infection caused by HIV-1 (n=40), hepatitis A virus (n=40), hepatitis B virus (n=40), or hepatitis C virus (n=40) was studied by standardised enzyme linked immunosorbent assay (ELISA) in the presence and absence of protein cofactor (mainly beta2-glycoprotein I). Serum samples from healthy volunteers and patients with syphilis and antiphospholipid syndrome were also included and served as negative and positive control groups respectively. RESULTS: The prevalence of one or more aCL isotypes in serum of patients with HIV-1, hepatitis A virus, hepatitis B virus, or hepatitis C virus infection was 47%, 92%, 42%, and 17% respectively (principally IgM and/or IgA). Most of these antibodies were mainly cofactor independent. CONCLUSIONS: The presence of aCLs in viral infections is principally cofactor independent, suggesting that cofactor dependence of the aCLs should be assessed to distinguish subjects most likely to suffer from clinical symptoms observed in the presence of these antibodies.

Antibodies, Anticardiolipin↗
PubMed2001

Acrylic hydrogel implants after spinal cord lesion in the adult rat.

Acrylic hydrogels, like the polymer of 2-hydroxyethyl methacrylate, are biocompatible, mechanically stable, porous materials that can be coated with collagen or laminin acting as bioadhesive substrates. Poly-2-hydroxyethyl methacrylate sponges have been proposed for restoring the anatomical continuity of damaged neural structures. In the present work, the ability of poly-2-hydroxyethyl methacrylate sponges to provide the injured spinal cord neurons with a conductive substrate for their regenerating axons was investigated in 32 adult Wistar rats. Collagen impregnated poly-2-hydroxyethyl methacrylate sponges were implanted into suction cavities of the dorsal funiculus of the spinal cord. Two to four months after implantation, the spinal cord was removed and processed for histology, and S100 and GFAP immunohistochemistry. To study axonal regeneration into the sponge, the spinal cord or the sensorimotor cortex were injected with 0.05-0.1 microl of an 8% solution of lectin-conjugated horseradish peroxidase or 10% dextran tetramethylrhodamine. The fibroglial reaction, accumulation of mononuclear cells, and angiogenesis at the interface between the spinal cord and the sponge were minimal. Cystic cavitation in the spinal cord was virtually absent. Anterograde labeled axons were seen to penetrate and to elongate the full length of the sponge. These results demonstrate that poly-2-hydroxyethyl methacrylate sponges represent a safe supportive material for regenerating spinal cord axons.

Animals↗
PubMed2001

Radial nerve palsy caused by spontaneously occurring nerve torsion. Case report.

An 18-year-old man presented with a spontaneously occurring radial nerve palsy that spared the triceps muscle. At surgery, the portion of the radial nerve located at the midarm level had an hourglass-like appearance. Under magnification, an external-internal neurolysis of the narrowed portion of the hourglass-shaped portion revealed nerve torsion. Straightening of the twisted nerve and fixation accomplished using epiperineurium-fascia stitches to avoid a new torsion resulted in complete functional recovery of the radial nerve.

Adolescent↗