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Biomedical subjects

E Fernandez

Publications and source records attributed to E Fernandez.

At least 55 records · Page 3Linked to original sources

Evidence for telomerase involvement in the angiogenesis of astrocytic tumors: expression of human telomerase reverse transcriptase messenger RNA by vascular endothelial cells.

OBJECT: Evidence from recent in vitro studies indicates that reactivation of telomerase, the enzyme that synthesizes the telomere ends of chromosomes, is a crucial event in the unlimited clonal expansion of endothelial cells that precedes the neoplastic conversion of these cells. It is known that high-grade gliomas express telomerase and that, in these neoplasms, proliferating endothelial cells may undergo transformational changes with development of sarcomatous components within the primitive tumor. To assess whether telomerase is involved in the endothelial cell proliferation that characterizes brain tumor angiogenesis, the authors investigated at the single-cell level the expression of messenger (m)RNA for the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) by vascular cells of astrocytic tumors. METHODS: The in situ hybridization (ISH) method was performed by processing histological sections with specific riboprobes for hTERT and for c-myc, an oncogene that is known to upregulate hTERT. Results of the ISH studies were compared with proliferative activity, as estimated by Ki-67 immunostaining. The expression of hTERT mRNA by vascular endothelial cells was related to the histological grade of the tumor because it was detected in five (29%) of 17 low-grade astrocytomas, nine (56%) of 16 anaplastic astrocytomas, and 19 (100%) of 19 glioblastomas multiforme (GBMs). Expression of c-myc mRNA was strictly correlated with that of hTERT mRNA. In low-grade astrocytomas and anaplastic astrocytomas, a dissociation was noted between hTERT mRNA expression and the proliferation rate of endothelial cells. Conversely, GBMs displayed a significant correlation between the level of hTERT mRNA expression and endothelial cell proliferation. Data from an in vitro assay in which human umbilical vein endothelial cells were stimulated to proliferate by adding vascular endothelial growth factor and an ISH study of newly formed vessels surrounding brain infarcts confirmed that expression of hTERT mRNA does not merely reflect the proliferative status of endothelial cells but represents a specific feature of brain tumor neovascularization. CONCLUSIONS: The results of this study are consistent with a role of telomerase in the angiogenesis of astrocytic tumors. Expression of hTERT mRNA by tumor vascular cells is an early event during the progression of astrocytic tumors, which precedes endothelial cell proliferation and may represent a first sign of dedifferentiation. Other than elucidating the mechanisms of tumor angiogenesis, these results encourage research on antitelomerase drugs for the treatment of malignant gliomas.

Adult↗

A maternal inherited translocation t(1;22)(q11;p11) in two infertile brothers.

We report two infertile brothers presenting with azoospermia and oligozoospermia. Cytogenetic studies using G-banding and FISH analysis on lymphocyte cultures revealed an autosomal balanced reciprocal translocation t(1;22)(q11;p11) in both males. The same translocation was found in their mother, but not in a third fertile brother and maternal uncle suggesting that this translocation might compromise the male but not the female gametogenesis in this family.

Adult↗

Premature cessation of breastfeeding in infants: development and evaluation of a predictive model in two Argentinian cohorts: the CLACYD study, 1993-1999. Córdoba Lactation, Feeding, Growth and Development study.

UNLABELLED: The objective of this study was to develop a model to predict premature cessation of breastfeeding of newborns, in order to detect at-risk groups that would benefit from special assistance programmes. The model was constructed using 700 children with a birthweight of 2000 g or more, in 2 representative cohorts in 1993 and 1995 (CLACYD I sample) in Córdoba, Argentina. Data were analysed from 632 of the cases. Mothers were selected during hospital admittance for childbirth and interviewed in their homes at 1 mo and 6 mo. To evaluate the model, an additional sample with similar characteristics was drawn during 1998 (CLACYD II sample). A questionnaire was administered to 347 mothers during the first 24-48 h after birth and a follow-up was completed at 6 mo, with weaning information on 291 cases. Premature cessation of breastfeeding was considered when it occurred prior to 6 mo. A logistic regression model was fitted to predict premature end of breastfeeding, and was applied to the CLACYD II sample. The calibration (Hosmer-Lemeshow C statistic) and the discrimination [area under the receiver operating characteristics (ROC) curve] of the model were evaluated. The predictive factors of premature end of breastfeeding were: mother breastfed for less than 6 mo [odds ratio (OR) = 1.84, 95% confidence interval (CI) 1.26-2.70], breastfeeding of previous child for less than 6 mo (OR = 4.01, 95% CI 2.58-6.20), the condition of the firstborn child (OR = 2.75, 95% CI 1.79-4.21), the first mother-child contact occurring after 90 min of life (OR = 1.88; 95% CI 1.22-2.91) and having an unplanned pregnancy (OR = 1.50, 95% CI 1.05-2.15). The calibration of the model was acceptable in the CLACYD I sample (p = 0.54), as well as in the CLACYD II sample (p = 0.18). The areas under the ROC curve were 0.72 and 0.68, respectively. CONCLUSION: A model has been suggested that provides some insight onto background factors for the premature end of breastfeeding. Although some limitations prevent its general use at a population level, it may be a useful tool in the identification of women with a high probability of early weaning.

Argentina↗

The structure of the mRNA export factor TAP reveals a cis arrangement of a non-canonical RNP domain and an LRR domain.

Human TAP is implicated in mRNA nuclear export and is used by simian type D retroviruses to export their unspliced genomic RNA to the cytoplasm of the host cell. We have determined the crystal structure of the minimal TAP fragment that binds the constitutive transport element (CTE) of retroviral RNAs. Unexpectedly, we find the fragment consists of a ribonucleoprotein (RNP) domain, which is not identifiable by its sequence, and a leucine-rich repeat (LRR) domain. The non-canonical RNP domain functions as the general RNA-binding portion of the fragment. The LRR domain is required in cis to the RNP domain for CTE RNA binding. The structural and biochemical properties of the domains point to a remarkable similarity with the U2B"(RNP)-U2A'(LRR) spliceosomal heterodimer. Our in vitro and in vivo functional studies using structure-based mutants suggest that a phylogenetically conserved surface of the LRR domain of TAP may have different roles in the export of viral and cellular RNAs.

Amino Acid Sequence↗

Catalytic asymmetric hydroboration/amination and alkylamination with rhodium complexes of 1,1'-(2-diarylphosphino-1-naphthyl)isoquinoline

Catecholboronate esters formed by asymmetric hydroboration of arylalkenes are not directly converted to amines by reaction with hydroxylamine-O-sulfonic acid. Prior conversion to a trialkylborane by reaction with ZnEt2 or MeMgCl permits a subsequent amination reaction to occur with essentially complete retention of configuration, leading to a range of primary alpha-arylalkylamines in up to 97% enantiomeric excess (ee). Secondary, but not tertiary amines may be formed by a related pathway when in situ generated alkylchloramines are employed as the aminating agent. The catalytic asymmetric hydroboration, beta-alkylation and amination steps may be combined in a single stage. Overall, this provides a practical procedure for the synthesis of enantiomerically enriched arylamines, exemplified inter alia by the synthesis of (S)-1,2,3,4-tetrahydro-1-naphthylamine in 95-97% ee and of (R)-N-(cyclohexyl)-1'-(4-methoxyphenyl)ethylamine in 93% ee.

Journal Article↗

A technique to prevent dural adhesions to chronically implanted microelectrode arrays.

Minimizing relative movements between neural tissues and arrays of microelectrodes chronically implanted into them is expected to greatly enhance the capacity of the microelectrodes to record from single cortical neurons on a long-term basis. We describe a new surgical technique to minimize the formation of adhesions between the dura and an implanted electrode array using a 12 microm (0.5 mil) thick sheet of Teflon film positioned between the array and the dura. A total of 15 cats were implanted using this technique. Gross examination of 12 implant sites at the time of sacrifice failed to find evidence of adhesions between the arrays and the dura when the Teflon(R) film remained in its initial position. In six implants from which recordings were made, an average of nine of the 11 (81%) connected electrodes in each array recorded evoked neural activity after 180 days post implantation. Further, on average, two separable units were identified on each of the implanted electrodes in these arrays. No significant change was found in the density of cell bodies around implanted electrodes of four of the implanted electrode arrays. However, histological evaluation of the implant sites revealed evidence of meningeal proliferation beneath the arrays. The technique described is shown to be effective at preventing adhesions between implanted electrode arrays and improve the characteristics of chronic recordings obtained with these structures.

Animals↗

Selection of the most common chromosome abnormalities in oocytes prior to ICSI.

So far, all preimplantation genetic diagnosis (PGD) protocols in use produce results after the eggs have been fertilized. However, these approaches are not acceptable for patients with moral objections to the generation and discard of supernumerary zygotes or embryos. In these circumstances, only those oocytes to be replaced may be inseminated. The purpose of this study was to develop a PGD protocol to diagnose first polar bodies (PBs) prior to Intracytoplasmatic Sperm Injection (ICSI) in order to inseminate only those oocytes found to be chromosomally normal. PB biopsy was performed 1 hour after ovum pick up, and after fixation, the PBs were analysed by FISH and the eggs inseminated by ICSI no later than 7 hours after retrieval. One third (33.3%) of the PBs were aneuploid. Fifty-four normal and 12 non-resolved oocytes were injected by ICSI, of which 65% became 2-PN zygotes. Embryo transfer on day 2 was possible in all 10 patients (average maternal age 35.2+/-3.2, range 29-39 years), of which 6 became pregnant with 8 fetuses (28.6% or 8/28 transferred embryos). The results indicate that PB analysis of some common chromosome abnormalities is feasible within time limits imposed by ICSI insemination (6 hours or less).

Adult↗

Diet diversity and colorectal cancer.

BACKGROUND: Food diversity has been recommended to achieve a healthy diet and prevent cancer. The relation between diet diversity and the risk of colorectal cancer was investigated using data from a multicenter case-control study carried out between 1992 and 1996 in Italy. METHODS: The study included 1225 subjects with cancer of the colon (688 men and 537 women), 728 with cancer of the rectum (437 men and 291 women), and 4154 controls (2073 men and 2081 women) residing in the same geographical areas. Odds ratios (ORs) of colon and rectal cancer and the corresponding 95% confidence intervals (CI) according to food diversity were derived from unconditional multiple logistic regression equations. RESULTS: For colon cancer, an inverse association for total diversity was found in males (adjusted OR of 0.65 for the highest vs the lowest quintile of total diversity; 95% CI: 0.46-0.93) and in females (OR = 0.85; 95% CI: 0.57-1.26). With respect to specific food groups, there was an inverse association only with diversity within vegetables (OR = 0.66; 95% CI: 0.54-0.81 in colon cancer and OR = 0.71; 95% CI: 0.55-0.91 in rectal cancer). CONCLUSIONS: This study suggests that total diversity is moderately related to a decreased risk of colorectal cancer risk. A better understanding of the potential influence of dietary patterns on colorectal cancer is needed.

Adult↗

Trends in social class inequalities in health status, health-related behaviors, and health services utilization in a Southern European urban area (1983-1994).

BACKGROUND: The objective of this study was to describe the evolution of social class inequalities in Barcelona (Spain) residents in perceived health status, health-related behaviors, and utilization of health services between 1983 and 1994. METHODS: The information was obtained from the Health Interview Surveys conducted in 1983, 1986, 1992, and 1994 in Barcelona. In this study we included noninstitutionalized people ages >14 years. Social class was obtained from the Spanish adaptation of the British Registrar General classification. We studied health status, health-related behaviors, and health services utilization variables. Age-adjusted percentages and the relative index of inequality were obtained. RESULTS: Of the health status variables, having been confined to bed and acute restriction of activity in the 2 weeks prior to the interview showed an increase in inequalities by social class in 1994. The pattern of chronic conditions by social class in men did not change between 1983 and 1994. Women had a higher prevalence of chronic conditions and the inequalities among social classes had increased. In men there were no social class inequalities in smoking in 1983. In 1992 and 1994 smoking was more prevalent in men of social classes IV and V. In women, smoking was more prevalent in social classes I and II in 1983 than in social classes IV and V, something that had changed by 1994. Lack of usual physical activity in men was always more prevalent in social classes I and II, and this difference increased since more people of advantaged classes moved into inactivity. Health services utilization showed no inequalities in the years studied. CONCLUSION: The changing pattern according to social class of smoking and physical activity practice needs to be taken into account by policy-makers and public health workers.

Adolescent↗

Transabdominal surgical approach in the management of renal tumors involving the retrohepatic inferior vena cava.

Multiple reports over the last decade have documented the clear superiority of surgery over other alternative treatments in the management of renal cell carcinoma with extension into the inferior vena cava (IVC). Controversy persists, however, regarding the management of tumor thrombus that extends retrohepatically, but not entering the right atrium. In this report, we retrospectively review our experience with the use of a feasible transabdominal technique without any form of bypass or anticoagulation for safe removal of renal tumor involving the retrohepatic IVC. From 1988 to 1998, 132 patients with renal cell carcinoma underwent radical nephrectomies at the urology service of our hospital. Five patients (3.8%) had retrohepatic venous extension through the renal vein into the IVC. Our transabdominal approach was accomplished by complete mobilization of the liver, control of the hepatocaval connection, total vascular exclusion of the IVC without heparin administration, removal of the tumor thrombus, and primary closure of the longitudinal vena cavotomy. From our results, we found the transabdominal approach with total vascular exclusion of the IVC to be satisfactory, with no early deaths, acceptable morbidity, and a remarkable limitation of blood loss and transfusion requirements.

Adult↗

N-Benzylpiperidine derivatives of 1,2,4-thiadiazolidinone as new acetylcholinesterase inhibitors.

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of alpha2-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds.

Acetylcholinesterase↗

Microsatellite instability in primary brain tumors.

Microsatellite instability has been reported in hereditary colorectal cancer syndrome and in various kinds of human sporadic tumors. It has also been shown in brain tumors, although with conflicting results. In the present study, DNA samples obtained from 20 primary brain tumors (10 glioblastomas, three astrocytomas, five meningiomas, one ependymoma, one hemangiopericytoma) were analyzed to detect microsatellite instability. Nine microsatellites, mono, di-, tri- and tetranucleotide repeat markers, located on nine different chromosomes, were used. Four of the 20 neoplasias (20%) showed microsatellite alterations in tumor DNA with respect to normal DNA. Two glioblastomas and one atypical meningioma (15%) showed additional bands or bands with shift of electrophoretic mobility, whereas allelic loss was observed in two glioblastomas (10%). In one glioblastoma, one allelic loss and one extra allele were observed at two different loci. These data indicate that in primary brain tumors there is not a high genetic instability. Although we used markers with inherently high levels of instability, only sporadic microsatellite alterations were found. Consequently, alterations in the mechanisms of DNA mismatch-repair, the most important cause of replication errors in hereditary and sporadic colorectal cancers, do not seem to play a major role in the oncogenesis of primary brain tumors.

Adult↗

Sex differences in colorectal cancer mortality in Europe, 1955-1996.

Colorectal cancer is the leading cancer in non-smokers in Western countries, and over the last decades its trends have been generally more favourable for women than for men. Possible explanations of the sex differentials in colorectal cancer relate to different exposure to exogenous hormones and to other risk factors including diet, physical activity and alcohol drinking. The objective of this investigation was to systematically analyse the trends in colorectal cancer mortality sex ratios in major European countries over the last four decades. Trends in death certification rates from colorectal cancer over the period 1955-1996 were analysed for 20 European countries (excluding the former Soviet Union and a few of the smaller countries). In all countries, the mortality sex ratios (M/F) were around or slightly above unity in the 1950s, and systematically increased to approach 1.5 in the 1990s. The extent of the rises varied across countries, ranging between + 0.8% in Germany, + 9.7% in Sweden, and + 12.1% in Denmark (the lowest increases) to + 65.3% in Spain, + 56.2% in Portugal, and + 50.4% in Hungary (the highest ones). Mortality sex ratios in Europe show more favourable trends for females, which may be attributable, in part, to the introduction of exogenous hormones in the late 1950s and 1960s, and, in part, to differential sex exposure to major environmental risk factors.

Adult↗

The quality of care and influence of double health care coverage in Catalonia (Spain).

AIMS: To analyse inequalities by social class in children's access to and utilisation of health services in Catalonia (Spain), private health insurance coverage, and certain aspects of the quality of care received. DESIGN: Cross sectional study using data from the 1994 Catalan Health Interview Survey. SETTING: Child population of Catalonia. PARTICIPANTS: A representative sample of non-institutionalised children younger than 15 years (n = 2433). MAIN OUTCOME MEASURES: Health services utilisation, perceived health, type of health insurance (only National Health System (NHS) or both NHS and private health insurance), and social class. RESULTS: No inequalities by social class were found for the utilisation of health care services provided by the NHS among children in most need. Double health care coverage does not influence the social pattern of visits. Nevertheless, social inequalities still remain in the use of those health services provided only partially by the NHS (dentist) and when characteristics of the last consultation are taken into account. That is, subjects who paid for a private service waited an average of 14.8 minutes less than those whose visit was paid for by the NHS only. CONCLUSION: Equitable access and use of medical care services in relation to need, regardless of the type of insurance and social class of their children and families, has been achieved in this region of Spain; differences by social class remain for those services incompletely covered by national health insurance and aspects of the quality of care provided.

Adolescent↗