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Biomedical subjects

R Fernández

Publications and source records attributed to R Fernández.

At least 19 recordsLinked to original sources
PubMed2001

Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase.

Tumor necrosis factor (TNF) ligand family members are synthesized as transmembrane proteins, and cleavage of the membrane-anchored proteins from the cell surface is frequently observed. The TNF-related ligands APRIL and BLyS and their cognate receptors BCMA/TACI form a two ligand/two receptor system that has been shown to participate in B- and T-cell stimulation. In contrast to BLyS, which is known to be cleaved from the cell surface, we found that APRIL is processed intracellularly by furin convertase. Blockage of protein transport from the endoplasmic reticulum to the Golgi apparatus by Brefeldin A treatment abrogated APRIL processing, whereas monensin, an inhibitor of post-Golgi transport, did not interfere with cleavage of APRIL, but blocked secretion of processed APRIL. Thus, APRIL shows a unique maturation pathway among the TNF ligand family members, as it not detectable as a membrane-anchored protein at the cell surface, but is processed in the Golgi apparatus prior to its secretion.

Antibodies, Monoclonal↗
PubMed2001

Stereoselective nucleophilic formylation and cyanation of alpha-alkoxy- and alpha-aminoaldehydes.

The spontaneous 1,2-addition of formaldehyde N,N-dialkylhydrazones to carbohydrate-derived alpha-alkoxyaldehydes takes place under neutral conditions and in the absence of catalysts or promoters to afford the corresponding alpha-hydroxyhydrazones in good to excellent yields and with highly anti diastereoselectivities. Subsequent transformations of the hydrazono group into aldehydes and nitriles following known procedures provide a new entry into the homologation of carbohydrates and the synthesis of cyanohydrins, respectively. Additionally, reaction of methyleneaminopyrrolidine with N-Boc-protected alpha-aminoaldehydes from natural amino acids efficiently affords the corresponding adducts under the same conditions. From these adducts, a variety of biologically interesting alpha-hydroxy-beta-aminocarbonyl compounds can be accessed upon manipulation of the hydrazone moiety.

Journal Article↗
PubMed2001

Bcl-2 targets protein phosphatase 1 alpha to Bad.

The diverse forms of protein phosphatase 1 (PP1) in vivo result from the association of the catalytic subunit with different regulatory subunits. We recently have described that PP1alpha is a Ras-activated Bad phosphatase that regulates IL-2 deprivation-induced apoptosis. With the yeast two-hybrid system, GST fusion proteins, indirect immunofluorescence, and coimmunoprecipitation, we found that Bcl-2 interacts with PP1alpha and Bad. In contrast, Bad did not interact with 14-3-3 protein. Bcl-2 depletion decreased phosphatase activity and association of PP1alpha to Bad. Bcl-2 contains the RIVAF motif, analogous to the well characterized R/KXV/IXF consensus motif shared by most PP1-interacting proteins. This sequence is involved in the binding of Bcl-2 to PP1alpha. Disruption of Bcl-2/PP1alpha association strongly decreased Bcl-2 and Bad-associated phosphatase activity and formation of the trimolecular complex. These results suggest that Bcl-2 targets PP1alpha to Bad.

Amino Acid Sequence↗
PubMed2001

Platinum and rhodium distribution in airborne particulate matter and road dust.

In this work the platinum and rhodium content in the atmosphere of Madrid was monitored for 1 year at seven different sites. Samples were taken with medium volume PM-10 collectors (< 10 microm) for 48 h and analysed by ICP-MS. The Pt and Rh content was dependent on the sampling site, ranging from < 0.1 to 57.1 and < 0.2 to 12.2 pg m(-3) with a medium value of 12.8 and 3.3 pg m(-3), respectively. These results show that the Pt and Rh content in airborne samples depends on the traffic density per day and also on medium driving speed. Road dust < 63 microm was analysed at the same time and at the same location. The Pt and Rh content at the six sites analysed was in the 31-2252 and 11-182 ng g(-1) range with an average of 317 and 74 ng g(-1), respectively. The average Pt/Rh ratio obtained was 4.3. similar to that obtained for airborne particles (4.0), and agrees with that of the more commonly used gasoline car catalyst [J.J. Mooney, Encyclopaedia of Chemical Technology (1996) 982]. Platinum distribution as a function of particle size in airborne particulate matter was also studied, by sampling with two high-volume sample collectors, a five-stage WRAC (from 10 to 65.3 microm and total) and a seven-stages PM-10) cascade impactor (from 9 to < 0.39 microm). Platinum is associated with a wide range of particle diameters. Due to the ultratrace level of Pt in airborne samples, its distribution in the atmosphere could not be considered as homogeneous. No trend could be established in Pt distribution in the different fractions, except that in most cases the highest value of Pt was obtained in the < 0.39-microm fraction. The Pt content was usually high in airborne samples when the Pb, Ce, Zr and Hf content was also high, thus confirming that the source of these pollutants is from traffic.

Air Movements↗
PubMed2001

Non-invasive mechanical ventilation in status asthmaticus.

OBJECTIVE: To evaluate our clinical experience with the use of non-invasive mechanical ventilation (NIMV) in patients with an acute asthmatic attack. DESIGN: Seven-year period retrospective observational study. SETTING: General intensive care department (ICU) of a county hospital. PATIENTS: From 1992 to 1998, we documented clinical data, gas exchange and outcome of every asthmatic patient admitted to our ICU because of status asthmaticus (SA) refractory to initial medical therapy. INTERVENTIONS: Clinical charts were reviewed and patients were allocated to two groups according to their suitability as participants in an NIMV trial. Patients who arrived in respiratory arrest and those who ultimately improved with medical management alone were not considered candidates for NIMV. For the present analysis, the rest of the patients were considered candidates for NIMV, while the decision to start a NIMV trial or to perform endotracheal intubation (ETI) remained at the discretion of the attending physician. When patients failed to improve with NIMV, standard mechanical ventilation (MV) with ETI was initiated. MEASUREMENTS AND RESULTS: Fifty-eight patients were included in the study. Twenty-five patients (43%) were not eligible for NIMV: 11 patients (19%) because of respiratory arrest on their arrival at the Emergency Room and 14 patients (24%) because of improvement with medical management (bronchodilators, corticoids and oxygen). The remaining 33 patients were eligible for NIMV (57%): 11 patients (33%) received invasive MV and 22 patients (67%) were treated with NIMV. Three NIMV patients (14%) needed ETI. We compared data at baseline, 30 min, 2-6 h and 6-12 h after the onset of ventilatory support. Significant differences were observed in arterial blood gases on admission to the Emergency Room between MV and NIMV: PaCO2 (89 +/- 29 mmHg vs 53 +/- 13 mmHg, p < 0.05), pH (7.05 +/- 0.21 vs 7.28 +/- 0.008, p < 0.05) and HCO3- level (22 +/- 5 mmol/l vs 26 +/- 6 mmol/l, p < 0.05). No differences were found in the median length of ICU stay (4.5 vs 3 days), median hospital stay (15 vs 12 days) and mortality (0 vs 4%). CONCLUSION: Face mask NIMV appears to be a suitable method for improving alveolar ventilation and can reduce the need for intubation in a selected group of patients with SA.

Acute Disease↗
PubMed2001

[Non-small cell bronchogenic carcinoma in advanced stages: prognostic value of weight loss and clinical implications].

UNLABELLED: This study of advanced-stage non-small cell bronchogenic carcinoma aimed 1) to identify prognostic factors collected at the moment of diagnosis, 2) to determine whether weight loss is a useful parameter to screen for subjects who will receive greater benefit from anticancer therapy.Patients and methods. Eighty-one patients were enrolled after diagnosis of stage III-B and IV non-small cell bronchogenic carcinoma and levels of activity < 2 according to Eastern Co-operative Oncology Group classification. The variables studied were age, sex, smoking history, associated disease, clinical data (weight loss, dyspnea, superior vena cava syndrome), laboratory parameters [hemoglobin, serum albumin, total lymphocytes, serum lactate dehydrogenase (LDH), calcium and liver enzymes], tumor-node-metastasis (TNM) staging, histologic type, activity, treatment received and survival in weeks. The results were analyzed in two groups: 1) the general group consisting of results for all patients, and 2) the no-weight-loss group consisting of results for those whose weight had been stable. Student t, chi-squared, Kaplan Meier, log-rank and Cox's regression model were used to analyze data and survival. RESULTS: Mean survival was 29 weeks (21-37). Survival was significantly related to weight loss, total lymphocytes, serum LDH, TNM and activity level in the general group. Only two factors continued to have prognostic value in the multivariate study: weight loss (OR: 1.48 (1.14-1.92), p = 0.002) and TNM (OR: 0.72 (0.54-0.96), p = 0.02). Among the patients with no weight loss, treatment received and TNM were significantly related to survival in univariable analysis and in Cox's regression model. CONCLUSIONS: In our experience with advanced lung cancer subjected to anticancer therapy, the presence of weight loss is the variable with the greatest prognostic value, such that it may be useful to consider it routinely, along with activity level, to try to identify patients who will receive the most benefit from cytostatic treatment.

Adult↗
PubMed2001

Effect of two antihypertensive combinations on metabolic control in type-2 diabetic hypertensive patients with albuminuria: a randomised, double-blind study.

The objective of this study was to compare, at equal blood pressure (BP) reduction, the effect of two different combinations on metabolic control and albuminuria in type 2 diabetic hypertensive patients with albuminuria. This was a prospective, randomised, double-blind, parallel, controlled trial carried out in 11 Spanish hospitals. A total of 103 type 2 diabetic patients with stable albuminuria and BP not controlled on monotherapy were randomised of which 93 finished the study. After a 4-week single-blind placebo period, patients were randomised to verapamil SR/trandolapril 180/2 mg (VT) or to enalapril/hydroclorothiazide 20/12.5 mg (EH). Treatment duration was 6 months. The main outcome measures were changes in BP, 24-h albuminuria, blood glucose and glycated haemoglobin. Overall BP was significantly reduced from 157.3 +/- 12.0/98.3 +/- 6.4 mm Hg to 140.5 +/- 14.5/86.1 +/- 8.2 mm Hg (P < 0.001) and albuminuria significantly decreased from 508.6 +/- 693.8 mg/24 h to 253.4 +/- 517.2 mg/24 h (P < 0.001), both without significant differences between treatments. Glycated haemoglobin was not modified on VT: baseline, 5.91 +/- 1.43%; end of treatment, 5.94 +/- 1.62%, but increased on EH: baseline, 5.96 +/- 1.25%; final, 6.41 +/- 1.51%, (ANOVA interaction P = 0.040). At the end of the study, a blood glucose <126 mg/dL was attained in 72.7% of the VT group-improving in 29.5% and worsening in 6.8% of patients (P = 0.021)-and in 50% of the EH group, 13.6% of patients improved and 11.4% worsened (P = 1.000). There were no changes in body weight, serum creatinine, uric acid, potassium, cholesterol, tryglicerides and serum albumin. In hypertensive type 2 diabetic patients not controlled on monotherapy, both treatments similarly reduced albuminuria. The combination verapamil/ trandolapril seems to allow a better metabolic control than enalapril/hydroclorothiazide.

Aged↗
PubMed2001

Two natural products from the algae Laurencia scoparia.

The structures and absolute stereochemistries of two chamigrene-type metabolites (spiro[5.5]undecane derivatives) isolated from the red algae Laurencia scoparia are described. One, a non-sesquiterpene named maĩlione (8-bromo-9-hydroxy-7,7-dimethyl-11-methylenespiro[5.5]undec-1-en-3-one), C(14)H(19)BrO(2), was detected previously in Laurencia cartilaginea, while the other, the sesquiterpene isorigidol (8-bromo-3,7,7-trimethyl-11-methylenespiro[5.5]-undec-1-ene-3,9-diol), C(15)H(23)BrO(2), is a new isomer of rigidol, first isolated from Laurencia rigida. The A rings of these spirocyclic compounds show the same carbon skeleton. However, the relative stereochemistry of the 8-Br and 9-OH substituents is different. While maĩlione displays the usual syn (or cis) relative stereochemistry of the bromohydroxy vicinal group, isorigidol shows an anti (or trans) arrangement. The 8-Br and 9-OH groups are both in equatorial positions in isorigidol, while the 9-OH group is axial in maĩlione, as in most chamigrenes. The absolute configurations of the chiral centers were determined as 6S, 8S and 9R in maĩlione, and 3R, 6S, 8S and 9S in isorigidol.

Alkenes↗
PubMed2001

Reference doses in dental radiodiagnostic facilities.

The present work describes an experiment undertaken using thermoluminescent dosemeters to obtain a local reference dose level in orthopantomography, based on patient measurements in 11 dentistry installations. In addition, a critical audit of the dose recommended by the International Atomic Energy Agency for intraoral X-ray diagnostics is performed, based on data gathered from over 300 intraoral X-ray facilities. The provisional local reference levels proposed are 0.7 mGy entrance surface dose at the occipital region for orthopantomography and 3.5 mGy entrance surface dose for intraoral radiology.

Adult↗
PubMed2001

[Addisonian crisis as first manifestation of adrenal gland insufficiency in patient diagnosed with lung cancer].

Adrenal insufficiency or Addison's disease is actually a rare illness associated with numerous pathologies. We describe the case of a fifty years old male with lung adenocarcinoma and metastasis in both adrenal glands, who was receiving chemotherapy with mytomicin, ifosfamide and cisplatin (MIC), and was diagnosed of adrenal insufficiency as a result of acute episode addisonian crisis. Many times, the clinic symptoms of adrenal insufficiency can go unnoticed due to its low specifity and to mixing up with other syndromes. Hypoadrenalism has been described in association with many tumours, specially with non-Hodgkin's lymphoma. It seems that there is a discordance between the number of patients with bilateral metastatic adrenal destruction and the documented cases of clinic insufficiency. Once the adrenal failure is suspected, the diagnosis and hormone replacement treatment are really easy. Addison's disease ethiologies are revised putting special emphasis on those related with cancer patients.

Addison Disease↗
PubMed2000

Lack of association of serum lipoprotein (a) levels with type-2 diabetes mellitus in patients with angiographically defined coronary artery disease.

Multiple studies have demonstrated that elevated serum lipoprotein (a) [Lp(a)] levels are independent predictors for coronary artery disease (CAD) in subjects without diabetes mellitus (DM). However, their contribution in patients with DM is controversial and still requires clarification. We determined serum Lp(a) levels in 355 consecutive Caucasian patients (271 men and 84 women) with angiographically documented CAD, and in 100 control subjects (58 men and 42 women) who were clinically free of cardiovascular disease. In addition, the association of serum Lp(a) levels with type-2 DM in patients with CAD was investigated after reassigning patients according to the diagnosis of type-2 DM (61 men and 40 women with type-2 DM and 210 men and 44 women without). No gender differences in Lp(a) levels were observed between men and women (patients and control subjects). Patients with CAD had higher Lp(a) levels than the control subjects (33 (14-74) vs. 13 (9-29) mg/dl, P<0.001). Elevated Lp(a) levels (defined as >90th percentile of controls) were significantly more prevalent in men and women with CAD (35% and 28%, respectively) than in control subjects (13% and 10%, respectively). Serum Lp(a) levels correlated with LDL cholesterol (r=0.22, P<0.001) and apo B levels (r=0.18, P<0.03) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was an independent risk factor for the presence of CAD, independent of smoking, hypertension, type-2 DM, LDL and HDL cholesterol or apo A1 and B levels. When patients were studied according to the spread of CAD (evaluated as the number of narrowed vessels), no differences in serum Lp(a) levels were observed, nor was there a higher prevalence of elevated Lp(a) levels. Finally, when patients were re-assigned according to the diagnosis of type-2 DM, no effect of apo B and LDL-C levels on Lp(a) was found (r=0.06, P=n.s. and 40.14, P=n.s., respectively) and serum Lp(a) levels neither associated nor contributed to the extent of CAD. Our results showed that serum Lp(a) levels are increased in patients with angiographically documented CAD, but there were no significant differences between diabetic and non-diabetic patients, which indicates that elevated Lp(a) levels are specifically associated with CAD but not with type-2 DM.

Adult↗
PubMed2000

A novel missense mutation (W797R) in the myophosphorylase gene in Spanish patients with McArdle disease.

OBJECTIVE: To investigate the degree of genetic heterogeneity of myophosphorylase deficiency (McArdle disease) in Spain through molecular studies of 10 new patients. DESIGN: The coding sequence of the entire myophosphorylase gene was sequenced in DNA extracted from muscle and blood. Restriction fragment length polymorphism analysis of polymerase chain reaction fragments was used to confirm and simplify detection of a novel mutation. SETTING: A collaborative study between 2 university laboratories in Spain and the United States. RESULTS: Five of the 10 patients harbored a novel missense mutation in exon 20, converting a tryptophan to an arginine (W797R). Three patients were homozygous for the "common" R49X mutation, and the remaining 2 patients were compound heterozygotes for R49X and a previously described missense mutation, G204S. CONCLUSIONS: The W797R missense mutation is the third novel mutation to be identified among Spanish patients. Its relative frequency suggests that it should be added to the R49X mutation in the molecular screening of McArdle disease in Spain.

Adult↗
PubMed2000

Mitochondrial DNA sequences for 118 individuals from northeastern Spain.

A population database was generated from 118 unrelated Caucasoid individuals living in Spain. Sequence polymorphisms of the mitochondrial DNA (mtDNA) control region, hypervariable regions I and II (HVRI and HVRII) were determined using the polymerase chain reaction (PCR) and direct sequencing. A total of 102 different sequences were found as defined by 105 variable positions. The most common sequence occurred six times, and this sequence is also the most frequent in other European populations such as Austria, Germany and Britain. The mean pair-wise difference for the two HVR regions taken together was 7.74. The study revealed that transitions made up the majority of the variations (88%), whereas we observed a significantly lower frequency of transversions (8%). Also one individual in this study was observed with two positions of heteroplasmy at nucleotides 150 (C/T) and 153 (G/A). A statistical estimate of the results for this population showed a genetic diversity of 0.99. The probability of two random individuals showing identical mtDNA haplotypes is 1.3%. In order to use the mtDNA analysis in forensic casework, we consider that it is of crucial importance to know the frequency of the different sequences of mtDNA, and this data base study could be a useful tool to statistically evaluate the results.

Automation↗
PubMed2000

Expression and prognostic significance of pepsinogen C in gastric carcinoma.

BACKGROUND: In this study we evaluated the expression and clinical significance of pepsinogen C, an aspartic proteinase involved in the digestion of proteins in the stomach, in patients with gastric cancer. METHODS: Pepsinogen C expression was examined by immunohistochemical methods in a series of 95 gastric carcinomas. The prognostic value of pepsinogen C was retrospectively evaluated by multivariate analysis taking into account conventional prognostic parameters. Follow-up period of patients was 21.4 months. RESULTS: A total of 25 (26.3%) gastric carcinomas stained positively for pepsinogen C. The percentage of pepsinogen C-positive tumors was higher in well-differentiated (50%) than in moderately differentiated (19.5%) and poorly differentiated (21.9%) tumors (P < .05). Similarly, significant differences in pepsinogen C immunostaining were found between node-negative and node-positive tumors (47.1% vs. 14.7%; P < .001). In addition, statistical analysis revealed that pepsinogen C expression was associated with clinical outcome in gastric cancer patients. Low pepsinogen C levels predicted short overall survival periods in the overall group of patients with gastric cancer (P < .001), and in 71 patients with resectable carcinomas (P < .005). Multivariate analysis according to Cox's model indicated that pepsinogen C immunostaining was an independent predictor of outcome for both overall and resectable gastric cancer patients (P < .05, for both). CONCLUSIONS: The expression of pepsinogen C in gastric cancer may represent a useful biological marker able to identify subgroups of patients with different clinical outcomes.

Adult↗