Biomedical subjects
Publications and source records attributed to C Fernández.
Patients with mitral stenosis in sinus rhythm are in a prothrombotic state and have fibrinolytic dysfunction, shown by an increase in levels of the inhibitor of tissue plasminogen activator, D-dimer, and modified antithrombin III. This state may be observed even in patients without dilated left atria (diameter < or =45 mm).
The NMR structures have been determined for a 13C/15N doubly labeled 14 base-pair DNA duplex comprising the BS2 operator sequence both free in solution and in the complex with the Antennapedia homeodomain. The impact of the DNA labeling is assessed from comparison with a previous structure of the same complex that was determined using isotope labeling only for the protein. Differences between the two structure determinations are nearly completely limited to the DNA, which retains the global B -conformation of the free DNA also in the complex. Local protein-induced conformational changes are a narrowing of the minor groove due to the interaction with the N-terminal arm of the homeodomain, and changes of the sugar puckers of the deoxyriboses G5 and C6, which are apparently induced by van der Waals interactions with Tyr25, and with Gln50 and Arg53, respectively. The high conservation of these amino acid residues in homeodomains suggests that protein-induced shifts in some sugar puckers contribute to the affinity of homeodomains to their cognate DNA. The data obtained here with the Antennapedia homeodomain-DNA complex clearly show that nucleic acid isotope-labeling can support detailed conformational characterization of DNA in complexes with proteins, which will be indispensable for structure determinations of complexes containing globally distorted DNA conformations.
Multivessel percutaneous transluminal coronary angioplasty (PTCA) is associated with a high requirement for further revascularization procedures. Although stenting can reduce restenosis and clinical events after 1-vessel intervention, little information is available after multivessel coronary stenting. We followed up 136 patients (9% of 1,481 undergoing stenting in our center) who had had stent implantation in at least 2 different major native coronary arteries and were followed-up for >6 months. Each patient had received a mean of 2.3 +/- 0.6 stents (1.13 +/- 0.4 stents per lesion) and procedural success was 95%. In-hospital complications included 1 death, 1 Q-wave infarction, 5 non-Q-wave myocardial infarctions, and 1 repeat PTCA. After a mean of 18 +/- 13 months, 7 patients died (3 of heart failure, 4 of noncardiac causes), 2 required coronary bypass surgery, 1 had a myocardial infarction, 13 target vessel repeat PTCA, and 4 non-target vessel PTCA. Survival free of major cardiac events was 75% at 3 years. A history of heart failure, dilation of a restenotic lesion, and 3-vessel dilation were independent negative predictors of event-free survival. Angiographic follow-up was available in 86 patients: 56 (65%) were restenosis free, 23 (27%) had 1-vessel restenosis, and 6 (7%) had 2-vessel and 1 patient 3-vessel restenosis. Restenosis per vessel was 23% (41 of 177). Reference diameter, past-PTCA minimal luminal diameter, and length of the stent were independent predictors of restenosis. We conclude that multivessel stenting provides good midterm results in selected patients with multivessel coronary artery disease. Midterm events are less frequent than previously reported after balloon PTCA.
Long-term prognosis and predictors of event-free survival were studied in 56 consecutive patients with in-stent restenosis successfully treated with balloon angioplasty. Most patients sustained prolonged clinical benefit, but during follow-up, those with diabetes or with a short time interval (<4 months) from stenting to repeat angioplasty experienced adverse cardiac events more often.
A two-dimensional [31P] spin-echo-difference constant-time [13C, 1H]-HMQC experiment (2D [31P]-sedct-[13C, 1H]-HMQC) is introduced for measurements of 3J(C4'P) and 3J(H3'P) scalar couplings in large 13C-labeled nucleic acids and in DNA-protein complexes. This experiment makes use of the fact that 1H-13C multiple-quantum coherences in macromolecules relax more slowly than the corresponding 13C single-quantum coherences. 3J(C4'P) and 3J(H3'P) are related via Karplus-type functions with the phosphodiester torsion angles beta and epsilon, respectively, and their experimental assessment therefore contributes to further improved quality of NMR solution structures. Data are presented for a uniformly 13C, 15N-labeled 14-base-pair DNA duplex, both free in solution and in a 17-kDa protein-DNA complex.
The aim of the present work was to study the seasonal as well as the site-specific variations in the structure of peroxisomes and in the activity of the peroxisomal marker enzyme catalase in digestive epithelial cells of mussels to validate the potential use of these parameters as early biomarkers of environmental organic pollution in estuarine ecosystems. For this purpose, mussels were sampled monthly for 14 months in two Basque estuaries (Bay of Biscay) with different degrees of pollution. Stereological procedures were applied to detect changes in peroxisome structure, and microspectrophotometry was used to quantify changes in catalase activity. The animals from the two studied sampling sites presented differences in polycyclic aromatic hydrocarbon (PAH) burdens, mussels from Plentzia generally showing lower total PAH contents than mussels from Galea. The peroxisome structure of the animals from the two estuaries suffered seasonal variations that were of different kind and intensity in both sites. In this way, a strong peroxisome proliferatory response was found in mussels sampled in Plentzia during the summer months, while mussels from Galea presented few variations along the year. Catalase activity behaved similarly in the animals sampled in the two estuaries, with higher values in spring. It appeared that mussels exposed chronically to PAHs and other pollutants, such as those from Galea, lost their ability to respond to this exposure in terms of peroxisome proliferation. In contrast, mussels collected in Plentzia effectively responded to an increased bioavailability of organic pollutants during the summer by increasing peroxisome volume and surface and numerical densities in digestive epithelial cells. However, these increases were transient because elevated PAH body burdens detected in mussels sampled in Plentzia in autumn were not accompanied by a peroxisome proliferatory response. Further studies are needed before changes in peroxisomal structure and in the activity of catalase could be used as early biomarkers to assess environmental quality in pollution monitoring programs like the Mussel Watch.
The possible interaction between the quantified overexpression of the oncoproteins p53 and p185 was evaluated. These proteins have already been independently defined as prognostic factors in non-small-cell lung cancer (NSCLC). p53 and p185 levels were determined in stage I patients (n = 40) from a sample of 102 NSCLC sufferers who underwent surgery for precocious disease during the period October 1991 to June 1994. The resected tumors were histologically classified and included 15 adenocarcinomas (37.5%), 1 large-cell carcinoma (2.5%), and 24 epidermoid (60%) carcinomas. The p53 concentration of tumor specimens was determined by luminescence immunoanalysis and was defined as positive if it was above the minimum value detectable by the method (0.01 ng/mg). The p185 protein was quantified by enzyme-linked immunoassay, and the 80th percentile of the frequency distribution was used as the reference cutoff value (348.8 U/mg). Survival and disease-free-survival (DFS) rates were estimated at 24 months after intervention. There were no significant differences in survival or DFS of patients with adenocarcinoma-type tumors for subjects with independent p185 values < 348.8 U/mg and those showing values >/= 348.8 U/mg. Neither were there differences observed between patients with positive and negative p53 values. In patients with epidermoid-type tumors the cumulative survival was significantly higher in p53-negative than in p53-positive patients (p = 0.03) and was also higher in patients with p185 levels < 348.8 U/mg than in those with values >/= 348.8 U/mg (p = 0.00001). These patients showed no significant differences with respect to recurrence rate. The possible synergistic behavior of p53 and p185 levels as a prognostic factor was evaluated in patients with epidermoid-type tumors. p53-negative and p53-positive patients were grouped according to a p185 level of less than or more than 348.8 U/mg. Significant differences were seen in both survival rates and DFS between groups. Individual analysis of relative risks showed an increased risk of death and greater recurrence rate in patients with p185 levels >/= 348.8 U/mg and a greater recurrence rate in patients with p53-positive values. Multivariate analysis established that the multiplicative, synergistic, prognostic effect of p53 and p185 was not significant. The existence of a significant, synergistic, prognostic effect of the p185 and p53 proteins in NSCLC could not be proven. However, a greater prognostic potential of the quantified overexpression of p185 with respect to that of p53 was established. An additive effect in the prognostic potential of both proteins was also observed (stratified analysis).
The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0-52 ng (mg-1)). Using an arbitrary cut-off value of 2.7 ng mg(-1), 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.
The aims of this study were to investigate whether a Th1- or a Th2-type response is stimulated in the first stages of experimental infection with Echinococcus granulosus, and to determine whether live or dead protoscoleces equally contribute to such Th1/Th2-type polarization. Live parasites stimulated the production of IL-10, IL-4 and IL-5 as early as week 1 postinoculation. The levels of IL-10 and IL-4 decreased towards week 4 p.i. and that of IFN gamma increased. The production of specific antibodies was characterized by high levels of systemic IgG1 and local IgM and IgG3 (measured in peritoneal lavages). In contrast, dead parasites induced elevated levels of IL-4, IFN gamma, IL-10 and IL-5 on week 1 postinoculation followed by a decrease of IFN gamma and an increase of IL-4. Low levels of specific antibodies were stimulated by dead parasites both systemically and in the peritoneal cavity. These results show that E. granulosus infection induced an early Th2-type response and that live parasites stimulated stronger antibody responses than dead parasites. In addition, they strongly suggest that both phenomena were modulated by live protoscoleces.
BACKGROUND: The variability in the diagnostic observations could be a problem both in the clinical and in the epidemiological field. Scarce data exist in the literature on this phenomenon, relatives to the field of the cerebrovascular illness, in their nosologic, semiologic and etiologic aspects. We pretend to study the interobserver variability in the diagnosis of the stroke, classifying it as absentee, present or possible in front of a given case. METHODS: 1. A questionnaire of 99 clinical cases has been elaborated, in order to be subjected to the evaluation of 10 neurologists (3 "junior", residents, 3 "senior" residents, and 4 "staff"); 2. The categories are: a) not stroke either transient ischaemic attack; b) probable stroke or transient ischaemic attack; c) transient ischaemic attack and d) stroke. 3. STATISTICAL ANALYSIS: by means of the statistic kappa of Fleiss (kappa) for several observers and several categories, determination of the standard error and 95% confidence intervals. RESULTS: In the diagnosis of the cerebrovascular illness: a) among all the observers: kappa = 0.49 (0.44-0.50); b) among staff: kappa = 0.51 (0.46-0.56); c) among residents: kappa = 0.47 (0.44-0.50). Global data in transient ischaemich attack diagnosis: kappa = 0.52 (0.49-0.55); in the diagnosis of the stroke: kappa = 0.57 (0.54-0.60); in the exclusion of stroke: kappa = 0.64 (0.62-0.67). CONCLUSIONS: With Fleiss' criteria, an acceptable to good agreement exists in the diagnosis of the stroke in base to the mere description of the clinical picture. This interobserver agreement is better if it is tried to exclude the stroke, and it could increase with the training of the neurologist.
OBJECTIVE: To compare medical students' simulated learning of two different techniques of cardiopulmonary resuscitation (CPR). One was conventional external cardiac massage (ECM) and the other was active compression-decompression (ACD-CPR). MATERIAL AND METHODS: The study group (group S) comprised 111 students enrolled in their fourth year of medical studies who had no prior experience of CPR. Group R, the control group, was made up of 32 medical residents in anesthesiology and post-anesthetic intensive care. Before the study, group S received 5 hours of theoretical classes on CPR and both groups saw a video explaining each technique just before performing the test. All subjects applied each method to an adult dummy for one minute. The variables evaluated were frequency of complete and effective thoracic compressions and the body weight of the resuscitator. RESULTS: Each group performed similarly using the two techniques in terms of frequency of total compressions achieved. For each technique, the number of effective compressions achieved by group S (49.4 +/- 22.9 with ECM and 42.5 +/- 20.7 with ACD-CPR) was significantly lower (p < 0.05) than the number attained by group R (71.2 +/- 18.6 with ECM and 58.8 +/- 12 with ACD-CPR). Group R's frequency of effective compressions was significantly higher (p < 0.05) with CPR than with ACD-CPR. Body weight had no influence on the number of total compressions or efficacy in group R, whereas lower body weight in group S was significantly related to lower frequency of effective compressions with ECM p < 0.05). Neither group achieved a frequency of 80 total compressions in one minute. CONCLUSIONS: With the present teaching method, the medical students' performance was poor for both types of CPR and was affected by body weight. The residents' performance was less effective with ACD-CPR, a technique that was new to them, than with conventional ECM, with which they were expert and on which body weight had no impact.
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This paper describes the NMR observation of 15N---15N and 1H---15N scalar couplings across the hydrogen bonds in Watson-Crick base pairs in a DNA duplex, hJNN and hJHN. These couplings represent new parameters of interest for both structural studies of DNA and theoretical investigations into the nature of the hydrogen bonds. Two dimensional [15N,1H]-transverse relaxation-optimized spectroscopy (TROSY) with a 15N-labeled 14-mer DNA duplex was used to measure hJNN, which is in the range 6-7 Hz, and the two-dimensional hJNN-correlation-[15N,1H]-TROSY experiment was used to correlate the chemical shifts of pairs of hydrogen bond-related 15N spins and to observe, for the first time, hJHN scalar couplings, with values in the range 2-3.6 Hz. TROSY-based studies of scalar couplings across hydrogen bonds should be applicable for large molecular sizes, including protein-bound nucleic acids.
Total trisomy 9 is a rare disorder with most patients dying before age 4 months. Herein, we report a 9-year-old girl with mental retardation, short stature, a peculiar face and other minor defects, who was diagnosed as having an unbalanced de novo X-autosome translocation with a 46,X,der(9)t(X;9)(q12;q32) karyotype resulting in almost a full trisomy 9(pter-->q32) and a partial monosomy X(q12-->pter). The clinical findings of our patient, almost exclusively resemble those of trisomy 9p and the Ullrich-Turner syndromes and has few manifestations of 9q trisomy. BrdU replication studies by Giemsa staining showed an earlier replication of 9p in the translocated chromosome, but a marked late-replication pattern for almost the complete 9q arm involved in the translocation. FISH studies confirmed the presence of three 9 centromeres, excluded the presence of the X centromere signal in the rearranged chromosome, and showed that both Xq telomeric sequences were present. BrdU replication studies by FISH showed an usual pattern of striking late-replication around the XIC of the derivative chromosome, but early replication of the chromosome 9p segment and distal Xq.
The human glioma pathogenesis-related protein (GliPR) is highly expressed in the brain tumor glioblastoma multiforme and exhibits 35% amino acid sequence identity with the tomato pathogenesis-related (PR) protein P14a, which has an important role for the plant defense system. A molecular model of GliPR was computed with the distance geometry program DIANA on the basis of a P14a-GliPR sequence alignment and a set of 1,200 experimental NMR conformational constraints collected with P14a. The GliPR structure is represented by a group of 20 conformers with small residual DIANA target function values, low AMBER-energies after restrained energy-minimization with the program OPAL, and an average rms deviation relative to the mean of 1.6 A for the backbone heavy atoms. Comparison of the GliPR model with the P14a structure lead to the identification of a common partially solvent-exposed spatial cluster of four amino acid residues, His-69, Glu-88, Glu-110, and His-127 in the GliPR numeration. This cluster is conserved in all known plant PR proteins of class 1, indicating a common putative active site for GliPR and PR-1 proteins and thus a functional link between the human immune system and a plant defense system.
This paper deals with the effect of fenitrothion (0.04 mg/liter) on the energy metabolism of the European eel, Anguilla anguilla, and its recovery from intoxication. Various parameters such as glycogen, lactate, proteins, total lipids, and glucose in eel liver and blood were analyzed after 2, 8, 12, 24, 32, 48, 56, 72, and 96 h of fenitrothion exposure. Subsequently, the fish were allowed recovery periods of 8, 12, 24, 48, 72, 96, 144, and 192 h in clean water, and the same parameters were evaluated. Liver glycogen and lipid contents decreased significantly during the exposure, while blood glucose levels increased markedly. Liver and blood lactate values increased during pesticide exposure, while proteins were decreased in comparison to unexposed controls. Most of the metabolic disorders did not persist after less than a week of recovery in clean water. The observed effects of fenitrothion on fish metabolism are discussed in relation to a stress syndrome, and probable reasons for alterations are also discussed.
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PURPOSE: To report a rare complication related to epidural analgesia for obstetrics: the association of unilateral trigeminal and facial nerve palsies in a patient with the clinical syndrome of intracranial hypotension. CLINICAL FEATURES: A 38-yr-old woman was admitted in pre-term labour (at 35 wk gestation). She was receiving 40 mg methadone po daily for opioid addiction. Epidural analgesia for labour was established with 9 ml bupivacaine 0.25%. The patient underwent normal vaginal delivery of a 2500 g female infant. She developed post-dural puncture headache (PDPH) on the third postpartum day which was managed by palliative measures: bed rest (patient's position of choice), increased hydration (water: 3 litres po per day), lysine acetyl salicylate (5.4 g po per day) and caffeine (600 mg po per day). She developed paraesthesiae and numbness of the right side of the face one day after the onset of PDPH and unilateral facial nerve palsy two days later. There was no evidence of dural puncture and no cause was found. Treatment of the nerve palsies with epidural blood patch or epidural dextran 40 was not considered to be indicated. Headache disappeared on the 10th postpartum day and trigeminal palsy regressed. At the time of discharge, on the 17th postpartum day, neurological examination showed minimal facial assimetry. The patient refused further exploration and follow-up. CONCLUSION: Post delivery trigeminal and facial nerve palsy in a 38 yr old woman recovered spontaneously with conservative therapy.