Biomedical subjects

J Ortega

Publications and source records attributed to J Ortega.

At least 55 records · Page 3Linked to original sources

PubMed2000

[Left ventricular pseudoaneurysm with a fistula to right ventricle following previous repair of septal defect after acute myocardial infarction].

A case of left ventricular pseudoaneurysm with a fistula to right ventricle is presented. It appeared following the repair of a ventricular septal defect after acute myocardial infarction. The left ventricular pseudoaneurysm is associated, in most cases, with acute myocardial infarction. However, we should not forget surgery as aetiology of this pathology. The most frequent post-surgery pseudoaneurysms appear after aneurysmectomy and after mitral valve replacement. They tend to develop fistulas which differ from post acute myocardial infarction pseudoaneurysms. Few cases have been described following the repair of septal defect and none of them complicated with a fistula to right ventricle, as in our case.

Aneurysm, False↗

PubMed2000

Visualization of substrate binding and translocation by the ATP-dependent protease, ClpXP.

Binding and internalization of a protein substrate by E. coli ClpXP was investigated by electron microscopy. In sideviews of ATP gamma S-stabilized ClpXP complexes, a narrow axial channel was visible in ClpX, surrounded by protrusions on its distal surface. When substrate lambda O protein was added, extra density attached to this surface. Upon addition of ATP, this density disappeared as lambda O was degraded. When ATP was added to proteolytically inactive ClpXP-lambda O complexes, the extra density transferred to the center of ClpP and remained inside ClpP after separation from ClpX. We propose that substrates of ATP-dependent proteases bind to specific sites on the distal surface of the ATPase, and are subsequently unfolded and translocated into the internal chamber of the protease.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2000

Statement of current majority practices in graft-versus-host disease prophylaxis and treatment in children.

Great variations exist in the prophylaxis and treatment of GVHD in children undergoing allogeneic stem cell transplantation (SCT). The EBMT Working Party Paediatric Diseases (EBMT-WP PD) and the International BFM Study Group--Subcommittee Bone Marrow Transplantation (IBFM-SG), aimed at evaluating current local standards in the prevention and treatment of GVHD and steps which can be taken to achieve a uniform policy for the individual methods. Several conferences with their members assessed practices which are mainly applied or under investigation in children and identified where additional information is needed. For prevention of GVHD, the majority of the paediatric centres prefer CsA +/- MTX. Addition of folinic acid to MTX was considered for reduction of side-effects. During treatment of acute GVHD most centres administer prednisolone and whole blood level-adjusted CsA as medications of first choice. In cases of poor or no response to this therapy, additional immunosuppressive agents such as ATG, mycophenolate-mofetile and tacrolimus are being increasingly used. The treatment of chronic GVHD usually consists of various combinations of prednisolone and CsA. In severe cases, extracorporeal photopheresis, psoralene-UVA (PUVA) and thalidomide are administered.

Adolescent↗

PubMed2000

Comparison between the switching dynamics of homeotropic and planar cells of chiral smectic-C liquid crystals

The molecular dynamics during the switching of homeotropic and planar cells of chiral smectic-C liquid crystals has been investigated using electrooptic measurements and second-harmonic-generation interferometry. Two ferroelectric liquid crystals with great differences in their molecular structures have been studied. It has been found that the molecular motion is rather different depending on the type of cell used. For planar cells, the azimuthal rotation of the molecules is limited within half the smectic cone and the molecules rotate in opposite directions in the two halves of the chevron structure. In contrast, for homeotropic cells there is no chevron structure and a uniform macroscopic optical indicatrix can be defined all over the sample during the whole switching process. However, the molecular reorientation takes place within numerous microdomains of size smaller than the optical wavelength. There are two types of microdomains that occur with different probabilities depending on the material. Within each domain the molecules rotate in opposite directions, and the molecules describe a complete cone during a whole switching period.

Journal Article↗

PubMed2000

Ultrastructural and functional analyses of recombinant influenza virus ribonucleoproteins suggest dimerization of nucleoprotein during virus amplification.

Influenza virus ribonucleoproteins (RNPs) were reconstituted in vivo from cloned cDNAs expressing the three polymerase subunits, the nucleoprotein (NP), and short template RNAs. The structure of purified RNPs was studied by electron microscopy and image processing. Circular and elliptic structures were obtained in which the NP and the polymerase complex could be defined. Comparison of the structure of RNPs of various lengths indicated that each NP monomer interacts with approximately 24 nucleotides. The analysis of the amplification of RNPs with different lengths showed that those with the highest replication efficiency contained an even number of NP monomers, suggesting that the NP is incorporated as dimers into newly synthesized RNPs.

Animals↗

PubMed2000

The replication activity of influenza virus polymerase is linked to the capacity of the PA subunit to induce proteolysis.

The PA subunit of the influenza virus polymerase complex is a phosphorylated protein that induces a proteolytic process that decreases its own accumulation levels and those of coexpressed proteins. The amino-terminal third of the protein is responsible for the induction of proteolysis. We mutated five potential casein kinase II phosphorylation sites located in the amino-terminal third of the protein. Mutations affecting position 157 almost completely abrogated proteolysis induction, whereas a mutation at position 162 produced a moderate decrease and mutations at positions 151, 200, and 224 did not affect proteolysis induction. Reconstitution of the influenza virus polymerase in vivo with viral model RNA containing the chloramphenicol acetyltransferase (CAT) gene indicated that the CAT activity obtained correlated with the capacity of each PA mutant to induce proteolysis. RNA protection assays of the products obtained with viral polymerase, reconstituted in vivo with model RNAs, indicated that mutations at position 157 led to a selective loss of the ability to synthesize cRNA from the viral RNA template but not to transcribe viral RNA, while a mutation affecting position 162 showed an intermediate phenotype. Collectively, these data provide a link between PA-mediated induction of proteolysis and the replication activity of the polymerase.

Amino Acid Sequence↗

PubMed2000

A quantitative study of fault tolerance, noise immunity, and generalization ability of MLPs

An analysis of the influence of weight and input perturbations in a multilayer perceptron (MLP) is made in this article. Quantitative measurements of fault tolerance, noise immunity, and generalization ability are provided. From the expressions obtained, it is possible to justify some previously reported conjectures and experimentally obtained results (e.g., the influence of weight magnitudes, the relation between training with noise and the generalization ability, the relation between fault tolerance and the generalization ability). The measurements introduced here are explicitly related to the mean squared error degradation in the presence of perturbations, thus constituting a selection criterion between different alternatives of weight configurations. Moreover, they allow us to predict the degradation of the learning performance of an MLP when its weights or inputs are deviated from their nominal values and thus, the behavior of a physical implementation can be evaluated before the weights are mapped on it according to its accuracy.

Journal Article↗

PubMed2000

Sustained but not transient phytochrome A signaling targets a region of an Lhcb1*2 promoter not necessary for phytochrome B action.

Current evidence is inconclusive regarding the point of signaling convergence downstream from different members of the phytochrome family. In transgenic Arabidopsis, the activity of a reporter enzyme under the control of the -453 to +67 fragment of an Lhcb1*2 promoter shows very low fluence responses (VLFRs) and high-irradiance responses (HIRs) mediated by phytochrome A and low-fluence responses (LFRs) mediated by phytochrome B. A 5' deletion of the promoter to -134 abolished the HIR without affecting VLFR or LFR. In transgenic tobacco, VLFR and LFR were observed for the -176 to -31 or -134 to -31 fragments of Lhcb1*2 fused to 35S cauliflower mosaic virus minimal promoters, but only the largest fragment showed HIR. We propose that sustained activation of phytochrome A with far-red light initiates a signaling cascade that deviates from phytochrome B signaling and transient phytochrome A signaling and that this divergence extends as far as the Lhcb1*2 promoter.

Arabidopsis↗

PubMed1999

Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group.

We have analyzed factors influencing the outcome of 102 children with acute leukemia given a cord blood transplantation (CBT) and reported to the Eurocord Registry. Seventy patients with acute lymphoblastic and 32 with acute myeloid leukemia were given either a related (n = 42) or an unrelated (n = 60) CBT. Children given CBT during first or second complete remission were considered as belonging to the good-risk group (n = 66), whereas those who received a transplant in a more advanced stage of disease were assigned to the poor-risk group (n = 36). In the related group (RCBT), 12 of 42 patients received transplantation from an HLA-disparate donor, whereas in the unrelated group (UCBT) 54 of 60 received an HLA mismatched CBT. Kaplan-Meier estimates for neutrophil recovery at day 60 were 84% +/- 7% in RCBT and 79 +/- 6% in UCBT (P =.16). In multivariate analysis, the most important factor influencing neutrophil engraftment in UCBT was a nucleated cell dose infused greater than 3.7 x 10(7)/kg (P =.05, relative risk [RR] of 1.85, 95% confidence interval [CI]: 0.98-3.4). The incidence of grade II through IV acute graft-versus-host disease was 41% +/- 8% in the RCBT group and 37% +/- 6% in the UCBT group (P =.59). Kaplan-Meier estimates of 2-year event-free survival (EFS) after RCBT or UCBT were 39% +/- 8% and 30% +/- 7%, respectively (P =.19). In multivariate analysis, the most important factor influencing EFS was disease status at time of transplantation: good-risk patients had a 2-year EFS of 49% +/- 7% as compared to 8% +/- 5% in patients with more advanced disease (P =.0003, RR: 0.40, 95% CI: 0.24 to 0. 65). This was a consequence of both an increased 1-year transplant related mortality and a higher 2-year relapse rate in the poor-risk group (65% +/- 9% and 77% +/- 14%, respectively), as compared with good risk patients (34% +/- 6% and 31% +/- 9%, respectively). These data confirm that allogeneic CBT from either a related or an unrelated donor is a feasible procedure able to cure a significant proportion of children with acute leukemia, especially if transplanted in a favorable phase of disease.

Acute Disease↗

PubMed1999

Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients.

Myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) of childhood are a heterogeneous group of clonal disorders of hematopoiesis with overlapping clinical features and inconsistent nomenclature. Although a number of genetic conditions have been associated with MDS and MPS, the overall contribution of inherited predispositions is uncertain. We report a retrospective study examining clinical features, genetic associations, and outcomes in 167 children with MDS and MPS. Of these patients, 48 had an associated constitutional disorder. One hundred one patients had adult-type myelodysplastic syndrome (A-MDS), 60 had juvenile myelomonocytic leukemia (JMML), and 6 infants with Down syndrome had a transient myeloproliferative syndrome (TMS). JMML was characterized by young age at onset and prominent hepatosplenomegaly, whereas patients with A-MDS were older and had little or no organomegaly. The most common cytogenetic abnormalities were monosomy 7 or del(7q) (53 cases); this was common both in patients with JMML and those with A-MDS. Leukemic transformation was observed in 32% of patients, usually within 2 years of diagnosis. Survival was 25% at 16 years. Favorable prognostic features at diagnosis included age less than 2 years and a hemoglobin F level of less than 10%. Older patients tended to present with an adult-type MDS that is accommodated within the French-American-British system. In contrast, infants and young children typically developed unique disorders with overlapping features of MDS and MPS. Although the type and intensity of therapy varied markedly in this study, the overall outcome was poor except in patients with TMS.

Child↗

PubMed1999

Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD).

Zinc deficiency is a common nutritional problem in adult sickle-cell disease (SCD) patients. Hyperzincuria and increased requirement of zinc due to continued hemolysis in SCD are probable bases for zinc deficiency in these patients. Zinc deficiency affects adversely T-helper1 (TH1) functions and cell mediated immunity and interleukin (IL)-2 production is decreased in zinc deficient subjects. We hypothesized that zinc supplementation will improve T-helper1 function and decrease incidence of infections in patients with SCD. We tested this hypothesis in 32 SCD subjects who were divided in three groups (Grs A, B, and C). Grs A (n = 11) and B (n = 10) were zinc deficient based on cellular zinc criteria and Gr C (n = 11) were zinc sufficient. Gr A subjects were observed for 1 year (baseline), following which they received zinc acetate (50 to 75 mg of elemental zinc orally daily) for 3 years. Gr B subjects were observed for 1 year (baseline), following which they received placebo for 1 year and then switched to zinc supplementation (50 to 75 mg of elemental zinc orally daily) for 2 years. Gr C subjects did not receive any intervention inasmuch as they were zinc sufficient. Prolonged zinc supplementation resulted in an increase in lymphocyte and granulocyte zinc (P = 0.0001), and an increase in interleukin-2 production (P = 0.0001), decreased incidence of documented bacteriologically positive infections (P = 0.0026), decreased number of hospitalizations and decreased number of vaso-occlusive pain crisis (P = 0.0001). The predominant pathogens isolated were staphylococci and streptococci involving the respiratory tract and aerobic gram-negative bacteria, particularly Escherichia coli, involving the urinary tract. Further confirmation of our observations will require prospective studies of zinc supplementation in a larger number of SCD patients.

Administration, Oral↗

PubMed1999

Autologous bone marrow transplantation for high risk acute lymphoblastic leukemia: clinical relevance of ex vivo bone marrow purging with monoclonal antibodies and complement.

Herein we describe our experience with 75 consecutive autologous BM transplants for patients with high-risk ALL, with special attention to the clinical impact of BM purging. Fifty-two patients received purged BM using monoclonal antibody (MoAb) cocktails and complement, and 23 patients received untreated BM. The distribution of prognostic factors was similar in both groups. Hemopoietic reconstitution was adequate and did not differ in the two groups. Transplant-related mortality was 9.6% and 13% in 'purged' and 'unpurged' groups. Median follow up was 11 months (2-71) and overall actuarial probability of disease-free survival (DFS) at 5 years was 40% (53% relapse probability). We found a beneficial effect of purging in patients over 15 years of age and in patients needing more than 1 month to reach CR1. Patients in CR1 receiving purged marrow had a longer DFS and a lower relapse probability (52% vs 12%, P = 0.02 and 35% vs 86%, P = 0.005, respectively) which were related to the efficacy of the purging procedure (more or less than one log of depletion). In further CR, no advantage of purging has been found. Our data strongly suggest the clinical relevance of BM purging in autologous BMT in high-risk ALL patients and support the need for prospective randomized studies.

Adult↗

PubMed1999

A new measurement of noise immunity and generalization ability for MLPs.

This paper shows a quantitative relation between the regularization techniques, the generalization ability, and the sensitivity of the Multilayer Perceptron (MLP) to input noise. Although many studies about these topics have been presented, in most cases only one of the problems is addressed, and only experimentally obtained evidence is provided to illustrate some kind of correlation between generalization, noise immunity and the use of regularization techniques to obtain a set of weights after training that provides the corresponding MLP with generalization ability and noise immunity. Here, a new measurement of noise immunity for a MLP is presented. This measurement, which is termed Mean Squared Sensitivity (MSS), explicitly evaluates the Mean Squared Error (MSE) degradation of a MLP when it is perturbed by input noise, and can be computed from the statistical sensitivities (previously proposed) of the output neurons. The MSS provides an accurate evaluation of the MLP performance loss when its inputs are perturbed by noise and can also be considered a measurement of the smoothness of the error surface with respect to the inputs. Thus, as the MSS can be used to evaluate the noise immunity or the generalization ability, it gives a criterion to select among different weight configurations that present a similar MSE after training.

Models, Neurological↗

PubMed1999

[Fibrous craniofacial dysplasia].

A case report of fibrous dysplasia affecting only the craniofacial right side, in a 56-year-old woman, seen in our outpatients Department suffering from fronto-orbital headache and subjective hypoacusis of the right side, besides a syndrome of dizziness of 6 years development.

Diagnosis, Differential↗

PubMed1998

Recommendations on the use of colony-stimulating factors in children: conclusions of a European panel.

UNLABELLED: During 1996 and 1997 a panel of European haematologists, oncologists, and neonatologists developed specific paediatric guidelines for the use of colony stimulating factors based on published literature and the clinical experience of these specialists within each of 13 countries. Well established indications for use comprise intervention in patients with life-threatening infection, adjunctive therapy post autologous bone marrow transplantation (BMT), mobilization of peripheral blood progenitor cells for autologous BMT, patients with acquired aplastic anaemia on anti-lymphocyte globulin and cyclosporin regimen, and severe congenital neutropenia. Less clear indications include primary prophylaxis to support dose intensification in children with high risk/advanced malignancies, secondary prophylaxis to prevent neutropenia in patients with a history of severe neutropenia, support therapy in cases of poor marrow function following BMT and for deteriorating marrow function following successful BMT, in neonatal sepsis and non infectious neonatal neutropenia, in drug induced neutropenia and in HIV-positive patients. Treatment is generally well tolerated and granulocyte colony stimulating factor appears better tolerated than granulocyte and macrophage colony stimulating factor. Economically colony stimulating factors have not been shown to induce excessive costs for a given patient. CONCLUSION: In general the adult guidelines are applicable to children but additional considerations (aggressive or very progressive childhood neoplasms, specific indications, neonatal use, congenital disorders) must be taken into account.

Bone Marrow Transplantation↗

PubMed1998

Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation: approach to size of necrosis.

BACKGROUND: We designed this study to determine the value of serum levels of several cardiac markers in patients who underwent radiofrequency ablation and to establish the utility of cardiac troponin I (cTnI). After radiofrequency ablation there is always a small localized endomyocardial necrosis. The volume of the necrosis may be estimated by the rise of several biochemical marker levels, classically creatinine kinase (CK) and CK-MB. cTnI is a newly available biochemical marker with a high cardiac specificity. METHODS AND RESULTS: We analyzed the data from 51 patients who underwent radiofrequency ablation and from 16 control patients who underwent an electrophysiologic study without ablation. The levels of CK, CK-MB mass, cTnI, and myoglobin were compared with clinical findings, ST-T wave abnormalities, and the presence of arrhythmias. The study shows that there is a higher release of cTnI compared with the standard markers CK, CK-MB, and myoglobin. A pathologic value of cTnI was found in 92% of the patients of the ablation group. CK-MB had a lower sensitivity (63%). The area under the receiver operating characteristic curve for cTnI was 0.9375, significantly superior to the other biochemical markers (P <.05). We found a moderate level of correlation between the number of radiofrequency pulses and cardiac cTnI release (r = 0.69, P <.0001). CONCLUSIONS: The serum level of cTnI detects the minor myocardial damage produced by radiofrequency ablation. This would be useful information to have in patients who might have the potential for other ischemic events. The other biochemical or ablation parameters usually reported, including the radiofrequency ablation parameters, have no good correlation with the size of the myocardial necrosis. Therefore we suggest that monitoring of cTnI is the best way to detect and quantify the size of myocardial necrosis created by radiofrequency ablation.

Adult↗

PubMed1998

[Electromagnetic interference between automatic defibrillators and digital and analog cellular telephones].

BACKGROUND AND OBJECTIVES: Functional pacemaker interference by mobile telephones has been described with analogical systems and with possible greater influence, digital systems, including inhibition and inadequate pacing. The influence of both system has not been extensively studied in patients with implantable cardioverter defibrillators (ICD). PATIENTS AND METHODS: We studied the influence of mobile phones, both digital and analogic network, on the performance of several models of defibrillators, in a standardised test set up designed to provide high sensitivity. The purpose of our study was to establish whether there are any influences on ICD functions, both in in vivo and in in vitro models. Several mobile phones, with different transmission powers, were moved towards the defibrillator and the electrode, under continuous documentation of defibrillator sensing and interrogation afterwards. The experimental model was performed with the aid of an arrhythmia simulator (Intersim) and demo-defibrillators. The tests were repeated both in and out of a solution of saline water with an impedance within normal human limits. RESULTS: Partial loss of telemetry was found in 14 patients, 8 with analogical phones and 6 with digital phones. Fourteen patients showed alterations only on the surface electrocardiogram channel and five on the intracavitary channel. The same results were reproduced in the in vitro model. However, the in vitro test allowed us to simulate multiple ventricular arrhythmias, and demonstrate the normal sensing and functioning of the defibrillator during a "spontaneous" arrhythmia. After testing, we demonstrate that no real oversensing/undersensing was documented in any device. There was no evidence of ICD reprogramming or pacing inhibition. In particular, no inadequate therapies were delivered. CONCLUSIONS: a) in our series, we have not demonstrated clinically significant electromagnetic interferences with mobile phones of digital or analogical networks: b) the in vitro model allowed us to conclude that even if a spontaneous arrhythmia appears, the function of the defibrillator is not altered; c) the use of mobile phones seems to be safe for defibrillator patients, and d) however, some basic rules, such as to maintain the phone at least 15 cm away from the defibrillator, are advised.

Defibrillators, Implantable↗

PubMed1998

The PA influenza virus polymerase subunit is a phosphorylated protein.

The induction of proteolysis by expression of the influenza virus PA polymerase subunit is the only biochemical activity ascribed to this protein. In the course of studying viral protein synthesis by two-dimensional gel electrophoresis, we observed the existence of several PA isoforms with different isoelectric points. These isoforms were also present when the PA gene was singly expressed in three different expression systems, indicating that a cellular activity is responsible for its post-translational modification. In vivo labelling with [32P]orthophosphate, followed by two-dimensional gel electrophoresis, clearly demonstrated the incorporation of phosphate into the PA molecule. Phosphoserine and phosphothreonine epitopes were present in PA, while phosphotyrosine residues were absent, as tested by immunoblotting with specific antibodies. These facts, as well as the presence of multiple consensus sites for casein kinase II (CKII) phosphorylation, prompted us to test the involvement of this kinase in PA covalent modification. PA protein purified by immunoprecipitation could be specifically labelled by the catalytic alpha subunit of human CKII, which was expressed and purified from bacteria. Collectively, these data demonstrate that the PA subunit of the influenza virus RNA polymerase is a phosphoprotein.

Animals↗