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E Domingo

Publications and source records attributed to E Domingo.

At least 163 records · Page 9Linked to original sources
PubMed1992

Non-additive effects of multiple amino acid substitutions on antigen-antibody recognition.

Synthetic peptides have been used to mimic the main antigenic site of foot-and-mouth disease virus (FMDV) of serotype C and of several variant isolates. This region includes multiple continuous B cell epitopes. The effect of single amino acid replacements, individually or in combination, on antigen specificity has been evaluated using monoclonal antibodies. Quantitative enzyme immunodot assays have shown that both additive and non-additive effects of multiple replacements occur in continuous B cell epitopes, with regard to antibody recognition. Antigenically critical single replacements may be compensated by other, non-critical replacements. Thus, the role of a single amino acid on antibody recognition depends on the sequence context in the antigenic domain. The non-additive effects of multiple replacements may modulate the extent of antigenic diversification of highly variable RNA viruses, and keep viruses confined within antigenic groups by precluding linear antigenic divergence.

Amino Acid Sequence↗
PubMed1992

Modifications of the 5' untranslated region of foot-and-mouth disease virus after prolonged persistence in cell culture.

The nucleotide sequence of the 5'-untranslated region (5'UTR) of the genome of foot-and-mouth disease virus (FMDV) R100, rescued after 100 passages of persistently infected BHK-21 cells, has been compared with that of the parental FMDV C-S8c1. The nucleotide sequence divergence between the two viruses in heteropolymeric regions is 1%. The few mutations located at the 5'-most terminal region (S fragment) and at the internal ribosome entry site (IRES) do not appear to affect significantly the tight secondary structure predicted for these RNA segments. Comparison of the 5'UTR of C-S8c1 or R100 RNA with that of other FMDV serotypes and subtypes indicates the presence of block deletions (or insertions) which do not correlate with the serological classification of FMDV. Remarkably, FMDV R100, a virus highly attenuated for mice and cattle, contains a polyribocytidylate (poly C) tract of about 420 nucleotides, 145 residues longer than its parental, virulent FMDV C-S8c1. This long poly C of R100 RNA includes a few uridine residues interspersed at fairly regular intervals. This is the longest highly homopolymeric tract described in a viral genome and, to our knowledge, in any informational biomolecule.

Animals↗
PubMed1992

Genetic variation and quasi-species.

During the past year the relative fitness, that is, overall replication ability, and the fitness gain of animal virus variants have been quantified, providing new insight into the dynamics for the generation of RNA virus quasi-species. Measurements of mutant frequencies and rates of genetic diversification have confirmed the extreme complexity of RNA virus and retrovirus populations.

Genetic Variation↗
PubMed1992

Generation of a subtype-specific neutralization epitope in foot-and-mouth disease virus of a different subtype.

An epitope involved in neutralization of foot-and-mouth disease virus (FMDV) of subtype C3 was generated by a single amino acid replacement in VP1 of FMDV of subtype C1. The replacement [Ser (139)----Ile, in the immunodominant site A] was consistently found in those FMDV C1 Santa Pau-Sp/70 mutants resistant to neutralization by monoclonal antibody (MAb) SD6 (specific for most C1 viruses) that acquired the capacity to be neutralized by MAb 7AB5 (specific for C3 viruses).

Amino Acid Sequence↗
PubMed1992

Extensive antigenic diversification of foot-and-mouth disease virus by amino acid substitutions outside the major antigenic site.

The antigenic sites A and C (the G-H loop and the C terminus, respectively) in VP1 of foot-and-mouth disease virus (FMDV) have been considered the immunodominant regions of the virus involved in the induction of protection. Other antigenic sites have been described but their involvement in protection has not been established. Here we report that two closely related but serologically different FMDVs (the field isolate C3 Argentina/84 and the vaccine strain C3 Resende Br/55) have identical A and C sites but differ as other antigenic sites. Such differences have been documented by reactivity with a panel of 28 monoclonal antibodies (MAbs). The two viruses reacted to the same extent with each of 13 MAbs which recognized epitopes within sites A or C, but reacted differently with six out of 15 MAbs that recognized other sites. Accordingly, sequencing of the entire region coding for the capsid proteins, for both viruses, revealed four amino acid substitutions at three antigenic sites other than A and C. The results suggest that identity of sites A and C may not be sufficient to induce cross-protection, and provide the first evidence of significant antigenic diversification of FMDV in the field mediated by amino acid substitutions outside sites A or C.

Amino Acid Sequence↗
PubMed1992

Studies on antigenic variability of C strains of foot-and-mouth disease virus by means of synthetic peptides and monoclonal antibodies.

Peptides representing the sequence of the immunodominant loop of foot-and-mouth disease virus strain C-S8 (YTASARGDLAHLTTTHARHLP, residues 136-156 of VP1) and of several variant viruses have been prepared by solid phase methods. In addition, five peptides with single-residue replacements at Leu147 (Ile, Nle, Val, Ala, Gly) have been synthesized. Tosyl and dinitrophenyl protections for histidine have been compared, the latter being found to give better synthetic products. The peptides have been tested in an immunodot assay against a panel of monoclonal antibodies directed towards the VP1 loop. Immunochemical results are discussed on the basis of the mobility of the region reproduced by the peptides and the nature of the side chain of residue 147.

Amino Acid Sequence↗
PubMed1992

Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades.

The genetic diversification of foot-and-mouth disease virus (FMDV) of serotype C over a 6-decade period was studied by comparing nucleotide sequences of the capsid protein-coding regions of viruses isolated in Europe, South America, and The Philippines. Phylogenetic trees were derived for VP1 and P1 (VP1, VP2, VP3, and VP4) RNAs by using the least-squares method. Confidence intervals of the derived phylogeny (significance levels of nodes and standard deviations of branch lengths) were placed by application of the bootstrap resampling method. These procedures defined six highly significant major evolutionary lineages and a complex network of sublines for the isolates from South America. In contrast, European isolates are considerably more homogeneous, probably because of the vaccine origin of several of them. The phylogenetic analysis suggests that FMDV CGC Ger/26 (one of the earliest FMDV isolates available) belonged to an evolutionary line which is now apparently extinct. Attempts to date the origin (ancestor) of the FMDVs analyzed met with considerable uncertainty, mainly owing to the stasis noted in European viruses. Remarkably, the evolution of the capsid genes of FMDV was essentially associated with linear accumulation of silent mutations but continuous accumulation of amino acid substitutions was not observed. Thus, the antigenic variation attained by FMDV type C over 6 decades was due to fluctuations among limited combinations of amino acid residues without net accumulation of amino acid replacements over time.

Amino Acid Sequence↗
PubMed1992

Orthostatic and exercise-induced advanced nodal atrioventricular block.

A 69-year-old woman was referred for asthenia and dizziness when walking in the last two months. No clinical abnormalities were found, and sinus rhythm was present when lying down. On orthostatism and walking, advanced AV block developed. Atropine and isoproterenol ameliorated the AV conduction abnormality, suggesting a nodal block. The patient remained asymptomatic after pacemaker implantation.

Aged↗
PubMed1992

[Clinical and angiographic course after coronary angioplasty. Analysis of predictor factors of restenosis].

In order to know the restenosis rate and its predictive factors and the short-term clinical outcome (6-12 months) after coronary angioplasty (PTCA), we prospectively followed 200 consecutive patients with 231 coronary stenoses successfully dilated (residual stenosis < 50%). Patients have been clinically and angiographically followed 6-9 months after the procedure. Forty-nine clinical, hemodynamic, angiographic and technical variables were analyzed. Restenosis (stenosis > or = 50% in late angiographic control) rate was 51.5%, and 61% of the study population was symptomless. Variables associated with restenosis in the univariate analysis were: pre-PTCA positive exercise test (p = 0.004); stenosis severity pre-PTCA (p = 0.04); eccentricity (p < 0.0001) and irregularity (p < 0.0001) of the pre-PTCA stenosis; total dilation time (p = 0.02) and post-PTCA dissection (p = 0.002). The multivariate analysis revealed the following variables as independent predictors of restenosis: presence of dissection after PTCA, eccentricity and irregularity of pre-PTCA stenosis, positive pre-PTCA stress test and duration of symptoms before the procedure. These data suggest that the probability of restenosis after PTCA is predominantly determined by the characteristics of the lesion being dilated and the degree of intimal injury produced during the procedure. These variables could define high and low risk populations and may modify PTCA indications and follow up strategies.

Angioplasty, Balloon, Coronary↗
PubMed1991

Uncomplicated first myocardial infarction: strategy for comprehensive prognostic studies.

To evaluate the prognostic role of combined cardiac studies (submaximal exercise test, thallium-201 scintigraphy, radionuclide exercise ventriculography, two-dimensional echocardiography, Holter monitoring and cardiac catheterization) in patients with a first acute myocardial infarction without complications during hospital admission, 115 consecutive patients aged less than 65 years were prospectively evaluated. The studies were carried out before hospital discharge and the patients were then clinically followed up for 12 months. During the follow-up period, 69 patients (60%) developed complications, which were severe in 23 (20%). Half of all complications and 70% of severe complications developed during the 1st follow-up month. Logistic regression analysis disclosed that the combination of studies with the highest predictive power for complications (probability of complications 99%) and severe complications (probability of severe complications 95%) was the association of exercise test + thallium-201 + echocardiogram. Four decision models (exercise test + echocardiography, exercise test + radionuclide ventriculography, thallium-201 scintigraphy + echocardiography, thallium-201 scintigraphy + radionuclide ventriculography) allowed the stratification of all patients in a particular risk category (high, intermediate or low). The best decision model was the association of thallium-201 scintigraphy + radionuclide ventriculography (probability of complications if both tests were positive 84%; probability of absence of severe complications if both tests were negative 88%), but there were no significant differences with the other models. Any association of a test detecting residual ischemia or functional capacity, or both (exercise test or thallium-201) and a test assessing ventricular function (echocardiography or radionuclide ventriculography) results in significant prognostic information in patients with an uncomplicated first acute myocardial infarction. Additional cardiac catheterization does not improve the predictive power of noninvasive studies, which should ideally be performed before hospital discharge because most complications develop during the 1st follow-up month.

Adult↗
PubMed1991

Fixation of mutations at the VP1 gene of foot-and-mouth disease virus. Can quasispecies define a transient molecular clock?

The number of nucleotide (nt) substitutions found in the VP1 gene (encoding viral capsid protein) between any two of 16 closely related isolates of foot-and-mouth disease virus (FMDV) has been quantified as a function of the time interval between isolations [Villaverde et al., J. Mol. Biol. 204 (1988) 771-776]. One of them (isolate C-S12) includes some replacements found in isolates that preceded it and other replacements found in later isolates. The study has revealed alternating periods of rapid evolution and of relative genetic stability of VP1. During a defined period of acute disease, the rate of fixation of replacements at the VP1 coding segment was 6 x 10(-3) substitutions per nt per year. Only small differences in the rate of evolution were observed between subsegments within the VP1 gene. The observation of a relatively constant rate of evolution during a disease episode was unexpected. We propose that such constancy may be a consequence of random sampling of mutants from the FMDV quasispecies, followed by their amplification in susceptible hosts (to generate a new quasispecies). Successive sampling and amplification events may result in a steady accumulation of mutations.

Amino Acid Sequence↗
PubMed1991

Percutaneous right brachial artery approach with 5F catheters for studying coronary artery disease.

We prospectively studied 60 ischemic patients with 5F catheters (Pigtail and Amplatz) using the percutaneous right brachial artery approach (group I), in order to compare this technique with two groups of 100 patients each randomly studied by the femoral route with either 5F (group II) or 8F (group III) catheters (Pigtail and Judkins). The following parameters were analyzed: need to change the initially elected catheter diameter or/and artery approach; technical difficulty for obtaining LV, LCA, and RCA angiograms; total time of X-ray exposure; quality image of LV, LCA, and RCA angiograms; incidence of arterial puncture related hematomas or total arterial occlusion; and duration of local compression after sheath removal. There were no differences between 5F brachial and femoral approaches except for the arterial compression time (p less than 0.01) and the X-ray exposure time (p = 0.03) which were longer with the brachial approach. Whatever the route used, 5F showed a mild increase difficulty (brachial p = 0.001; femoral p = 0.01) and a mild decreased quality image for LCA (branchial p = 0.006; femoral p less than 0.05). Mild hematomas were more frequent with 8F catheters (p less than 0.05). The procedure could be completed by the elected first artery and type of catheter (5F or 8F) in 57/60 patients in group I, in 95/100 in group II, and in 96/100 in group III (nonsignificant differences). Thus, the percutaneous right brachial artery approach using 5F catheters is similar to the femoral artery approach with the same catheters. Although both of them showed a mild increased technical difficulty and a mild decreased quality image compared to 8F, mainly for LCA angiograms, they allowed complete and reliable angiograms reading and analysis.

Angiography↗
PubMed1991

Effect of drugs on a noninvasive index of arterial compliance in healthy and heart failure patients.

Ten healthy (aged 28 to 39) and ten heart failure NYHA II (aged 19 to 49) male subjects were prospectively studied under no drugs, under furosemide (40 mg/day), under captopril (150 mg/day) and under their association. Arterial compliance (ml/mmHg) was measured in all subjects at rest and supine. Heart failure etiology was dilated cardiomyopathy or ischemic heart disease without significant regurgitation. Arterial compliance was significantly higher in healthy than in heart failure patients in all studied conditions (p less than 0.001) (healthy = 2.2 + 0.29 vs. heart failure = 0.79 + 0.14). Neither single drug nor their association induced any change in healthy subjects. Arterial compliance progressively increased in heart failure with furosemide, captopril, and their association (no drug = 0.79 + 0.14; furosemide = 0.87 + 0.15; captopril = 0.94 + 0.15 and furosemide + captopril = 0.99 + 0.14). Captopril induced a higher increment than furosemide (p less than 0.001) and their association even a higher increment (p less than 0.001) than any single drug. Thus captopril and/or furosemide increased arterial compliance in heart failure but not in healthy subjects, possibly through changes in arterial wall edema and smooth muscle contraction.

Adult↗
PubMed1991

Two mechanisms of antigenic diversification of foot-and-mouth disease virus.

The amino acid replacements that underlay the diversification of the main antigenic site A (VP1 residues 138 to 150) of foot-and-mouth disease virus (FMDV) of serotype C have been identified. Sixteen new VP1 sequences of isolates from 1926 until 1989 belonging to subtypes C1, C2, C3, C4, C5, and unclassified are reported. The reactivities in enzyme-linked immunoelectrotransfer blot assays of capsid protein VP1 with a panel of neutralizing monoclonal antibodies that recognize sites A or C (the VP1 carboxy-terminus) have been correlated with the amino acid sequence at the relevant epitopes. The analyses involving the immunodominant site A reveal two mechanisms of antigenic change. One is a gradual increase in antigenic distance brought about by accumulation of amino acid replacements at two hypervariable segments within site A. A second mechanism consists of an abrupt antigenic change manifested by loss of many epitopes, caused by one replacement at a critical position (particularly Ala (145)----Val or His (146)----Gln). The identification of the amino acid substitutions responsible for such large antigenic changes provides new information for the design of synthetic anti-FMD vaccines. However, the screening of isolates from six decades suggests that the virus, even within the confines of a single serotype, has exploited a minimum of its potential for antigenic variation.

Amino Acid Sequence↗
PubMed1991

Repetitive nucleotide sequencing of a dispensable DNA segment in a clonal population of African swine fever virus.

Repetitive nucleotide sequencing of a dispensable genomic segment of a clonal population of African swine fever (ASF) virus has been carried out to estimate the mutant frequency to neutral alleles. Since no mutations have been detected in a total of 54026 nucleotides screened, the maximum mutant frequency is 5.5 x 10(-5) substitutions/nucleotide (95% confidence level). The result renders very unlikely the occurrence of hypermutational events during ASF virus DNA replication, at least within the selected DNA fragment.

African Swine Fever Virus↗