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Biomedical subjects

E Román

Publications and source records attributed to E Román.

18 recordsLinked to original sources

Synthetic peptides non-covalently bound to bacterial hsp 70 elicit peptide-specific T-cell responses in vivo.

We have examined the immunogenicity of complexes formed by non-covalent association of a synthetic peptide corresponding to influenza A virus nucleoprotein, residues 206-229 (pNP) and Mycobacterium tuberculosis heat-shock protein 70 (hsp 70). One or two injections of these complexes given to BALB/c mice without any additional adjuvant, were capable of eliciting very strong peptide-specific proliferative T-cell responses in the spleen. These responses were dependent on the stability of the complex since immunogenicity was lost when dissociated with ATP prior to immunization. T-cell responses to hsp 70 were easily generated by immunization with the purified chaperone alone, either after primary or secondary immunization. Injection of pNP-hsp 70 complexes, however, although generating good primary responses, resulted in very much decreased proliferative responses to the hsp 70.

Adenosine Triphosphate

[Nutrient and food consumption by ages and gender in school children from the Community of Madrid (CAENPE)].

UNLABELLED: The objective of the present work was to know the consume of foodstuffs and nutrients among schoolchildren in the Madrid Autonomous Community and also the relative contribution of each group of foodstuffs to the overall intake of macronutrients. This study had a sectional observational design involving 2,608 children (51% males and 49% females) with ages ranging from 6 to 14 years who were randomly recruited from conglomerate of schools, according to socio-economic status and rural/urban residence. The inquiry on nutrients in 4 non consecutive days was analyzed (2 "24 hour-recall" and 2 "intake recall"). RESULTS: a) the consume of proteins, lipids, and carbohydrates represented 17%, 43% and 40% of the total caloric value, respectively; b) the intake of meats, sausages, sweets, tidbits, and processed products was very high. This fact is in origin of the excessive total and saturated lipid intake; c) there was a scarce intake of vegetables, cereals and potatoes among children of all ages and dairy products in children older than 12 years; d) the intake of legumes, eggs and fruits was appropriate; e) males consumed proportionally higher amounts than females of the following groups of foodstuffs: cereals, sweets and tidbits. The consume of meat, sausages, fish, eggs, potatoes, dry fruits and dairy products was similar in both sexes. Females consumed proportionally more fat foodstuffs, vegetables, fruits, legumes and processed products; f) females consumed a diet with a still higher lipid and protein content than males. These findings can serve as a basis to develop educational guidelines with a practical impact on family and school menus.

Adolescent

H-2-associated effects of flanking residues on the recognition of a permissive mycobacterial T-cell epitope.

Previously we have identified an immunodominant, eight-residue, epitope core sequence (TAAGNVNI) from the 19,000 MW protein of Mycobacterium tuberculosis, which is recognized in the context of multiple H-2 I-A molecules. In this study, the role of residues flanking this T-cell epitope core was examined, using a series of 20 mer analogue peptides in which the native flanking residues were progressively replaced with L-alanine. Analogue peptides were tested for their capacity to stimulate a CD4+ 19,000 MW protein-specific T-cell line, revealing that all but one N-terminal flanking residue could be replaced collectively by alanine without significant loss of stimulatory activity. However, clear H-2-associated differences in the requirement for flanking residues were demonstrated with peptide-specific T-cell hybridomas. In particular, H-2d-derived hybridomas were much more stringent in their requirement for flanking residues than were H-2b hybridomas. All polyalanine-substituted peptides bound I-Ab molecules, with affinities similar to the native unsubstituted peptide. In contrast, significantly reduced binding to I-Ad was observed with several analogue peptides, although without a clear relationship to the degree of substitution. Furthermore, in H-2b mice, neither immunogenicity nor cross-reactivity with the native peptide showed a clear inverse relationship with respect to the degree of alanine substitution. The results presented in this paper indicate that flanking residues can influence T-cell specificity and that these effects may be controlled by major histocompatibility complex (MHC) haplotype.

Alanine

Mapping of Hsp70-binding sites on protein antigens.

Hsp70-binding sites were mapped on three antigens, the 16-, 19- and 38-kDa proteins of Mycobacterium tuberculosis, using overlapping synthetic peptides in a competitive-binding assay. In each protein, two or three prominent hsp70-binding sites were identified when peptides 20-amino-acid long were used, predominantly in regions containing clusters of aliphatic amino acids. Although there was an overall concordance in the pattern of peptide binding to hsp70 from bacterial (M. tuberculosis) and mammalian sources (immunoglobulin heavy-chain-binding protein), some differences in the specificity of polypeptide binding and the effect of peptides on ATPase activity were observed.

Adenosine Triphosphatases

Genetically permissive recognition of adjacent epitopes from the 19-kDa antigen of Mycobacterium tuberculosis by human and murine T cells.

The specificity of the T cell-immune repertoire at the level of individual antigenic determinants could play a fundamental role in the immunopathogenesis of tuberculous infections. Therefore, we analyzed the immunogenicity, genetic restriction, and epitope core structure of two adjacent, yet distinct, immunodominant T cell determinants from the 19-kDa Ag of Mycobacterium tuberculosis. After immunization with two peptides comprising residues 45 to 64 and 61 to 80, vigorous in vitro proliferative responses to the homologous peptide were elicited in five different strains of C57BL/10 mice (H-2b,k,d,s,f), indicating that both epitopes were recognized in a genetically permissive manner. When immunized with intact 19-kDa protein, lymph node cells from the same mouse strains responded to both peptides, with the exception of H-2b mice, which did not respond to p45-64. Delayed-type hypersensitivity responses in C57BL/10 (H-2b) mice were elicited by p61-80 only, whereas in H-2d mice both peptides were delayed-type hypersensitivity negative, despite eliciting pronounced proliferative responses. Analysis of the proliferative responses of human PBMC in purified protein derivative-positive healthy subjects and tuberculosis patients revealed significant differences in the antigenicity to the two peptides. All purified protein derivative-positive healthy and diseased individuals manifested strong responses to p45-64, indicating HLA permissive recognition. In contrast, pronounced responses to p61-80 were detected only in patients with lymphatic tuberculosis. Epitope core structures, composed of 6 or 7 residues within each peptide, have been mapped with peptides of overlapping sequence. Significantly, for both epitopes, the core sequences recognized by both human and murine T cells were almost identical. We conclude that despite many similarities between murine and human T cell epitope recognition, distinct differences in the responsiveness of the infected host could play a role in pathogenesis. Furthermore, the genetically permissive nature of the identified epitopes is a potentially important attribute for the development of peptide-based diagnostic reagents and vaccines.

Adult

T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope of the 38-kDa antigen in patients with active disease.

It is generally accepted that both host protection and pathogenic reactions in tuberculosis are mediated by T lymphocytes. However, little is known about the structures and discreet functions of epitopes stimulating the immune response. In this study, proliferative responses of blood T lymphocytes to synthetic peptides derived from the sequence of the 38-kDa antigen from Mycobacterium tuberculosis have been investigated in 41 healthy individuals and in 36 patients with active tuberculosis. Of the healthy purified protein derivative (PPD)-positive donors, 90% responded to a permissively recognized peptide, 38.G (residues 350-359), located at the carboxy terminus of the molecule. Four other permissively recognized epitopes of this molecule (38.A, 38.I, 38.E, 38.K) were stimulatory for more than 50% of healthy PPD-positive individuals. Patients with lymphatic tuberculosis responded to these peptides in a similar manner. In contrast, we observed a selective anergy to stimulation with peptide 38.G in the majority of patients with pulmonary (11% responders) and nonlymphatic extrapulmonary tuberculosis (25% responders). The lack of responsiveness to 38.G was epitope specific since the degree of responsiveness to the other four permissively recognized peptide epitopes was similar for patients and PPD-positive controls. Using the PEPSCAN technology and truncated peptides, the core epitope of 38.G was localized to a peptide 10 amino acids long (HFQPLPPAVV). This minimal structure was capable of inducing a proliferative response in all healthy 38.G responders tested. The mechanisms influencing this epitope-specific anergy in patients could give new insights into the immunopathogenesis of tuberculosis.

Amino Acid Sequence

Tumour necrosis factor induction by malaria exoantigens depends upon phospholipid.

In patients with malaria, the clinical manifestations of the disease are associated with the presence of high concentrations of tumour necrosis factor (TNF) in the serum. Blood-stage parasites of human and rodent malarial parasites release serologically related exoantigens which induce the production of TNF in vitro and in vivo and which can kill mice made hypersensitive to TNF by pretreatment with D-galactosamine. They also elicit the production of T-independent antibody, which blocks these effects. The capacity of the exoantigens to stimulate macrophages to secrete TNF does not require the presence of protein or carbohydrate, but is associated with a lipid whose activity can be abolished by treatment with phospholipase C. Treatments of the exoantigens which destroyed their activity in vitro also abrogated their immunogenicity and their toxicity for mice. No TNF-inducing activity could be detected in preparations of parasitized erythrocytes that was not associated with phospholipid, and the TNF-inducing properties of the malarial phospholipids are quite distinct from those of bacterial lipopolysaccharide. We conclude that release of potentially toxic phospholipids by parasites may be responsible for some of the pathology of malaria.

Animals

[Anatomo-morphologic aspects of the jaws as indications for osseointegrated implants in the partially edentulous].

Considering the great apogee reached in the last few years by the osseointegrated implants used in modern odontology it makes necessary to go deeper into the analysis of some anatomo-morphologic mandible aspects on partial edentates. Actually, these make the major percentage of patients who ask or are in effect candidates to rehabilitation by means of this technic. So it is described on individual analysis for each clinical case classified according to Kennedy's classification, giving emphasis to determination and real evaluation of height, thickness and form of partial edentates' mandibles. Furthermore, there are given some prosthetic models to be considered in the osseointegrated implant indications on partial edentates.

Alveolar Bone Loss

[Food consumption and the nutritional status of schoolchildren of the Community of Madrid (CAENPE): general methodology and overall food consumption. Consumo de alimentos y estado nutricional de la población escolar].

The CAENPE study (Food Consumption and Nutritional State of the School Population) was a transversal observational study funded and promoted by the Directorate-General of Food Hygiene in the Ministry of Health, implemented in 1991-93, with the main aim of quantifying food consumption in the school population (6-14 years of age) in the Regional Community of Madrid, together with an anthropometric study and nutritional analysis of that population. This project sets our the General Methodology for the study, paying particular attention to the sampling design, to ensure that the sample is representative of the community, and the results of the overall consumption of food and its comparison with recommended diet and other population studies. Quantification shows a high and rising consumption of meat, meat products, sweets, snacks and prepared dishes, suitable consumption of eggs, legumes and fruit and a notable lack of greens, vegetables and potatoes. The basic results underline the need to introduce educational measures with practical effect on home and school menus.

Adolescent