[Pseudotumor cerebri caused by vitamin excess due to intake of milk enriched with A and D vitamins. Letter].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C Moreno
Publications and source records attributed to C Moreno.
[Disseminated Mycobacterium genavense infection in patients with HIV infection. Description of 5 cases and review of the literature].
BACKGROUND: Five cases of disseminated infection by Mycobacterium genavense in patients with HIV infection are reported with a review of the literature. MATERIAL AND METHODS: A description of the clinical, epidemiologic and therapeutic characteristics of five cases are presented. The initial isolation of the microorganism was performed in Bactec 13A from blood and bone marrow aspirates. Subcultures were made in different media and the growth characteristics evaluated. Sensitivity to NAP was determined by radiometric techniques and gas chromatography allowed a possible identification. Definitive identification was based on PCR amplification of the gene which codifies the 65kDa protein and the posterior restriction of the amplified fragments by using BstEII and HaeIII. RESULTS: All five patients were males with HIV infection and a lymphocyte count of less than 25 cells/mm3 with an non-specific clinical picture similar to that produced by M. avium complex (MAC). Empiric antiMAC treatment was administered in four of the patients with good clinical response. All five strains were sensitive to NAP. The greatest growth rate was obtained in the subcultures with acid pH in liquid medium. Gas chromatography was very similar to that of M. simiae. Amplification of the gene which codifies the 65 kDa protein and posterior restriction with BstEII resulted in 2 fragments of 325 and 125 bp, while restriction with HaeIII resulted in two fragments of 140 and 105 bp. CONCLUSIONS: Mycobacterium genavense represents 9% of the disseminated infections by mycobacteria in AIDS patients. The clinical manifestations, empiric treatment and response is similar to that of infection by M. avium complex. Growth is favored by acid pH in liquid medium. Susceptibility to NAP leads to possible identification which should be confirmed by molecular techniques.
AIDS-Related Opportunistic Infections↗
Electrochemical studies on nitrite reductase towards a biosensor.
A c-type hexaheme nitrite reductase (NiR) isolated from nitrate-grown cells of Desulfovibrio desulfuricans (Dd) ATCC 27774 catalyses the six-electron reduction of nitrite to ammonia. Previous electrochemical studies demonstrated that a simple electrocatalytic mechanism can be applied to this system (Moreno, C., Costa, C., Moura, I., LeGall, J., Liu, M. Y., Payne, W. J., Van Dijk, C. and Moura, J. J. G. (1992) Eur.J.Biochem. 212, 79-86). Its substrate specificity, availability and stability under ambient conditions makes this enzymatic system a promising candidate for use in a biosensor device. An electrochemical study of gel-immobilized Dd NiR on a glassy carbon electrode revealed both enzymatic activity and amperometric response to nitrite. In this study it was observed that the catalytic current density is a function of the nitrite concentration in solution and follows a characteristic Michaelis-Menten-type substrate dependence. Such a biosensor device (NiR-electrode) bears the option to be used for analytical determination of nitrite in complex media.
Biosensing Techniques↗
[The routine determination of HDL cholesterol].
Explore the source record for details and available documents.
Cardiovascular Diseases↗
Abundance of H-2 promiscuous T cells specific for mycobacterial determinants in H-2b/d F1 hybrid mice.
A majority of immunodominant epitopes of mycobacterial antigens are known to be recognized by murine T cells in the context of several H-2 haplotypes. In this study, we established the frequency of T cells able to recognize these peptides promiscuously, i.e. in the context of allogeneic antigen-presenting cells, using hybridomas from peptide-immunized H-2 homologous and heterologous mice. The degree of promiscuity in homozygous mice varied between 4-27% between different specificities and genetic backgrounds. In particular, the results showed that promiscuity between Ab and Ad in respect to a peptide from the Mycobacterium tuberculosis 38-kDa protein (residues 350-369) was displayed by 22% of BALB/c and 4% of C57BL/10-derived hybrids, but by 42% of [BALB/c x C57BL/10] F1-derived clones. This represents a significant increase (p < 0.001) of T cell promiscuity compared to the parental haplotypes. It is noteworthy that considerably lower peptide concentrations were able to stimulate the promiscuous hybridomas compared to the H-2-restricted hybrids. This finding suggests a functional advantage of promiscuous T cells which enables them to expand preferentially in the initial stages of infections with M. tuberculosis and thus enables the host to mount a rapid protective immune response.
Animals↗
Cross-recognition by T cells of an epitope shared by two unrelated mycobacterial antigens.
The molecular mimicry represented by cross-recognition of determinants shared by unrelated antigens by antibodies or T cells is of broad immunological interest. In this study, we analyzed the cross-recognition by CD4+ T cells of a peptide epitope shared by two mycobacterial proteins of diverse sequence, represented by the 19-kDa antigen of Mycobacterium tuberculosis and the 28-kDa antigen of Mycobacterium leprae. This epitope was immunodominant with respect to the 19-kDa antigen, but cryptic in relation to the 28-kDa antigen. The cross-reactive epitope cores were identified by Pepscan window analysis and found to be eight residues long in both antigens (residues 69-76 and 127-134). Alignment of these octameric sequences revealed two identical and five conservatively related amino acids. Within the epitope core, two residues (73Asn and 76Ile) were identified as critical for recognition on the basis of inhibition of the cross-reactive T cell proliferative response using singly substituted analog peptides. These results suggest that T cell cross-reactive epitopes can exist in proteins with apparently not more than random levels of sequence homology. Their potential for unsuspected cross-sensitization may play a role in the maintenance of T cell memory, in the pathogenesis of autoimmune diseases and possibly in a wide range of host immune responses to infectious pathogens.
Amino Acid Sequence↗
Sister-chromatid exchanges in cattle: breed, sex and BrdU dose effects.
The spontaneous incidence of sister-chromatid exchanges (SCE) was investigated in a group of cattle, composed of 21 animals of both sexes and from two different breeds (Fleckvieh and Pirenaica). Peripheral lymphocytes of these animals were cultured in three different bromodeoxyuridine (BrdU) concentrations: 5, 15 and 30 micrograms/ml. The work was carried out following a randomized block design. Among the analyzed sources of variability, group, breed and BrdU dose factors had significant effects on the SCE frequency. No differences between sexes were found. Comparisons of the BdrU doses showed that the 5 micrograms/ml dose differed from both the 15 and 30 micrograms/ml doses, whereas the 15 and 30 micrograms/ml doses did not differ from each other. The results indicate that the breed of cattle as well as the BrdU dose chosen for the analysis must be considered when the SCE test is used for the biomonitoring of environmental mutagens.
Analysis of Variance↗
The nature of the immunogen determines the specificity of antibodies and T cells to selected peptides of the 38 kDa mycobacterial antigen.
We report in this study that the nature of the injected immunogen or infection of mice can change the specificity of antibodies against different epitopes of the mycobacterial 38 kDa antigen. Following immunization with a selection of 14 peptides, only p65-83 and p285-304 resulted in antibodies binding to the whole antigen, whereas the recombinant antigen induced antibodies to p201-220 and p230-249, which are non-immunogenic following peptide immunization. Killed tubercle bacilli stimulated antibodies exclusively against the N-terminal 1-20 peptide, whilst infection with live tubercle bacilli led to antibodies recognizing non-continuous epitopes, demonstrable by binding to the 38 kDa protein, but to none of the tested peptides. The most striking finding is that protein immunization failed to induce antibodies to p65-83, although this epitope is immunodominant for T cells, irrespective of the mode of sensitization. Since this peptide contains non-overlapping B (69-75) and T (75-81) cell stimulatory cores, it appears that T help dedicated to the adjacent B epitope following peptide immunization may have shifted in favour of B cells reacting either with distantly located linear epitopes p1-20 and p201-220 following immunization with the whole protein, or to conformational epitopes following tuberculous infection of mice. The mechanisms which can deviate T help from one to another B cell specificity could involve regulation of antigen processing, liable to the nature of the immunogen. The described results suggesting distinct functional pairing between T and B epitopes, but with limited fidelity, may have general implications for the design of subunit vaccines.
Amino Acid Sequence↗
Changes in cancer mortality in Catalonia and Spain (1975-77 and 1987-89). A comparison with other European countries.
Comparisons of cancer mortality in Catalonia and Spain have shown an intermediate position of these areas in relation to the rest of Europe. This study compares the overall cancer mortality in Catalonia and Spain in the periods 1975-77 and 1987-89 in relation to other European countries selected on the basis of geographical proximity and availability of information. Adjusted and truncated cancer mortality rates and relative changes in these rates have been assessed for both sexes. The mortality rate for males in Catalonia, Spain, Italy, Portugal and France has increased from 1975-77 to 1987-89 with relative increments of 13.5%, 13.7%, 10.1%, 9.6% and 4.3% respectively, whereas in Switzerland and England and Wales this rate has decreased. The mortality rate for females showed a slight drop between the two periods in all the studied countries except England and Wales and Portugal. By age groups, in males, the 0-44 year interval in Catalonia, Spain, France and Portugal, in descending order, showed the highest rates. The marked contrast of the evolution of the cancer mortality rate in Catalonia, Spain, Italy, France and Portugal, compared with Switzerland and England and Wales, and especially the considerable increase of the mortality in young people in Catalonia, indicates the extremely urgent need for all countries to adopt the measures to control cancer that have already shown themselves to be effective elsewhere.
Adult↗
Defects in antigen-driven lymphocyte responses in common variable immunodeficiency (CVID) are due to a reduction in the number of antigen-specific CD4+ T cells.
T cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette-Guérin (BCG) was reduced to 1 in 109,000 T cells compared with 1 in 18,600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells.
Adult↗
Human T cell responses to peptide epitopes of the 16-kD antigen in tuberculosis.
The 16-kD protein constituent of the Mycobacterium tuberculosis complex has been known mainly for its prominent serological immunogenicity and species specificity in tuberculous infection. In this study, we evaluated the T cell immune repertoire in 27 sensitized healthy subjects and 46 patients with active tuberculosis using 14 overlapping 20mer peptides spanning the entire sequence of this protein. Four of the tested peptides individually stimulated proliferation of blood mononuclear cells from more than 50% of healthy controls. Tuberculosis patients reacted to a narrower peptide range and with a 17-27% lower rate of responses to the four most immunogenic peptides, but these differences do not distinguish in any simple way between the T cell repertoire of patients and sensitized healthy subjects. The most immunogenic peptide (91-110) was recognized by 67% of healthy subjects and by 50% of tuberculosis patients. Importantly, several non-responders to this peptide were stimulated with the other three most permissive peptides with sequences of 111-130, 71-91 and 21-40, resulting in an overall response rate to at least one of these four peptides of 93% in healthy controls and 74% in tuberculosis patients. In view of this additive effect between the most immunogenic peptides, their combined use may achieve sufficient sensitivity in a test aimed at the specific discrimination between infected and non-infected healthy subjects. The major interest in testing with these peptides rests in their species specificity, which is not achieved using purified protein derivative (PPD).
Amino Acid Sequence↗
Antigenic and structural similarities between Mycobacterium tuberculosis 50- to 55-kilodalton and Mycobacterium bovis BCG 45- to 47-kilodalton antigens.
The relationship between Mycobacterium tuberculosis 50- to 55-kDa protein and Mycobacterium bovis BCG 45- to 47-kDa antigen was examined by using immunological and biochemical criteria. Reciprocal cross-reactivity with a rabbit polyclonal antiserum against the M. bovis BCG protein and with a monoclonal antibody raised against the M. tuberculosis antigen was observed. The epitope recognized by this antibody was apparently present only in proteins of M. tuberculosis and M. bovis BCG among the 11 mycobacterial species tested. The amino-terminal sequences and total amino acid contents of these proteins showed strong similarities. Both antigens are glycoproteins as assessed by binding of concanavalin A, labeling of carbohydrate moieties with biotin-hydrazide, and digestion of carbohydrates with jack bean alpha-D-mannosidase, which produced a reduction of the molecular weights of the proteins and totally eliminated concanavalin A binding. Both M. tuberculosis and M. bovis BCG proteins are secreted, since they were found mainly in the culture medium. Analysis of M. tuberculosis 50- to 55-kDa antigen by two-dimensional gel electrophoresis showed at least seven different components, as previously described for the M. bovis BCG antigen. Solid-phase immunoassays showed that the purified M. tuberculosis 50- to 55-kDa protein was recognized by serum specimens from 70% of individuals with pulmonary tuberculosis from a total of 77 Mexican patients examined.
Amino Acid Sequence↗
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↗
Immunosuppression is not related to the response to steroids in acute liver rejection.
Explore the source record for details and available documents.
Acute Disease↗
[Demonstration of a cross contamination in the 460TB Bactec system by molecular typing of the strains with IS6110].
Explore the source record for details and available documents.
Adult↗
Permissive recognition of a mycobacterial T-cell epitope: localization of overlapping epitope core sequences recognized in association with multiple major histocompatibility complex class II I-A molecules.
Most T-cell epitopes are recognized in the context of a single or limited number of major histocompatibility complex (MHC) class II molecules. We have shown previously, however, that the immunodominant p61-80 epitope from the Mycobacterium tuberculosis 19,000 MW protein is recognized in a genetically permissive manner. In this study, permissive recognition of p61-80 was analysed in three murine MHC haplotypes (H-2b,d and k) with respect to: (i) T-cell-epitope core structure; (ii) I-A/I-E class II MHC restriction; and (iii) the identification of critical amino acid residues within the core region. Overlapping epitope core sequences composed of 6 to 8 amino acids were identified for each of the three H-2 haplotypes by T-cell epitope scanning (PEPSCAN) using peptide-specific T-cell lines. The epitope core sequences recognized by peptide and 19,000 MW protein-specific T cells were similar. In all three haplotypes, responses to p61-80 were restricted by class II MHC I-A molecules. To identify residues within the epitope core critically required for recognition, single substitution (alanine or leucine) analogue peptides were tested for their capacity to stimulate p61-80-specific T-cell hybridomas. A heterogeneous pattern of reactivity was observed, even among individual hybridomas derived from the same H-2 haplotype. Although every core residue could be defined as critical for at least one hybridoma, only one critical substitution (74Val-->Ala) was common to all hybridomas. The identification and structural analysis of genetically permissive epitopes of mycobacteria may be a useful strategy for the rational design of peptide-based vaccines for tuberculosis.
Amino Acid Sequence↗
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↗
Redox properties of Desulfovibrio gigas [Fe3S4] and [Fe4S4] ferredoxins and heterometal cubane-type clusters formed within the [Fe3S4] core. Square wave voltammetric studies.
The same polypeptide chain (58 amino acids, 6 cysteines) is used to build up two ferredoxins in Desulfovibrio gigas a sulfate reducing organism. Ferredoxin II (FdII) contains a single [Fe3S4] core and ferredoxin I (FdI) mainly a [Fe4S4] core. The [Fe3S4] core can readily be interconverted into a [Fe4S4] complex (J.J.G. Moura, I. Moura, T.A. Kent, J.D. Lipscomb, B.H. Huynh, J. LeGall, A.V. Xavier, and E. Munck, J. Biol. Chem. 257, 6259 (1982)). This interconversion process suggested that the [Fe3S4] core could be used as a synthetic precursor for the formation of heterometal clusters. Co, Zn, Cd, and Ni derivatives were produced (I. Moura, J.J.G. Moura, E. Munck, V. Papaephthymiou, and J. LeGall, J. Am. Chem. Soc. 108, 349 (1986), K. Sureurs, E. Munck, I. Moura, J.J.G. Moura, and J. LeGall, J. Am. Chem. Soc. 109, 3805 (1986), and A.L. Macedo, I. Moura, J.J.G. Moura, K. Surerus, and E. Munck, unpublished results). The redox properties of a series of heterometal clusters (MFe3S4] are assessed using direct electrochemistry (square wave voltammetry--SWV) promoted by Mg(II) at a glassy carbon electrode (derivatives: Cd (-495 mV), Fe (-420 mV), Ni (-360 mV), and Co (-245 mV) vs normal hydrogen electrode (NHE)). In parallel, the electrochemical behavior (cyclic voltammetry--CV, differential pulse voltammetry--DPV and SWV) of FdI and FdII were investigated as well as the cluster interconversion process. In addition to the +1/0 (3Fe cluster) and +2/+1 (4Fe cluster) redox transitions, a very negative redox step, at -690 mV, was detected for the 3Fe core, reminiscent of a postulated further 2e- reduction step, as proposed for D. africanus ferredoxin III by F.A. Armstrong, S.J. George, R. Cammack, E.C. Hatchikian, and A.J. Thomson, Biochem. J. 264, 265 (1989). The electrochemical redox potential values are compared with those determined by independent methods (namely by electron paramagnetic resonance (EPR) and visible spectroscopy).
Desulfovibrio↗