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Biomedical subjects

C Moreno

Publications and source records attributed to C Moreno.

At least 163 records · Page 9Linked to original sources

Murine T cell-stimulatory peptides from the 19-kDa antigen of Mycobacterium tuberculosis. Epitope-restricted homology with the 28-kDa protein of Mycobacterium leprae.

Fifteen overlapping synthetic peptides, spanning the entire amino acid sequence of the Mycobacterium tuberculosis 19-kDa protein, were used to identify epitopes recognized by murine T cells. Five of the 15 peptides tested were able to elicit in vitro lymph node T cell proliferative responses in C57BL/10 mice primed by footpad inoculation with homologous peptide. Analysis in congenic strains of mice revealed H-2 restriction in the response to four peptides. However, one peptide, 19.7 (residues 61 to 80), induced T cell responses in all four haplotypes tested. This peptide was also unique in being able to stimulate lymph node cells from C57BL/10 mice immunized with recombinant 19-kDa protein, killed M. tuberculosis, or live bacillus Calmette Guerin infection. T cell lines specific for peptide 19.7 were of the CD4 phenotype. Significantly, sequence analysis revealed that residues 61 to 80 of the 19-kDa protein exhibited considerable homology with a single 20-amino acid sequence (residues 120 to 140), but not with any other region of the 28-kDa protein expressed in Mycobacterium leprae. This finding is the first evidence of epitope-restricted homology between otherwise structurally unrelated microbial Ag.

Amino Acid Sequence↗

Identification of T cell stimulatory peptides from the 38-kDa protein of Mycobacterium tuberculosis.

T cell specificity to individual antigenic epitopes could determine the distinction between protective and pathogenic host reactions in tuberculous infections. Therefore, T cell stimulatory epitopes of the Mycobacterium tuberculosis 38-kDa lipoprotein, of known structure and specificity and of prominent immunogenicity, have been examined. To identify potential T cell epitopes, eight peptides, seven of which were predicted to form amphiphatic helices, were used for immunization of various inbred mice and for elicitation of in vitro T cell proliferative responses. Three different response patterns were observed. 1) Lymph node cells from mice immunized with peptide, recombinant 38-kDa Ag, killed M. tuberculosis strain H37Ra, or live Mycobacterium bovis bacillus Calmette Guerin infection responded to peptide 38.G (residues 350 to 369). Responses were observed in mice of H-2b, H-2d, and H-2k haplotypes. 2) Peptide 38.C (residues 201 to 220) induced proliferation of lymph node cells from 38-kDa protein-, but not from peptide-immunized mice. 3) Peptide 38.F (residues 285 to 304) only elicited a response of the homologous peptide-primed cells. Analysis of CD4+ T cell lines confirmed the distinct specificities and stimulatory features of peptides 38.F and 38.G. The described attributes of peptide 38.C and 38.G could be of potential interest for diagnostic evaluation in tuberculous infections.

Amino Acid Sequence↗

Immunogenicity in adult males of a Neisseria meningitidis group B vaccine composed of polysaccharide complexed with outer membrane proteins.

Twenty five adult male volunteers were given a vaccine composed of the capsular B polysaccharide non-covalently complexed to serotype 6 outer membrane proteins (OMP) of Neisseria meningitidis. Subjects were divided into three dose groups receiving 50, 100 or 150 micrograms vaccine in aluminium hydroxide in each of three injections spaced 4 weeks apart. Systemic signs/symptoms considered clinically significant were recorded on 6% (4/70) of occasions and were succeeded by withdrawal of two volunteers from the study. Local injection site reactions, mostly mild to moderate, were reported after all vaccinations with one such reaction leading to a third volunteer withdrawing from the study. Geometric mean anti-B responses before immunization and 1 week after the third immunization (9 weeks) were 3.60 and 7.12 micrograms ml-1 in the 50 micrograms group (p less than 0.05) 2.05 and 12.19 micrograms ml-1 in the 100 micrograms group (p less than 0.001), and 3.68 and 14.20 micrograms ml-1 in the 150 micrograms group (p less than 0.001). The anti-B response was predominantly of the IgM isotype and persistence above prevaccination levels was evident for at least 12 months. Anti-type 6 OMP responses were also evidenced with geometric mean multiplicative increases over prevaccination levels at 9 weeks and 6 months of 7.8 and 4.2 for the 50 micrograms group, 11.6 and 5.6 for the 100 micrograms group and 6.8 and 3.4 for the 150 micrograms group. The bulk of this response was of the IgG isotype. Passive protection of mice was achieved with both pre- and post-vaccination (9 weeks; 100 and 150 micrograms groups) pools of sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Scopolamine intoxication as a model of transient global amnesia.

In Colombia (South America) during recent decades the administration of scopolamine, extracted from plants belonging to the Datura or Brugmansia genus, has become an important neurologic and toxicologic phenomenon. These extracts have been popularly known as "Burundanga." Chemical characteristics and clinical features of scopolamine intoxication are described. Anterograde amnesia and submissive behavior found in patients intoxicated with scopolamine are analyzed. Burundanga intoxication is related to other toxic phenomena found in different countries and similitudes with transient global amnesia are emphasized.

Adult↗

Xenogeneic monoclonal antibodies in the management of cancer: control of their in vivo immunogenicity and induction of specific unresponsiveness using an antibody-drug immunoconjugate.

A bispecific mouse monoclonal antibody (mAb) that recognises carcinoembryonic antigen (CEA) with one binding site and vinblastine (VLB) with the other was used, and its in vivo immunosuppressive effect specific for anti-mouse immunoglobulin (Ig) was studied. The antibody was incubated with VLB at a molar ratio (MR) of 1:1, and administered i.v. to rabbits. Control animals received either the MAb alone, or the MAb with VLB covalently linked (MR 1:1), or the parental anti-CEA with equimolar amount of VLB. Seven days later, the rabbit anti-mouse Ig primary response was measured, and found to be almost 55% reduced in the animals that received the VLB 'loaded' MAb. In vivo kinetics and stability experiments revealed that the T1/2 of the MAb was 68 +/- 5 h, whereas free VLB disappeared within minutes. It was concluded that as soon as the drug dissociates from the antibody's binding site, it is rapidly removed. This problem was overcome by subcutaneously implanting osmotic mini-pumps containing VLB. The pumps released the drug at a constant rate for a period greater than 1 week, saturating the antibody's binding site. Under these conditions rabbits developed 80% less anti-mouse Ig antibodies when the bispecific antibody was administered (compared with the parental anti-CEA). The immunosuppression observed was specific for the mouse Ig, under conditions compatible with the full clinical therapeutic potential of the MAb. In conclusion, these experiments show, that it is possible to develop hybrid antibodies that can act as a 'lethal bait' to any specific lymphocyte in vivo, thus preventing undesirable responses against the xenogeneic MAb.

Animals↗

Humoral immunity in different phases of contact dermatitis.

Although cell-mediated hypersensitivity seems to be the main immunological response of man in contact dermatitis, recent studies suggest the potential involvement of antibody-mediated and basophilic cutaneous hypersensitivity in the physiopathology of this affection. The aim of this work was to contribute data intended to clarify the possible involvement of factors traditionally assigned to humoral hypersensitivity in the pathology of contact dermatitis. For this purpose blood levels of the different immunoglobulins were determined in patients with contact dermatitis. Three phases were considered, namely, one in which the patients showed typical clinical signs (acute phase), another in which the lesions had subsided (intercrisis phase) and a third in which the signs had recurred (acute outbreak). All those patients who concomitantly suffered from or had any personal or family antecedents of type I hypersensitivity were excluded from the study. The results found were compared with those obtained for a control gorup consisting of healthy individuals with no atopic antecedents. No significant differences were found between the results obtained in the three phases. However, the IgE levels of the patients were significantly higher than those of the control group, whereas the differences in the IgE, IgA and IgM levels were insignificant.

Acute Disease↗

Analysis of human T-cell epitopes in the 19,000 MW antigen of Mycobacterium tuberculosis: influence of HLA-DR.

The potential number of T-cell epitopes in the 19,000 molecular weight (MW) antigen has been investigated using overlapping peptides which comprise the complete sequence. Sixteen potential epitopes could be deduced from the responses to these peptides by polyclonal T cells derived from 22 antigen-responsive donors. The majority of epitopes were not predicted by either of the major paradigms, the Rothbard motif and the amphipathic helix. A hierarchy of epitopes was indicated by the responses, which ranged from strong and frequent in the N-terminal region, to moderate or weak elsewhere. Some epitopes were restricted by single HLA-DR determinants, or families of determinants sharing structural features in common, whilst the two N-terminal peptides were recognized by donors with a diversity of DR types. The high degree of T-cell recognition of the N-terminal region may be of relevance to the design of a sub-unit vaccine capable of priming T cells against Mycobacterium tuberculosis.

Amino Acid Sequence↗

[Detection of pneumococcal capsular polysaccharide antigen in urine by counterimmunoelectrophoresis. Technical features and correlation with serotype].

The effectiveness of CIE in detecting capsular polysaccharide antigen of pneumococci in urine is revised. Using CIE, we studied urine samples from 57 patients with systemic pneumococcal infections, proved bacteriologically by means of isolation of the microorganisms from sterile sites. We compare the usefulness of CIE with the microorganism isolation from organic products. We also determine the sensitivity gain after passive diffusion at 4 degrees C and bright blue Coomasie staining (CBB R-250). We correlate the CIE results with the serotype of isolated pneumococci. CIE was positive in 17 of all 35 pneumonia cases (48.6%), in 2 of all 5 bacteremias (40%), 4 of all 15 meningitis (26.7%) and in none of all two peritonitis. Direct urine examination was positive in 12 out of 23 patients with positive CIE (52.2%) and concentrated urine in 22 patients (95.6%). Passive diffusion at 4 degrees C and CBB R-250 stain increases the positive rate of the test. The correlation of serotype with our results is difficult due to the wide variety of serotypes identified. However, particular serotypes such (3, 4 or 8) had been identified with increased sensitivity. Global sensitivity of CIE in detecting capsular polysaccharide antigen in urine samples is not high enough (40.3%), even under the best circumstances. Antigen detection in urine is more sensitive than blood cultures, and therefore we believe that could be used in clinical microbiology laboratories until a more effective method is available.

Antigens, Bacterial↗

Spanish version of the Nottingham Health Profile: translation and preliminary validity.

We report the transfer into Spanish of a multi-dimensional measure of perceived health originally developed in Great Britain, the Nottingham Health Profile (NHP), and an assessment of the preliminary validity of the version is presented. Translation of the questionnaire was obtained from experts and from a Spanish monolingual lay group. Construct validity of the version was assessed in two studies: testing relationship of NHP scores to other self-reported measures of health in a general population survey; and comparing NHP scores for a group of frequent users and for a group of non-users of primary health services. Mean scores of NHP dimensions were higher for people with poorer self-reported health and higher for the frequent health services users than for the non-users. Findings suggest that the Spanish version of the NHP is culturally equivalent to the original questionnaire, and has a similar level of construct validity. Nevertheless, further research on reliability and on the weighting system is required to establish the equivalence of the Spanish version definitively.

Adult↗

Coexistence of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis.

To the best of our knowledge, only two patients with concurrent diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) have been reported so far. Here we present 3 patients in whom clinical and radiological findings indicative of DISH and AS coexisted. Two of these cases exhibited HLA B27. Although the presence of sacroiliitis would appear to exclude DISH, calcification and ossification of the anterior common vertebral ligament (ACVL) confirmed diagnosis of the latter disease.

Calcinosis↗

Passive transfer of meningococcal group B polysaccharide antibodies to the offspring of pregnant rabbits and their protective role against infection with Escherichia coli K1.

Pregnant rabbits vaccinated with meningococcal group B polysaccharide complexed to outer membrane proteins (serotype 6) responded to produce IgG, IgM and IgA anti-B polysaccharide antibodies, which were passively transferred to the offspring (IgG preferentially) and could be detected in their sera immediately after birth. These antibody levels were sustained in the mothers but diminished in the offspring to background levels at day 22 after birth. In a subsequent experiment, rabbits immunized with the group B vaccine had offspring that proved considerably more resistant to infection with Escherichia coli K1 than the control litters from non-immune mothers. Although not complete, protection was statistically of high significance and correlated well with the anti-B polysaccharide titres obtained in the mothers.

Animals↗

Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages.

We show here that purified lipoarabinomannan (LAM) from Mycobacterium tuberculosis can cause the release of tumour necrosis factor (TNF) in vitro from human blood monocytes and activated mouse peritoneal macrophages, and the production of TNF in vivo in mice pretreated with Propionibacterium acnes, with a potency comparable to that of lipopolysaccharide (LPS) from Gram negative bacteria. Like LPS, LAM binds to polymyxin B. We confirmed that its activity was distinct from any contaminating LPS and was associated with the antigenic activity by affinity chromatography, using a monoclonal antibody specific for LAM. Treatment with dilute alkali greatly diminished the TNF-inducing activity, suggesting that omicron-acyl groups may be involved. When LAM was fractionated by electrophoresis on SDS-Page and blotted on nitrocellulose, most TNF-inducing capacity coincided with the bulk of the LAM, as estimated by molecular weight and antigenic activity. This modification of the Western blotting technique may be generally useful for the study of macrophage-triggering molecules. The ability of LAM to cause the release of TNF may be responsible for some of the characteristics of tuberculosis, such as fever, weight loss, raised acute phase reactants and necrosis that can be mediated by this cytokine.

Animals↗

Nasal obstruction and human communication.

Nasal obstruction may cause a variety of communication disorders, particularly in children. The effects of nasal obstruction on hearing, speech, language, and voice are examined. Methods for assessing the effects of nasal obstruction are delineated, and recommendations for therapeutic interventions are described.

Airway Obstruction↗