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Biomedical subjects

D López

Publications and source records attributed to D López.

At least 73 records · Page 4Linked to original sources
PubMed1993

Clonal heterogeneity in LFA-3 and ICAM-1 requirement for lysis by alloreactive T lymphocytes.

HLA-B27-specific CTL are heterogeneous in their capacity to lyse murine P815 cells transfected with HLA-B27. Failure to kill murine transfectants could be caused by insufficient avidity of the human effector cells towards murine targets. Alternatively, it may imply alteration of allospecific T cell epitopes upon expression of HLA-B27 on mouse cells. To discern between these alternatives, P815 cells were co-transfected with HLA-B27, human ICAM-1, and LFA-3, and the transfectants were used as target cells with a series of HLA-B27-specific alloreactive CTL. Thirty-seven percent of the CTL tested significantly lysed HLA-B27(+)-P815 cells, without requiring simultaneous expression of human adhesion molecules. Twenty-one percent of the CTL showed significant lysis of only the murine transfectants expressing ICAM-1 or ICAM-1 + LFA-3. These CTL were shown by mAb-blocking analysis to have lower avidity than CTL from the previous group. In addition, they recognized HLA-B27 on murine cells not expressing human adhesion molecules, as assessed by cold target competition assays. As many as 42% of the CTL were unable to kill, or did so very inefficiently, P815 transfectants regardless of the presence of human ICAM-1 and LFA-3. With one detected exception, these CTL did not recognize HLA-B27 on murine cells in cold target competition assays. In contrast, they were able to recognize HLA-B27(+)-M1 fibroblast transfectant cells in direct cytotoxicity or cold target competition assays. Failure to kill murine transfectants by CTL from this group did not correlate with lower avidity, relative to CTL from the other groups, as shown by blocking experiments with mAb against human T cell adhesion molecules and their counter-receptors. These results indicate that lack of lysis of murine transfectants expressing class I HLA molecules by alloreactive CTL can be accounted for by low avidity of interspecies cell interactions in some cases but, more often, it is caused by alteration of allospecific T cell epitopes. Most likely, the basis for such alteration is allorecognition of HLA-B27-bound peptides that are expressed on human but not on mouse cells, mainly as a consequence of phylogenetic protein divergence between both species.

Animals↗
PubMed1993

[Physical punishment in children: opinions and behaviors of adults].

Five hundred twenty seven parents and tutors from three schools of Santiago were surveyed, using anonymous inquiry, to know behaviors and opinions towards child abuse. Sixty three percent of the sample judged physical punishment useless as an educational tool. However, 75% tacitly admitted to hit children, when they were asked a question about the ways they used to punish them. This question was answered by a significantly higher proportion of women. The principal reasons to use physical punishments were defying attitudes, lack of study and running away from home. The principal ways of physical punishment were hand blows (49%), lashes with belts (13%) and shaking (19%). The principal punitive restrictions were restrains from going out of home (70%) or watching television (46%) and not talking to children (14%). Sixty six percent of parents reminded physical punishments during their childhood. This background was associated with a higher frequency of actual battering. It is concluded that there is incoherence between real behavior and opinions towards child battering among parents and that the magnitude of this problem precludes its short term eradication.

Adult↗
PubMed1992

Role of binding pockets for amino-terminal peptide residues in HLA-B27 allorecognition.

The peptide binding site of HLA-B27 and other class I Ag consists of a series of pockets that bind peptide side chains. Two of these pockets interact with the amino-terminal peptide residue (pocket A) and with the highly conserved second residue (pocket B). In this study, the role of pockets A and B in HLA-B27-specific T cell allorecognition has been analyzed. Four HLA-B27 mutants with single or double changes in pocket B (24T----A, 45E----M, 67C----V, and 24,67T,C----A,V) and three mutants with single changes in pocket A (163E----T, 167W----S, and 171Y----H) were constructed by site-directed mutagenesis and expressed in HMy2.C1R cells after DNA-mediated gene transfer. These transfectants were used as target cells in cytotoxicity assays with a series of HLA-B27-specific CTL. All the mutations analyzed affected allorecognition by a significant proportion of the CTL tested, but no single change abrogated recognition by all CTL. The global effects of each mutation on allorecognition were comparable to one another, except for the effect of the change at position 67, which was smaller. The behavior of individual CTL with the mutants was very diverse, ranging from CTL that did not recognize most of the mutants to CTL recognizing all of them. Thus, some alloreactive CTL can withstand drastic alterations in pockets A and B. Two CTL showed heteroclytic effects towards the V67 and M45 mutants. CTL behavior with the H171 mutant was closely parallel to that with the B*2703 subtype, having a single Y----H change at position 59. This parallelism correlates with the similar role of Tyr59 and Tyr171 in establishing hydrogen bonds with the amino termini of HLA-B27-bound peptides. The results demonstrate that altering the structure of pockets that interact with the amino-terminal first and second residues of HLA-B27-bound peptides significantly affects recognition by alloreactive CTL, and they strongly suggest widespread peptide involvement in HLA-B27 allorecognition.

Epitopes↗
PubMed1992

Asymmetric selection of T cell antigen receptor alpha- and beta-chains in HLA-B27 alloreactivity.

Endogenous peptides constitutively bind to class I MHC Ag and are thought to be integral parts of allospecific T cell epitopes. However, allospecific TCR can recognize structural features of the alloantigen as foreign. To define some crucial parameters determining HLA-B27 allorecognition, the structure of TCR alpha- and beta-chains from HLA-B27-specific CTL was analyzed. A strategy, based on V alpha and V beta family-specific oligonucleotides, was used for specific amplification and direct sequencing of TCR-alpha and -beta cDNA. We observed nonrandom usage of V beta segments and recurrent structural motifs within beta-chain junctional regions. In contrast, no structural restrictions were apparent among alpha-chains, even from CTL clones of related fine specificity. These results indicate an asymmetric contribution of TCR alpha- and beta-chains to HLA-B27 allospecificity among the CTL clones analyzed. They suggest recognition of multiple peptides and involvement of beta-chain junctional regions in recognizing shared motifs among some of these peptides.

Amino Acid Sequence↗
PubMed1992

Peptide-presenting similarities among functionally distant HLA-B27 subtypes revealed by alloreactive T lymphocytes of unusual specificity.

Functional dissection of HLA-B27 subtypes using alloreactive or B27-restricted CTL has shown that the structurally related B*2704 and B*2706 are the most distant subtypes relative to the prototype B*2705. In particular, previous studies have failed to find anti-B*2705 CTL cross-reacting with B*2704 or B*2706. Such failure can be accounted for by the drastic effect on T cell recognition of the change at residue 152 in both subtypes relative to B*2705, as established with site-directed mutants. B*2704 and B*2706 are also related in ethnic distribution, as they are restricted to Orientals, jointly being the predominant HLA-B27 subtypes in this population. As far as it is known, there are no differences relative to B*2705 in their linkage to ankylosing spondylitis. In our study, 5 of 13 examined anti-B*2705 limiting dilution CTL lines from a particular HLA-B27- individual were shown to crossreact with B*2704, B*2706 or both. The monoclonal nature of this cross-reaction was established by cold target competition analysis. This result demonstrates that the apparent differences in T cell antigenicity among anti-B27 subtypes are strongly influenced by the responder individual, as the spectrum of clonal specificities in anti-B27 responses may show significant differences among unrelated responders. Fine specificity differences among the cross-reactive CTL allowed unambiguous functional distinction between B*2704 and B*2706. The molecular basis of such cross-reactivity was examined by correlating CTL reaction patterns with the structure of both subtypes, which differ only by two residues located in the beta-pleated sheet bottom of the peptide binding site, and with site-directed mutants mimicking HLA-B27 subtype polymorphism. The results suggest that: 1) distinct peptides are involved in the allospecific epitopes recognized by the various crossreactive CTL, and 2) B*2704, B*2706, and B*2705 differ in their peptide-presenting specificity, but can present some identical or structurally similar peptides.

Clone Cells↗
PubMed1992

Pulmonary capillary hemangiomatosis: report of a case and review of the literature.

We describe a case of pulmonary capillary hemangiomatosis in a 60-year-old woman with a 1-year history of progressive exertional dyspnea. Four years before admission a diagnosis of breast cancer was made, and she underwent mastectomy plus radiation therapy and treatment with oral antiestrogens. The chest X-ray showed bilateral interstitial infiltrates. Pulmonary function studies revealed a severe restrictive pattern. Abundant red blood cells were found in the bronchoalveolar lavage fluid. On the basis of open lung biopsy, interstitial fibrosis was diagnosed. Cardiac catheterization revealed pulmonary hypertension. Steroids were prescribed, but the patient's condition continued to deteriorate and she died approximately 3 years after presentation. The identification of proliferating and invasive capillaries, which are unique to pulmonary capillary hemangiomatosis, led to the correct diagnosis at autopsy.

Biopsy↗
PubMed1992

[Osteopenia in anorexia nervosa evaluated by dual photon-densitometry. Role of malnutrition and hypogonadism].

30 female patients with anorexia nervosa (AN) were studied and compared with 45 age-matched normal controls. All the patients had severe weight loss and nutritional involvement. Mean and SE body mass index, BMI (kg/m2) were 15.8 +/- 1.8 in anorectics compared to 21.7 +/- 4.7 in normals (p < 0.0001). All the patients presented amenorrhea lasting between 3 and 120 months (mean 24.8 +/- 25.3). A nutritional survey and a dual photon bone densitometry, including spine, hip, total body and total mineral content were performed. The mean values +/- SE in patients and controls were: spine densities (L2-L4) in g/cm2: AN 0.84 +/- 0.1, controls 1.03 +/- 0.1 (p < 0.002). Total mineral content (g): AN mean 1733 +/- 261, controls 2045 +/- 276 (p < 0.0001). In anorectic patients the correlations between bone density and BMI for spine were r: 0.52 (p = 0.002), for hip r: 0.37 (p = 0.04), and total mineral content vs BMI gave r: 0.64 (p = 0.0001). Mean calcium intake in 23 studied patients was lesser than the classic recommended dietary allowance in the whole group, it was less in the pure restricters as compared to vomiters. The relation between duration of amenorrhea and bone density showed than a decrease in the later was evident when the absence of menses was longer than 24 months. In conclusion, in patients with AN there is a real decrease in bone density which is strongly related to low weight and in lesser proportion to the duration of amenorrhea, particularly when it was longer than 24 month.

Absorptiometry, Photon↗
PubMed1992

[Alternatives for closure of the rectal "stump" in Hartmann's operation. A comparative experimental study which includes the resorbable mechanical suture (polysorb)].

Five different kinds of sutures which can be used for closure of the rectal stump in Hartmann's operation are evaluated in the same animal. They are compared at six different phases of the cicatrization process: 7-30-45-60-90 and 150 days. In the analysis, the degree of complete cicatrization is considered as well as the thickness of the cicatriced tissue, and other factors such as persistence of suture material and the result of it. All of the sutures involved accomplished the goal of a good joint of the planes of intestinal suture. Although, two of them, the metal stapler and Polyglactin (Vicryl) in extramucosal surgery fulfill almost in an ideal way the goals concerning security, rare reaction to suture material, and consequently less thickness in the cicatriced tissue (2 x 2 and 1 x 1 mm respectively) as well as complete cicatrization in ninety days. Stapler is performed quicker and in a more aseptic way, but the scar resulting from Polyglactin is smaller. In separate extramucosal points, silk produces a more important tissue reaction with a thicker scar (3 x 3 mm) coming to an end in 150 days. "Albert Lembert" type suture is really far away from being a good mean because it creates an important tissue reaction with a thick scar (3 x 3 mm), with late consolidation (150 days) and granulomatous reaction. Resorbable stapler--Polisorb--has a considerable volume and it causes an important tissue reaction which determines a very thick (4.5 x 4.5 mm) and "unfinished" scar within 150 days; really far away for practical use.

Absorption↗
PubMed1991

Conservation and alteration of HLA-B27-specific T cell epitopes on mouse cells. Implications for peptide-mediated alloreactivity.

Alloreactive CTL responses generate a great variety of clonal specificities. Such diversity may be related to recognition of multiple peptides constitutively bound to any given MHC alloantigen. Among human alloreactive CTL, only a fraction of the clones lyse mouse P815 cells expressing class I HLA proteins. In this study the fine specificity of HLA-B27 allorecognition on human or mouse cells by five human HLA-B27-specific CTL clones was comparatively analyzed. This was done to examine what degree of variation in epitope structure is compatible with recognition of HLA Ag on mouse cells. Nine site-specific HLA-B27 mutants were expressed on both human and mouse cells, after DNA-mediated gene transfer, to construct two analogous series of target cells. The reaction patterns of four of the five CTL clones with these cell panels were compatible with conservation of their corresponding epitopes upon expression of HLA-B27 on mouse cells. The reaction pattern of the fifth clone was different with either cell panel, indicating that its epitope was structurally altered on mouse cells. It also suggested a selectively increased expression of the determinant on these cells. The results suggest that most of the epitopes recognized by allospecific CTL clones reacting across species are either independent of any bound peptide or involve identical peptides from both cell types. However, some of these clones recognize alloantigen-bound peptides that are somewhat different in structure depending on the cell type, and may be expressed at the mouse cell surface in greater amounts. Such peptides could arise from related proteins in both species, and be polymorphic as a result of phylogenetic divergence.

Animals↗
PubMed1991

[Wegener's granulomatosis. Apropos of a new case and review of the literature].

A case of Wegener's granulomatosis (WG) is presented, high-lighting the long-term evolution of affliction of the upper airways without diagnosis, as well as the rapid evolution after detection of the rest of the compounds of the syndrome. We show the difficulties in making a differential diagnosis and the clinical improvement with immunosuppressor treatment.

Adult↗
PubMed1990

Structure and diversity of HLA-B27-specific T cell epitopes. Analysis with site-directed mutants mimicking HLA-B27 subtype polymorphism.

HLA-B27 subtype polymorphism is amenable to differential recognition by CTL. Site-directed mutagenesis was used to construct a series of HLA-B27 mutants reproducing most of the changes occurring in the natural subtypes. The reactivity of 21 anti-HLA-B27 CTL clones was examined with these mutants to address three issues concerning the alloreactive response against HLA-B27: 1) diversity of clonotypic specificities, 2) structural features of the epitopes recognized by these clones, and 3) role of individual positions in the differential recognition of HLA-B27 subtypes. Virtually all CTL clones displayed unique reaction patterns with the mutants, indicating a corresponding diversity of epitopes. However, these share some molecular features, such as certain amino acid residues and related locations. Individual mutations induced complex effects on multiple B27-specific CTL epitopes, revealing some of their very precise stereochemical constrains. An important feature of HLA-B27 subtype polymorphism is that every individual change was relevant, altering recognition by many CTL clones. Although the specific set affected by each mutation was partially different, the global number of clones affected by most changes was very similar. This suggests that the antigenic profile of any given subtype is not dominated by one particular change but is uniquely defined by its corresponding set of changes. An exception was the change at position 152, which totally abrogated recognition by all 20 anti-B*2705 CTL clones. This effect decisively influences the profound differences in T cell recognition between B*2705 and the two subtypes, B*2704 and B*2706, carrying this change. The results are compatible with the idea that HLA-B27 allorecognition may involve multiple peptides bound to the alloantigen on the cell surface.

Amino Acid Sequence↗
PubMed1990

T cell receptor V beta gene usage in a human alloreactive response. Shared structural features among HLA-B27-specific T cell clones.

A strategy, based on using V beta family-specific oligonucleotides, was developed for specific amplification and direct sequencing of human TCR V beta genes. With this strategy, it was possible to undertake a structural analysis of TCRs from human T cell clones in specific responses. 12 HLA-B27-specific cytotoxic clones were examined. The results reveal a nonrandom use of V beta gene diversity in this alloreactive response in that: (a) the clones express a restricted number of V beta segments, including a subset of V beta families that are significantly more related to one another than to most other V beta families; (b) five of seven clones having a particular reaction pattern with HLA-B27 subtypes possess Alanine at the D-J junction; and (c) identical J beta segments are found associated in several instances with identical or highly homologous V beta gene segments. In addition, two new V beta 13 members are reported.

Amino Acid Sequence↗
PubMed1990

Numerical analysis of electrophoretic periplasmic protein patterns, a possible marker system for epidemiologic studies.

The whole-cell and periplasmic protein (PP) compositions of 22 Serratia marcescens isolates were examined. Numerical analysis of whole-cell protein patterns was not a useful procedure for measuring relationships between organisms at the subspecific level. However, there was a very good correlation between electrophoretic PP pattern results and those obtained previously from multilocus enzyme electrophoresis (electrophoretic type) and biotype (D. Gargallo-Viola, J. Clin. Microbiol. 27:860-868, 1989). Clustering of isolates by using PP patterns compared by coefficients based on peak position (Dice coefficient) gave more precise information than that obtained by correlation coefficients. PP patterns appeared to be a useful tool that may be of value for epidemiologic studies.

Bacterial Proteins↗
PubMed1990

Structure and immune recognition of HLA-B27 antigens: implications for disease association.

HLA-B27 is strongly associated with susceptibility to ankylosing spondylitis and other spondyloarthropathies. Structural analysis of this antigen has revealed the existence of multiple variants, or subtypes, in human populations. The structural microheterogeneity of these subtypes deeply affects allospecific T cell recognition and most of it occurs at an spatial cluster within the peptide binding groove of the molecule. Many polymorphic residues whose combination is unique to HLA-B27 but is conserved among subtypes are clustered in a spatially separated site of the groove from that where most subtype polymorphism occurs. Site-directed mutagenesis and DNA-mediated gene transfer has been used to show that the positions that are polymorphic among subtypes are highly relevant for modulating T cell recognition, so that immunologically silent changes do not occur. These studies have also revealed an extremely high clonotypic diversity in the alloreactive response against HLA-B27. The structural basis for this diversity has been examined by sequencing the clonotypic T cell receptors. The analysis shows a certain bias in V beta gene segment usage, as well as other recurrent structural motives, among T cell receptor beta chains from HLA-B27-specific cytotoxic T cell clones.

Amino Acid Sequence↗