PubMed Health⌕ Search

Biomedical subjects

P Aparicio

Publications and source records attributed to P Aparicio.

At least 19 recordsLinked to original sources
PubMed1995

Primary midline developmental field. II. Clinical/epidemiological analysis of alteration of laterality (normal body symmetry and asymmetry).

Lubinsky [Am J Med Genet 3:23-28, 1987] has suggested that the properties of the midline involve early determinative informational processes and are related to the midline's position and definition of the body's plane of symmetry. Opitz [Am J Med Genet 21:175-176, 1985, BD: OAS XXIX(1):3-37 1993] has pointed out that the laterality sequences represent a midline developmental field complex. Thus, bilateral left-sidedness (with asplenia) and bilateral right-sidedness (with asplenia) have been considered laterality sequences or syndromes if cause is known. Using the malformed infants registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC), we performed a clinical/epidemiological analysis of the relationship between midline defects and alteration of normal body asymmetry and symmetry. The results support the assumption that both conditions could be consequence of disturbances in the midline primary developmental field.

Congenital Abnormalities↗
PubMed1995

Interleukin-7 rescues human activated T lymphocytes from apoptosis induced by glucocorticoesteroids and regulates bcl-2 and CD25 expression.

We studied the ability of several interleukins to inhibit the cellular death of IL-2-dependent human T cells deprived of IL-2 testing viability, DNA integrity, and expression of bcl-2 gene product. Our in vitro results showed that the addition of IL-7, and in a far less efficient manner IL-4, augmented the viability of IL-2-dependent T-cell clones of different origin, specificity, and phenotype. Furthermore, IL-7 reduced the percentage of apoptotic T cells inhibiting DNA fragmentation. In addition, IL-7 but not IL-4 was consistently able to suppress the cell death of IL-2-dependent T cells triggered by DEX, a synthetic GC. The suppression of T-cell death triggered by IL-7 was not affected by the addition of anti-IL-2 antibody. Interestingly, IL-7 inhibited the downregulation of bcl-2 gene product expression that appeared on TCCs after IL-2 withdrawal and also shared with IL-2 the ability to induce the upregulation of CD25 antigen on activated T lymphocytes in the presence of DEX. These experiments establish a novel role for IL-7 in regulating viability and GC-induced apoptosis on activated human T cells and suggest that the maintenance of bcl-2 levels is a general mechanism by which interleukins preserve activated T cells from undergoing apoptosis.

Apoptosis↗
PubMed1992

An epidemic methicillin-resistant strain of Staphylococcus aureus in Spain.

During 1990, a strain of methicillin-resistant Staphylococcus aureus became epidemic in Spain and spread in a manner analogous to that of EMRSA-1 in England. Isolates of this strain produced little protein A and were resistant to a number of antibiotics including ciprofloxacin. Beta-lactamase production was encoded by a c. 39 kb plasmid, which also conferred resistance to mercury, cadmium, ethidium bromide and propamidine isethionate. Investigation showed that two variants, separable by supplementary and Fisk phage typing, were circulating. The B variant appeared to spread more readily than the A variant. The opportunity was taken to compare the discriminatory power of traditional typing methods with molecular techniques. The discriminatory power of the molecular techniques used only reached the same level as the traditional methods when double enzyme digestion of total cellular DNA by EcoR I and Cla I was performed.

Bacterial Typing Techniques↗
PubMed1991

Functionally distinct subsets of human gamma/delta T cells.

To determine if effector subsets exist among human gamma/delta T cells, we examined the cytokine production and cytotoxic activity of gamma/delta T cell clones with different accessory molecule phenotypes, V delta and V gamma gene expression, and J gamma rearrangements. T cell clones bearing gamma/delta T cell receptor produce an array of cytokines like alpha/beta T cell clones. Individual gamma/delta T cell clones produced a characteristic array of cytokines without correlation with V delta or V gamma gene expression. However, when phenotypic subsets were considered, CD4+ gamma/delta clones produced significantly higher levels of interleukin 2 and granulocyte-monocyte colony-stimulating factor compared with CD4-CD8- and CD8+ gamma/delta clones. Similarly, when cytotoxic potential was assessed, CD4+ gamma/delta clones exhibited minimal activity when compared with CD4-CD8- and CD8+ adult peripheral blood gamma/delta clones. We conclude that functionally distinct gamma/delta T cell subsets exist and suggest that these subsets may correlate with expression of the CD4 accessory molecule.

Amino Acid Sequence↗
PubMed1990

Low IgG2 and polysaccharide response in a T cell receptor expression defect.

B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens.

B-Lymphocytes↗
PubMed1990

An experimental model of chronic osteomyelitis caused by Escherichia coli treated with cefotaxime.

An experimental model in Wistar rats, of osteomyelitis caused by Escherichia coli, was used to evaluate the efficacy of cefotaxime in two treatment regimens of different durations. Four groups of rats were set up: a group of rats receiving short-term treatment (14 days) with subcutaneous cefotaxime (100 mg bd), killed after 56 days; a control group receiving no treatment, killed after 56 days; a group of rats undergoing long-term treatment (28 days) with subcutaneous cefotaxime as above, killed after 70 days and a control group of rats receiving no treatment, killed after 70 days. Analysis of histopathological and microbiological findings revealed significantly better results in the long-term treatment group. No side-effects were observed during treatment or afterwards.

Animals↗
PubMed1990

Cefotaxime in the treatment of chronic osteomyelitis caused by gram-negative bacilli.

Fifty patients with chronic osteomyelitis due to aerobic or facultative Gram-negative bacilli, alone or in mixed infections with Gram-positive cocci, were treated with cefotaxime. The diagnosis of osteomyelitis was made on the basis of clinical, roentgenographical, isotopic, microbiological and histopathological evidence of infection. Only those patients with infection sensitive to cefotaxime were treated. Most patients received 2 g cefotaxime qid iv for 30-60 days (mean 40 days). Some patients received metronidazole in addition. The following results were obtained at the six month follow-up: 40 patients cured, six improved, no failures and four relapses. The surgical technique had an impact on these results. No clinically important side-effects were encountered, nor were any cefotaxime resistant strains found.

Adolescent↗
PubMed1990

[Influence of bacterial combinations on the post-antibiotic effect].

A study of the post-antibiotic effect (PAE) and letality curves of different concentrations of clavulanic acid, amoxycillin, amoxycillin + clavulanic acid, netilmycin and ofloxacin on mixed cultures of S. aureus and E. coli. The post-antibiotic effect was measured after one hour of exposure of bacteria to antimicrobial and the elimination of the latter by the dilution method. Amoxycillin did not induce PAE on the association. PAE only appeared at high concentrations on S. aureus when evaluated alone. Clavulanic acid induced a greater PAE than amoxycillin. The association clavulanic acid + amoxycillin was synergistic and induced a greater PAE than its components. Netilmycin and ofloxacin were the drugs that induced the greatest PAE on the bacterial association and on its strains independently evaluated.

Amoxicillin↗
PubMed1989

Isolation and characterization of (gamma, delta) CD4+ T cell clones derived from human fetal liver cells.

Lymphocytes isolated from human fetal liver and expanded in vitro in IL-2-containing media reveal the existence of CD4+ gamma, delta T cells. These cells display differential features of double-negative and CD8+ gamma, delta T cells as well as of CD4+ alpha, beta T cells. Thus, they failed to lyse targets in lectin-mediated killing assays and to perform classical helper functions. These results add new information necessary for a better understanding of the physiological role of the gamma, delta T cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

CD8 is involved in both class I- and class II-induced proliferation of a cytolytic T-cell clone with dual specificity for HLA-B27 and HLA-DR2 antigens.

A CD3+ CD4- CD8+ cytolytic T-lymphocyte (CTL) clone, CTL 47, could be induced to proliferate in the presence of exogenous interleukin 2 by either HLA-B27.1+ or HLA-DR2+ cells. B27.1-induced proliferation was strongly and equally inhibited by an anti-B27 and by an anti-CD8 monoclonal antibody (MoAb). DR2-induced proliferation was inhibited by the same anti-CD8 MoAb less efficiently and with a different time course than anti-class II blocking, only being significant when the antibody was added ab initio or very early during the assay. These results indicate that CD8 is essential for class I-induced proliferation but that it also enhances class II-induced stimulation of this CTL clone. It is proposed that the necessary role of CD8 in class I-induced proliferation is related to its interaction with the same class I molecule bound by the T-cell receptor. The accessory role in class II-induced proliferation would be due to an additive effect on the avidity of cell adhesion, resulting from interaction of CD8 with the class I antigens on the stimulator cell, or perhaps to a regulatory role of CD8 as a transducer of early signals for T-cell activation.

Antibodies, Monoclonal↗
PubMed1988

Avidity dictates the lytic capacity of human cytolytic T lymphocyte clones with similar fine specificity against murine cells expressing HLA-B27 antigen.

The role of the avidity of human CTL in the recognition and lysis of murine P815 cells expressing HLA-B27.1 Ag has been examined. Seven B27-specific alloreactive CTL clones were tested for their ability to lyse a B27.1+-P815 transfectant clone 1-7E, obtained after cotransfection of P815-HTR cells with HLA-B27.1 and human beta 2-microglobulin genes. The expression level of HLA-B27.1 on 1-7E cells was comparable to that on a human lymphoblastoid cell line, as determined by flow cytometry. Of the seven CTL clones used, CTL 1, 26, and 29 displayed the same fine specificity as established with a panel of target cells expressing six structurally different HLA-B27 variants. However, CTL 1 and 29 were of higher avidity than CTL 26, in that the lysis of human target cells by only this latter clone was inhibited by an anti-CD8 mAb. Based on the same criteria, CTL 2, 15, and 48 possessed the same or very similar fine specificity, but CTL 48 was of higher avidity than CTL 2 or 15. The seventh clone, CTL 40, was of a different fine specificity and its lysis of human target cells was also inhibited by the same anti-CD8 mAb. Only those clones whose lysis of human targets could not be inhibited by anti-CD8 antibody were able to lyse the 1-7E murine transfectants. These results indicate that, for human CTL clones with identical or very similar fine specificity, only those of higher avidity are able to lyse P815 murine cells expressing the HLA-B27 antigen. The lysis of HLA-B27.1+-murine transfectants by relevant clones was inhibited by anti-CD8 antibody. This result strongly suggests that the relative contribution of CD8 in stabilizing the interaction between human CTL and HLA-B27+-murine target cells is more significant than with human target cells.

Animals↗
PubMed1988

Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites.

The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues.

Antibodies, Monoclonal↗
PubMed1988

Modulation on immunogenicity by HLA-B27 subtype polymorphism.

Cells from the same HLA-B27- individual, PA, were stimulated in vitro in primary mixed lymphocyte culture, with either B*2705+ or B*2704+ lymphoblastoid cell lines, in independent experiments. Cytolytic T lymphocytes (CTL) were cloned at limiting dilution and the clones obtained were screened for anti-B27 alloreactivity. Most of the CTL clones generated against the B*2705+ stimulator cells were directed against the B*2705 antigen. In contrast, no anti-B27 CTL clones were found among those derived against the B*2704+ stimulator cells. This was not due to a poor cytotoxic response against these cells because a large proportion of the T cell clones derived from this stimulation were cytotoxic. B2704 differs from B*2705 by only two amino acid changes at positions 77 and 152. Previous studies (Aparacio, P. et al., Eur. J. Immunol. 1988.18: 203) have shown that none of the anti-B*2705 CTL clones derived from donor PA and amenable to detailed characterization cross-reacted with B*2704, suggesting that most of this cytotoxic response was directed against an immunodominant determinant contributed for by residues 77 and/or 152 from B*2705. The present results further suggest that the changes at these positions in B*2704 alter this determinant in such a way that B*2704 becomes less immunogenic for the particular individual PA. Furthermore, a similar poor anti-B*2704 CTL response was obtained from a second B27- responder individual, AE, stimulated with another B2704+ cell line. The single anti-B*2704 CTL clone, 64.8P, isolated from this second individual, displayed an unusual reaction pattern in that it cross-reacted with all B27 subtypes with changes only at or close to positions 77 and 152, including B*2705. Significantly, the only HLA-B27 subtype that was not recognized by CTL 64.8P was B*2703, which differs from B*2705 only at residue 59. This residue is located in the three-dimensional structure at the opposite end from residues 77 and 152 at the surface of the antigen-binding groove of the class I molecule. Thus, the area around residues 77 and 152 is not an essential part of the epitope recognized by CTL 64.8P.

Antibodies, Monoclonal↗