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Biomedical subjects

D López

Publications and source records attributed to D López.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation.

Cyclin D1 is part of the molecular system regulating the cell cycle G1 to S transition point. Its overexpression, a common finding in carcinomas of the breast, oesophagus, and head and neck, has also been demonstrated in a high percentage of non-small cell lung carcinomas (NSCLCs). The role of cyclin D1 in NSCLC has been studied by correlating its immunoreactivity with the Ki67 labelling index in paraffin-embedded, autoclaved surgical samples of 56 NSCLC cases. In addition, flow cytometric determination of ploidy and cell cycle status was carried out on 172 fresh tumour samples from the same cases. Twenty-four (42.8 per cent) NSCLCs showed positive cyclin D1 immunostaining, a finding which showed no relationship to ploidy pattern, cell cycle phase, histological subtype, or lymph node metastasis, but was significantly associated with the Ki67 labelling index (P = 0.03) and with poor cytoplasmic differentiation (P = 0.01). Cyclin D1-positive nuclei were abundant in poorly differentiated zones and absent in the best differentiated areas, particularly in heavily keratinized fields. These data indicate that in NSCLC, cyclin D1 overexpression is not only associated with a high cell proliferation rate, but also seems to play a role in the process of tumour differentiation.

Adult↗
PubMed1996

Expression of CD15 in normal and metaplastic Paneth cells of the digestive tract.

AIMS: To substantiate that incubation with monoclonal antibody CD15 (C3D-1) elicits a distinctive immunoreaction in normal small intestinal Paneth cells, normal and metaplastic Paneth cells along the digestive tract were assessed to determine whether they are also immunoreactive to CD15. METHODS: Paneth cells in paraffin wax embedded specimens of normal small intestine, appendix and proximal ascending colon, and from cases of chronic gastritis and ulcerative colitis were investigated immunohistochemically for lysozyme and CD15 antigen expression by means of the avidin-biotin peroxidase complex method. RESULTS: CD15 antibody reacted with a high proportion of both normal and metaplastic Paneth cells. Paneth cell immunoreactivity to CD15, however, was less intense and less extensive than to antilysozyme antibody, though the latter also stained many other cell types and was more commonly associated with nonspecific background staining. CONCLUSIONS: CD15 seems to be a valuable adjuvant for the study of Paneth cells in the normal and diseased digestive tract. Furthermore, as CD15 has been shown to be involved in activation of phagocytes, its expression in Paneth cells reinforces their proposed role as antimicrobial agents and regulators of the intestinal flora.

Appendix↗
PubMed1995

T cell receptor diversity in alloreactive responses against HLA-B27 (B*2705) is limited by multiple-level restrictions in both alpha and beta chains.

The T cell receptors (TCR) in HLA-B27 (B*2705) alloreactivity were analyzed in cytotoxic T lymphocytes (CTL) from two individuals. Non-random usage was found in V beta, N+D beta, V alpha, and J alpha, but not in J beta segments or N alpha-regions. V beta segments from homology subgroup 4 were predominant and not associated to a particular donor or fine specificity, suggesting involvement in recognizing the HLA-B27 molecule. In contrast, preferential V alpha usage was associated with particular individuals and fine specificities, indicating distinct V beta and V alpha recruitment and contribution to allorecognition. Recurrent N+D beta motifs and J alpha segments, even from different donors, limited junctional diversity, suggesting that CDR3 usage was determined by the alloantigenic epitope independently of individuals. TCR were selected differently at various levels, as indicated by the following findings. Four clonotypes with similar fine specificity had identical beta and unrelated alpha chains. Similar alpha were associated with unrelated beta chains, and vice versa. CTL using V beta subgroup 4 did not globally show concomitant predominance of other TCR elements. V alpha 7, one of the preferred V alpha segments, was always associated with V beta subgroups other than 4. Sometimes, a TCR showed homology in elements of one chain to a second TCR or group of TCR, and to another in the other chain. These results are best explained by differential selection of TCR elements by different epitopes, providing a key to the inner structure of allospecific TCR repertoires.

Antigen Presentation↗
PubMed1995

Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type.

Cluster of differentiation 44 (CD44) encompasses a polymorphic family of cell membrane glycoproteins involved in the mechanism of tumour invasion and metastasis. Since non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) display very different rates of progression, a significant discrepancy in their CD44 expression profiles is to be expected. An immunohistochemical study was undertaken on the expression of standard CD44 (CD44s) and the variant isoforms containing the domains encoded by variant exon 3 (CD44v3) or variant exon 6 (CD44v6) in paraffin-embedded bronchial biopsy specimens from 32 NSCLC cases and 11 SCLC cases. An absolute lack of immunoreactivity for CD44s, CD44v3, and CD44v6 was obtained in every case of SCLC, whereas 28 of the 32 NSCLC cases showed a positive immunoreaction for at least one of the three epitopes investigated. In conclusion, the occurrence of standard and variant CD44 isoforms in NSCLC and their absence in SCLC suggest the possibility that CD44 is in some way instrumental in conditioning the biological behaviour of NSCLC, but not of SCLC, whose metastatic cascade would be set in motion by the activation of hitherto unidentified, CD44-independent pathways.

Adult↗
PubMed1995

Role of CD44 in the invasiveness of glioblastoma multiforme and the noninvasiveness of meningioma: an immunohistochemistry study.

CD44 is a polymorphic family of cell adhesion molecules that seems to be instrumental in the mechanism of tumor invasion and metastasis. Tumor cell expression of CD44, or lack thereof, may be one of the factors conditioning the highly disparate ability to penetrate the brain extracellular matrix (ECM) exhibited by glioblastoma multiforme (GM) and conventional meningioma. To assess the presence of CD44 in these two tumor types we have immunohistochemically investigated the expression of CD44 standard form (CD44s) and the variant isoforms containing the domain encoded by variant exon 3 (CD44v3) and variant exon 6 (CD44v6) in paraffin-embedded tissue from 10 conventional meningiomas and 10 GMs. A CD44s-/CD44v-phenotype was discerned in the meningioma cases, whereas GMs featured a CD44s+/CD44v- expression profile. Consequently, the growth patterns of meningioma and GM seem to be, at least in part, a reflection of their CD44 expression status. Paucity of CD44 in meningioma cells would render them unable to infiltrate the brain ECM, whereas CD44-rich glioma cells would successfully migrate through it. Conversely, lack of CD44v expression would contribute to explain the lack of metastatic potential characterizing both conventional meningioma and GM.

Adult↗
PubMed1995

Parental attitude and practice regarding physical punishment of school children in Santiago de Chile.

Four hundred and twenty-three parents from two free, nonconfessional, public schools placed in medium and low income areas, and 104 parents from a private, for-pay Catholic school in a medium and high income zone filled out an anonymous self-applied survey to learn attitudes and practices regarding child physical punishment. In the for-pay school parents declared better education. Child battering was admitted by 80.4% (public schools) and 56.7% (private school) despite that 34.1% (public schools) and 51.9% (at the private school) declared that battering should never be used. Females admitted and justified physical punishment in higher proportions than males. Poor school performance, defiance, and running away from home were the preferred reasons to justify battering at public schools, while defiance was preferred at the private school where poor performance was sent to the fourth place. To check parents data and get children's opinions, 192 seventh and eighth grades students were surveyed in one public school (n = 84) and the private school (n = 98). At the public school, 85.7% of children, and 54.1% of the children at the private school admitted to having been physically punished, with no sex differences. Stronger rejections to this punishment were found at the private school. Mother (87 [5%] at the public school and 77 [4%] at the private) and father (36 [1%], and 67 [9%], respectively) were singled out as leading users of physical punishment. Physical punishment differences according to social environment were detected while eradication seems difficult given its cultural basis.

Attitude↗
PubMed1995

[Effectiveness of modified atmospheres against psychrotrophic pathogenic microorganisms in proteinaceous food].

Modified atmosphere packaging (MAP) of proteinaceous raw foods (meat, poultry and fish) extends their shelf-lives. It is well established that modified atmospheres (MA) inhibit the psychotropic aerobic Gram-negative bacteria, the main spoilage microflora of proteinaceous raw foods stored under refrigeration. Several researchers have warned about the possible growth of food poisoning microorganisms on them. Considering the minimal growth temperatures of pathogens, this review only deals with Aeromonas hydrophila, Clostridium botulinum, Listeria monocytogenes and Yersinia enterocolitica. C. botulinum produces its toxin in many different atmospheres, but it is unable to grow at temperatures below 3.3 degrees C, and its production rate of the toxin at temperatures below 4.5 degrees C is very low, to the extent that fish can be spoiled before the toxin is detected. Therefore, the control of the storage temperature of MAP fish seems to be indispensable to assure the absence of botulinal toxin. With regard to the other pathogens, vacuum is the atmosphere that may support more readily its growth; the higher the CO2 concentration in the atmosphere, the lower the growth rate is. Some investigations have shown that the growth rates of the psychotropic pathogens in MAP are lower than those of the spoilage flora. It has been shown also that A. hydrophila and L. monocytogenes growth rates are lower under MA than under aerobic storage. In relation to Y. enterocolitica, more investigations should be carried out in order to clear up its behaviour, because the available data in the literature are still confusing and sometimes even contradictory. In conclusion, there are no evidences that support the concern about MAP of proteinaceous raw foods representing a greater hazard than its conventional storage under air.

Cold Temperature↗
PubMed1995

[Program of hypertransfusion and chelation with desferrioxamine in 10 patients with thalassemia major].

PURPOSE: Thalassaemia maior is an inherited severe anaemia due to abnormal haemoglobin synthesis. Hypertransfusion therapy is based on the reduction of ineffective erythropoiesis and improvement of the anaemia. To prevent iron overload, continuous chelation therapy was performed with desferrioxamine (DFO). The efficacy of such management in 10 thalassaemia maior patients followed-up for 11 years has been evaluated. PATIENTS AND METHODS: Packed red-cell transfusions were administered to maintain haemoglobin rates over 100 g/L; 40 mg/Kg DFO was given five days a week subcutaneously. The mean age at the start of such treatment was 9.3 years. Clinical problems due to iron overload were evaluated, such as heart function, growth and development, endocrinopathies, along with DFO toxicity and complications of transfusion (positive indirect antiglobulin test (IAT), hepatitis, HIV infection). RESULTS: Two patients died of heart haemosiderosis. The mean ferritin values at the end of the study were around 3.031 mg/mL. Heart dysfunction was seen in 2 cases; 2 patients had retarded growth, decreased IGF-1 being found in both; 3 cases had hypogonadotropic hypogonadism, and 2 had clinical hypoparathyroidism. Bilateral opacification of the eye lens appeared in one patients as a consequence of prolonged DFO therapy. Positive IAT was found in 3 cases, and one patient developed positive hepatitis C serology. CONCLUSIONS: Control of iron deposits by iron chelators can prevent the damages of iron overload. Adequate accomplishment of programmes may be difficult, especially in children.

Adolescent↗
PubMed1994

Clonal analysis of alloreactive T cell responses against the closely related B*2705 and B*2703 subtypes. Implications for HLA-B27 association to spondyloarthropathy.

Alloreactive responses against closely related HLA-B27 subtypes were compared at the clonal level by fine specificity analysis of anti-B*2705 and anti-B*2703 CTL clones from unrelated HLA-B27- individuals with target cells expressing B*2701 to B*2706, and other HLA Ags. T cell epitope sharing between B*2705 and other subtypes was B*2705 > B*2703 > B*2702 > B*2701 > B*2704 > B*2706, and correlated with their amino acid differences. This suggests that identical or similar peptides, or peptide motifs, can be presented by multiple HLA-B27 subtypes to T cells, a feature that may be critical for the similar linkage of several subtypes to spondyloarthropathies. Other cross-reactions were predominantly with HLA-B61 and HLA-B60. Marked differences were observed in the nature and frequency of clonal reaction patterns among individuals. They correlated with structural features of the HLA-B Ags from each donor, suggesting that anti-HLA-B27 T cell responses are partially determined by the HLA-B phenotype of the responder. Ability to respond to particular HLA-B27-associated epitopes may determine differences in disease susceptibility among HLA-B27+ individuals. The anti-B*2703 and anti-B*2705 responses in the same individual were different. A major feature of anti-B*2703 CTL was that a large majority cross-reacted with B*2705. This can be explained by the effect of the single amino acid change in B*2703 on peptide binding and suggests that the B*2703-bound peptide repertoire is mainly a subset of that bound to B*2705, with few peptides being specifically presented by B*2703 to T cells.

Cross Reactions↗
PubMed1994

T cell allorecognition and endogenous HLA-B27-bound peptides in a cell line with defective HLA-B27-restricted antigen presentation.

The B*2702+ lymphoblastoid cell line NW is unable to present at least some HLA-B27-restricted viral antigens to T cells. This defect was genetically inherited, and was suggested to be related to the nature of the HLA-B27 binding peptides reaching the endoplasmic reticulum in these cells (Pazmany et al., J. Exp. Med. 1992. 175: 361). In the present study 17 of 19 HLA-B27-specific alloreactive cytotoxic T lymphocyte clones recognizing the B*2702 subtype on other cells also lysed NW cells. Only two cytotoxic T lymphocyte clones failed to lyse NW while efficiently killing other B*2702+ cell lines. The high-performance liquid chromatography profiles of the B*2702+ bound peptides extracted from NW cells was similar, but not identical, to those from two other cell lines. These results indicate that the HLA-B27-bound peptide repertoire in NW cells is not fundamentally different from those in other B*2702+ cells. Our data argue against gross differences in peptide processing or transport as being responsible for the defective presentation of particular HLA-B27-restricted viral antigens to T cells, but do not rule out distinct presentation of some endogenous peptides. Differences in the capacity to present certain peptides could cause differential susceptibility among HLA-B27+ individuals to ankylosing spondylitis.

Antibodies, Monoclonal↗
PubMed1994

Structure of HLA-B27-specific T cell epitopes. Antigen presentation in B*2703 is limited mostly to a subset of the antigenic determinants on B*2705.

The structure of HLA-B27-specific epitopes recognized by anti-B*2705 and anti-B*2703 cytotoxic T lymphocytes (CTL) from three unrelated donors was examined with site-specific mutants at various side-chain pockets in the antigen-binding site. The effect of any given mutation on allorecognition correlated strongly with its predictable effect on peptide binding. Acidic charges in the C/F pocket of HLA-B27, which binds C-terminal peptide residues, strongly modulated allorecognition. Anti-B*2705 CTL from different donors were differently affected by some mutations, indicating individual differences in the structure of epitopes recognized by alloreactive CTL from each donor. Most anti-B*2703 CTL recognized a subset of epitopes that were also present on B*2705, but differed from the bulk of allospecific epitopes on this subtype in their smaller dependence on pocket A structure, where the difference between these subtypes is located, and in their greater dependence on Glu45, in the B pocket. The structure of the very few epitopes on B*2703 not shared by B*2705 was quite different from that of the much more predominant cross-reactive epitopes. The results strongly suggest that B*2703 is antigenically defective as compared with B*2705 and that this is due to the fact that the repertoire of peptides presented by B*2703 consists mainly of a subset of the B*2705-bound peptides which do not critically require the canonic binding of the peptidic N-terminus to a B*2705-like A pocket, because they are sufficiently stabilized by other contacts through the peptide binding site.

Antigen-Presenting Cells↗
PubMed1994

Late recurrent metastasis in Wilms' tumour.

Recurrence of Wilms' tumour after 5 years of disease-free survival is rare. We present the case of a 26-year-old man who had been diagnosed of Wilms' tumour at the age of 6 years treated by surgery, chemotherapy, and radiotherapy and who remained disease free for 8 years, after which lung metastases were detected. Second complete remission was attained with surgery and chemotherapy and 20 years after initial diagnosis he again presented with lung metastases, similarly achieving complete remission with surgery and second-line chemotherapy. The clinical and biological aspects of late metastasis in this neoplasm are discussed.

Adult↗
PubMed1994

[Child physical punishment: opinions of the children from 2 schools].

To measure the proportion, reasons and frequency of battering and punishment, we surveyed seventh and eight grade children coming from a low and middle income area, state funded school (n = 84) and from a payed, private and catholic school (n = 98). Of children coming from the payed school, 67% lived with both parents and battering was more intensely rejected, compared to 85% of children coming from the state funded school. The most frequent type of punishments were admotions and restrictions; limb pulling and shaking at the payed school whereas hand and belt battering at the state funded school were the most frequent types of physical punishment. Eighty six percent of children coming from the state funded school and 54% coming from the payed school admitted having been battered. The mother was the leading user of battering for 87% of children at the state funded school and for 77% of children at the payed school; the figures for the father were 36 and 68% respectively. Lack of academical performance, defiance and running away from home were the principal justifications for punishment at the state funded school; defiance and sexual relations were so at the payed school. It is concluded that the frequency of battering is related to the social environment and that its eradication is difficult since 26% of children considered it as an acceptable rearing method.

Adolescent↗
PubMed1993

Cross-reactive T cell clones from unrelated individuals reveal similarities in peptide presentation between HLA-B27 and HLA-DR2.

HLA-B27- responder cells were stimulated in vitro with B*2705+ lymphoblastoid cell lines and alloreactive CTL clones were obtained by limiting dilution. Of the CD3+ CD4-CD8+ HLA-B27-specific CTL clones obtained, two of them, possessing the same TCR, cross-reacted with HLA-DR2. The fine specificity of these CTL was established with HLA-B27 and HLA-DR2 subtypes. They recognized the B*2701 to B*2706 subtypes, but only DR2Dw2. Lysis of DR2+ target cells was specifically inhibited by anti-CD3, anti-class II, and anti-DR mAb, but not with an anti-CD8 antibody. The monoclonal nature of the cross-reaction was established by the mutual inhibition of HLA-B27 and DR2Dw2 cells in cold target competition experiments. The DR2 protein involved in the cross-reaction was the heterodimer carrying the B5*0101 product, as shown by using L cell transfectants expressing each of the two molecules encoded in the DR2Dw2 haplotype. A correlation between the fine specificity of these CTL clones and the amino acid sequences of HLA-B27 and HLA-DR2 subtypes revealed a shared structural motif between HLA-B27 and the DR2 B5*0101 chain, which could be related to the observed cross-reaction. This motif was contributed for by several residues located in adjacent beta strands, at the floor of the peptide-binding site. The contribution of two of these residues, as well as other beta-pleated sheet residues to HLA-B27 allorecognition by the cross-reactive CTL clones was directly demonstrated with site-directed mutants. These results suggest that the dual reactivity pattern reflects presentation of identical or structurally related peptide by HLA-B27 and HLA-DR2Dw2. As T cell cross-reactivity between HLA-B27 and HLA-DR2 was previously found in cells from an unrelated individual the results reported here are likely to reflect an intrinsic property of HLA-B27, rather than the fortuitous finding of a rare clonal reaction pattern. We speculate on the potential implications of these results for the pathogeny of HLA-B27-associated spondyloarthropathies.

Amino Acid Sequence↗