S-adenosyl-L-methionine and the liver.
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Animals↗
Biomedical subjects
J Moreno
Publications and source records attributed to J Moreno.
Optimal meshes for integrals in real- and reciprocal-space unit cells.
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Journal Article↗
Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules.
Exon-shuffled constructs between mouse (IA beta b) and human (DR3 beta) class II beta chains were made to study the interaction sites between CD4 and major histocompatibility complex (MHC) class II molecules, and to determine whether a species barrier is involved. The overall structure and the peptide binding groove appeared to be unaffected by the exon shuffling procedure as determined by monoclonal antibody and peptide binding assays, respectively. While purified CD4+ BALB/c T cells responded strongly in a mixed leukocyte reaction to transfectants expressing the whole IA molecule, the response to IA molecules containing a DR beta 2 domain was substantially reduced. In addition, the presence of an IA beta 2 domain in DR failed to restore the weak xenoreactivity to the whole DR molecule. Similar observations were made with murine HEL-specific, IA alpha k beta b-restricted T cell hybridomas which responded significantly stronger to the whole compared with the exon-shuffled IA molecules. The involvement of CD4 in these differential responses was confirmed by the observation that CD4 loss variants responded to both molecules comparably, and transfection of CD4 into these cells restored the parental phenotype. In contrast, CD4 loss variants transfected with human CD4 responded equally to both the whole and the exon-shuffled molecules. Taken together, these data imply the existence of a partial species barrier, and suggest that CD4 interacts with the beta 2 domain of MHC class II molecules, probably in addition to other contact sites. Models for the interaction of CD4 with MHC class II molecules are presented.
Binding Sites↗
Does CD4 help to maintain the fidelity of T cell receptor specificity?
During antigen presentation, a close association between CD4 and the T cell receptor (TCR) occurs as a result of interacting with the same major histocompatibility complex class II molecule. The potential consequences of such an intimate interaction on TCR specificity was addressed using CD4 loss variants of four different murine T cell hybridomas specific for the immunodominant hen egg lysozyme (HEL) peptide 46-61. While all the CD4+ and CD4- variants tested possessed comparable surface expression of TCR, CD3, CD2 and LFA-1, and responded similarly to immobilized anti-TCR and anti-CD3 monoclonal antibodies, they differed dramatically in their responses to either the naturally processed HEL antigen, synthetic peptide 46-61 or staphylococcal enterotoxin superantigens. While one hybridoma was comparatively unaffected by the loss of CD4, another lost its responsiveness to antigen and peptide completely while retaining reactivity to SE. In contrast, two other hybridomas still responded to antigen but lost reactivity to synthetic peptide and SE. These data could not be readily explained on the basis of affinity or signal transduction requirements alone, and thus suggest that the intimate association of CD4 with the TCR may result in a subtle modulation of its fine specificity for some but not all T cells.
Animals↗
Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease.
Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohn's disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohn's disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohn's disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohn's disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease.
Adolescent↗
Invasive aspergillosis in a patient with idiopathic thrombocytopenic purpura without underlying lung disease.
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Aspergillosis↗
[Polyps of the colon and the rectum].
This is a retrospective study en 189 cases of colorectal polyps, from 1985-1989 including medical record review, pathologic diagnosis and surgical management. The main symptom was rectal bleeding. The follow up period and it's relation to colorectal cancer was evaluated, considering this entity as a premalignant lesion. 189 histopathology slides were reclassified according to the actual classification. Males were predominant (69%), with increasing incidence from the fifth decade (62% of the total); a 2% malignization rate was found.
Adolescent↗
Beta-endorphin inhibits interleukin-2 release and expression of interleukin-2 receptors in concanavalin A-stimulated splenic lymphocytes.
beta-endorphin, when added at the same time as the mitogenic lectin concanavalin A to mouse BALB/c spleen lymphocytes, inhibits cell proliferation. The suppressive effect of beta-endorphin is not exercised through a cAMP-dependent mechanism and is also observed when splenic lymphocytes are stimulated with phytohemagglutinin (4 micrograms/ml), anti-CD3 monoclonal antibody, or the Ca2+ ionophore A23187 (250 nM) and phorbol 12-myristate 13-acetate (1 ng/ml). The inhibitory effect of beta-endorphin on lymphocyte proliferation is dose and time dependent: when beta-endorphin is added 20 h after Con A stimulation no suppression of lymphocyte proliferation is observed. beta-Endorphin inhibits, in a dose-dependent manner, the release of interleukin-2 in concanavalin A-stimulated splenic lymphocytes, measured 24 h after stimulation. beta-Endorphin also controls the appearance of interleukin-2 receptors in the plasma membrane, but does not regulate the expression of the c-myc protooncogene. These data indicate that beta-endorphin inhibits lymphocyte activation signal transmission, downstream the generation of the second messengers Ca2+ and diacylglycerol and the expression of the protooncogene c-myc, by blocking interleukin-2 release and interleukin-2 receptors expression. Once the cells are in the G1 stage, beta-endorphin is no longer able to block lymphocyte proliferation.
Animals↗
Method for determining high-Mr (biliary) alkaline phosphatase in plasma.
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Alkaline Phosphatase↗
[Cor triatriatum in the adult. Its diagnosis by Doppler echocardiography].
We present an adult with echocardiographic diagnosis of cor triatriatum. Continuous wave Doppler echocardiography was able to assess correctly the severity of the left ventricular inflow obstruction caused by the intra-atrial membrane. Even though the diagnosis was confirmed by catheterization, the surgical decision was based in noninvasive data. Postoperative Doppler echocardiography proved the disappearance of the intra-atrial obstruction. The anatomical information obtained by echocardiography as well as the assessment of the intra-atrial obstruction by cardiac Doppler seem to be sufficient to make surgical decisions in patients suffering from this disease. Both are also suitable to test the result of the surgical intervention.
Adult↗
Processing of an endogenous protein can generate MHC class II-restricted T cell determinants distinct from those derived from exogenous antigen.
Class II MHC molecules on the surface of an APC present immunogenic peptides derived mainly from exogenous proteins to CD4+ T cells. During its transport to the cell surface, class II molecules intersect the endocytic pathway where they acquire peptides derived from endocytosed proteins. However, class II-restricted presentation of endogenously derived peptides can also occur. The current studies were undertaken to examine the ability of different types of APC to generate and present four different T cell determinants derived from an endogenous, nonsecreted, truncated form of hen-egg white lysozyme (HEL[1-80]-Kk). This was compared with the ability of these APC to generate the same determinants from exogenous HEL. All the peptides derived from endogenous HEL[1-80]-Kk tested, were presented by B cells to HEL-specific T cell hybridomas with an efficiency similar to presentation of the same determinants from exogenous HEL. In contrast, an I-Ak-bearing rat fibroblast was unable to generate the HEL peptide 25-43 from exogenous HEL, but could efficiently produce it from endogenous HEL[1-80]-Kk. The results indicate first, that peptides derived from an endogenous Ag can be presented by MHC class II molecules with an efficiency comparable to that of the presentation of the exogenous Ag. Second, that Ag-presenting B cells can generate the same repertoire of antigenic peptides from endogenous Ag as those generated from the exogenous protein. And third, that in contrast to B cells, certain "nonprofessional" APC can generate, from an endogenous protein, T cell determinants distinct from those generated after endocytosis of the exogenous protein. These results suggest that processing of exogenous and endogenous Ag by different APC take place in different intracellular compartments.
Animals↗
Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells.
Antigen-presenting cells (APC) transfected with a construct encoding the hen egg-white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II-restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade.
Actins↗
Combined therapy with recombinant granulocyte colony-stimulating factor and erythropoietin decreases hematologic toxicity from zidovudine.
Twenty-two patients with acquired immunodeficiency syndrome (AIDS) or severe AIDS-related complex and multilineage hematopoietic defects were treated with recombinant granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) in a phase I/II trial. All patients were neutropenic and anemic after withdrawal of all bone marrow-suppressive drugs. Daily, G-CSF was subcutaneously self-administered until an absolute neutrophil count (ANC) greater than 6,000/microL was achieved and maintained for 2 weeks. Subcutaneous EPO was added to the regimen and the dose increased until an increase of 15 g/L of hemoglobin was observed. Groups of patients were administered increasing doses of zidovudine to determine their tolerance. G-CSF and EPO therapy was continued with dose modification to maintain an ANC greater than 1,500/microL and hemoglobin greater than 100 g/L. The dose of zidovudine was not altered. All 22 patients responded to G-CSF with a mean 10-fold increase in neutrophils occurring in less than 2 weeks. Significant increases in CD4 and CD8 cell number, lymphocyte proliferative response, and bone marrow cellularity were seen. EPO therapy increased hemoglobin in all 20 evaluable patients within 8 weeks. Sixteen patients received 1,000 mg and four patients received 1,500 mg of zidovudine per day. The reinstitution of zidovudine resulted in a decline in reticulocytes and hemoglobin and the reappearance of transfusion requirements in eight of the 20 patients, six of whom had the study medications stopped. No patient had the study medications stopped because of neutropenia or thrombocytopenia. Toxicities were mild and did not require dose modifications. Limiting dilution plasma and lymphocyte co-cultures for HIV as well as serum p24 antigen levels did not change significantly during G-CSF or combined G-CSF and EPO therapy. HIV p24 antigen decreased significantly with zidovudine therapy. Opportunistic infections occurred in 14 patients but were successfully treated with myelosuppressive antimicrobial agents, including ganciclovir, without the development of neutropenia. These results suggest that combined therapy with G-CSF and EPO may improve the neutropenia and anemia of AIDS. Combined therapy may allow the resumption of full-dose zidovudine in most patients intolerant of the hematologic effects of zidovudine without apparent alteration of HIV expression or the efficacy of zidovudine.
Acquired Immunodeficiency Syndrome↗
Antigen presentation of hen egg-white lysozyme but not of ribonuclease A is augmented by the major histocompatibility complex class II-associated invariant chain.
The influence of the class II-associated invariant chain (Ii) on the presentation of the protein antigens hen egg-white lysozyme (HEL) and ribonuclease A (RNase) was investigated. For this purpose the Ii- rat-2 fibroblasts were transfected with I-Ak genes with or without Ii. Transfectants expressing Ii were superior in the presentation of the complete HEL protein to a panel of I-Ak-restricted T hybridomas characterized by distinct specificities for different HEL peptides and by different sensitivities to antigen concentration. There appeared to be a correlation between the antigen-presenting capacity and the amount of Ii, in that transfectants expressing large amounts of Ii were the best antigen presentors. The presentation of synthetic HEL peptides was not influenced by Ii. In contrast to the findings with HEL, the presentation of RNase by the same set of transfectants was clearly independent of Ii. Both antigens, HEL and RNase, required processing in the chloroquine-sensitive compartment. However, only the presentation of HEL but not of RNase could be efficiently blocked by brefeldin A. These data confirm that presentation of HEL depends on de novo synthesized class II molecules, whereas the presentation of RNase seems to be predominantly mediated by a pool of pre-existing class II molecules whose interaction with endocytosed antigen does not depend on Ii. These results suggest different mechanisms for the presentation of HEL and RNase and they raise the possibility that different antigens intersect the class II pathway at distinct intracellular locations.
Animals↗
A comparative in vitro study of transdermal absorption of a series of calcium channel antagonists.
The in vitro transdermal absorption of five calcium channel antagonists (nifedipine, nitrendipine, nicardipine, felodipine, and nimodipine) was studied using the skin of hairless rats as a membrane. The aim of this study was to determine the penetration parameters [permeability constant (Kp), lag time (T1, and flux (J)] as measures of the intrinsic transdermal permeabilities of these drugs, in order to predict the potential capacity of these drugs to be formulated in a therapeutical transdermal system (TTS). Reliable prediction of Kp values, using K'w (extrapolated capacity factor in 100% water) and P (n-octanol-water partition coefficient) values as independent variables in the parabolic, bilinear, and hyperbolic functions, were assayed. Nicardipine showed a higher mean transdermal penetration (Kp; 4.9 x 10(-3) cm.h-1) value than the other dihydropyridines. Nifedipine showed the shortest mean T1 value (5.1 h). The permeability rate constants of the calcium channel antagonists assayed can be predicted from their n-octanol-water partition coefficients, using the parabolic function (r = 0.984, p less than 0.01). Nicardipine would be the most suitable candidate for formulation in a TTS design.
Administration, Cutaneous↗
Protection and enhancement of ribulose 1,5 bisphosphate carboxylase activity by exogenous proteins.
When assayed in vitro, the activity of the photosynthetic enzyme ribulose 1,5 bisphosphate carboxylase oxygenase is both enhanced and protected from spontaneous decay by exogenous proteins such as hemoglobin, serum albumin, and aldolase. Other proteins and amino acids tested are either ineffective (lysozyme, ferritin, lysine, and cysteine) or afford only partial protection (catalase, glycine, and phenylalanine). Protective proteins do not bind to, or exchange disulfides with, ribulose 1.5 bisphosphate carboxylase/oxygenase. Since their effect can be mimicked by reductively treated detergents such as Triton X-100, it appears that proteins protect from decay by quenching the spontaneous oxidative degradation and inhibiting surface adsorption which could lead to enzyme unfolding. Release of adsorbed molecules from the container surface is likely to be the cause of carboxylase activity enhancement.
Detergents↗
[The satisfaction of the primary care consumer: a comparison between distinct models of care].
The results of a questionnaire about satisfaction in the users of an urban health area of the city of Alicante, where the traditional model of primary care (the clinic, C), the new model (the health center, HC) and private practice (P) coexist are reported. The questionnaires were administered by staff unrelated with the health center. In general, satisfaction was significantly greater (p = 0.001) in users of HC and P than in C users. no significant difference was found between HC and P. The specific satisfaction was also greater (p less than 0.05) for all services in HC than in C: General practice (GP), nursing care (N), pediatrics (PED), and administration-information (ADMON). The general satisfaction did not correlate with sociodemographic variables; it was weakly correlated with the service use variables, and was clearly correlated (p less than 0.001) with the specific satisfaction with the use of services such as GP (r = 0.57), PED (r = 0.49), ADMON (r = 0.56), and N (r = 0.58).
Community Health Centers↗
Comparative study "in vitro" of transdermal absorption of a series of antiemetic drugs.
The "in vitro" transdermal absorption characteristics of various antiemetic drugs (Alizapride, Bromopride, Clebopride, Domperidone, Metoclopramide, Metopimazine) were studied. Franz diffusion glass cells were used. The skin of hairless rat was used as a permeation membrane. The following parameters were evaluated for each drug: Permeation constant (Kp), lag time (T1), and flux (J). A comparative study of permeation characteristics of the assayed drugs was carried out. Their potential use as transdermal dosage forme was also studied. Based on the results, Bromopride and Clebopride have showed the best "in vitro" permeation profile to be used by transdermal administration.
Administration, Cutaneous↗