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Biomedical subjects

A Lopez

Publications and source records attributed to A Lopez.

At least 19 recordsLinked to original sources

Antigen phenotype and cytotoxic activity of natural killer cells in hemodialysis patients.

The antigen phenotype and cytotoxic activity of peripheral blood natural killer (NK) cells have been studied in 35 patients on hemodialysis, evaluating the influence exerted by different types of dialysis membranes and diverse clinical and biologic features of end-stage renal disease. Two-color immunofluorescent analyses with different monoclonal antibodies and flow cytometry were performed to identify the NK cells. Functional cytotoxic assays were simultaneously performed in the same patients. The results show that hemodialysis elicits higher proportions of CD3-/CD56+ and CD3-/CD16+ NK cells and a decrease in their cytotoxic activity compared with the control group. This alteration is related to the use of cuprophan membranes; biocompatible membranes would not significantly affect NK cells. The cuprophan membranes were also found to induce a higher degree of NK cell activation, measured as the number of CD16+/HLA-DR+ cells. Age appeared to be associated with NK cell function. Regarding age, in patients older than 65 years the change from cuprophan to biocompatible membranes was associated with a recovery of NK cytotoxic activity to normal levels. In summary, hemodialysis with cuprophan membranes induces an increased proportion of both NK cells and activated NK cells associated with decreased NK cytolytic activity.

Adult

Recombinant desmoglein 3 has the necessary epitopes to adsorb and induce blister-causing antibodies.

The development of an animal model for studying the pathogenesis of pemphigus vulgaris (PV) has been hampered by the unavailability of the purified full-length autoantigen desmoglein 3 (Dsg 3).Therefore, we expressed Dsg 3 using a baculovirus expressed system. The expressed protein was identified as Dgs 3 by its reactivity with a pan-cadherin anti-serum, an anti-serum to a Dsg 3 synthetic peptide, or patient serum, and by amino-terminal sequencing. Carbohydrate analysis showed that recombinant Dsg 3 was glycosylated. While a majority of the recombinant protein was cell associated, by immunoprecipitation, some Dsg 3 was demonstrated in the medium. The Dgs 3 could adsorb out blister-causing antibodies from patient sera. Rabbit anti- Dsg 3 antibodies induced by the recombinant Dsg 3 showed specific binding to intercellular spaces of monkeys esophagus by indirect immunofluorescence. Moreover, these antibodies induced PV-like blisters in neonatal mice and weakly bound perilesional epidermis. Availability of large quantities of relatively pure Dsg 3 should now facilitate studies aimed at understanding Dsg 3 structure and pathogenesis of PV, with implications for developing specific immunotherapies.

Animals

Gastroenteritis caused by Aeromonas trota in a child.

A case of acute diarrhoea caused by Aeromonas trota (formerly HG 13 group) in a Spanish child is reported. The strain was isolated in the faeces using the CIN agar (cefsulodin-irgasan-novobiocin) culture media. The strain was initially identified as A sobria by the commercial GNI card and API 20E biochemical systems. The strain was, however, VogesProskauer and sucrose negative, so complementary tests of cellobiose fermentation and gluconate oxidation were performed. These tests, together with the strain susceptibility to ampicillin (MIC 1 microgram/ml) and carbenicillin (MIC < 16 micrograms/ml) led to the final identification of A trota. The microbiological characteristics of this new species and the principal tests required for its identification are presented. The isolation, for the first time, of A trota in the Mediterranean area confirms the suspected worldwide distribution of this species.

Acute Disease

Pemphigus foliaceus and pemphigus vulgaris autoantibodies react with the extracellular domain of desmoglein-1.

Pemphigus foliaceus is associated with an autoimmune response against desmoglein-1; however, the fine specificity of these autoantibodies and the role that they play in pathogenesis have not yet been elucidated. In an attempt to develop a system to facilitate the detection and characterization of this antigen/antibody system, recombinant human desmoglein-1 was expressed in COS-1 cells, a mammalian epithelial cell line. The desmoglein-1 transgene product was shown to be expressed on the surface of the COS-1 cells in the appropriate transmembrane orientation. All pemphigus foliaceus sera (endemic form, n = 24; nonendemic form, n = 7) reacted strongly with nonpermeabilized desmoglein-1-transfected cells, exhibiting a punctate cell-surface staining pattern. This reactivity against the desmoglein-1 ectodomain was predominantly an IgG4-restricted response and was calcium dependent. Ten of 18 pemphigus vulgaris sera also reacted with the extra-cellular domain of recombinant desmoglein-1. Use of this eukaryotic expression system should greatly facilitate further characterization of the anti-desmoglein-1 autoimmune response associated with pemphigus foliaceus and pemphigus vulgaris and may aid in determining its pathogenic relevance.

Animals

Administration of lipid-emulsion versus conventional amphotericin B in patients with neutropenia.

OBJECTIVE: To evaluate the usefulness of a 20% lipid emulsion as a delivery system for amphotericin B (1 mg/mL) administered over 1 hour to patients with neutropenia with hematologic malignancies compared with amphotericin B (0.1 mg/mL) administered in dextrose 5% solution over the same time. DESIGN: A prospective, comparative, randomized, labeled study. SETTING: Hematology unit, pharmacy service, university general hospital. PARTICIPANTS: Twenty patients with neutropenia with hematologic malignancies and proven or suspected fungal infections, 10 in the fat emulsion group (group 1) and 10 in the dextrose 5% group (group 2). MAIN OUTCOME MEASURES: Clinical tolerance (i.e., fever, shaking chills, nausea, blood pressure, pulse rate) and biologic tolerance (i.e., urea, creatinine, sodium, potassium). RESULTS: Clinical tolerance was comparable in both groups although amphotericin B in fat emulsion was better tolerated. Medication for symptoms related to the administration of amphotericin B was given in 6 cases in group 1 and in 8 cases in group 2. There was a statistically significant difference in the urea concentrations between the 2 groups (p = 0.023); there was an observed increase between the initial and the final serum urea (56.8 mg/d in group 1, 79.8 mg/dL in group 2). Statistically significant differences in creatinine serum concentrations (84.9 mumol/L in group 1, 123.8 mumol/L in group 2) (p = 0.047) were found. No differences were found in the antifungal efficacy of the treatment. However, as amphotericin B was started in the majority of cases (75%) as empiric treatment for fever unresponsive to antibiotic therapy, it is difficult to compare the efficacy of both preparations. CONCLUSIONS: The clinical tolerance of lipid-emulsion infusions is similar to that of conventionally administered amphotericin B therapy. Renal toxicity appears to be decreased when the drug is administered in a fat emulsion. This type of preparation permits the reduction of the volume and the time of administration for amphotericin B therapy.

Adolescent

Quantification of pneumothorax size on chest radiographs using interpleural distances: regression analysis based on volume measurements from helical CT.

OBJECTIVE: The aim of this study was to define the relationship between interpleural distance measurements on an erect posteroanterior chest radiograph and pneumothorax size as measured by helical CT in a series of patients. SUBJECTS AND METHODS: Twenty pneumothoraces from 19 patients (10 males, nine females) were analyzed. Most pneumothoraces were on the right side (n = 16). The etiology was spontaneous in seven patients and iatrogenic in thirteen. All patients underwent an erect inspiratory posteroanterior radiograph and a helical CT scan of the thorax on the same visit to the radiology department. The interpleural distance was measured at three locations and the figures added together. Following helical CT of the thorax, the percentage pneumothorax size was calculated by drawing regions of interest around the relevant hemithorax and lung on 10-mm reconstructed slices. A scattergram of the sum of interpleural distances in centimeters versus percentage pneumothorax size was plotted. RESULTS: Analysis of results showed that percentage pneumothorax size could be calculated by the formula Y = 4.2 + [4.7 x (A + B + C)], r = .98, p < .0001. CONCLUSION: This study identified a formula for accurately calculating percentage pneumothorax size as determined by helical CT from an erect posteroanterior radiograph. Using this formula with the clinical status of the patient should more easily identify patients requiring active intervention.

Adolescent

Flow cytometry in the diagnosis of cancer.

Flow cytometry has rapidly expanded from basic research to clinical laboratories mainly due to its unique characteristics regarding cell analysis. Among the clinical uses of flow cytometry cancer represents one of the most relevant. Several applications of flow cytometry can currently be applied to the study of cancer, including the detection of tumour cell DNA aneuploidy, the analysis of tumour cell proliferation and the immunophenotyping of leukemias. Although standardized flow cytometry protocols for these applications are scanty, the clinical value has been clearly established. The presence of DNA aneuploidy and a high proportion of S-phase tumour cells have been associated with tumour malignancy and a poor prognosis. The immunophenotype of leukaemia is of great help both for the diagnosis and classification of chronic lymphoproliferative disorders and acute leukaemias, especially in acute lymphoblastic leukemia cases and the M0, M3-variant, M6 and M7 acute myeloblastic leukaemia subtypes. In addition, it allows the identification of relatively rare leukemia cases such as the biphenotypic and the Nk-cell lineage leukemias. The development of flow cytometry is continuously bringing new applications into the clinical laboratory in the area of cancer diagnosis.

Flow Cytometry

Flow cytometric DNA analysis of fine-needle aspirates of prostatic benign lesions.

Fine-needle aspiration samples from 54 consecutive patients suffering from prostatic benign lesions were analyzed for both cytological diagnosis and DNA cell content, by means of standard cytological criteria and flow cytometry, respectively. Of these patients, 13 displayed prostatitis: three being classified as acute prostatitis, 7 as chronic and 3 as granulomatosous prostatitis. All cases had a diploid DNA cell content, with a mean percentage of S-phase cells of 1.8 +/- 2.7%. Although no major differences were detected between patients with and without prostatitis, the former group had a slightly higher proportion of S-phase cells (1.4 +/- 2.2% vs 2.7 +/- 3.7%). Moreover, within those patients with prostatitis, acute prostatitis cases showed the highest proliferation rates although differences did not reach statistical significance.

Biopsy, Needle

[Clinical features, diagnosis, and treatment of tumor lesions arising in the adrenal gland].

Between 1981 and 1993, 14 patients with tumoral adrenal disease were diagnosed and treated in the Urology Services of both Hospitals. Nature of the adrenal disease was functional in 8 patients (two carcinomas and six pheochromocytomas) and non-functional in the rest (three carcinomas, two adenomas and one myelolipoma). Reference is made to the clinical manifestations and laboratory tests related to hormonal activity, depending on whether the tumour is functional or non-functional, chromaffin or non-chromaffin. Patients with functional carcinomas had Cushing's syndrome, with very clear virtilization signs. Urine 17-hydroxycorticosteroid, 17-cetosteroides and cortisol were all increased, same as plasma cortisol. Patients with pheochromocytomas had hypertension and headaches (six patients), sweating (five patients), anxiety (four patients) and loss of weight (two patients). All of them had increased urine vainillylmandelic acid and catecholamines. Clinical signs and symptoms of non-functional tumours were related to bulk growth and size (in the three carcinomas), and sometimes was highly anodyne, or even absent (in the two adenomas and the myelolipoma), the cause of discovery being accidental during an ultrasound examination. An analysis is made of the different imaging diagnostic procedures performed, such as IVU (performed in 13 patients) with a 38.4% resolutory power; ultrasound (performed in 11 patients) with an 81.8% resolution; CAT (performed in 6 patients) with a 100% resolution capacity and arteriography (performed in 3 patients) with a 100% resolution power, although patients had previously undergone ultrasound and CAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms

Is the length of the calcarine sulcus associated with the size of the human visual cortex? A morphometric study with magnetic resonance tomography.

PURPOSE: To determine whether the length and depth of the calcarine sulcus are associated and can be used for estimating the size of the primary visual area (area 17) and other regions in MR images of the human occipital lobe. METHODS: The length and depth of the calcarine sulcus and the projection areas of the mesial surface of the occipital lobe and of the total hemisphere were measured in MR images of 23 healthy subjects. RESULTS: A higher variability of the size of the projection area of the mesial surface of the occipital lobe compared with that of the remaining part of the hemisphere is found. The projection area of the mesial cortical surface of the occipital lobe is correlated with the length of the calcarine sulcus, but both parameters are not correlated with the depth of the calcarine sulcus and, therefore, also not with the size of the part of area 17 buried in the sulcus. CONCLUSION: The size of area 17 cannot be estimated by the length of the calcarine sulcus in MR images. Depth and length of the calcarine sulcus grow independently in the human brain. Different degrees of folding may cause the variability of architectonic areas.

Adolescent

Lipid domains and lipid/protein interactions in biological membranes.

In the fluid mosaic model of membranes, lipids are organized in the form of a bilayer supporting peripheral and integral proteins. This model considers the lipid bilayer as a two-dimensional fluid in which lipids and proteins are free to diffuse. As a direct consequence, both types of molecules would be expected to be randomly distributed within the membrane. In fact, evidences are accumulating to indicate the occurrence of both a transverse and lateral regionalization of membranes which can be described in terms of micro- and macrodomains, including the two leaflets of the lipid bilayer. The nature of the interactions responsible for the formation of domains, the way they develop and the time- and space-scale over which they exist represent today as many challenging problems in membranology. In this report, we will first consider some of the basic observations which point to the role of proteins in the transverse and lateral regionalization of membranes. Then, we will discuss some of the possible mechanisms which, in particular in terms of lipid/protein interactions, can explain lateral heterogenities in membranes and which have the merit of providing a thermodynamic support to the existence of lipid domains in membranes.

Animals

A mutation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 that leads to ligand independence and tumorigenicity.

The cytokines interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor bind with high affinity to a receptor complex that contains a ligand-specific alpha-chain and a common beta-chain, h beta c. We report here the isolation of a mutant form of h beta c, from growth factor-independent cells, that arose spontaneously after infection of a murine factor-dependent hematopoietic cell line (FDC-P1) with a retroviral h beta c expression construct. Analysis of this h beta c mutation shows that a small (37 amino acid) duplication of extracellular sequence that includes two conserved sequence motifs is sufficient to confer ligand-independent growth on these cells and lead to tumourigenicity. Because this is a conserved region in the cytokine receptor superfamily, our results suggest that the large family of cytokine receptors has the capacity to become oncogenically active.

Amino Acid Sequence

Influence of obstacles on lipid lateral diffusion: computer simulation of FRAP experiments and application to proteoliposomes and biomembranes.

Fluorescence Recovery After Photobleaching experiments were simulated using a computer approach in which a membrane lipid leaflet was mimicked using a triangular lattice obstructed with randomly distributed immobile and non-overlapping circular obstacles. Influence of the radius r and area fraction c of these obstacles and of the radius R of the observation area on the relative diffusion coefficient D* (Eq. (1)) and mobile fraction M was analyzed. A phenomenological equation relating D* to r and c was established. Fitting this equation to the FRAP data we obtained with the probe NBD-PC embedded in bacteriorhodopsin/egg-PC multilayers suggests that this transmembrane protein rigidifies the surrounding lipid phase over a distance of about 18 A (approximately equal to two lipid layers) from the protein surface. In contrast, analysis of published diffusion constants obtained for lipids in the presence of gramicidin suggests that in terms of lateral diffusion, this relatively small polypeptide does not significantly affect the surrounding lipid phase. With respect to the mobile fraction M, and for point obstacles above the percolation threshold, an increase in R led to a decrease in M which can be associated with the existence of closed domains whose average size and diffusion properties can be determined. Adaptation of this model to the re-interpretation of the FRAP data obtained by Yechiel and Edidin (J Cell Biol (1987) 115:755-760) for the plasma membrane of human fibroblasts consistently leads to the suggestion that the lateral organization of this membrane would be of the confined type, with closed lipid domains of approximately equal to 0.5 microns 2 in area.

Bacteriorhodopsins