Biomedical subjects
D Rodriguez
Publications and source records attributed to D Rodriguez.
Regulation of (1-3)-beta-glucan-stimulated Ca(2+) influx by protein kinase C in NR8383 alveolar macrophages.
Stimulation of (1-3)-beta-glucan receptors results in Ca(2+) influx through receptor-operated channels in alveolar macrophages (AMs), but the mechanism(s) regulating Ca(2+) influx is still undefined. In this study we investigated the role of protein kinase C (PKC) regulation of Ca(2+) influx in the NR8383 AM cell line using the particulate (1-3)-beta-glucan receptor agonist zymosan. PKC inhibition with calphostin C (CC) or bisindolymaleimide I (BSM) significantly reduced zymosan-induced Ca(2+) influx, whereas activation of PKC with phorbol-12-myristate 13-acetate (PMA) or 1, 2-dioctanoyl-sn-glycerol (DOG) mimicked zymosan, inducing a concentration-dependent Ca(2+) influx. This influx was dependent on extracellular Ca(2+) and inhibited by the receptor-operated Ca(2+) channel blocker SK&F96365, indicating that zymosan and PKC activate Ca(2+) influx through a similar pathway. NR8383 AMs expressed one new PKC isoform (delta) and two atypical PKC isoforms (iota and lambda), but conventional PKC isoforms were not present. Stimulation with zymosan resulted in a translocation of PKC-delta from the cytosol to the membrane fraction. Furthermore, inhibition of protein tyrosine kinases (PTKs) with genistein prevented zymosan-stimulated Ca(2+) influx and PKC-delta translocation. These results suggest that PKC-delta plays a critical role in regulating (1-3)-beta-glucan receptor activated Ca(2+) influx in NR8383 AMs and PKC-delta translocation is possibly dependent on PTK activity.
Reconstruction of the aesthetic units of the face with microsurgery: experience in five years.
Since the description of the aesthetic units of the face by González-Ulloa, surgical attempts have been made to achieve excellent results with skin grafts, pedicled flaps, and free flaps. At our institution, we preferentially use microsurgical replacement of the aesthetic units independent of the etiology. The objective of this article is to present a retrospective review of the outcome of patients who underwent these procedures. The etiology, the choice of the procedure, and the functional and aesthetic results are assessed. We suggest the main features according to the results obtained. In this retrospective review, 43 procedures in a 5-year period are analyzed and the results reported. We conclude that the operative procedure is both technically simple and effective over the long term.
Foamy cells with oligodendroglial phenotype in childhood ataxia with diffuse central nervous system hypomyelination syndrome.
Childhood ataxia with diffuse central nervous system hypomyelination syndrome (CACH) is a recently described leukodystrophy of unknown etiology. To characterize the neuropathological features and gain insight as to the pathogenesis of this disorder, we studied cerebral tissue from six patients with the CACH syndrome. Evaluation of toluidine blue-stained, semithin sections of white matter from CACH patients disclosed unusual cells with "foamy" cytoplasm, small round nuclei and fine chromatin. Electron microscopy (EM) revealed cells in the white matter with abundant cytoplasm containing many mitochondria and loosely clustered, membranous structures, but lacking the lysosomal structures seen in macrophages. Further analysis of tissue sections with antibodies and special stains demonstrated that the abnormal cells with abundant cytoplasm labeled with oligodendroglial markers, but did not react with macrophage or astrocytic markers. Double immunolabeling with macrophage and oligodendroglial markers clearly distinguished macrophages from the "foamy" oligodendroglial cells (FODCs). Proteolipid protein (PLP) mRNA in situ hybridization demonstrated PLP mRNA transcripts in a high proportion of oligodendrocytes in CACH patients compared to control patients, and PLP mRNA transcript signal in cells, morphologically consistent with FODCs. Normal and pathological brain control tissues did not contain FODCs. These neuropathological findings will be useful pathological identifiers of CACH, and may provide clues to the pathogenesis of this disorder.
When do children with optic pathway tumours need treatment? An oncological perspective in 106 patients treated in a single centre.
UNLABELLED: Progression patterns of optic pathway tumours (OPT) need to be precisely defined for treatment planning. In patients with neurofibromatosis type 1 (NF1), this disease is usually indolent and the available literature rarely reports progression after the age of 6 years. In patients without NF1, the disease course seems to be less favourable. We reviewed the clinical and radiological files of 106 children referred to our institution for the treatment of a symptomatic OPT since 1980. NF1 was present in 51 of them. Progression patterns in children with NF1 differed markedly from those in the other patients. A total of 83 children had tumour extension beyond the chiasm (Dodge type III). Children with NF1 had progressive tumours later during follow-up (47% after the age of 6 years), had more often proptosis and infiltrating tumours but less frequently nystagmus or increased intracranial pressure. 32 children were not treated at diagnosis because they had only mild symptoms related to the OPT. In these patients, progression occurred more often in children without than with NF1 (12/12 versus 12/20 respectively, P = 0.04). A high number of patients needed treatment for progression or severe symptoms after 6 years of age. Of the patients, 33% needed treatment for progression or severe symptoms after 6 years of age. CONCLUSION: Progression patterns of optic pathway tumours in children with neurofibromatosis type 1 differ markedly from those in other patients. This study emphasises the need for prolonged follow-up of children with optic pathway tumours, especially in neurofibromatosis type 1.
Generation of monoclonal antibodies to cryptic collagen sites by using subtractive immunization.
The extracellular matrix (ECM) plays a fundamental role in the regulation of normal and pathological processes. The most abundantly expressed component found in the ECM is collagen. Triple helical collagen is known to be highly resistant to proteolytic cleavage except by members of the matrix metalloproteinase (MMP) family of enzymes. To date little is known concerning the biochemical consequences of collagen metabolism on human diseases. This is due in part to the lack of specific reagents that can distinguish between proteolyzed and triple helical forms of collagen. Here we used the technique of Subtractive Immunization (SI) to generate two unique monoclonal antibodies (MAbs HUIV26 and HUI77) that react with denatured and proteolyzed forms of collagen, but show little if any reaction with triple helical collagen. Importantly, HUIV26 and HUI77 react with cryptic sites within the ECM of human melanoma tumors, demonstrating their utility for immunohistochemical analysis in vivo. Thus, the generation of these novel MAbs not only identify specific cryptic epitopes within triple helical collagen, but also provide important new reagents for studying the roles of collagen remodeling in normal as well as pathological processes.
Use of arm veins for lower extremity arterial bypass--results, anatomical features and technical considerations.
Forty lower limb bypasses using arm veins were performed on 37 patients. The indications for surgery were limb threat in 50% of cases, graft failure in 33%, aneurysms in 10% and claudication in 7%. Saphenous veins were absent because of prior use in 73% of cases, and because they were unsuitable in 27%. A single vein was used in 48%, 2 veins in 40% and 3 veins in 12% of cases. Seventy-four per cent of cases had a single-vessel run-off below the distal anastomosis. Eighty-two per cent of the distal anastomoses were to infrapopliteal arteries. The primary and secondary rates of these 40 bypasses at a mean follow-up of 14 months (range 1-40 months) were 74% and 90%, respectively. Limb salvage was 94%. Peri-operative morbidity and mortality were 23% and 3%, respectively. The anatomical and technical aspects of harvesting arm veins are critical to the success of this procedure and will be emphasised. We have found arm veins to be a durable source of accessible autogenous grafts for lower limb revascularisation in the absence of suitable saphenous veins.
Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma.
Occlusive vasculopathy is a potential complication of radiotherapy in children with optic pathway glioma. With a median follow-up of 7 years, 13 of 69 children in this study developed clinical and radiological signs of occlusive vasculopathy after radiotherapy within a median interval of 36 months. The major risk factor was neurofibromatosis type 1. Radiotherapy should no longer be the first treatment in these settings. When radiotherapy is unavoidable, regular screening for cerebral vasculopathy is mandatory, as preventive treatment is available.