RESUMEN

Mesangial IgA in IgA nephropathy are dimers with a J chain but no poly-Ig receptor. This molecular structure has led to the hypothesis that these IgA are issued from the lamina propria of mucosal areas, reaching the kidney by way of the peripheral blood. The availability of hybridomas producing IgA dimers provided an opportunity to test this hypothesis in a new experimental model of IgA nephropathy. Mice were injected subcutaneously (back-pack mice) or intraperitoneally with hybridoma cells secreting either monoclonal IgA dimers, or monoclonal IgA monomers. The influence of immune complex formation was also tested in both these models. Renal IgA deposition was investigated 12 days after the injection of hybridoma cells. Backpack mice developed highly vascularized subcutaneous tumors. Mesangial IgA deposits were observed only in dimeric IgA hybridoma back-pack animals. No significant staining was observed in glomeruli from animals injected with hybridoma cells producing monomeric IgA. None of the hybridomas induced mesangial deposition when injected intraperitoneally. This animal model demonstrates the capacity of circulating IgA dimers to spontaneously form mesangial deposits and contributes to confirm the involvement of abnormalities of mucosal immunity in the pathogenesis of IgA nephropathy.

Asunto(s)

Mesangio Glomerular/inmunología , Mesangio Glomerular/metabolismo , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/metabolismo , Hibridomas/trasplante , Inmunoglobulina A/inmunología , Inmunoglobulina A/metabolismo , Animales , Anticuerpos Monoclonales/metabolismo , Linfocitos B/inmunología , Linfocitos B/fisiología , Trasplante de Células , Técnica del Anticuerpo Fluorescente , Hibridomas/inmunología , Sistema Linfático/inmunología , Sistema Linfático/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Tonsila Palatina/inmunología , Tonsila Palatina/patología , Células Plasmáticas/inmunología , Receptores Mensajeros de Linfocitos/fisiología

RESUMEN

The correlations between semi-automated sputum cytometry (ASC), conventional cytology and the final diagnosis was investigated in industrially-exposed workers. Slides of sputum samples from 201 former uranium miners with silicosis, 100 patients with asbestosis, 103 workers resected for lung cancer, and 200 controls (50% smokers), were stained using the Papanicolaou (Pap) method and the Feulgen reaction with thionin. Cytometry was performed using the Cyto-Savant automated system. Atypical nuclei were found in 72 of 404 patient samples, 327 samples were normal and five were inadequate for ASC analysis. Thirteen tumours (Pap IV, Pap V) and 11 cases of severe dysplasia were identified by cytology. Lung cancer was confirmed in 20 patients. Compared to the final diagnosis of lung cancer, the sensitivity of ASC was 75% (15 out of 20) and specificity 89.8% (520 out of 579). The results represent a diagnostic efficiency of 89.3%. The combination of ASC with cytology increased sensitivity to 80% (16 out of 20) without significant loss of specificity (89.7% or 523 out of 581). In this investigation of a limited number of patients with occupational radon or asbestos exposure, semi-automated sputum cytometry appears to be sensitive and reliable for the detection of malignant changes in the tracheobronchial mucosa. Together with conventional cytology, it would be reasonable to test the validity of the combined methods in a large-scale feasibility study of early lung cancer detection.

Asunto(s)

Procesamiento de Imagen Asistido por Computador , Neoplasias Pulmonares/patología , Tamizaje Masivo/métodos , Esputo/citología , Adulto , Anciano , Asbestosis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , Silicosis/patología

RESUMEN

Twenty four male Sprague-Dawley albino rats in three equal (n = 8) groups were injected on two consecutive days with either p-chloroamphetamine hydrochloride (PCA) (10 mg/kg), H 102/09, an inhibitor of 5-hydroxytryptamine (5-HT) uptake (20 mg/kg) half an hour before PCA, or saline (1 ml/kg). Seven days later the acquisition of a two-way active avoidance response was studied in 8 daily sessions of 20 trials. PCA injections reduced 5-HT concentration of the whole brain 64% at the end of testing (15th day) whereas pretreatment with H 102/09 completely blocked this effect. PCA-treated rats were severely retarded in learning the avoidance response but there was no change in the acquisition of the escape. In contrast, rats pretreated with H 102/09 acquired the avoidance response as rapidly as the saline control group. These results suggest that the impaired learning of the two-way avoidance response may be related to the long-term effects of PCA on the 5-HT neurons in the rat brain. It is concluded that 5-HT neurons may play a role in acquisition of behaviors motivated by aversive events.