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B Nabarra

Publications and source records attributed to B Nabarra.

At least 55 records · Page 3Linked to original sources

Thymic dysfunction in the mutant diabetic (db/db) mouse.

Thymic function has been explored in genetically diabetic homozygous C57BL/KsJ (db/db) mice by evaluating their serum thymic factor (FTS) levels with a rosette assay. As previously reported for other autoimmune mice (NZB or MRL/I mice), the age-dependent decline of FTS levels was significantly accelerated in diabetic mice when compared to heterozygous littermates. Furthermore, FTS inhibitory molecules were detected in db/db mouse sera (as early as 10 wk of age) as evaluated by their ability to absorb in vitro the activity of synthetic FTS in the rosette assay, and in vivo for their capacity to induce the disappearance of endogenous FTS when injected into normal mice. These inhibitors were shown to be immunoglobulins. Histologically, the thymus presented an accelerated involution starting with a cortical lymphocytic depletion and an increased number of Hassall's corpuscles. Ultrastructural studies showed alterations in thymic epithelial cells, mainly represented by an increasing number of cytoplasmic vacuoles. By means of indirect immunofluorescence with anti-FTS monoclonal antibodies, it was shown that the number of FTS+ cells was reduced in db/db mouse thymuses: at the age of 22 wk, diabetic mice had 10 times fewer FTS+ cells than heterozygotes of the same age. Taken together, these results indicate important abnormalities in the thymus of diabetic mice. It is possible that the associated lymphocyte dysfunction plays a role in the pathogenesis of the autoimmune disease presented by db/db mice.

Aging↗

Contribution of zinc and other metals to the biological activity of the serum thymic factor.

The serum thymic factor (FTS) utilized in its synthetic or natural form loses its biological activity in a rosette assay after treatment with a metal ion-chelating agent, Chelex 100. This activity is restored by the addition of Zn salts and, to a lesser extent, certain other metal salts. FTS activation is secondary to the binding of the metal to the peptide. The metal-to-peptide molar ratio of 1:1 provides the best activation. These data indicate the existence of two forms of FTS. The first one lacks Zn and is biologically inactive; the second one contains Zn and is biologically active, for which we propose the name of "thymulin" (FTS-Zn). The presence of Zn in synthetic FTS was confirmed by atomic absorption spectrometry. The interaction between Zn and FTS was further suggested by microanalysis demonstrating the presence of this metal in thymic reticuloepithelial cells.

Animals↗

Rat enterocyte Na+ transport in vitro. Action of parathyroid hormone and calcitonin.

Parathyroid hormone (PTH) and calcitonin exert well known effects on the renal tubule which are thought to involve specific hormone receptors and adenyl cyclase. In the intestine, it is not clear whether the action of PTH and calcitonin is only indirect or also direct, and their mechanisms of action are much less well established. In the present study, possible direct effects of PTH and calcitonin on Na+ transport in isolated intestinal epithelial cells of rats were investigated. In the presence of bovine PTH (1.2 I.U/ml) in the incubation medium, the Na+ efflux rate constant (oKNa) of isolated enterocytes was significantly reduced when compared to that in control experiments with the hormone vehicle only. The mean depression of oKNa induced by bovine PTH was 26% as compared to the control (100%) and to that induced by ouabain (4.0 mM) which was 44%. No depressant effect of bovine PTH on oKNa was observed when the isolated enterocytes were incubated with ouabain (4.0 mM). Thus, bovine PTH appeared to inhibit the ouabain-sensitive Na+ pump. When incubating the isolated epithelial cells in an EGTA-containing CA2+-free medium, bovine PTH lost its capacity to inhibit oKNa. Thus, the presence of extracellular Ca2+ appeared necessary for the inhibitory effect of bovine PTH. In contrast to its effect on oKNa, bovine PTH induced no change in net Na+ uptake by isolated enterocytes. Moreover, no significant effect on enterocyte Na+ transport could be demonstrated for salmon or porcine calcitonin at two different concentrations in the incubation medium, Neither bovine PTH nor salmon calcitonin induced significant changes in enterocyte cyclic AMP or cycle GMP concentrations. It was concluded that bovine PTH, but not calcitonin, exerted a directed inhibitory effect on the ouabain-sensitive oKNa of isolated rat enterocytes. The effect of bovine PTH occurred without measurable activation of the cyclic nucleotide system but needed the presence of Ca2+ in the incubation medium to be operative.

Animals↗

Thymic reticulum in mice. I. Cellular ultrastructure in vitro and functional role.

Qualitative and quantitative electron microscopic studies of thymic and splenic stroma cultured in vitro are described. Under our technical conditions, 60% of thymic stromal cells in vitro are endodermic epithelial cells, while the remaining cells are mesenchymal reticular cells and macrophages. These last two types of cells, together with fibroblasts are the constituents of splenic stroma. In seven experiments, the coculturing of thymic lymphocytes with thymic monolayers led to an enhancement of the Con A response, while coculturing with splenic monolayers did not. These results underline the specific role of thymic epithelial cells in the process of T-cell maturation. Bone marrow cells and spleen cells from B mice are not modified by coculture with thymic epithelium. Reinjection of B mice with bone marrow cells pre-incubated on thymic monolayers did not lead to any reconstitution of T-cell function when tested 1 mth later. These results are interpreted as the inability of thymic stroma from adult mice alone to induce the maturation of pre-T cells.

Animals↗

The dense deposits disease of the renal basement membranes.

Dense-deposits disease is characterized by an original morphological aspect of the renal basement membranes which have an electron-dense appearance. The immunofluorescence studies showed C3 alone in kidney. Low serum C3 levels and the presence of C3 NF activity have been detected in this disease, demonstrating an activation of the complement alternative pathway. The observation of recurrence in transplanted kidneys contributed to establish the sequence of the morphological events and showed the dissociation between the serological complement profiles and the lesions. Although the nature of the dense deposits remains still unknown, the altered membranes are recognized by at least some anti-GBM antibodies.

Antigens↗

Recurrence of dense deposits in transplanted kidneys: I. Sequential survey of the lesions.

Serial specimens from transplanted kidneys were obtained in 11 patients with dense deposit disease (DDD). The recurrence of DDD was obvious in 9 patients and appeared very early after grafting. Three different types of evolution of the lesions were observed. In 4 patients no modification of the lesions occurred with time, and in 2 of them the dense alteration alone persisted without any other glomerular changes. In 3 patients a progression of the lesions was observed, whereas a regression occurred in 1 other patient. From these observations the following sequence of the morphologic changes can be proposed: the dense alteration appears first and constitutes the specific marker of that disease; the C3 deposition in the kidney occurs later following the appearance of the dense lesion.

Basement Membrane↗

Morphological study of autologous rosettes (A-RFC).

The morphology of autologous rosette forming cells (A-RFC) has been studied by light and electron microscopy. Autorosette forming cells were obtained from the spleen of adult thymectomized (ATx) or nude mice, and from neonatal thymus grafts during the regeneration phase. Among the autorosettes seen by light microscopy, 76% of them were formed by lymphoid cells which included a high proportion of large lymphocytes (48%). Electron microscopy study performed after isolation of A-RFC by micromanipulation demonstrated that 74% were formed by large lymphoid cells with an immature nucleus. The finding of such large-sized lymphoid cells with immature nuclei is in agreement with our previous results indicating that A-RFC might belong to an immature T cell class.

Animals↗

[Histological and ultrastructural study of intestinal ganglioneuromatosis. The multiple endocrine neoplasms type IIb syndrome].

The syndrome known as the Multiple Endocrine Neoplasia type III or type IIb presents a particular histological intestinal lesion: hyperplasia of the myenteric plexus. The electron microscopic study of the plexus of Auerbach in our observation suggests a disequilibrium of the different types of individual axonal sheaths compared to the descriptions of a normal plexus. The possible role of this anomaly in the genesis of intestinal manifestations in this syndrome is here discussed.

Female↗

Ultrastructural study of spontaneous bone marrow rosette-forming cells.

Mouse bone marrow contains spontaneous rosette-forming cells (RFC) which include more than 70% T-cell precursors, as assessed by their transformation into theta-positive cells after incubation with thymic hormone. Such spontaneous RFC, examined in C57B1/6 mouse bone marrow by electron and scanning electron microscopy, have consistently been shown to be small, inactive mouse lymphocytes when macrophages have been eliminated by cell preincubation. These data suggest that thymic hormone target cells include small quiescent lymphocytes.

Animals↗

Ultrastructure of a polysome-lamellae complex in a human paraganglioma.

Study of a human abdominal paraganglioma under electron microscopy revealed an unusual cytoplasmic inclusion appearing as a hollow cylinder made up of one or several concentric lamellae surrounded by single or aggregated granules. Cross sections of the lamellar element show a discontinuous juxtaposition of particles. It is moderately dense and is bordered by 140--to 250-A granules of sure ribosomal nature. The inclusion is closely connected to the rough endoplasmic reticulum. The origin and significance of this complex are discussed.

Abdominal Neoplasms↗

Glomerular changes in patients with cirrhosis of the liver.

Deposits with IgA as the main component frequently are found in the glomeruli of patients with cirrhosis of the liver. These deposits usually are latent. In some cases, however, they may be associated with proliferative changes and clinical manifestations of glomerular involvement.

Adult↗

Susceptibility and resistance of Candida to 5-fluorocytosine in relation to the cell wall ultrastructure.

Studies on the susceptibility of Candida albicans to 5-fluorocytosine (5FC) demonstrated a high rate of resistance (85%) for serogroup B strains, more frequently isolated in Africa, and a low incidence (<1%) for serogroup A, predominating among Whites (Drouhet et al., 1974). Determination of the electrophoretic mobility of various strains did not provide a correlation between the charged groups of the surface and their phenotype to 5FC and antigenic groups. Adsorption of the surface antigens with a hyperimmune antiserum did not modify the phenotypic expression of Candida to 5FC. Electron microscopy studies revealed that susceptible strains had an additional granular layer dividing the inner stratum into two parts. After trypsin digestion of these strains, the disappearance of this layer was concomitantly associated with the emergence of resistance. Thus, it appears that the cell wall contains a proteinic material, which is located in the interior of the electron-transparent region and acts in the metabolism of 5FC.

Animals↗

Ultrastructure of cells infiltrating human kidney allografts.

Cell infiltration is commonly observed in human renal allograft biopsies. This infiltration was investigated using electron microscopy for a more precise assessment of the nature of these cells. More than 3000 cells infiltrating twenty-five renal allograft biopsies were studied. Six cellular types were distinguished and a mean percentage of each type was calculated. Only one-half of these cells were normal or transformed lymphocytes (including small lymphocytes: 22-3 +/- 3-8%, 'intermediary' cells: 22 +/- 3-6%, blast-like cells similar to MLC transformed lymphocytes: 8-1 +/- 2-4%. A relatively high number of plasmocytes (12-4 +/- 2-5%) and a still higher percentage of macrophages (28-5 +/- 4-6%) were found. Granulocytes represented only 2 +/- 0-8%of the cell population. Variations of the mean percentage of these cellular types were studied in various clinical situations.

Cell Movement↗

[Sensitivity and resistance of Candida to 5-fluorocytosine. Relationship to the cell wall ultrastructure].

The study of ultrafine sections of the yeasts of Candida show a difference in the cell between sensitive and resistant strains to 5-fluorocytosine (5-FC). The sensitive strains show a thin border of granular material inside of the clear internal layer which is absent for the majority of resistant strains. After trypsinization, the sensitive strains show a resistance which is reversible and the granular layer disappears. These data permit the conclusion that the middle layer of resistant strains is of protein nature and interferes with the metabolization of 5-FC.

Candida↗