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Biomedical subjects

B Nabarra

Publications and source records attributed to B Nabarra.

At least 37 records · Page 2Linked to original sources
PubMed1991

Ultrastructural studies of mouse thymic reticulum. II. Non-epithelial component.

In this study we describe two types of non-epithelial cells forming a part of the thymic reticulum: macrophages with high phagocytic function, present in the cortex and medulla of the organ, and interdigitated cells present at the corticomedullary junction and in the medulla. These cells, in relation with epithelial cells, form a meshwork, a thymic microenvironment which influences the differentiation and maturation of T lymphocytes. These non-epithelial cells were probably mobile and their precursors exist in bone marrow. It has not yet been determined whether they are both of the same lineage and whether there is or is not common lineage between macrophages and interdigitated cells. Their role as accessory cells in the immune response seems evident. We will compare our observations with those of other authors. We will also discuss several issues concerning these two cell types; their nomenclature, their interrelationship in the thymic reticulum, their function, and their relationship to other similar cells in situ and to cells isolated in vitro, which perhaps are similar.

Animals↗
PubMed1990

Thymic reticulum of autoimmune mice. II: Ultrastructural studies of mice with lupus-like syndrome (NZB, BXSB, MRL/l).

We examined the thymic reticulum of three strains of mice showing symptoms of lupus-like disease. Ultrastructural pathology revealed several features common to the three mouse strains in varying degrees according to sex and age of the mice. Main anomalies included vacuolized aspect of the thymic epithelium, an increased number of macrophages, interdigitating cells and cystic cavities, the presence of a great number of plasmocytes and mastocytes and extensive interstitial fibrosis and arteriosclerosis. The most intriguing finding was the presence of crystal-like inclusions in epithelial cells. Some thymuses also showed premature histologic modifications similar to those observed in the ageing involuted thymus. Dysfunction of the epithelial cell secretory system, accumulation of denatured thymic hormone as well as premature organ ageing associated with a loss of thymic function could contribute significantly to the autoimmune phenomenon observed in lupus mice.

Age Factors↗
PubMed1990

Ultrastructural and functional abnormalities of intestinal and renal epithelium in the SHR.

Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.

Alkaline Phosphatase↗
PubMed1990

Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat.

A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1990

Visceral neuropathies responsible for chronic intestinal pseudo-obstruction syndrome in pediatric practice: analysis of 26 cases.

Twenty-six children aged from 1 day to 15 years (18 boys and 8 girls) with visceral neuropathies are analyzed. Clinical symptomatology is dominated by abdominal distension, attacks of occlusion, abdominal pain, and malnutrition. Intestine bacterial overgrowth is frequent. From aspiration biopsies, surgical rectal biopsies, and, in some cases, ileal or ileocolic biopsies, histopathological studies revealed two patterns. One group had abnormalities of the myenteric plexus identified by conventional light microscopic studies, with two patterns: [myenteric plexus hyperplasia (9 patients), characterized by large ganglionic nodes, penetration into the mucosal zone, and altered argyrophilic neurons]. Clinically this pattern was observed in four patients with multiple endocrine neoplasia syndrome with risk of medullary thyroid carcinoma. The second pattern observed was characterized by glial cell hyperplasia (15 patients). Ganglion cells are present but are small and sparse, often infiltrated by collagen tissue; Schwann nerve fibers are hypertrophic. Eleven patients presented with neonatal intestinal obstruction. The second group is characterized by normal conventional light microscopic examination, but silver stains revealed important abnormalities of argyrophobic cells (one case) or argyrophilic cells (one case). In the two groups, most of the patients needed intestinal derivation and prolonged nutritional support with total parenteral nutrition.

Adolescent↗
PubMed1989

Male BXSB mice develop a thymic hormonal dysfunction with presence of intraepithelial crystalline inclusions.

The thymus is morphologically abnormal in male BXSB mice with cortical involution densification of the epithelium and the presence of intraepithelial crystals. The thymic endocrine function in BXSB mice was appraised using a biological assay to measure the level of the zinc-dependent thymic hormone, thymulin, and an indirect immunofluorescence technique to evaluate the number of cells synthesizing the hormone within the thymus. Unlike the dramatically accelerated age-linked decline of thymulin production reported in females of other autoimmune strains (measured as early as 6 weeks of age), only male BXSB were affected, as compared to normal strains. The number of hormone-producing cells was significantly reduced in male BXSB thymuses, in parallel with this hormonal decrease. Thymulin inhibitory molecules were detected in male BXSB sera, as early as 8 weeks of age, as evaluated by their capacity to absorb in vitro and in vivo the biological activity of the hormone. These inhibitors are thymus dependent since they disappear after adult thymectomy. They are low MW molecules (less than 10 kDa), as previously found in normal aging mice, rather than autoantibodies, as evidenced in two autoimmune strains (B/W and db/db mice). These findings demonstrate that male BXSB mice develop thymic abnormalities very similar to those observed in other autoimmune strains. The presence of intrathymic crystals and of low MW inhibitors suggests the role of abnormal storage and the excretion of thymulin. This thymic dysfunction may play a role in the maintenance of B cell hyperactivity previously shown in BXSB males.

Aging↗
PubMed1989

Differential diagnosis between undifferentiated tumor and thymoma by electron microscopy and immunohistochemical labelling.

This study of a particular case of tumor posed and resolved problems of differential diagnosis between an undifferentiated tumor and a thymoma by using electron microscopy in association with immunocytochemical methods. The first step was the distinction between an epithelial and a mesenchymal tumor, which was done by electron microscopy and immunofluorescence observation with anti-keratin antibody. The second step, a new approach to this problem, was the distinction between an epithelial tumor of thymic origin and another tumor located in the mediastinal lodge. A clear distinction was made by observation in immunofluorescence using anti-thymulin monoclonal antibody. This double approach permits differential diagnosis, excludes neoplasms of germ-cell origin, malignant lymphomas and leukemias, as well as mesenchymal tumors, and affirms the thymic origin of the tumor observed. A second type of cell observed in this tumor with a peculiar aspect, different from all types of epithelial cells observed in normal thymus, is discussed.

Diagnosis, Differential↗
PubMed1988

Phenotype of thymic stromal cells. An immunoelectron microscopic study with anti-IA, anti-MAC-1, and anti-MAC-2 antibodies.

To better comprehend the thymic microenvironment, it is necessary to identify the antigenic profile of cells forming the thymic reticulum which are involved in intrathymic T cell differentiation. These cells are of three types: epithelial cells, macrophages, and interdigitating cells (IDC). Although several studies have been done on thymus section in light microscopy, identification of the positive cells, and mainly the antigenic equipment of the macrophages and IDC has not been clearly analyzed. Morphology, in electron microscopy is so far the best method to identify the different types of cells, and immunoelectron microscopy on thymic sections may be the best method to define clearly stromal cell phenotypes. In the present paper, we analyzed two antigens which classically define the macrophage family, Mac-1 and Mac-2, as well as major histocompatibility complex class II antigen which is present on epithelial cells and on bone marrow derived stromal cells. We show that epithelial cells are Ia+ Mac-1-, Mac-2-; macrophages are all Mac-1+, Mac-2+ but only half are Ia+; IDC are Ia+, Mac-1+, Mac-2+. These results show that IDC and macrophages both express antigens which were originally described as macrophage-specific.

Animals↗
PubMed1988

Light- and electron-microscopic analysis of the kidney in newborn rats exposed to gentamicin in utero.

Kidneys of newborn rats, whose mothers were given 75 mg/kg of gentamicin daily from the tenth day of gestation to its term, were examined by light and electron microscopy, as were kidneys of control rats whose mothers were given saline during the same period. In the gentamicin-treated group, the numbers of differentiated glomeruli and of S-shaped bodies counted in a median cross-section of the kidney were reduced, compared with those in the control group, but the glomerular volume was the same. In newborn rats issued from gentamicin-treated mothers, the proximal tubular lumen of the mature nephron lying in the deepest cortex was dilated, and their proximal tubular cells exhibited extensive damage, resembling that described in tubular cells of adult rats exposed to gentamicin. The subcapsular nephrogenic zone exhibited focal alterations of cytoplasmic organelle membranes, as well as nuclear lesions of several types, in cells of the nephron anlagen of the undifferentiated metanephric blastema, which were otherwise of normal appearance.

Animals↗
PubMed1987

Pattern of secretion in thymic epithelial cells: ultrastructural studies of the effect of blockage at various levels.

The observation of secretory phenomena in mouse thymic epithelial cells is disappointing since no real secretion image is found. An adequate technique for such a study is to block the secretion pathway and to observe by electron microscopy cells accumulating secretory products. For this purpose, we used three means of blocking secretion: Firstly, since the thymic epithelial cell is regulated by a feedback phenomenon, secretion was blocked by antibodies against thymulin, one of the hormones secreted by these cells. Secondly, colchicine was used to modify the intracellular transport of the secretory product. In both of these types of experiments, electron microscopy showed a great increase in the number of "clear vacuoles" and their granular contents in epithelial cells. In a third series of experiments, we used monensin at a concentration that blocks the intracellular transport of secretory proteins at the various levels of the Golgi apparatus. In this series, only an increased number of vacuoles was observed, but they appeared devoid of all granular content. It can be concluded that in the thymic epithelial cell, a discrete system of secretion directs the passage of the product, originating in the cisternae of the endoplasmic reticulum, into "clear vacuoles", the terminal element of the cellular secretory apparatus.

Animals↗
PubMed1987

Ultrastructural studies of thymic reticulum: I. Epithelial [corrected] component.

In studying the epithelial component of the mouse thymic reticulum, we identified by their ultrastructural aspect three types of epithelial cells: type I, present in the cortical and medullary zones; and type II and type III, present only in the medulla. These cells form a network entrapping lymphocytes. In addition, some cells are regrouped and form two types of associations that are found in the medulla: cystic cavities and Hassall's corpuscles [corrected]. Comparisons are made between our observations and those described in older publications. The morphologies and roles of these cells as well as the terminologies used to describe them are discussed in light of the new knowledge acquired concerning the function of the thymus.

Animals↗
PubMed1986

Thymic reticulum of autoimmune mice. I. Ultrastructural studies of the diabetic (db/db) mouse thymus.

The thymus of the db/db mouse, an autoimmune strain with insulin-dependent diabetes mellitus and manifesting hyperglycemia, polyuria, glycosuria and obesity, was observed by electron microscopy. Its comparison with normal thymuses and thymuses from non-diabetic obese mice has revealed two major differences: first, the presence of crystal-like structures in some of the numerous clear vacuoles in cells, and second, a modification of the cells forming the border of cystic cavities. These cells contain two types of granules which are quite plentiful. One variety is clear and big, and a second type is small and dense, with an aspect similar to that of secretion granules. It is hypothesized that the crystalloid formations found in epithelial cells, and the presence of small, dense granulations in cells bordering the cystic cavities, are a consequence of the abnormal storage of the thymic hormone, thymulin, which results from a secretory function defect. These observations suggest a possible role for the thymic reticulum in thymic function deficiencies.

Animals↗
PubMed1984

Localization of zinc in the thymic reticulum of mice by electron-probe microanalysis.

Thymulin, a thymic hormone, is a nonapeptide requiring zinc for biological activity. It has been shown that epithelial cells, forming part of the thymic reticulum, secrete this hormone and/or store it within cytoplasmic vacuoles. X-ray electron-probe microanalysis (EPMA) has been used to detect zinc in the thymus. Low concentrations of zinc have been demonstrated in the dense granules contained in clear vacuoles of some epithelial cells in normal and ZnCl2-injected mouse thymuses, thus suggesting that the metal may be coupled to the peptide before the secretion of the hormone from the cells.

Animals↗
PubMed1984

Ultrastructural study on long-term cultures of bone marrow cells with histamine-producing stimulating factor (HCSF).

In a previous study (Dy et al. 1981) we have demonstrated that histamine-producing cell stimulating factor (HCSF), a lymphokine released by T-cells, is present in supernatants obtained from secondary mixed lymphocyte cultures set up with cells from the donor and the recipient of a skin allograft, and that HCSF causes an increased production of histamine from target cells present in bone marrow. The most abundant source of target cells was found in the less dense layer of a discontinuous Ficoll gradient of bone marrow cells. Ultrastructural studies of this layer showed that it is composed of four types of cell: type I, immature cells; type II, mastocyte-like cells; type III, macrophages and type IV, lymphocytes. We have examined the effect of HCSF on this cell population; in long-term cultures we observed a progressive numerical decrease in type I cells, accompanied by an increase in type II cells (clearly observed as early as 48 h), leading to a pure population of mastocytes cells after 45 days of culture.

Animals↗
PubMed1983

Thymic reticulum in mice. II. Culture and characterization of nonepithelial phagocytic cells of the thymic reticulum: their role in the syngeneic stimulation of thymic medullary lymphocytes.

In the present report the characteristics of nonepithelial phagocytic cells of the murine thymic reticulum are described. Primary cultures were established from thymic fragments. Nonadherent cells with hairy membranes proliferated on the surface of established primary monolayers. These cells were recovered and replated in secondary cultures were they appeared as large adherent cells with dendritic shape. At the electron microscopic level, phagocytic cells of the thymic reticulum in culture (P-TR-C) appear as clear vacuolated cells with an indented nucleus and few lysosomes; this morphological aspect makes them different from the common macrophage, despite their phagocytic capacity. P-TR-C are positive for nonspecific esterase, acid phosphatase which is found in the few lysosomes present, 5'-nucleotidase and alpha-D-mannosidase, but negative for peroxidase. A high proportion of alpha-mannosidase-positive cells is inconsistent with the common macrophage, but in common with other cells with dendritic shape such as Langerhans cells. They are Thy-1-, Ig- and nearly half of them are IA+. P-TR-C can be defined as the stimulator cells for syngeneic stimulation; they are able to induce the proliferation of lymphocytes enriched in mature syngeneic medullary thymocytes, but not in immature cortical ones. Characteristics of P-TR-C make them very similar to the interdigitating cells described in the peripheral lymphoid organs and in the thymus in situ.

Animals↗