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J Ionescu

Publications and source records attributed to J Ionescu.

At least 19 recordsLinked to original sources
PubMed1997

T cell development in mice expressing splice variants of the protein tyrosine phosphatase CD45.

The transmembrane protein tyrosine phosphatase CD45 is expressed in multiple isoforms as a result of alternative splicing of variable exons encoding the extracellular domain. CD45 expression is critical for T cell development, and thymocyte maturation is blocked at the immature CD4+ CD8+ double-positive stage in CD45 gene-deficient (CD45 -/-) mice. Moreover, splicing of variable CD45 exons changes during thymocyte selection. To test the role of CD45 extracellular splice variants in T cell selection and development, we introduced CD45RO (a low-m.w. splice variant lacking exons 4, 5, and 6) and CD45ABC (a high-m.w. isoform containing all exons) transgenes under the control of a thymocyte-specific promoter into a CD45 -/- background, generating CD45RO transgene-positive CD45 -/- (CD45RO) and CD45ABC transgene-positive CD45 -/- (CD45ABC) mice. We demonstrate that both CD45 splice isoforms can rescue development of CD4+ and CD8+ TCR-alphabeta+ thymocytes. Neither CD45 isoform rescued positive selection of H-Y TCR transgene thymocytes, and these cells were blocked at a HSA(high) CD69- CD5(low) stage of development. Peripheral T cells from CD45RO and CD45ABC mice proliferated in response to allogeneic stimulator cells and anti-CD3epsilon cross-linking. However, only CD45RO mice, not CD45ABC mice, generated cytotoxic T cell responses and neutralizing, Th cell-dependent IgG Abs after viral infections. In addition, we show that T cells from CD45RO and CD45ABC mice accumulate in lymph nodes but not in the spleen, liver, or skin, indicating that the CD45 phosphatase may control the homing behavior and trafficking of T cells.

Alternative Splicing↗
PubMed1996

Induction of autoimmunity in the absence of CD28 costimulation.

Ag-specific activation of T lymphocytes requires two signals, one by the TCR and a second by costimulatory molecules. In a CD4+ T helper cell-dependent experimental autoimmune myocarditis model, we provide genetic evidence that cardiac myosin-induced autoimmune myocarditis and the production of IgG auto-Abs is dependent on functional T cells and did not occur in mice lacking the tyrosine kinase p56lck or the tyrosine phosphatase CD45. By contrast, animals lacking the T cell-costimulatory molecule CD28 (CD28 -/-) developed autoimmune heart disease, although at significantly lower severity than in heterozygous littermates, and produced IgG auto-Abs depending on the concentration of the autoantigen administered. In addition, the isotypes of IgG auto-Abs specific for cardiac myosin differed between CD28 +/- and CD28 -/- mice. Whereas CD28 +/- mice predominantly produced Th2-mediated IgG1 auto-Abs, CD28 -/- mice produced predominantly IgG2a. These data suggest that CD28 costimulation plays a crucial role in induction and maintenance of autoimmune heart disease and that CD28 expression is required for predominant Th2-IgG1 responses in an autoimmune setting.

Animals↗
PubMed1995

Alloreactive gamma delta thymocytes utilize distinct costimulatory signals from peripheral T cells.

Interactions between CD28/CTLA-4 on T cells and CD80 (B7.1) and CD86 (B7.2) counter receptors provide crucial costimulatory signals for TCR-alpha beta+ lymphocytes. To test the role of CD28 in thymic development and activation of TCR-gamma delta+ T cells, we introduced the alloreactive V gamma 2V alpha 11.3 TCR into CD28-deficient mice (CD28-/-). We show that positive and negative selection of gamma delta Tg thymocytes proceeded normally in the absence of CD28. Although mature Tg gamma delta+ thymocytes required a second costimulatory signal for proliferation, gamma delta+ thymocytes from CD28-/- and CD28+/- littermates responded equally well to the alloantigen Tlab. Alloreactivity of CD28-/- and CD28+/- Tg gamma delta+ thymocytes could not be blocked with mAbs against CD80 and CD86 ligands. Thus gamma delta thymocytes utilize a costimulatory system during development and alloresponses that is independent of CD28/CD80 and CD28/CD86 interactions. By contrast to V gamma 2V alpha 11.3+ thymocytes, alloreactivity of V gamma 2V alpha 11.3+ lymph node T cells depended on CD28 costimulation and was severely impaired in CD28-/- mice. These data provide functional evidence that maturation and selection of gamma delta cells is independent of CD28. These results also indicate that distinct costimulatory pathways are operational in mature thymocytes and peripheral T cells.

Animals↗
PubMed1983

Immunochemical studies on Brucella abortus lipopolysaccharides.

The antigenic-toxic complex of B. abortus isolated in the phenol phase of phenol/water system, is a lipopolysaccharide (LPS)-protein macromolecule. The specific side chain was isolated from this complex by means of pronase treatment and mild HCl cleavage, followed by fractionation on Sephadex. The side chain thus isolated lost its capacity to coat erythrocytes but not that of neutralizing antibodies, as shown in the hemagglutination inhibition test. Esterification of the side chain with lauryl sulfat restored its erythrocyte coating capacity. In view of transforming this haptene into an immunogen, it was attached to S. minnesota Re cells. Immunization of rabbits with this conjugate engendered the formation of antibodies that agglutinated B. abortus and B. melitensis cells as well. As the side chain could only be isolated from the smooth strain, it proves that a defect in the synthesis of this moiety gave rise to the rough Brucella mutant. In the latter fraction glucose, mannose and quinovosamine were identified. Fraction II separated on Sephadex was identified as the core polysaccharide, present in the preparation obtained from smooth and rough strain. In the core region 2-keto-3-deoxy-octonate, glucose, glucosamine (from the smooth but not from the rough strain) and protein were identified. Following the mild HCl hydrolysis, the lipid-protein moiety i.e. region 3, is also split off but without precipitating and, during the fractionation on Sephadex, it adsorbs onto the gel. The absence of beta-hydroxymyristic acid and glucosamine in Brucella lipid dissociates it from the enteric lipid A. In the LPS-protein's toxicity a major role has the protein present only in the smooth strain.

Animals↗
PubMed1975

Morphogenesis and pathogenesis of chronic lung diseases. IX. Development of reticulinic fibrillogenesis during the evolution of an associated experimental silicosis and tuberculosis.

Well developed silicotic nodules of rabbit lungs were infected with tuberculosis and treated with tuberculostatics. The spatial evolution of lesions, as well as the density of intralesional and perilesional reticulinic fibrils were quantitatively analysed, measured by planimetric and target methods, and statistically analysed. Under tuberculostatics, the size of lesions, expressed in the dynamics of the SL/ST % ratio, rapidly diminished to half after three months. In the some period, the density of reticulinic fibrils expressed by the PA of the target method, increased, with significant differences between treated silicotuberculotic lesions and tuberculotic ones. The correlation analysis between these two divergent changes showed the interfering with other factors.

Animals↗
PubMedDate not supplied

Experimental viral lung fibrosis. Quantitative study of the relationships between cell accumulations and fibrillogenesis.

The relationships between mesenchymal lung cell accumulations and reticulinic fibrillogenesis were analysed morphologically and quantitatively during the development of a viral infection in the rabbit lung, induced by intranasal administration of influenza A2 virus. Cells and fibrils accumulated in the alveolar walls and in the interlobular areas of the lung were counted during the evolution of the experiment and statistically analysed. A significant statistical correlation between lung cell accumulations and fibrillogenesis could be demonstrated during the development of viral lung fibrosis.

Animals↗
PubMedDate not supplied

Morphogenesis and pathogenesis of chronic lung diseases. XI. Histoenzymatic study of the experimentally developing lung granulomas.

The development of lung granulomas induced in rabbits by an intravenous injection of the complete Freund adjuvant containing dog pulmonary proteins was followed by histologic and histoenzymatic methods. By comparison with normal rabbit lungs. the developing structures of the induced lung granulomas showed an increase of all tested enzymes at 15 days, and a secondary intensity decrease of the activity of malic dehydrogenase, of acid and alkaline phosphatases, and of alanyl-aminopeptidase at 30 days. Only the hydroxyproline-epimerase showed at these intervals an increasing activity in the lung granulomas. The developed reticulinic fibrils appeared to have a highly intense alkaline phosphatase activity.

Animals↗
PubMedDate not supplied

Proline-oxidase and hydroxypyroline-2-epimerase activities in experimental fibrosing granulomatous processes of the lung.

Three experimental fibrosing granulomatous processes of the lung (pulmonary granulomas induced by complete Freund adjuvant, viral pneumonitis induced by the A2 influenza virus, and tuberculosis induced in animals exposed to tobacco smoke) were produced in rabbits and the results confronted in view of establishing some relationships between mesenchymal cell accumulations, reticulin fibrillogenesis, and the enzymic activities of proline-oxidase (PO) and of hydroxyproline-2-epimerase (HEP), enzymes intervening in the control of hydroxyproline incorporation in the procollagen molecule. Histopathologic, histochemical and histoenzymic methods, quantification of cells and fibrils, statistical analyses, including the regression lines method, were used. The confrontation of the three processes made obvious that the cell accumulation invariably preceded the fibrillogenetic process, that the immune nature of the process was accompanied by larger cell accumulations than the non-immune one, that between cell accumulations and fibrillogenesis there existed highly significant correlations, and that the increase of the enzymic activities of proline-oxidase and of hydroxyproline-2-epimerase always accompanied these tissular changes, being topographically coincident with them (interlobular areas, alveolar walls).

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Histoenzymology of the lung. I. Enzyme activities of the lung tissue of acult humans; relationships between structure and functions.

Human adult lung fragments removed from macroscopically undamaged and anthracosis exempted zones of lungs of 20 pneumonectomies made for cancer, were tested for 25 enzymic activities. The location and intensities of these enzymic activities were different in the lung tissue components; The bronchial epithelia contained highly active LDH, MDH, SDH, NADH-TR and NADPH-TR, glucose-6-phosphate dehydrogenase, active hydroxyproline-2-epimerase, alkaline phosphatase. Ca2+-activated ATP-ase, and beta-galactosidase. Bronchial and vascular muscles presented intense activities of LDH, MDH and SDH of alkalinephosphatase, AMP-ase and Ca2+-activated ATP-ase, as well as of beta-galactosidase. The alveolar walls presented high activities of SDH, MDH and LDH, of alkaline and acid phosphatases, of beta-galactosidase and of Tween-40 and 60-esterases, of HEP, cytochrome-oxidase and peroxidase. The free alveolar macrophages were active for LDH, MDH, SDH, NADH-TR and NADPH-TR, G1-6-ph-DH, acid and alkaline phosphatase, cytochrome-oxidase and peroxidase, HEP, AMP-ase and Mg2+-activated ATP-ase, Tween-esterases, naphthol-ASD-acetate esterase, and beta-galactosidase. The endothelia contained high activities of alkaline phosphatase, of AMP-ase and Mg2+-activated ATPase, of LDH, MDH and SDH, and of beta-galactosidase. In bronchial lymphoid nodules it was the LDH, MDH, SDH, cytochrome-oxidase and peroxidase, HEP, alkaline phosphatase and AMP-ase, Tween-60-esterase and beta-galactosidase that were active. The interlobular areas of the lung presented intense activities of SDH, MDH, LDH, HEP and cytochrome-oxidase. The activities of the other tested enzymes were weaker or absent in the adult human lung components, the same as those of aminopeptidases which were present only in some free alveolar macrophages. The discussion of some relationships between these enzymic actitivies and the morphology of the human adult lung tissue asserted that the latter could not be considered as a "normal" tissue but as one overstrained by the components of blood and polluted air.

Adult↗
PubMedDate not supplied

Histoenzymology of the lung. II. The behaviour of lung hydrolytic enzymes during some experimental pulmonary processes.

The enzymic activity of acid alkaline phosphatases, of alanyl- and leucine-aminopeptidases, of beta-galactosidase and beta-glucuronidase, and of Tween-60-esterase was tested in the rabbit lung tissue during the following experimental processes: a) the sensitization with Freund adjuvant containing PPD and challenge of the delayed hypersensitivity reaction to PPD), b) the sensitization with gamma-globulin in Freund adjuvant, c) the pulmonary Arthus reaction, d) the lung granulomas induced by intravenous administration of Freund adjuvant containing heterologous lung proteins, e) the tuberculosis and silicotuberculosis under the influence of tuberculostatics. A metabolic intensification expressed by a marked increase of the tested hydrolytic enzymes was observed comparatively with controls in all these immune, granulomatous and inflammatory processes experimentally induced in the lung. The morphologic substrate of this behaviour was represented by the numerous cell proliferation and differentiations of the reticulomacrophagic type occurring during these experimental processes under the stimulation of antigenic elicitors. The latter also induced an increase of the lysosome-formation as submicroscopic site of these hydrolytic enzymes.

Animals↗
PubMedDate not supplied

Experimental chronic obstructive lung disease. I. Bronchopulmonary changes induced in rabbits by prolonged exposure to formaldehyde.

The prolonged exposure to formaldehyde induces in the rabbit lung reactional and dystrophic changes involving the intrapulmonary bronchi, the bronchioli and the lung tissue. These changes are represented by bronchial cell hyperplasia with hypermucigenesis, extrusion of bronchial cells, bronchiolar hypermucigenesis, parcellary squamous metaplasia or necrobiosis of epithelia, thickening of bronchial and bronchiolar walls by subepithelial cell accumulations, destruction of musculo-elastic structures with stenosis or ectasia; the vascular reactions are hyperhaemic and proliferative with an obstructive and fibrous tendency; the parenchymal lesions are atelectasias, intralobular emphysema, and cellular thickening of alveolar walls and interlobular areas. The acid phosphatase, Tween-60-esterase, naphthol-AS-D-acetate-esterase, proline-oxidase and hydroxyproline-2-epimerase activities are increasing, while the leucyl-aminopeptidase and beta-glucuronidase ones are decreasing. The qualitative observations are completed and sustained by quanitative studies of mucous cell kinetics, of cell accumulations and differentiations.

Animals↗
PubMedDate not supplied

Pulmonary blastoma.

A case of pulmonary blastoma in a 8-year-old girl is reported. The histopathologic analysis evidenced carcinomatous tubes with several cell layers developing into a mesenchymal cell mass with undifferentiated elements forming a dendroreticulated network with minimal endothelial, fibroblastic and collagenous differentiations. The initial tumoral formation within the lower left lobe was rapidly followed after resection by a local recidive and nine months later by a voluminous metastatic formation within the upper left lobe, radiologically treated. Discussion of the histopathologic characteristics of this case supports the hypothesis of a peculiar neoplastic entity of the lung, in which only the epithelial component of the lung was involved, while the mesenchymal mass presented an unaffected fetal structure.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

[Influence of tobacco smoking on the development of experimental pulmonary tuberculosis].

The present investigation was designed to the study, in rabbits, of morphologic and enzymatic pulmonary alterations produced by tobacco smoke and the course of tuberculosis under these conditions. The histologic examination revealed muciparous hyperplasia and pavementing metaplasia of the bronchic epithelium, accompanied by interstitial cellular reactions, reticulin, fibrilogenesis, atelectasis, emphysema and marked debility of the animals. In the animals treated with tobacco smoke the tuberculous lesions were very extensive and had an exudative-necrotic character. Under the influence of chemotherapy, applied during three months, reorganization of the lesions was reduced in comparison to the controls and an intense bacteriological activity persisted.

Animals↗
PubMedDate not supplied

[Epidemic of tuberculosis in a maternity hospital triggered by congenital tuberculosis in a newborn infant].

The development of several cases of miliary tuberculosis in infants aged 3--4 months, born in the same maternity led to an epidemiological investigation. On this occasion it was discovered that one of the patients that had been discharged immediately after delivery had pulmonary granulia a monthlater. The immature newborn was left in the maternity and died after one month with a diagnosis of "pulmonary microabscesses". The histopathologic examination of the lungs showed the presence of necrotic foci without any cellular reaction. Five months after the death of the infant a new examination of a pulmonary fragment was performed and Ziehl-Neelsen staining evidenced a large number of acido-resistant bacilli filling the lung alveoles. It was shown in this way that the infant with tuberculosis was the primary source of infection. All the 8 children that had developed the disease had been hospitalized in the same ward with the sick child. The transmission of the bacilli was done indirectly, through the feeding tubes that had not been sufficiently serilised, and the penetration ronte was the digestive tract. In two cases an otic primary focus was discovered and in one case an intestinal one was found on necropsy.

Cross Infection↗