New insights in the pathogenesis of atopic disease.

A causal link between the increasing environmental pollution and the fast spreading of allergic diseases is currently discussed. The exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic, sensitizing and neurotoxic mechanisms in animal experiments and in humans. Beside classic allergic-triggering factors (allergen potency, intermittent exposure to different allergen concentrations, presence of microbial bodies and sensitizing phenols), the adjuvant role of environmental pollutants gains increasing importance in allergy induction.

Increased levels of transition metals in breast cancer tissue.

Objectives: High levels of transition metals such as iron, nickel, chromium, copper, and lead are closely related to free radical generation, lipid peroxidation, formation of DNA strand breaks, and tumor growth in cellular systems. In order to determine the correlation to malignant growth in humans, we investigated the accumulation of heavy metals in 20 breast cancer biopsies and compared the findings to the levels found in 8 healthy biopsies.

Methods: The concentration of transition metals in breast cancer and control biopsies was assessed by a standardized Atomic Absorption Spectrofotometry technique with acidic hydrolysis for sample preparation.

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.

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.

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.

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.

Recurring thoracal mesenchymoma.

A four-times-recurring thoracal mesenchymoma is presented. Each tumor evolved for 2-5 years before resection, the general evolution of the case being of about 30 years. Histologically, the tumors, which involved the thoracal wall presented at the same time the predominating fibroblasto-fibrocytic structure sometimes forming whirls, different mesenchymal derivatives as vessels and angiomatous formations, osseous trabeculae, chondroblastic areas, and more or less dense zones with leiomyocytes sometimes forming myomatous and myofibromatous aspects.

Bronchiolar pathology. IV. a morphometric analysis of the incidence and location of lesions induced in rabbits by intratracheally injected detergent solutions.

An experimental model of bronchiolar lesions was elaborated. It consisted of three intratracheal administrations in rabbits of 2 ml of a 3 per cent detergent solution, pH 2.5-3; the adequate development of the process was induced when the second injection was given 48 h after the first and the third on days 5-6.

Eosinophilic granulomas of the lung. Histopathology of three cases.

Three cases of eosinophilic granuloma of the lung were histopathologically analyzed on surgical materials (two resections and lung biopsy). The analysis insisted upon the cell components of pulmonary lesions, histiocytic and eosinocytic accumulations involving lobular air spaces, alveolar walls and interlobular areas, and forming bullae by histiocytic enzymic activity and lipid dysmetabolism; the fibrotic evolution of the lesions varied from case to case. The lesional histogenesis is discussed in the light of recent electronmicroscropic, histochemical and immunopathological data, stress being laid upon the local influence on the development of the process.

Histoenzymology of the lung. V. Histoenzymatic analysis of sixty lung tumors.

A series of sixty lung tumors operated during 1977 were histoenzymatically investigated (12 macrocellular carcionomas, 4 microcellular, 18 epidermoid, 18 cylindrocubic, 2 bronchiolo-alveolar cell carcinomas, 4 lung fibroblastic sarcomas, and 2 benign lung tumors: a haemangioma and a carcinoid tumor). There were tested 25 enzymes, hydrolases and oxidoreductases of different metabolic pathways. The histoenzymatic analysis of the neoplastic lung tissue compared with the normal adult human lung tissue pointed to a shifting of the metabolic balance, with the decrease of enzyme activities belonging to the Krebs tricarboxylic acid cycle and with the increase or maintenance of the level of enzymic activities belonging to the Embden-Meyerhoff-Parnas pathway and to the pentose shunt.

[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".

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.

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.

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.

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.

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).

[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.

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.