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Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus.

1. The effect of sensory neuropeptides and capsaicin on basal and stimulated tone of mouse bronchial smooth muscle has been evaluated. 2. In basal conditions neither sensory neuropeptides (substance P, neurokinin A or calcitonin gene-related peptide (CGRP) nor capsaicin exerted any contractile effects. However, when a tonic contraction was induced with carbachol (1 microM) a prompt relaxation was induced by substance P (1- 100 nM) and by neurokinin A (1- 100 nM), with substance P being more potent. A second application of substance P was without effect. CGRP (10 nM) produced only a very small and erratic relaxation. Relaxation was also induced by capsaicin (1 microM), and this response could be evoked only once in each preparation. In 4 out of 6 preparations a cross-desensitization between substance P and capsaicin was observed. 3. The selective NK1 tachykinin agonist, [Pro9]-SP sulphone (1 microM), exerted potent bronchodilator actions on carbachol-contracted mouse bronchial preparations. In contrast, neither [beta Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a concentration of 1 microM), selective synthetic agonists for NK2 and NK3 receptors, exerted significant relaxant effects. Furthermore, the selective NK1 tachykinin antagonist, (+/-)-CP 96,345 (1 microM), abolished substance P (1 nM)- but not isoprenaline (0.1 microM)-induced relaxations. 4. Application of electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s) to carbachol-contracted preparations evoked a transient contraction followed by a relaxation. The tetrodotoxin-sensitive slow component of this relaxation was reduced following capsaicin desensitization. 5. In the presence of indomethacin (5 microM) the relaxation induced by substance P, capsaicin or EFS was suppressed.6. In conclusion, the mouse main bronchus appears to be a monoreceptorial tissue containing only NK, receptors which subserve bronchodilator functions. Such receptors could be activated by exogenous or endogenously (capsaicin or EFS) released tachykinins and the consequent relaxation is probably mediated by the generation of prostanoids.

Animals↗

Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.

1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human bronchial tissue. PDEs I, II and V were also identified. 6. Theophylline and pentoxifylline were, as expected, non-selective inhibitors of the human enzymes, but there was a good correlation between PDE IV inhibitory and bronchorelaxation potencies, suggesting that PDE IV inhibition is important for the clinical bronchodilator activities of the two xanthine compounds. 7. We have confirmed the ability of selective PDE IV inhibitors to cause bronchodilatation in guinea-pigs in vivo. 8. We conclude that our study has provided further evidence that selective PDE IV inhibitors could act as bronchodilators in the clinic.

3',5'-Cyclic-AMP Phosphodiesterases↗

Localized peribronchial adenomyomatous hyperplasia arising from an ectatic bronchus with aspergilloma.

A cavitary lesion containing a mobile nodule was found in the right lower lung of a 68-year-old woman. Suspecting bronchiectasis with a fungus ball, we performed wedge resection of the right lower lobe. Light microscopy revealed that a uniformly thickened muscular layer around the ectatic bronchus with aspergilloma had formed a focally protruding mass. It was composed of bundles of hyperplastic smooth muscle and entrapped glandular structures. Given the histological similarity between the lesion and adenomyomatous hyperplasia of the gallbladder, we diagnosed the previously undescribed lesion as "localized peribronchial adenomyomatous hyperplasia". This condition should be recognized as a tumor-like form of smooth muscle hyperplasia induced by bronchiectasis and inflammation.

Adenocarcinoma↗

Case report: infantile sub-lobar emphysema and tracheal bronchus.

Localised disturbance of aeration in children is as often the result of mucosal swelling due to infection as resulting from an inhaled foreign body. The present report adds another cause: tracheal bronchus. Elucidation of this cause of localised disturbance of aeration usually includes bronchoscopy, the anesthesia and direct trauma involved being highly undesirable if i infection is the cause. The case for limited, careful bronchography, before or instead of bronchoscopy, when the history of foreign body is lacking is presented.

Ampicillin↗

A study of bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa.

The immunologic pathogenesis of conditions characterized by chronic pulmonary infections, such as diffuse panbronchiolitis and those associated with cystic fibrosis, had not been fully clarified. Organized lymphoid tissue along the airway has been termed bronchus-associated lymphoid tissue (BALT), and hyperplasia of BALT is frequently observed in chronic pulmonary infections in humans. To investigate the role of BALT, we intratracheally inoculated rats with Pseudomonas aeruginosa (PA) enmeshed in agar beads according to the method of Cash et al., thereby establishing a chronic pulmonary infection model. Histopathological examination of tissue from this rat model revealed the accumulation of lymphocytes and foamy cells around bronchioles. This finding corresponds to chronic bronchiolitis in humans. Hyperplasia of BALT was also observed. Immunohistochemical examination demonstrated that Ia+ cells, helper T cells, surface IgM-positive (sIgM+) cells and sIgA+ cells had gradually increased in BALT and the walls of peripheral airways during the period from day 4 to 7. The anti-PA IgA antibody titer in bronchoalveolar lavage fluid (BALF) was also elevated during this period. After day 21, non-helper T cells became predominant in tissue sections, and the numbers of various immunoglobulin-positive cells as well as the anti-PA IgA antibody titer in BALF were reduced. Histological examination revealed that the inflammatory findings had also diminished. The time course of changes in the various immune cells in BALT and the walls of peripheral airways, paralleled the reductions in anti-PA IgA antibody titers in BALF. Our findings suggest that hyperplastic BALT may be one source of the Ig producing cells which play an important role in the local immune response characteristic of chronic pulmonary infections.

Animals↗

Morphological and immunohistochemical studies of the lungs and bronchus-associated lymphoid tissue in a rat model of chronic pulmonary infection with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the most frequently encountered bacterial pathogens in patients with chronic pulmonary infections, including cystic fibrosis and diffuse panbronchiolitis. Bronchus-associated lymphoid tissue (BALT), noted frequently in patients with cystic fibrosis and diffuse panbronchiolitis, is considered to play an important role in the local immunologic defense mechanisms in the respiratory tract. To investigate the role of BALT in chronic pulmonary infections, we developed an animal model for chronic pulmonary infection and studied the morphological and immunohistochemical characteristics of BALT. Experimental pneumonia was produced in rats by intratracheal inoculation of P. aeruginosa enmeshed in agar beads. The histological changes corresponded to those occurring in chronic bronchiolitis. Immunohistochemically, surface immunoglobulin M-positive (sIgM+) cells and sIgA+ cells were recognized in the inflamed bronchial walls from day 4, and sIgG+ cells were recognized from day 14, W3/25+ cells exceeded OX8+ cells in number until day 14. In the BALT, there was a massive accumulation of lymphocytes in the lymphatics and high endothelial venules. The development of germinal centers was accompanied by increased numbers of sIgM+ and sIgA+ cells. W3/25+ cells exceeded OX8+ cells in number in the BALT until day 14. On the other hand, OX8+ cells were predominant in comparison with W3/25+ cells at day 21, and then both sIgM+ and sIgA+ cells and inflammatory changes in the lung decreased at day 28. These findings suggest that BALT regulates the local immune responses against chronic pulmonary infection due to P. aeruginosa.

Animals↗

Carcinoma of bronchus and the smoking habit in Rhodesian Africans.

Comparison of the smoking habits of 32 adult male Africans with carcinoma of the bronchus and 32 controls showed that 87.5% of the patients with lung cancer were cigarette smokers compared with only 22% of the controls. The distribution of histological types of growth confirmed findings by other workers.The absence of atmospheric pollution in Rhodesia makes it likely that cigarette-smoking is the most important causative factor in the aetiology of lung cancer among Rhodesian Africans. Further work is needed to determine the level of consumption of cigarettes and type of smoking habits which lead to a serious risk of cancer.

Adenocarcinoma↗

Scintillation scanning of lungs in preoperative assessment of carcinoma of bronchus.

Lung scans with the use of macroaggregated human serum albumin labelled with technetium-99m were carried out in 52 patients before thoracotomy.Forty-three patients had carcinoma of the bronchus. Tumours less than 2 cm. in diameter on the chest radiograph were not detected. Larger tumours showed defects in perfusion, ranging in size from the mass seen on the chest radiograph to almost absent perfusion of the entire lung. The extent of the defect in perfusion was closely related to involvement of the pulmonary vessels at the hilum by distortion, compression, or invasion by the tumour. Bronchial obstruction played a less important part in producing the defects.The larger the defect in perfusion the greater was the involvement of the hilar and mediastinal structures and the more extensive was the surgery required. When perfusion of the affected lung was less than one-third of the total the tumour was found to be unresectable.

Adult↗

Differential expression and distribution of epithelial adhesion molecules in non-small cell lung cancer and normal bronchus.

BACKGROUND: Changes in epithelial cell interactions have been implicated in carcinogenesis, tumour invasion and metastasis. AIM: To screen for altered expression of epithelial adhesion genes in lung cancer development. METHODS: Gene expression profiles were assessed with cDNA expression arrays in eight non-small cell lung cancer (NSCLC) and eight normal bronchi obtained from the same patient. Immunohistochemistry (IHC) and RNA in situ hybridisation (ISH) were used to confirm the most prominently expressed adhesion molecules and to investigate their distribution at protein and mRNA levels. RESULTS: 43 differentially expressed cancer-related genes were identified in adenocarcinoma, squamous cell carcinoma (SCC) and normal bronchus. Five of these genes are related to epithelial adhesion-that is, integrin alpha3 (ITGA3), integrin beta4 (ITGB4), desmoplakin I and II (DSP), plakoglobin, and desmocollin 3 (DSC3). ITGA3 and ITGB4, showing predominantly cell-matrix staining, were up regulated in adenocarcinoma and SCC, respectively. ITGB4 also showed strong staining in SCC with IHC and ISH. Components of the desmosome adhesion complex DSP, plakoglobin and DSC3 were strongly up regulated in SCC and showed a distinct cell-cell staining pattern. DSP and plakoglobin were predominantly present at central, more differentiated tumour cells, whereas DSC3 showed a stronger staining in the peripheral basal cells of SCC tumour areas. CONCLUSIONS: Lack of cellular adhesion may have an important role in the metastatic potency of a primary tumour. A possible association of strong presence and normal-distributed desmosomal molecules in SCC with the less frequent and late pattern of metastasis in SCC as compared with adenocarcinoma is suggested.

Adenocarcinoma↗

Poorly differentiated squamous carcinoma of the bronchus: a light and electron microscopic study.

As there is little published information on the ultrastructure of poorly differentiated squamous carcinoma of the bronchus 18 examples of this tumour were studied. On light microscopy 10 of the tumours contained foci of keratinisation or intercellular bridges and therefore fulfilled the World Health Organisation's diagnostic criteria. In eight these features were absent, but the overall appearance was sufficiently squamoid to preclude their placement in any other category. On electron microscopy many cells showed the characteristic desmosomes and tonofilament of of squamous carcinoma, but there were also areas of adenodifferentiation. The ultrastructure of both light microscopic groups was identical. In conclusion, this type of tumour is dimorphic with characteristics of adenocarcinoma and squamous carcinoma on electron microscopy. Keratinisation and bridges are not essential diagnostic criteria: the overall pattern and cellular morphology are more important.

Adenocarcinoma↗

Malignant melanotic schwannoma of the bronchus.

A case of malignant melanotic schwannoma arising in the right upper lobe bronchus of a 27 year old man is presented. Tumours of this type most commonly occur in spinal nerve roots and are generally considered to be benign. The behaviour of those originating elsewhere is less predictable. As far as we are aware this is the first reported case affecting the respiratory tract.

Adult↗

Pleomorphic adenoma of the bronchus.

An example of pleomorphic adenoma of the bronchus is described in a 27 year old male student who was referred for evaluation of a coin lesion identified incidentally on chest x ray. The tumour exhibited the classic histological, immunohistochemical and ultrastructural features of this rare entity but, in addition, contained mature and immature adipose tissue in the stroma and showed transition, in its superficial portion, between ostensibly normal bronchial mucus glands and tumour tubules. Neither of these features has been commented upon previously.

Adenoma, Pleomorphic↗

Degeneration of muscle in association with carcinoma of the bronchus.

The clinical features and necropsy findings are described in three cases in which severe and rapidly progressive muscle weakness developed in association with carcinoma of the bronchus. In all three cases, muscular weakness was directly responsible for death. Histological and ultramicroscopical examination in all cases showed an unusual type of degeneration of muscle fibres accompanied by degeneration of intramuscular nerve fibres, but without involvement of the central nervous system, or of the peripheral nerve trunks. The findings are compared with those of previously reported cases, and possible mechanisms for the muscle degeneration are discussed.

Aged↗

Severe orthostatic hypotension associated with carcinoma of the bronchus.

A patient is described who had severe orthostatic hypotension. An account is given of his treatment with a monoamine oxidase inhibitor and tyramine. At post-mortem, 8 months after the illness began, a small oat cell carcinoma of the bronchus was found. It is suggested that the orthostatic hypotension was a nonmetastatic manifestation of the underlying carcinoma.

Aged↗

Neurotensin-secreting carcinoma of the bronchus.

Neurotensin, a neuroendocrine peptide present in gut and brain has previously been found in pancreatic tumours secreting several other peptides. We report here the first case of a patient with a neurotensin-secreting adenocarcinoma of the bronchus.

Adenocarcinoma↗

Minimal change nephropathy associated with anaplastic carcinoma of bronchus.

Nephrotic syndrome associated with extra-renal malignancy shows a characteristic pattern: carcinoma is most frequently associated with membranous glomerulonephritis and Hodgkin's disease with minimal change nephropathy. We report a patient with minimal change nephropathy in association with anaplastic carcinoma of the bronchus. Strong temporal evidence of a causal relationship is presented. The dissociation in the response of the two conditions to treatment of the tumour after relapse may be evidence of an indirect pathogenesis.

Bronchial Neoplasms↗

Tumour production of alkaline phosphatase in a patient with giant-cell carcinoma of bronchus.

A patient with a giant-cell carcinoma of the bronchus was found to have a raised serum alkaline phosphatase without any evidence of bone or liver involvement. After necropsy the excised tumour was found to be producing alkaline phosphatase. The alkaline phosphatase found in the serum during life was heat-labile but that in the tumour was heat-stable. The significance of this is unknown.

Alkaline Phosphatase↗