uPA/plasmin system-mediated MMP-9 activation is implicated in bronchial epithelial cell migration.

To examine the effects of the uPA/plasmin system on cell migration in relation to the activation of MMP-9, we used ex vivo and in vitro wound-repair models of human bronchial epithelial cells and videomicroscopy techniques that make possible cell tracking and quantification of cell migration speeds. We observed that uPA was only detected in migrating cells at the wound edges and located at crucial sites for cell/extracellular matrix interactions. The implication of uPA in human bronchial epithelial cell migration was studied by incubating cultures with a monoclonal antibody raised against uPA and these experiments led to a 70% reduction in cell velocity. To examine the effects of the plasmin system on cell migration, we incubated cultures with increasing concentrations of plasmin or activated MMP-9. We observed a significant dose-dependent increase in cell migration velocity with plasmin (P < 0.001) and MMP-9 (P < 0.001). Moreover, addition of exogenous plasmin led to a twofold increase of activated MMP-9 in migrating cells. We also demonstrated that the addition of anti-uPA IgG led to an inhibition of 43% of activated MMP-9. In conclusion, these results show that uPA is involved in human bronchial epithelial cells migration. This action is mediated by the generation of plasmin, which in turn activates MMP-9, thus making possible cell migration.

Detection of human papillomavirus DNA in bronchopulmonary carcinomas by hybrid capture II: a study of 185 tumors.

BACKGROUND: Some human papillomaviruses (HPVs) are oncogenic in the cervix and are also associated with benign and malignant proliferations in other organs. Currently, the association of HPV with tumors of the lower respiratory tract is not so clearly defined because the studies are difficult to compare; series of cases reported from different geographic regions have used frozen or formalin fixed samples and a variety of techniques of HPV detection. METHODS: The authors studied the prevalence of HPV in a large series of 185 frozen bronchopulmonary tumor samples with a new solution hybridization technique, Hybrid Capture II assay. This test is largely applied in cervical pathology. Its sensitivity is very close to the sensitivity of PCR. It allows the detection of 18 mucosal HPV types, divided into 1 oncogenic and 1 nononcogenic group. RESULTS: Oncogenic HPV DNA was detected by the Hybrid Capture II assay in 5 cases (2.7%) of 185 (3 males and 2 females). In the rare positive cases detected, the authors could not find any consistent morphologic changes classically associated with HPV infection in anogenital lesions, such as koilocytosis. CONCLUSIONS: Oncogenic HPV DNA is detected in a small proportion of cases of bronchopulmonary carcinoma, and thus HPV infection appears to play a limited role in the tumorigenesis of most lung carcinomas.

Anthropotechnological analysis of industrial accidents in Brazil.

The Brazilian Ministry of Labour has been attempting to modify the norms used to analyse industrial accidents in the country. For this purpose, in 1994 it tried to make compulsory use of the causal tree approach to accident analysis, an approach developed in France during the 1970s, without having previously determined whether it is suitable for use under the industrial safety conditions that prevail in most Brazilian firms. In addition, opposition from Brazilian employers has blocked the proposed changes to the norms. The present study employed anthropotechnology to analyse experimental application of the causal tree method to work-related accidents in industrial firms in the region of Botucatu, São Paulo. Three work-related accidents were examined in three industrial firms representative of local, national and multinational companies. On the basis of the accidents analysed in this study, the rationale for the use of the causal tree method in Brazil can be summarized for each type of firm as follows: the method is redundant if there is a predominance of the type of risk whose elimination or neutralization requires adoption of conventional industrial safety measures (firm representative of local enterprises); the method is worth while if the company's specific technical risks have already largely been eliminated (firm representative of national enterprises); and the method is particularly appropriate if the firm has a good safety record and the causes of accidents are primarily related to industrial organization and management (multinational enterprise).

Expression of matrix metalloproteinases and their inhibitors in human bronchopulmonary carcinomas: quantificative and morphological analyses.

The expression of various matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in 88 primary bronchopulmonary cancers and in 13 neighbouring pulmonary parenchyma samples was quantified by Northern-blot analysis, and morphologically examined by in situ hybridization and immunohistochemistry in order to evaluate the involvement of MMPs in the pathophysiology of these carcinomas and to look for potential markers of aggressivity of lung tumours. Northern-blot analysis showed that the predominantly expressed MMPs in bronchopulmonary cancers were gelatinase A (66%), its activator MT1-MMP (membrane-type-1 matrix metalloproteinase) (56%) and stromelysin-3 (61%). MMP expression frequencies and mRNA levels increased progressively with malignant phenotype, lack of differentiation and TNM stage of the tumours, whereas TIMP expression decreased very early during tumour progression. Moreover, the principal MMPs were significantly co-expressed in primary tumours, suggesting their co-regulation. Morphological studies revealed the expression of MMPs and TIMPs essentially in stromal cells in close contact with tumour clusters. These results indicate that tumour progression in bronchopulmonary carcinomas implies a progressive disruption of the MMP/TIMP balance leading to an excess of several MMPs that act in concert in vivo. Furthermore, the fact that stromal cells are the principal source of MMPs emphasizes the close cooperation between host cells and cancer cells in tumour invasion.

[Anaplastic small-cell bronchial carcinoma of the composite type]. / Carcinome bronchique anaplasique à petites cellules de type composite.

The authors report an anatomico-clinical case (with ultrastructural study) of bronchial anaplastic carcinoma with composite, triple differentiation oat-cell subtype. The patient underwent early surgical excision followed by radiotherapy and chemotherapy. With the help of data from the literature concerning this composite subtype which suggests new theories on the histogenesis of bronchial cancer, the authors emphasize the value of surgical treatment for this unusual subtype of anaplastic carcinoma.

[Thymic carcinoid tumors. A clinico-anatomic study of 3 cases]. / Carcinoïdes du thymus. Etude anatomo-clinique de 3 cas.

The carcinoid tumour of the thymus was first detailed by Rosai in 1972. The authors describe three cases of this tumour with particular reference to their histogenesis. It appears to be a tumour predominantly affecting males with an often unfavourable, though slow, progression. Some pathological associations are frequent and characteristic. In one third of cases there is an associated endocrine neoplasia. As a rule the tumour is sited in the anterior mediastinum. The precise diagnosis rests on histochemical criteria (specific granulations). These carcinoids are tumours of the APUD system of endodermal origin. The treatment is surgical.

[Thymic seminomas (author's transl)]. / Les séminomes thymiques.

The authors report on three cases of thymic seminoma treated between 1971 and 1981. These tumours, first described by Friedman in 1981. These tumours, first described by Friedman in 1951, belong to the group of extra-gonadal germinal tumours. They constitute about 2.5% of all thymic masses. The most probable pathogenic theory is abnormal migration of germinal cells from the vitelline sac to the embryonic thymus. Thymic seminomas are usually found in young men and are asymptomatic in 30% of the cases. Macroscopically, they present as solid tumours capable of invading the surrounding structures. Histologically, they resemble gonadal seminomas but are sometimes difficult to identify, which is unfortunate since treatment is dependent upon an accurate histological diagnosis. The authors suggest that the tumour should be biopsied under mediastinal fluoroscopy, so that an accurate histological diagnosis can be made. Treatment consists of surgical excision, which should be restricted and on no account should destroy important structures, completed by mediastinal radiotherapy. The mean survival time is 6.3 years; the 5-year survival rate is 75%.

[Results of surgical treatment for rupture of the achilles tendon]. / Bilan du traitement chirurgical des ruptures du tendon d'achille

The authors analyse the results obtained on 53 cases of rupture of the Achillis tendon. Early minor complications were numerous (26 p. 100) the average follow-up, in 38 cases, was about 6 years. A number of ankle limitations, triceps weakness were noted. All patient had a calf atrophy. Final results were not related to the surgical technique (suture or grafting using plantaris). The authors conclude that the results obtained after surgical treatment are not as good as generally thought.