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S Philippou

Publications and source records attributed to S Philippou.

At least 37 records · Page 2Linked to original sources

Proliferative activity, p53 accumulation and neoangiogenesis in pulmonary carcinosarcomas and pulmonary blastomas.

Carcinosarcoma and pulmonary blastomas are rare biphasic tumors. Lung cancer pathogenesis is a multistep process. Proliferative activity, p53 accumulation and angiogenesis are of well-known relevance and ought to be evaluated in the epithelial and mesenchymal components of these tumors. Using antibodies against Ki-67 epitope MIB1 and proliferating cell nuclear antigen (PC 10) in 10 carcinosarcomas, tumors revealed a significantly higher proliferative activity in the epithelial component compared with the mesenchymal component in the MIB1 reaction (p = 0.013). In three pulmonary blastomas of the biphasic subtype, proliferative activity was similar in both parts. In five of 10 carcinosarcomas and in one of three pulmonary blastomas, accumulation of the p53 epitopes Pab 1801 and/or DO-1 was found. At the tumor front, a significantly higher vessel density was found compared with the central parts (p < or = 0.015) using a monoclonal antibody against human endothelium (CD 31). No differences were found between carcinosarcomas and pulmoblastomas. Higher proliferative activity in carcinosarcomas revealed a better prognosis regarding metastasis behavior (p = 0.05) and tumor-associated death in the follow-up (p < or = 0.017). p53 accumulation and microvessel density were of no prognostic value. This is in contrast to results in non-small cell lung cancer, pointing to a different biologic behavior.

Aged↗

[Expression of proliferation markers PCNA and MIB 1 in verrucous squamous epithelial carcinoma of the oral cavity].

Expression of proliferation markers PCNA and MIB 1 was evaluated in 17 verrucous carcinomas and in five cases of normal squamous epithelium of the oral cavity. Immunohistochemistry revealed no significant differences in the proliferative activities. Highest expression was seen in the basal zones. Proliferative activity in more than 26% of cells is no longer compatible with verrucous carcinoma, but favours the diagnosis of squamous cell carcinoma.

Aged↗

[Aggressive growth of hemangiopericytoma in the area of the facial skull].

Hemangiopericytoma is a rare tumor that originates from the pericytes. Only histology permits a reliable diagnosis. There are no known parameters to predict the biological behavior of the tumor, so every hemangiopericytoma has to be treated as potentially malignant. No age or gender prevalence of this tumor in the region of the head neck has yet been observed. Hemangiopericytoma should be treated by radical surgery; chemotherapy or radiation should be reserved for incompletely removed or metastatic tumors. Metastasis and recurrences have been described even decades after first tumor treatment, so that all patients should undergo life-long follow-up. As an example for a fulminant course of a malignant hemangiopericytoma (G3) we present the case of a 24-year-old female patient who initially presented nonspecific symptoms, was diagnosed late, and eventually died of her tumor despite chemotherapy and surgical treatment.

Adult↗

Role of sensory neuropeptides in PIV-3-infection-induced airway hyperresponsiveness in guinea pigs.

Viral respiratory tract infections are known to induce transient airway hyper-responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by nasal route. 16 animals served as untreated controls. Viral infection was proven by histological changes and by demonstration of viral antigen using immunohistochemical techniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheotomized guinea pigs. The ACH concentration which produced an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8 noninfected control animals were pretreated with capsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus inoculation. Measurements of airway responsiveness to ACH were performed 4 days after virus inoculation. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supermatant. PIV-3 infection increased airway responsiveness to ACH compared to noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn 0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected animals, airway hyperresponsiveness was completely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion with capsaicin completely prevented the increase in airway constrictory response to ACH following virus infection, we conclude that neuropeptides are effectively involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.

Acetylcholine↗

Persistence of airway hyperresponsiveness and viral antigen following respiratory syncytial virus bronchiolitis in young guinea-pigs.

Respiratory syncytial virus (RSV) bronchiolitis in infancy is known to be followed by chronic respiratory symptoms and airway hyperresponsiveness in a subgroup of patients. To further investigate the pathogenesis of RSV-induced chronic airway pathology, we infected young guinea-pigs at 4 weeks of age with RSV applied as an aerosol (n=30), and control guinea-pigs with virus-free culture medium (n=24). Infection was confirmed by positive antibody titre to RSV after 6 weeks, and by typical pathological changes of bronchiolitis after 1 week in six animals from each group. Airway hyperresponsiveness was measured weekly for 5 weeks by histamine challenge, using body-plethysmographic measurement of compressed air (CA). The provocative concentration of histamine producing significant airway obstruction (i.e. CA = 0.1 mL) (PC0.1 mL CA in mg x mL(-1)) was calculated from dose-response curves. Six weeks postinfection, the lungs were investigated for the presence of inflammation and of viral antigen by immunofluorescence and immunohistochemistry using a rabbit hyperimmune serum and monoclonal antibodies. Airway responsiveness was increased in the RSV group 1 week postinfection compared to the control group (PC0.1 mL CA median 2.50 vs >10 mg x mL(-1); p<0.001) and this persisted up to 5 weeks postinfection (PC0.1 mL CA median 1.61 vs >10 mg x mL(-1); p<0.001). During the same period, viral antigen persisted in the lungs of infected animals, although there was less inflammation at 6 weeks postinfection than at 1 week postinfection. In guinea-pigs, respiratory syncytial virus infection of the airways causes persistent airway hyperresponsiveness over a period of at least 5 weeks. During this time, viral antigen, but not inflammation, remains detectable in the lungs and might be responsible for ongoing airway hyperresponsiveness.

Animals↗

[Staging mesenteric ischemia based on histopathologic findings in the animal model].

With a minimal invasive access, a segmental intestinal ischemia of different duration was established in 25 pigs. After 24 h of reperfusion, the bowel was resected and examined by light microscopy. Considering these results, we developed a histopathological grading of intestinal ischemia to distinguish between viable and necrotic segments.

Animals↗

Detection of respiratory syncytial virus (RSV) antigen in the lungs of guinea pigs 6 weeks after experimental infection and despite of the production of neutralizing antibodies.

Infections with respiratory syncytial virus (RSV) are characterized by frequently occurring reinfections and are regarded to be responsible for bronchial hyperreactivity. In this report we describe a small-animal model suited to study RSV-induced pathogenesis and immune response. Guinea pigs are infected by inhalation of an RSV-aerosol. Lungs of infected animals show signs of a bronchiolitis at 7 days after the initial infection. Although neutralizing serum antibodies are synthesized viral proteins are still detectable at 6 weeks post infection. Therefore, the presence of neutralizing antibodies is obviously not sufficient for rapid clearance of persistent RSV-proteins from the lungs of infected guinea pigs.

Animals↗

A model for respiratory syncytial virus (RSV) infection based on experimental aerosol exposure with bovine RSV in calves.

Five conventionally kept calves aged between 17 and 24 days were experimentally infected with bovine respiratory syncytial virus (BRSV) by aerosol in order to mimic the natural infection route. The calves were killed and autopsies performed 7 days after the first virus challenge. The BRSV isolate used induced tracheitis, bronchitis and atelectasis in infected calves. The only virus which could be isolated from the lungs of the calves was BRSV. In addition, Mycoplasma bovirhinis was isolated from the lungs or/and trachea of two calves. The clinical and histopathological findings, as well as the detection of BRSV antigens by immunofluorescence in the epithelial cells of lung and trachea, and the reisolation of the virus from bronchoalveolar lavage fluids of all inoculated calves, provided confirmation of successful infection with BRSV.

Aerosols↗

Morphological studies of the respiratory syncytial virus induced bronchiolitis in experimentally infected calves.

RSV-infections of the lower respiratory tract in infancy and early childhood are the most frequent causes of a hyperreactive bronchial system and obstructive lung disease. Studies concerning the morphological alterations of the bronchial mucosa during an RSV-infection are dependent on an experimental animal model. In this study the alterations of the lower respiratory tract from five infected colostrum-fed calves during the initial stage of the infection are described. BRSV strain 375 was applied as an aerosol on four consecutive days. The animals showed clinical symptoms already on the first day after infection. 7 days after the first infection the calves were necropsied. Lobular distributed atelectasis of the lung were found. The corresponding bronchioli were collapsed. The bronchiolar lumina were filled with a putrid exudate. In the bronchiolar wall a band-like lymphocytic infiltrate was found. By confocal laserscanning microscopy and by scanning electron microscopy intracellular viral components marked by an antibody against the viral P-protein were depicted. The intracellular virus inclusions were arranged along the bundles of filaments of the cytoskeleton. By transmission electron microscopy an alteration of the ciliogenesis and in cases of severe cell damage, cell death could be observed. The morphological findings suggest that the cytoskeleton plays an important role in the development of bronchiolitis.

Animals↗

Tracheal carcinoma and mixed pneumoconiosis. A causal relationship?

We report on a 58-year-old man who had worked as a plumber and fitter for over 41 years and had been exposed to asbestos, man-made mineral fibers and welding fumes. Eighteen months before death, squamous cell carcinoma of the trachea occurred. Energy-dispersive X-ray analysis revealed intrapulmonal dust deposits in accordance with his exposure. A relationship between the tracheal carcinoma and the dust exposure causing a mixed pneumonoconiosis seems to be probable.

Asbestos↗

[Malignant fibrous histiocytoma in the area of a total endoprosthesis of the hip joint].

Up to now 8 cases of malignant fibrous histiocytoma are reported in whom the tumor had developed after total hip replacement. Direct contact between tumor and prosthesis was proved in 7 cases. We report on a female patient of 74 years of age in whom a malignant fibrous histiocytoma of the gluteal region had formed 15 years after total hip replacement. Tumor was located in the old operation scar. Not only a direct effect of the foreign material, but also the scar has to be regarded as an etiological factor in pathogenesis of malignant fibrous histiocytoma in these cases.

Aged↗

[Primary germ cell tumors of the mediastinum].

This is a report on 5 cases of mediastinal germ cell tumours. Of three mature teratomas seen in a 48-year old male and a 21-year old and 19-year old female, one was asymptomatic, another one associated with streptococcal pneumonia and the third associated with progressive cough irritation. In addition, a seminoma was seen in a male of 58 years of age and a yolk sac tumour (mesonephroma type 2) in a male of 23 years. Whereas in mature teratomas surgical resection can be considered sufficient, resection combined with chemotherapy should be performed in patients suffering from malignant germ cell tumours, and in addition also radiotherapy in case of seminoma. This approach may result in a significant improvement of the prognosis in malignant mediastinal germ cell tumours.

Adult↗

[Pneumocystis carinii pneumonia with recurrent pneumothorax and pleuritis].

A report on three HIV-positive patients with recurrent pneumothorax in pneumocystis carinii pneumonia on whom partial parietal pleurectomy and in two cases also a wedge-shaped pulmonary resection were performed. Histology revealed granulomatous necrotising pneumonia involving the visceral pleura, and a partly honeycomb-shaped metaplasia of the pulmonary tissue. A fibrinous and partly granulomatous necrotising pneumocystis carinii pleuritis of both pleural membranes was seen, being the morphological correlate of an in all cases prolonged exudation to the pleural cavity. Conservative treatment remained unsuccessful due to the marked lung and pleura involvement in the inflammatory process, necessitating surgical revision.

AIDS-Related Opportunistic Infections↗

The morphological substrate of autonomic regulation of the bronchial epithelium.

Observations of explanted bronchial mucosa show that ciliary function is maintained for 7 days subsequent to explanation. This finding demonstrates that non-neural mechanisms exist which regulate ciliary function. Ultrastructural and immunohistochemical studies both for light and electron microscopy were performed on human bronchial biopsy material and lung resection specimens in order to recognize the morphological substrate of this regulatory mechanism. A complex system of cytokeratin filaments and microtubules radiate through the whole cytoplasm of ciliated cells with direct contact to the nucleus, cilia, microvilli, desmosomes and to the apical terminal adhesive complex. Between the basal bodies and the apical terminal adhesive complex microfilaments can be found. In the apical cytoplasm a dense filamentary network is seen in association with the adhesive complex. These morphological findings indicate that the cytoskeleton of the bronchial epithelium plays a key role in the co-ordination of ciliary function.

Bronchi↗

Ultrastructural study of rabbit lung tissue subsequent to capsaicin treatment over several days.

The neurogenic basis of nonspecific airway hyperresponsiveness (NAH) is poorly understood. Under experimental conditions isocyanates can elicit bronchial hyperresponsiveness in animals. The purpose of our study was to determine whether reactions of neurosecretory granules in nonmedullated C fibers might play a role in NAH. Our experiments were based on the fact that capsaicin treatment causes depletion of neurosecretory granules in vicinity of C fibers. We gave rabbits repeated subcutaneous injections of capsaicin. The animals were then treated with toluene diisocyanate (TDI), inducing airway hyperresponsiveness upon acetylcholine (ACH) inhalation. In capsaicin-treated animals the neurosecretory granules were not evident ultrastructurally and airway hyperresponsiveness did not occur in response to TDI treatment. Controls that were not treated with capsaicin displayed both neurosecretory granules ultrastructurally as well as airway hyperresponsiveness to ACH. We conclude that in the rabbit, NAH is related to the presence of neurosecretory granules adjacent to nonmedullated C fibers.

Acetylcholine↗

[Effect of the humoral immune response on the pathogenesis of respiratory syncytial virus (RSV) infection].

Direct cytopathic effects and components of the humoral immune response may contribute to the pathogenesis of respiratory syncytial virus (RSV) infections. Using synthetic peptides as an analytical tool, it could be demonstrated that the primary immune response of young children is directed against other epitopes compared to the situation in adults. RSV-specific antibodies are not only considered to possess protective properties but also to contribute to the pathogenesis of the infection. In our experiments, human adherent cells from lavage could be infected by RSV more effectively in the presence of murine monoclonal antibodies specific for RSV surface proteins.

Antibodies, Viral↗

[Detection of asbestos in thoracic lymph nodes in patients with asbestosis].

To detect a possible lymph transport of inhaled asbestos fibres and fragments from the human lung we examined via light and scanning electron microscope a total of 224 intrapulmonary, extrapulmonary and paratracheal lymph nodes of 6 postmortem cases and 3 lung resectates from patients with histologically proven pulmonary asbestosis. The lymph nodes were subdivided into 3 groups and examined separately. We found partly sharp-edged staff-shaped and partly amorphous dust particles that were mostly embedded in phagolysosomes of macrophages, using energy-dispersive x-ray microanalysis; these particles yielded a spectrum like that of asbestos, which means they must be identified as asbestos fragments. Besides these, typical asbestos bodies and asbestos needles were also identified.

Aged↗