Impact of Induced Th1/Th2 Shift on Trichobilharzia regenti Infection in Mice.

Bird schistosomes parasitize mammals as non-specific hosts. Neurotropic Trichobilharzia regenti migrates extravasally via nervous tissue in experimentally infected mice. The majority of successfully penetrated larvae remain in the skin; the rest migrate through peripheral nerves to the spinal cord and brain. The potential of schistosomula to leave the skin and enter the central nervous system vary, and may be associated with Th1/Th2 polarization of the host cell immune response. The aim of the present study was to evaluate the impact of induced shift in polarization of cell immune response on the migration of T. regenti larvae in mammals. For this purpose, non-specifically immunomodulated mice were infected. The localization and abundance of schistosomula and associated histopathological changes were followed using routine histological techniques. Markers characterizing Th1 and Th2 systemic immune responses were followed using flow cytometry. The study revealed that the shift towards Th1 response at the time of infection correlates with the speed and intensity of schistosomula migration towards the brain and with the severity of accompanying pathologies. This indicates increased health risks associated with T. regenti infection for mammals (potentially including human) with previously modulated cell immune response that may occur under natural conditions, e.g. due to the exposure to another infectious agent.

[Treatment results of Langerhans cell histiocytosis with LSH II protocol]. / Výsledky lécby histiocytózy z Langerhansových bunek protokolem LCH II.

BACKGROUND: The aim of study was to evaluate outcome of international treatment protocol LCH II for children with Langerhans cell histiocytosis treated in FN Motol. METHODS AND RESULTS: Between November 1995 and December 2003, 46 children were treated, sex ratio M:F 29:17 and median age at diagnosis 6 years 8 months. 28 children (60.9%) suffered from monosystem disease with majority of bone lesions (23 times) with skull predominance (16 times). Surgery was primary treatment modality for monosystem disease. Five children with recurrence were successfully treated by protocol LCH II - LR (3x) and LCH III - LR /G2/, respectively. Eighteen children (39.1%) suffered from multisystem disease. 6 out of 18 patients were treated according to low-risk protocol LCH II - LR and 12 children by high-risk scheme LCH II - HR at the non-randomized branch included etoposide. Recurrence was revealed in 11 patients and 10 of them reached 2nd or 3rd complete remission (CR) by 2 - chlorodeoxyadenosine (CDA) monotherapy, and 1 child reached 2nd CR by LCH II - HR scheme. Two children underwent irradiation after bone lesion excision as well as 1 child as supplemental treatment. Totally, 29 children (63.0%) achieved 1st CR, 14 (30.4%) 2nd CR, 2 (4.4%) 3rd CR, and 1 child died because of LCH progression. There were no severe side effects of chemotherapy. Follow-up median time was 5 years 8 months (range 9 months - 9 years 6 months). CONCLUSIONS: LCH II protocol is safe and effective. Results revealed that treatment of patients with multisystem disease might demand some treatment modification.

Expression of thyroid transcription factor 1 in primary brain tumours.

BACKGROUND: Thyroid transcription factor 1 (TTF-1) is expressed in a proportion of carcinomas derived from follicular thyroid cells and respiratory epithelium. Immunohistochemical detection of this protein was shown previously to be a helpful aid in tumour diagnosis, specifically in deciding whether a tumour is primary to the lung/thyroid gland or metastatic. Recently, TTF-1 expression was also observed in certain areas of postnatal brain. AIM/METHOD: To investigate the expression of TTF-1 protein in a spectrum of 73 primary brain tumours including astrocytomas, glioblastomas, ependymomas, oligodendrogliomas, medulloblastomas, and gangliogliomas of different sites. RESULTS: All the tumours were negative for TTF-1 except for two ependymomas of the third ventricle. CONCLUSIONS: The expression of TTF-1 in brain tumours appears to be site specific rather than associated with tumour dedifferentiation. The presented expression of TTF-1 protein in certain primary brain tumours should be taken into consideration when interpreting the immunohistochemical staining of brain tumours of uncertain primary site.

Distribution of the extracellular matrix glycoproteins in ependymomas--an immunohistochemical study with follow-up analysis.

The extracellular matrix (ECM) plays a critical role in influencing the biological behavior of brain tumors and the diagnostic detection of ECM components in ependymomas might be of prognostic value. In the present study we evaluated immunohistochemically the expression of a spectrum of ECM glycoproteins (tenascin, vitronectin, fibronectin, laminin, collagen types II, IV and VI) in a series of 36 pediatric intracranial ependymomas. The distribution of the ECM glycoproteins was evaluated both within the tumor tissue and at the tumor invasion front, and the prognostic value of the results was tested in a survival analysis. The expression of most of the ECM glycoproteins was associated only with blood vessels. Tenascin and vitronectin were found in a more diffuse pattern around the tumor cells and at the tumor invasion fronts of several cases. The progression-free survival was significantly decreased for patients with tenascin positive tumors (in any of the studied compartments) and for the tumors with vitronectin accumulation at their invasion fronts. In one ependymoma containing foci of cartilage with metaplastic ossification we demonstrated that collagen types II and VI and tenascin were present in ECM of both the cartilage and the ependymoma, and were accompanied by areas of necrosis and dystrophic calcifications. We suggest, that the rare simultaneous production of the specific ECM components might lead to the formation of chondroid areas in ependymomas. An abundant production of some ECM glycoproteins (tenascin and vitronectin) is present in a proportion of ependymomas and its immunohistochemical detection is of prognostic relevance.

Gene aberrations in childhood brain tumors.

We present the results of the examination of prognostic markers in 40 children suffering from brain tumors. Prognostic markers such as amplification of the N-myc and c-myc, deletion of the 17p, and DNA ploidy are indispensable factors for the determination of diagnosis. An increased number of c-myc gene copies was found in malignant brain tumors, especially embryonal, more often than reported in the literature. N-myc amplification occurs in our group seldom, but it seems to be a sign of worse prognosis in glial and embryonal brain tumors. DNA aneuploidy was not found very frequently, but in high-grade tumors only.

[Primary lung tumors in childhood]. / Primární nádory plic v detském veku.

The authors give an account of their experience with the treatment of primary lung tumours in children during 1989-1998. Primary lung tumours in children are extremely rare and represent a varied spectrum of pathological conditions (pneumoblastoma, rhabdomyosarcoma, mucoepidermoid carcinoma, pulmonary endodermal tumour and benign tumours). During the mentioned period 10 children were operated on account of primary lung tumours, 5 with malignant tumours and 5 with benign tumours. In these patients during the above period 3 pneumonectomies, 5 lobectomies and 3 segmental resections were made. Chemotherapy was indicated in children with pneumoblastoma and rhabdomyosarcoma. Two patients with pneumoblastoma died, 3 children with malignant and 5 children with benign tumours live without symptoms of the disease.

Trichobilharzia szidati: the lung phase of migration within avian and mammalian hosts.

The passage of Trichobilharzia szidati schistosomula through the vertebrate lungs was examined in natural and abnormal hosts--birds (ducks Anas platyrhynchos f. domestica) and mammals (mice Mus musculus Bagg albino/c [BALB/c]), respectively. Using the methods of classical histology, the migratory route of worms was characterized, and the impact of migration on host tissues and the host cell reactions were evaluated. Living schistosomula were recorded in the lungs of ducks 2-10 days post infection (p.i.) and in the lungs of mice 2-4 days p.i. In ducks, the schistosomula migrated from the blood vessels through the blood capillaries to the lung tissue; then, they entered free air space of the lungs. The infection resulted in inflammatory reaction with nodules composed of infiltrated lymphocytes, heterophils, eosinophils and macrophages. These structures were formed around the blood vessels and in the gas-exchange tissues of the parabronchial walls and, consequently, in the walls of secondary bronchi. An extensive inflammation of secondary bronchi and parabronchi was observed. In the lungs of mice, the parasites were localized extravascularly in the alveolar walls. No migratory pattern similar to that in the lungs of ducks was recorded. No specific inflammatory reaction occurred. However, alveolar wall congestion, edema and lymphocyte infiltrates appeared and, therefore, pathogenicity of T. szidati was also confirmed in the murine host.