Sarcoidosis with upper respiratory tract involvement

SummaryThe aim of the study was to investigate the upper respiratory tract as a site of extrapulmonary sarcoidosis. Diagnosis of sarcoidosis with upper respiratory tract involvement was performed on the basis of clinical, laboratory, radiographic and histological evidence and by excluding other granulomatous diseases in eight patients followed by the Sarcoidosis Regional Reference Centre pneumologists in collaboration with an experienced ENT specialist at Siena University. In five cases, sarcoidosis was localized in the parotid glands, in the other three subjects larynx, nasopharynx and nose were involved. In four patients parotid gland, nasopharynx and upper respiratory tract mucous membrane involvement was the only clinical manifestation at onset of the disease.Upper respiratory tract involvement should be suspected in all patients with systemic sarcoidosis and in patients with persistent upper respiratory tract symptoms of unknown cause. What a general practitioner should do as not to miss SURT is underlined. Interdisciplinary management and collaboration are of paramount importance for rapid diagnosis and to avoid the possible complications of this form

Method for inducing experimental pneumococcal meningitis in outbred mice

BACKGROUND: Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines. RESULTS: In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4), and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 10(2 )colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans. CONCLUSIONS: The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used

Mesenchymal Stem Cell-Based Immunomodulation in Allogeneic Heterotopic Heart-Lung Transplantation

Mesenchymal stem cells are able to differentiate in various cell lineages and they have shown immunomodulatory properties in vitro, altering the cytokine secretion profile of T helper, T effector and dendritic cells and stimulating natural killer cells towards an anti-inflammatory and tolerant phenotype. In vivo they prolong skin allograft survival and may decrease graft-versus-host disease after hematopoietic stem cell transplants. In this work we studied the effects of mesenchymal stem cell treatment in an allogeneic heterotopic heart-lung transplant model. The following experimental groups were formed: A) Control B) Immunosuppressive therapy (Cyclosporine A) C) Mesenchymal stem-cell intravenous infusion D) Mesenchymal stem-cell infusion plus immunosuppressive treatment. The infusion of mesenchymal stem cells improved the mean graft survival up to 14.5±3.7 days with respect to the control group (3±0.6 days). Treatment with Cyclosporine A plus mesenchymal stem cells (group D) produced a mean survival time of 18.25±4.9 days, and was not significantly different to the results for group B (21.75±3.5 days). Furthermore, in the immunosuppressive treatment and the mesenchymal stem cell treatment, histological analysis revealed a reduction in the grade of rejection in heart and lung grafts. This decrease was most significant in group D. In conclusion, mesenchymal stem cells alone or in combination with Cyclosporine A were able to prolong graft survival time. These data suggest that, in vivo, mesenchymal stem cells retain their ability, already shown in vitro, to suppress lymphocyte activation and proliferation

Distribution of cytoskeletal and contractile proteins in normal and tumour bearing salivary and lacrimal glands

We have evaluated by means of immunocytochemistry the distribution of various cytoskeletal and contractile proteins (cytokeratins, vimentin, desmin and α-smooth muscle actin) in 23 salivary or lacrimal gland primary tumours (15 pleomorphic adenomas and 8 carcinomas in pleomorphic adenoma), one third of which contained areas of normal gland. Normal epithelial luminal cells were stained by cytokeratin antibodies with a general specificity, while myoepithelial cells were selectively stained by a monoclonal antibody (SK2-27) reacting in immunoblots with cytokeratin polypeptides 14, 16 and 17, according to the classification of Moll et al. (1982) and by an antibody directed against α-smooth muscle actin (Skalli et al. 1986). In pleomorphic adenomas, both epithelial and myoepithelial cells displayed typical topographic distributions; moreover, myoepithelial cells showed two distinct cytoskeletal phenotypes. These findings could account in part for the heterogeneity of aspects observed in this tumour. In carcinomas, malignant cells were always positive to cytokeratin antibodies with general specificity and myoepithelial cells were absent as judged by anticytokeratin SK2-27 and anti-α-smooth muscle actin immunostainings. However, interestingly, there was in all cases a strong positivity for α-smooth muscle actin in stromal cells, similarly to what has previously been described for mammary carcinoma (Skalli et al. 1986). Our findings may be useful for the interpretation of the histogenesis of salivary and lacrimal tumour and stromal cells. © 1988 Springer-Verlag

Interferons and their receptors in human papillomavirus lesions of the uterine cervix.

PURPOSE OF INVESTIGATION: In this study we analyzed the immunohistochemical expression of specific types of interferon (IFN) in human papillomavirus (HPV) associated cervical lesions. METHODS: Reactivity to anti-IFN-alpha,-beta and -gamma and to anti-IFN-alpha/beta- and gamma-receptors was tested in 33 cervical punch biopsies from 24 HPV-infected women and nine healthy controls. The HPV-infected cases were subdivided into low-risk and high-risk groups, according to the known "oncogenic" potential of the HPV-types detected by PCR. RESULTS: Cervical epithelium and stroma in HPV-negative as well as low-risk HPV-positive samples were diffusely stained by anti IFN-alpha, beta and gamma antibodies. In contrast, a significantly lower percentage of high-risk HPV-infected tissues was immunoreactive to IFN-beta in the stroma and IFN-gamma in the epithelium. There were no relevant differences between control and HPV cases in the expression of IFN-receptors. CONCLUSION: We show that a decreased production of some specific classes of IFN is associated with high-risk-type HPV lesions suggesting an important role of IFN distribution patterns in the pathogenesis of HPV lesions

Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients

6nononeIntroduction: Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. Aim of the Study: In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. Materials and Methods: The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). Results: In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. Conclusion: In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.openOlivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, PaolaOlivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, Paol

Pelvic urothelial carcinoma with nested pattern of growth and an uncommon clinical presentation: a case report

Nested variant of urothelial carcinoma (NVUC) is a rare and often unrecognized urothelial neoplasia. Diagnosis is based on morphology only, and no immunohistochemical or cytogenetic differences from usual high-grade urothelial carcinomas have been reported