Immunohistological identification of cell subsets in human gingival after local treatment for gingivitis or periodontitis

The cellular infiltrate present in human diseased gingiva was analyzed in biopsies from 12 patients with gingivitis or periodontitis. The samples studied had been obtained in the course of surgery at inflammatory sites remaining after institution of periodontal treatment. Histological and immunological techniques were used to identify macrophages, B-cells, plasma-cells, T-cells and T cell subsets, as well as cells expressing class II HLA membrane antigens. T-cells appeared as the predominant population, but plasma-cells were also visualized in nearly all samples. Both OKT4+ and OKT8+ cells were seen in all cases, the latter being more numerous in periodontitis patients. Interdigitating-like cells were observed, positively labelled for class II antigens, as well as macrophages which were more numerous in periodontitis patients. These results suggest the participation of all components of the immune response in gingival disease, in a way resembling chronic recurrent inflammatory diseases.     

Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3.

The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy.     

Adrenocortical carcinoma and sudden death

A 26-year-old man who presented with a 2-year history of intermittent gynecomastia with recent onset of fever, night sweats, and abdominal distension was found to have a left-sided adrenocortical carcinoma with metastases to the liver and spine. Sudden death occurred 1 month after his presentation. At autopsy a saddle pulmonary thromboembolus was found occluding the pulmonary outflow tract, with smaller more peripheral pulmonary thromboemboli. No tumor deposits were identified in the thromboemboli. The thromboemboli had arisen from a tongue of tumor that had grown through the left adrenal vein into the inferior vena cava. Despite a high rate of angio-invasion there are very few reports of sudden death resulting from this phenomenon in patients with adrenocortical carcinoma.