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Objectives Nupharidine (6,6'-Dihydroxythiobinupharidine), purified from the aquatic plant Nuphar lutea leaves (Water lily) prompts antimicrobial activity of immune cells. The aim of the study was to test the effect of Nupharidine on neutrophil function against Aggregatibacter actinomycetemcomitans, JP2 clone (Aa-JP2). Methods Neutrophils derived from the human cell line HL60 and human peripheral blood derived from aggressive periodontitis and periodontally healthy subjects were incubated with Nupharidine or vehicle and inoculated with JP2. Bacterial survival was tested using viable counts on blood agar (CFU's). Neutrophils' necrosis/apoptosis, reactive oxygen species (ROS) production, phagocytosis and neutrophil extracellular traps (NET) production following infection were tested, as well as markers of neutrophil priming. Results Nupharidine had no direct bactericidal effect on JP2, but it enhanced Aa-JP2 clearance by neutrophils. Nupharidine enhanced neutrophil phagocytosis, ROS production and NET formation during JP2 infection. Furthermore, Nupharidine enhanced the expression of certain markers of neutrophils priming, specifically iCAM1, DECTIN-2 and intracellular IL-1β. Conclusion Nupharidine was shown to promote neutrophil effector bactericidal functions, boosting Aa-JP2 clearance. The results point to the potential of Nupharidine as an adjunctive agent in the treatment of Aa-JP2 periodontitis, but this should be tested initially using pre-clinical and clinical studies.

We scrutinized the role of apoptosis of the Hodgkin-Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) and critically reviewed its features in the light of conflicting evidence. In this study, we found that tumor cells in this neoplasm showed inhibition of apoptosis in 55% of the 217 cHL cases only. It is also suggested that the two factors considered responsible for apoptosis inhibition in HRS cells, nuclear factor-kappaB and the latent membrane protein-1 of the Epstein-Barr virus, do not correlate with apoptosis inhibition, in contrast with the findings in the consensual pathogenetic scheme. The most significant association of HRS cell apoptosis was with p53, the negative expression of which related with a high apoptotic index (p = 0.001). These findings support our contention that the role of apoptosis in the HRS cells of Hodgkin lymphoma has not been completely elucidated and is at variance with that in the consensus.

The oncogenes c-myc and c-ras are known to elicit a cooperative tumorigenicity. In this study we investigated their role in the pathogenesis of Hodgkin's disease. The expression of these oncogenes was determined in Hodgkin's disease patients by avidin-biotin peroxidase complex immunohistochemical staining and was compared to their expression in patients with non-Hodgkin's lymphomas and inflammatory reactive lymph nodes. Of 29 examined patients with different histological types of Hodgkin's disease, 21 (72.4%) showed an elevated expression of c-myc and 28 (96.5%) of c-ras. Although this expression was marked especially in the neoplastic Reed-Sternberg cells, it was also noted in the numerous reactive cells present in the involved lymph nodes. By contrast, a much lower frequency of increased expression of these oncogenes was recorded in 19 patients with different grades of non-Hodgkin's lymphoma and in 29 patients with inflammatory reactive lymph nodes. The elevated expression of c-myc and c-ras in the neoplastic Reed-Sternberg cells may reflect an oncogenic event that directly activates these genes. However, their increased expression in the surrounding non-neoplastic cells probably results from signal transduction induced by certain growth-promoting factors possibly released by the Reed-Sternberg cells and that act paracrinally to stimulate the proliferation of the neighboring cells. Furthermore, the continuous c-ras elevation may impair the normal cell cycle control and thereby promote mutagenesis and overt malignancy.

Epstein-Barr virus (EBV) has been frequently documented in the putative neoplastic Hodgkin-Reed-Sternberg (HRS) cells, in lymph nodes from patients with Hodgkin's disease (HD). This association varies in different geographic areas and between industrialized and developing countries, as does the epidemiological pattern of the disease. In the present study of 106 cases of HD from the Soroka Medical Center in Beer-Sheva, which serves as the only hospital for most of the southern part of Israel, we found an association with EBV expression in only 30% of the patients; 45% of mixed cellularity (MC) cases compared with 21% of nodular sclerosis (NS) cases were positive for EBV. The number of patients in the 0-14-year-old age group was limited; however, 8 of these 11 children were EBV positive. This low association rate of HD with the presence of EBV sequences is probably related to the small number of children in our series. A low proportion of EBV-associated disease in older adults may be contributory. Other factors may be involved. Int. J. Cancer, 71:138–141, 1997. © 1997 Wiley-Liss, Inc.

In this study, the composition and the role of membrane glycoproteins in phagocytosis were determined in G6PD deficient RBCs. G6PD deficient RBCs were recognized and significantly phagocytosed by murine macrophages, without pre-exposure to oxidants in vivo. Phagocytosis was partially (60%) inhibited by incubating macrophages with either galactose or mannose, or by incubating RBCs with beta-galactosidase, indicating the involvement of lectin-like receptors in the recognition of G6PD deficient RBCs. Membrane glycoproteins on G6PD deficient cells were detected by binding of Con A to both intact RBCs and to purified membrane proteins. The results demonstrated modifications in the glycoprotein pattern of G6PD deficient RBCs compared to untreated controls. These included reduction in the amounts of several high molecular weight glycoproteins and appearance of lower molecular weight bands. These results suggest that G6PD deficient RBCs undergo glycoprotein modifications, which may lead to premature removal from circulation, even in non-acute hemolysis.

The effects of the H-ras oncogene on fibroblast cell tumorigenicity and immunogenicity was studied in transfectants of the BALB/c 3T3 clone A31 fibroblastoid cell-line. Cells that were transfected with MC29-LTR-H-ras (98/6) or MC29-LTR-v-myc + H-ras (98/4v) and were inoculated into syngeneic BALB/c mice were tumorigenic in 100% and 60% of animals respectively. By contrast, transfectants containing the pSV2neo plasmid alone (98/1) displayed normal characteristics both in vitro and in vivo. Inoculation of mice with mitomycin-C-treated 98/1 or 98/4v cells induced an effective protective immunity to a challenge of live 98/4v cells, and a partial immunity against 98/6 cells. Mitomycin-C-treated 98/6 cells failed to render immunity against a challenge of either 98/6 or 98/4v cells. To correlate immunogenicity and tumorigenicity of the different cell types with cell-surface-antigen expression, we prepared MAbs against 98/4v cells in syngeneic mice. Immunohistochemical and immunoblot analysis revealed that MAbs 102 and 104 recognized 2 protein band of 70 and 45 kDa respectively, which were expressed predominantly in 98/1 and 98/4v cells. A third immunoreactive protein band of 44 kDa that reacted with MAb 6 was expressed at a similar cell-surface density on all cell types. Cell-differentiation-inducing agents, such as DMSO, retinoic acid or sodium butyrate, were all found to induce 98/6 cell flattening and morphological changes toward a normal phenotype that were followed by up-regulation of the 70- and 45-kDa antigens. The results suggest that regulation of expression of the 70- and 45-kDa molecules is affected by H-ras, and that expression of these cell-surface molecules may be relevant to tumor cell immunogenicity.

We have used the 3-Methylcholanthrene induced T-10 fibrosarcoma tumour cell system (H-2b xH-2k)F1 to elucidate the possible correlation between metastatic potential, expression of individual H-2 antigens and susceptibility to NK cells. Transfection of the non-metastatic and NK sensitive IC9 cells (Db+, Dk-, Kb-, Kk-) with the H-2Dk gene, altered the metastatic phenotype of the parental cells, yet had no effect on the susceptibility of these tumour cells to lysis by NK and did not elicit a specific CTL response in syngeneic hosts. Variants of the metastatic and NK resistant IE7 clone (Db+, Dk+, Kb-, Kk-), lacking H-2Dk, were selected by treatment with monoclonal anti H-2Dk antibodies and complement. These variants were sensitive to NK and poorly or non metastatic. Retransfection of 'Dk' 'loss' variants with the H-2Dk gene, resulted in the isolation of several clones expressing a wide range of metastatic phenotypes but maintained sensitivity to NK. These results indicate that the H-2D region of the MHC and or closely linked genes may be involved in the complex interrelationship between target susceptibility to NK and metastasis.