Flavonoids such as luteolin, fisetin and apigenin are inhibitors of interleukin-4 and interleukin-13 production by activated human basophils

BACKGROUND: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. METHODS: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. RESULTS: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. CONCLUSIONS: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases.     

Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1: possible implication in apoptotic resistance against irradiation

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy irradiation. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In the succeeding study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells, that mitochondrial membrane potential was preserved, and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. In the present study, we examined the immunocytochemical characteristics of the apoptotic-resistance of the HS-Os-1 cell line against irradiation in order to clarify its possible implications regarding radiosensitivity. The results showed that these cells lack P53 and Bax protein expression, and strong peroxidase activity was confirmed in the nuclei of the cells. Moreover, SODII (manganese superoxide dismutase II) protein expression was gradually increased in spite of irradiation of up to 30 Gy. Therefore, it is concluded that HS-Os-1 cells are originally apoptotic-resistant and that the cells possess a strong ability to scavenge for free radicals. To convert these cells to a state of apoptotic-susceptibility, a powerful oxidant such as hydrogen peroxide might exert such an effect in terms of the production of hydroxyl radicals in lysosomes in the cells as shown in our previous studies. The origin of the radioresistance of the human osteosarcoma cell line HS-Os-1 is considered to to be low degree of ROS formation following irradiation, reflecting the strong scavenging ability of these cells for free radicals including hydroxyl radicals.     

Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules

The histogenesis of meningothelial-like nodule or so-called minute pulmonary chemodectoma remains unclear, with various immunohistochemical analyses giving inconsistent results. We performed an immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules. Thirty-one histologically defined meningothelial-like nodules in 14 cases were stained immunohistochemically. One case had multiple lesions with brown pigment granules, which were positively stained with Berlin blue method, indicating the presence of hemosiderin. All meningothelial-like nodules were positive for vimentin and epithelial membrane antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24 lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen. Alveolar macrophages were intensely positive for CD68 and lysozyme in all examined cases. We analyzed the clonality of 11 minute pulmonary meningothelial-like nodule lesions in two female cases based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). The HUMARA was found to be amplified with or without prior digestion by the methylation-sensitive restriction endonuclease HpaII. Six of 11 lesions showed monoclonal expansion. Five lesions in a multiple case showed different patterns of monoclonality. Our findings showed that minute pulmonary meningothelial-like nodules have meningothelial-like and phagocytic characteristics but no muscular phenotype. Furthermore, some minute pulmonary meningothelial-like nodules may show monoclonal expansion, whereas others are polyclonal. Our data indicate that minute pulmonary meningothelial-like nodules are reactive rather than neoplastic.     

M pathway and areas 44 and 45 are involved in stereoscopic recognition based on binocular disparity

We characterized the visual pathways involved in the stereoscopic recognition of the random dot stereogram based on the binocular disparity employing a functional magnetic resonance imaging (fMRI). The V2, V3, V4, V5, intraparietal sulcus (IPS) and the superior temporal sulcus (STS) were significantly activated during the binocular stereopsis, but the inferotemporal gyrus (ITG) was not activated. Thus a human M pathway may be part of a network involved in the stereoscopic processing based on the binocular disparity. It is intriguing that areas 44 (Broca's area) and 45 in the left hemisphere were also active during the binocular stereopsis. However, it was reported that these regions were inactive during the monocular stereopsis. To separate the specific responses directly caused by the stereoscopic recognition process from the nonspecific ones caused by the memory load or the intention, we designed a novel frequency labeled tasks (FLT) sequence. The functional MRI using the FLT indicated that the activation of areas 44 and 45 is correlated with the stereoscopic recognition based on the binocular disparity but not with the intention artifacts, suggesting that areas 44 and 45 play an essential role in the binocular disparity.     

ASO Author Reflections: Perspectives of Laparoscopic Hepatectomy with Venous Tumor Thrombectomy for Hepatocellular Carcinoma

Annals of Surgical Oncology -     

ASO Author Reflections: Laparoscopic Arantius’ Approach as Shortcut Access for Major Hepatic Veins

Annals of Surgical Oncology -