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We have generated a cell line (F cells) producing a secreted form of Japanese encephalitis virus (JEV) subviral particle (extracellular particles [EPs]) that contains the JEV envelope glycoprotein (E) and a precursor (prM) of the virion membrane protein (M). The F cells were engineered to synthesize these JEV products from a cDNA encoding a mutated (furin proteinase resistant) form of prM, since stable cell lines expressing E and the authentic form of prM could not be obtained, due (in part) to the cell-fusing ability of EPs containing E and M. Our biochemical alteration of the prM protein was critical for the successful production of EP-producing cell lines. EPs produced by F cells share the biochemical properties of empty viral particles produced by JEV-infected cells, except that the F-cell EPs lack hemagglutinating activity and M. F-cell EPs were recognized by a panel of monoclonal antibodies to E, and EPs were shown to be useful as vaccine candidates in mice and as diagnostic reagents in evaluating human immune responses to JE vaccination. The amounts of E antigen released into the culture fluid of F cells were similar to those found in virion fractions of JEV-infected cell culture fluids or JEV-infected weanling mouse brains (the current source of antigen used to produce human vaccines for JE). Thus, the F-cell line would appear to be a useful source of antigen for JE vaccines and diagnostics.

[1] Case studies are used to elucidate the relationship between stratospheric planetary wave reflection and blocking formation in the troposphere. The enhanced upward propagation of a planetary-scale wave packet from the Eurasian sector, involving a Euro-Atlantic blocking, leads to a stratospheric sudden warming (SSW). Following the weakening of the stratospheric westerly jet due to polar warming, the stratospheric planetary wave packet then propagates downward over the American sector, inducing a ridge over the North Pacific as well as a trough over eastern Canada in the upper troposphere. The ridge promotes the formation of a Pacific blocking. This result explains why Pacific blockings tend to form after SSW, and why they are associated with suppressed upward propagation of planetary waves.Citation: Kodera, K., H. Mukougawa, and A. Fujii (2013), Influence of the vertical and zonal propagation of stratospheric planetary waves on tropospheric blockings,

The expression of "growth arrest and DNA damage inducible genes 45 and 153" (GADD45 and 153) is induced by both genotoxic and non-genotoxic stress. 1)Although GADD45 is the first stress-inducible gene activated by p53 tumor suppressor-it can also be induced in a p53-independent manner 2) -the exact function of GADD45 is not yet clear. Numerous investigators have reported that GADD45 protein is a new molecular target for human cancer therapy, since it is associated with cell-cycle regulation, apoptosis, DNA repair and genomic stability, along with immune responses.1) The expression of GADD153 has been extensively studied in cells treated with various stress conditions-oxidative stress, endoplasmic reticulum stress and deprivation of essential nutrients, such as glucose and glutamine-and also cells treated with DNA damaging agents.3) Results suggest that GADD45 and GADD153 proteins play vital roles in apoptotic induction of cells, so we focused on them for our study of lung cancer prevention in humans.Lung cancer is the leading cause of cancer-related death world wide. In 2006 it caused 62000 deaths in Japan and an estimated 160000 deaths in U. S.A. in 2009. 4,5) In Japan, lung cancer is the leading cause of death from cancer among both men and women, and death from lung cancer has been increasing by a factor of 10.7 for men and by a factor of 9.6 for women over the past 40 years. 6,7) To combat this, lung cancer prevention trials were conducted in western countries in the 1990s, but they were not successful for various reasons. 8) In the developing nation of Bangladesh, lung cancer for males shows the highest mortality rate because the risk of lung cancer development is increased by widespread cigarette smoking, and the 5 year survival rate is only 15%.9) The reason for the high mortality rate is that the majority of lung cancers are diagnosed in the late stages, when conventional therapeutic regimens are no longer effective. 10) So the best strategy is to minimize the development of lung cancer using cancer preventive agents, and in countries like Bangladesh there is strong interest in cancer prevention with widely investigated natural products, such as green tea, curcumin, resveratrol and capsaicin. In the Indian subcontinent, curcumin, for example, is commonly ingested in daily meals with turmeric.Curcumin is a compound found in turmeric, which is a product of the plant Curcuma longa (LINN) and contains 2-5% total spices. Since curcumin is traditionally well-known to have therapeutic effects on various types of diseases, the cancer preventive activity of curcumin is being intensively studied all over the world, and experiments with curcumin in animal models indicate it is a preventive agent against various types of cancer.11) Specifically, curcumin inhibited cell growth of various cancer cell lines, and induced apoptosis of cancer cells, such as A549.12-17) Moreover, curcumin was effective on cell-cycle regulation of the cells. [18][19][20] Based on these results, we think that it is possible to intensify th...

Poor healing of epithelial wounds in cornea is a major clinical problem, leading to persistent epithelial defects and ulceration. The primary cause is poor cell migration over the wound. Carbohydrate-binding protein galectin-3 binds to extracellular matrixes (ECMs) and promotes lamellipodia formation by cross-linking to α3 integrin. Recombinant galectin-3 also facilitates wound healing in the rodent cornea. The purposes of the present experiments were to: (1) establish epithelial wound healing models in monkey corneal explant culture, the models more relevant to human, (2) evaluate the healing effect of galectin-3 in our models, and (3) determine if galectin-3 enhances cell adhesion by interacting with ECMs on corneal surface and their ligand integrins. Monkey corneas with central wounds produced by sodium hydroxide (NaOH) or n-heptanol were incubated with or without recombinant galectin-3. The defected area was stained with sodium fluorescein. Primary isolated corneal epithelial cells from monkey were cultured with or without galectin-3 on plates coated with ECMs or integrins, and the number of adhering cells was counted. Galectin-3 expression in various eye tissues was visualized by immunoblotting. NaOH caused loss of epithelial cells and basement membrane. n-Heptanol removed epithelial cells, but the basement membrane was retained. These corneal defects spontaneously became smaller in a time-dependent manner. Exogenous galectin-3 enhanced wound healing in both NaOH and n-heptanol models. Galectin-3 also enhanced cell adhesion onto the major ECMs found in the basement and Bowman’s membranes and onto integrins. Relatively high levels of galectin-3 were detected in corneal and conjunctival epithelium, but tear fluid contained negligible galactin-3. These results suggested that the enhanced binding of epithelial cells to ECMs and integrins caused by galectin-3 might promote cell migration over wounded corneal surfaces. Since tear fluid contained relatively low levels of galectin-3, exogenous galectin-3 may be a beneficial drug to enhance re-epithelialization in human corneal diseases.

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PURPOSE. During inflammation of the ocular surface, increased proinflammatory cytokines depress tear protein secretion, suggesting that a decline in lacrimal cell function contributes to dry eye. Lacritin, a glycoprotein secreted from lacrimal acinar cells, may function as an autocrine factor to stimulate tear protein secretion. The purpose of the present experiment was to investigate lacritin-induced protein secretion in normal and cytokine-pretreated (inflammation model) monkey acinar cells.METHODS. Acinar cells from monkey lacrimal glands were cultured with or without tumor necrosis factor alpha (TNF-a) plus interferon gamma (IFN-c). Protein secretion was induced by lacritin or carbachol (Cch, positive control). Proteins were detected and identified by immunoblotting and immunocytochemistry. Intracellular Ca 2þ was measured with the fluorophore Calcium-4, and cell damage was determined by LDH leakage into the culture medium. RESULTS. In cultured monkey acinar cells, lacritin stimulated tear protein secretion in normal cells without elevating intracellular Ca 2þ. In contrast, Cch elevated intracellular Ca 2þ and release of tear proteins. This contrast suggested an alternate, calcium-independent mechanism for lacritin-induced protein secretion. TNF-a plus IFN-c caused LDH leakage from sensitive human corneal epithelial cells, but even higher doses of TNF-a plus IFN-c did not cause LDH leakage from monkey acinar cells, suggesting a higher tolerance against these cytokines. In cytokine-treated acinar cells, lacritin stimulated protein secretion as much as that in normal cells. In contrast, Cch-induced elevation of Ca 2þ and release of proteins were depressed by cytokines.CONCLUSIONS. Lacritin might be a useful biotechnology-based treatment agent against ocular surface diseases where endogenous lacritin is inadequate.

ABSTRACT:Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture, on the levels of serum thyroid hormones such as total thyroxine (T 4 ) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. Four days after a single intraperitoneal injection of KC500, significant decreases in the levels of the serum total T 4 and free T 4 occurred in all the animals examined, whereas a significant decrease in the level of serum triiodothyronine was observed only in guinea pigs among the animals examined. In addition, no significant change in the level of serum thyroid-stimulating hormone was observed in any of the rodents examined. A significant increase in the activity of hepatic T 4 -UDP-glucuronosyltransferase after the KC500 administration