Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past two decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehension of the “education” of NK cells to achieve functional competence during their maturation and the discovery of “memory” responses by NK cells suggesting that they may also contribute to adaptive immunity. The improved understanding of NK cell biology has forged greater awareness that these cells play integral early roles in immune responses. In addition, several promising clinical therapies have been used to exploit NK cell functions in treating cancer patients. As our molecular understanding improves, these and future immunotherapies should continue to provide promising strategies to exploit the unique functions of NK cells to treat cancer, infections, and other pathological conditions.

A growing body of evidence indicate that carotenoids possess anticarcinogenic, anti-mutagenic and immunomodulating effects. Saffron obtained from the dried stigmas of Crocus sativus L., is an important spice, rich in carotenoids, consumed commonly in different parts of the world. Our laboratory first reported the anticancer activity of saffron extract (dimethyl-crocetin) against a wide spectrum of murine tumors and human leukemia cell lines. The present report reviews the role of saffron in serving as a chemopreventive agent in modifying cancer risk. Dose-dependent cytotoxic effect to carcinoma, sarcoma and leukemia cells in vitro were noted. Saffron delayed ascites tumor growth and increased the life span of the treated mice compared to untreated controls by 45-120%. In addition, it delayed the onset of papilloma growth, decreased incidence of squamous cell carcinoma and soft tissue sarcoma in treated mice. Understanding the mechanisms of action of saffron have been solitarily based on their carotenoid-like action. Our results indicated significant inhibition in the synthesis of nucleic acids but not protein synthesis. It appears now that saffron (dimethyl-crocetin) disrupts DNA-protein interactions e.g. topoisomerases II, important for cellular DNA synthesis.

Reliable synaptic transmission depends not only on the release machinery and the postsynaptic response mechanism but also on removal or degradation of transmitter from the synaptic cleft. Accumulating evidence indicates that postsynaptic and glial excitatory amino acid transporters (EAATs) contribute to glutamate removal. However, the role of presynaptic EAATs is unclear. Here, we show in the mouse retina that glutamate is removed from the synaptic cleft at the rod to rod bipolar cell (RBC) synapse by presynaptic EAATs rather than by postsynaptic or glial EAATs. The RBC currents evoked by electrical stimulation of rods decayed slowly after pharmacological blockade of EAATs. Recordings of the evoked RBC currents from EAAT subtype-deficient mice and the EAAT-coupled anion current reveal that functional EAATs are localized to rod terminals. Model simulations suggest that rod EAATs are densely packed near the release site and that rods are equipped with an almost self-sufficient glutamate recollecting system.

Objective. Rheumatoid arthritis (RA) is characterized by chronic inflammation of multiple joints. Large numbers of T cells, which produce type 1 cytokines, infiltrate into RA synovium. Chemokines and chemokine receptors are considered to contribute to the T cell infiltration. In this study, we examined the role of CX3CL1/fractalkine and its receptor CX3C chemokine receptor 1 (CX3CR1) in the T cell migration into RA synovium.Methods. Using flow cytometry, immunohistochemistry, and reverse transcription-polymerase chain reaction, we analyzed CX3CR1 expression by peripheral blood and synovial T cells, and CX3CL1 expression in synovium from patients with RA. Cytokine and cytotoxic molecule expression by CX3CR1-positive T cells was analyzed by flow cytometry.Results. CX3CR1 expression by peripheral CD4؉ and CD8؉ T cells was up-regulated in RA patients. The peripheral CD4؉ and CD8؉ T cells expressing CX3CR1 predominantly produced interferon-␥ and tumor necrosis factor ␣, and expressed cytotoxic molecules such as granzyme A and perforin. Furthermore, CX3CR1؉,CD3؉ T cells infiltrated into RA synovium. CX3CL1, the unique ligand of CX3CR1, was expressed by endothelial cells and synoviocytes in RA synovium, but not in osteoarthritis synovium.Conclusion. Our findings suggest that the interactions of CX3CL1 and CX3CR1 might contribute to the accumulation of CX3CR1؉ T cells expressing type 1 cytokines and possessing cytotoxic granules in RA synovium.

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Isopower or topographic electrogastrograms (EGG) correspond to topographic electroencephalograms. Both project the topographic localizations of the spectral frequencies on the abdominal surface or scalp. This paper compares the pre-operative control isopower EGG maps with those of total gastrectomy or total colectomy. EGGs were recorded simultaneously at 27 locations on the epigastro-abdominal surface. Spectral analysis by the maximal entropy method (MEM) was performed and the ensemble means of pre-prandial and post-prandial spectra were calculated. The spectral frequencies were arbitrarily classified into five groups, 1 cycle per minute (cpm) (0-2.4 cpm), 3 cpm (2.5-4.9 cpm), 6 cpm (5.0-7.4 cpm), 8 cpm (7.5-9.9 cpm) and 10 cpm (10.0-12.9 cpm). Maximal power peaks in each spectral group, and electrode locations which were expressed by x-y coordinates were the indicators for making the isopower EGG maps by using a contour map program. Thereafter, the maximal power spots or foci in each spectral group were determined. The pre-operative maximal power foci of the 1, 8 and 10 cpm groups were distributed rather evenly on the epigastro-abdominal surface. Those of the 3 and 6 cpm groups, mainly concentrated in the epigastric region, were absent in almost all patients who had undergone total gastrectomy. The infra-umbilical foci of the 3 and 6 cpm groups completely disappeared after total colectomy. The infra-umbilical foci of the 3 and 6 cpm groups (2.5-7.4) may reflect the colonic activities and the epigastric 3 cpm foci, the gastric activities. The pre-operative maximal power of the 3 cpm foci decreased significantly after total or sub-total gastrectomy.

Hepatic butyltin concentrations were determined in 63 cetaceans belonging to 14 species and four pinnipeds belonging to two species collected from North Pacific and Asian coastal waters. Butyltin compounds (BTs) including tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) were detected in almost all the liver samples suggestive of its worldwide distribution. The elevated residues detected in coastal species and low concentrations found in off-shore species indicate a high degree of butyltin contamination in coastal waters than in the open sea. Mammals inhabiting waters of developed nations were found to contain higher BT concentrations compared with those collected from the waters proximal to developing countries. These observations strongly suggest serious BT contamination in the waters of developed countries than in developing nations at present. Among the samples collected off Japanese coastal waters, lower BT concentrations were found in pinnipeds compared with the cetaceans, suggestive of a possible difference in degradation capacities and excretory moulting between these two groups of animals. The estimated concentration ratio of BT in the liver of killer whale fetus to its pregnant mother was relatively low (0.015), indicative that transplacental transfer of BTs from the mother to her fetus is a deal less. Among the BT breakdown products, DBT was predominant in most of the liver samples analyzed, followed by TBT and MBT.