To clarify an involvement of angiotensin II signaling in lung neoplasia, we have examined the effect of angiotensin II receptor deficiency on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis. Male angiotensin II type 2 receptor (AT 2 )-null mice with an SWR/J genetic background and control wild-type mice were treated with NNK (100 mg/kg, i.p.) or saline vehicle. NNK treatment caused the development of lung tumors in all wild-type control mice (100 % tumor prevalence), but only 85% of AT 2 -null mice developed tumors. The tumor multiplicity in AT 2 -null mice (1.9 F 0.3) was significantly smaller than that in wild-type mice (4.1 F 0.9). Primary cultured lung fibroblasts prepared from both AT 2 -null and wild-type mice markedly increased the colony counts of A549 lung cancer cells in soft agar, but a consistently higher colony count was observed with the wild-type fibroblasts ( fold increase in colony number, 5.6 F 0.5) than with the AT 2 -null fibroblasts (3.5 F 0.8). The underlying mechanism by which angiotensin II regulates cancer cell growth is due to the regulation of active transforming growth factor-B (TGF-B) production. Although the total level of TGF-B was significantly stimulated when A549 cells were cocultured with either type of fibroblasts, the level of active TGF-B in the conditioned medium was consistently higher with AT 2 -null fibroblasts than with wild-type fibroblasts. These results imply that the AT 2 receptor negatively regulates the level of active TGF-B and thus increases NNK-induced lung tumorigenesis. The AT 2 receptor function in lung stromal fibroblasts may be a potential modulator of tumor susceptibility in chemical carcinogen-induced lung tumorigenesis. (Cancer Res 2005; 65(17): 7660-5)
SummaryTo elucidate the effect of ␥ -aminobutyric acid (GABA) on both psychological and physical fatigue and on the performance advances for task solving, we assigned an arithmetic task for the Uchida-Kraepelin Psychodiagnostic Test (UKT) to 30 healthy Japanese subjects, 9 of whom were diagnosed as having chronic fatigue. The subjects were administered 250 mL of a test beverage containing GABA at the dose of 0, 25, and 50 mg before assigning task for the UKT. Psychological fatigue assessed by the Visual Analogue Scale (VAS) was significantly lower in the group administrated the beverage containing 50 mg GABA than in the control group ( p Ͻ 0.05). The results of the Profile of Mood States (POMS) also indicated that psychological fatigue was significantly reduced in the 50-mg-GABA group. The salivary secretion levels of chromogranin A and cortisol-markers of physical fatigue-in both 25-mg and 50-mg-GABA groups were significantly lower than those in the control group. The 50-mg-GABA group also showed higher score on UKT by solving the arithmetic task more accurately than the control group ( p Ͻ 0.01). The results suggest that intake of GABA-containing beverages, especially those containing 50 mg of GABA, may help reduce both psychological and physical fatigue and improve task-solving ability.
A phytoplasma was discovered in diseased specimens of f ield-grown hortensia (Hydrangea spp.) exhibiting typical phyllody symptoms. PCR amplification of DNA using phytoplasma specific primers detected phytoplasma DNA in all of the diseased plants examined. No phytoplasma DNA was found in healthy hortensia seedlings. RFLP patterns of amplified 165 rDNA differed from the patterns previously described for other phytoplasmas including six isolates of foreign hortensia phytoplasmas. Based on the RFLP, the Japanese Hydrangea phyllody (JHP) phytoplasma was classified as a representative of a new subgroup in the phytoplasma 165 rRNA group I (aster yellows, onion yellows, all of the previously reported hortensia phytoplasmas, and related phytoplasmas). A phylogenetic analysis of 16s rRNA gene sequences from this and other group I phytoplasmas identified the JHP phytoplasma as a member of a distinct sub-group (sub-group Id) in the phytoplasma clade of the class Mollicutes. The phylogenetic tree constructed from 165 rRNA gene sequences was consistent with the hypothesis that the JHP phytoplasma and its closest known relatives, the Australian grapevine yellows (AUSGY), Phormium yellow leaf (PYL), Stolbur of Capsicum annuum (STOL) and Vergilbungskrankheit of grapevine (VK) share a common ancestor. The unique properties of the DNA from the JHP phytoplasma clearly establish that it represents a new taxon, Candidatus Phytoplasma japonicum '.
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