Recent studies have shown that certain types of transformed cells are extruded from an epithelial monolayer. However, it is not known whether and how neighbouring normal cells play an active role in this process. In this study, we demonstrate that filamin A and vimentin accumulate in normal cells specifically at the interface with Src-or RasV12-transformed cells. Knockdown of filamin A or vimentin in normal cells profoundly suppresses apical extrusion of the neighbouring transformed cells. In addition, we show in zebrafish embryos that filamin plays a positive role in the elimination of the transformed cells. Furthermore, the Rho/Rho kinase pathway regulates filamin accumulation and filamin acts upstream of vimentin in the apical extrusion. This is the first report demonstrating that normal epithelial cells recognize and actively eliminate neighbouring transformed cells and that filamin is a key mediator in the interaction between normal and transformed epithelial cells.

To validate the Clock Drawing Test (CDT) as a screening method for detecting mild cognitive impairment (MCI) and to find the appropriate scoring protocol and its cutoff point, we compared the sensitivity and specificity of three CDT protocols. Subjects included 219 outpatients with memory complaints, who were attending the geriatric memory clinic. Cahn’s protocol, with a cutoff point of 7, was more successful at differentiating clinically diagnosed MCI subjects from normal elderly individuals, with higher sensitivity (74.7%) and specificity (75.6%), than were the other protocols. The CDT, as a handy screening method, may be useful for clinicians to reliably identify subjects with MCI, and it may contribute to early detection of dementia.

In recent years, deep-sea water has been applied not only in food production but in industry and the medical field in an attempt to utilize its properties, 1) its wealth of inorganic materials, its purity and mineral content, which have attracted attention.2) In particular, various minerals in their characteristic dissolved states, including indispensable trace elements abundant in deep-sea water have demonstrated their usefulness and attracted attention in each field, and various applications have been tried. 3)A major problem of insufficient minerals caused by the recent westernization of lifestyles and eating habits, has resulted in so-called lifestyle-related illnesses such as hyperlipemia, hypertension, and diabetes. 4) In order to prevent or treat these illnesses, it is important to adjust disorders in body functioning. However, although deep-sea water contains minerals used in the treatment of lifestyle-related illness and the production of health food, there is no scientific proof of its usefulness.To examine the lifestyle-related illness, hyperlipemia, in which eating habit disorders are considered to particularly influence the development of symptoms, we medicated normal rabbits with deep-sea water (desalinated water, hardness 28, 300, and 1200) simultaneously with cholesterol loading, and examined its preventive effect on hyperlipemia. Furthermore, prepared hyperlipemia rabbits 5) carrying the same cholesterol load as normal rabbits, were administered deep-sea water, and its medical treatment effect on hyperlipemia was examined. MATERIALS AND METHODS AnimalsMale Japanese white rabbits weighing 1.8 to 2.0 kg (Shimizu, Kyoto, Japan) were used in this study. These animals were maintained on a 12 h light/dark cycle in a humidity-and temperature-controlled facility and allowed free access to food and water for 1 week during acclimatization before the experiment.Deep-Sea Water Deep-sea water pumped up from a depth of 374 m off Muroto Cape (Kochi, Japan) was desalinated and concentrated by reverse osmosis. Various concentrations of water with eliminated sodium etc. were added to the desalinated water and deep-sea water samples of varying hardness (28, 300, 1200) were prepared. The mineral ingredient content of each deep-sea water sample is shown in Table 1.Administration of Deep-Sea Water Normal rabbits were divided into four groups and administered 150 ml/d of deep-sea water (desalinated water, hardness 28, 300, and 1200) in a water supply bottle ad libitum, and fed normal food (CR-3, Clea, Osaka, Japan) for 4 weeks ( Table 2). It was confirmed that the rabbits consumed the water each time.Cholesterol-loaded rabbits were similarly divided into four groups and were each administered deep-sea water, and fed a 1% cholesterol-containing diet (CE-2, Clea, Osaka, Japan) for 4 weeks ( Table 2).Hyperlipemia rabbits fed a 1% cholesterol diet for 4 weeks and with a raised total cholesterol (T-Cho) level before this experiment, were similarly divided into four groups, admin- * To whom correspondence should be addresse...

The results suggest that a short and simple non-lexical olfactory identification test can be useful as a clinical marker of AD appropriate for Japanese elderly population.

Cell cycle G 2 checkpoint abrogation is an attractive strategy for sensitizing cancer cells to DNA-damaging anticancer agent without increasing adverse effects on normal cells. However, there is no single proven molecular target for this therapeutic approach. High-throughput screening for molecules inhibiting CHK1, a kinase that is essential for the G 2 checkpoint, has not yet yielded therapeutic G 2 checkpoint inhibitors, and the tumor suppressor phenotypes of ATM and CHK2 suggest they may not be ideal targets. Here, we optimized two G 2 checkpoint-abrogating peptides, TAT-S216 and TAT-

Normal epithelial cells have an ability to sense and actively eliminate neighboring transformed cells, a process called epithelial defense against cancer (EDAC). Exogenous S1P plays a crucial role in EDAC; the S1P–S1PR2 pathway regulates Rho–Rho kinase–filamin in the surrounding normal cells, promoting apical extrusion of RasV12-transformed cells from epithelia.

EBV DNA was detected by qualitative PCR in ocular fluids of many uveitis patients, but only a small proportion of patients showed high viral loads on quantitative real-time PCR, indicating that replication of the virus takes place only in a few patients.

Our results demonstrated that a category fluency performance reflected not only AD-specific changes but also educational background. These results suggest the limitation of using the category fluency task for screening subjects at risk for developing AD without taking subjects' educational background into consideration.