This paper describes the present Japanese oral healthcare system and outlines the future challenges and perspectives for Japan. Japan has developed a system for providing high-quality and appropriate health care efficiently through a universal health insurance system which has been in operation since 1961. This health insurance covers most restorative, prosthetic and oral surgery treatment. Therefore, all people can receive dental treatment at a relatively low cost, with the same fees applying throughout the nation. In Japan, public oral health services are provided by the local governments according to the life stage of their populations. These services are mainly conducted by private dental practitioners under contracts with local governments. National oral health data shows that the oral health of the Japanese population has improved over the last several decades. Future challenges and perspectives for Japanese dentistry include: tackling the regional differences in oral health, decreasing the cost of health expenditure, establishment of sustainable emergency oral healthcare services in times of disaster, and the development a new tele-dental system for remote areas without access to dental professionals.

As a part of our studies of selectin blockers, we prepared 1-(2-tetradecylhexadecyl)-3'-O-sulfo Le(X) 1 and 1-(2-tetradecylhexadecyl) sLe(X) 2 and examined their inhibitory activities against natural ligand (sLe(X)) binding to E-, P-, and L-selectins. Compounds 1 and 2 were 2 times more potent than the sLe(X) tetrasaccharide toward E-selectin binding and up to 4 times more potent than sLe(X) toward P- and L-selectin binding. Interestingly, compound 1 provided dose-dependent protective effects against an immunoglobulin E-mediated skin reaction in mouse ears. This protective effect was associated with diminished tissue accumulation of neutrophils in the ear (as assessed by myeloperoxidase). These findings indicate that the modification of sLe(X) or 3'-O-sulfo Le(X) with a "branched anchor", a 2-tetradecylhexadecyl group, is useful in the design of a more potent selectin blocker, which has broad inhibitory activities toward all selectins.

Sera from a patient with macroprolactinoma (case 1) and from a hyperprolactinemic woman with regular menstruation (case 2) were analyzed for prolactin activity by gel filtration using Sephadex G-100, Sephadex G-200 and TSK G3000SW columns. The chromatographic profile by Sephadex G-100 showed that the percentage of immunoreactive big-big hPRL was 10.7% in case 1 and 64.1% in case 2. On Sephadex G-200 and TSK G3000SW columns, the molecular weight of big-big hPRL was estimated to be more than 500,000 daltons (big-big1 hPRL) in case 1 and approximately 250,000-300,000 daltons (big-big2 hPRL) in case 2. Big-big1 hPRL in case 1 was converted to big and little hPRLs when the serum was treated with 2-mercaptoethanol (2-ME), but part of the big-big2 hPRL in case 2 was converted to a larger molecule. Radioactive big-big hPRL generated by mixing labeled hPRL with the serum from case 1 was eluted with the void volume on Sephadex G-100 column and was not converted to the other molecular forms after 2-ME treatment. There were two radioactive big-big hPRL on TSK G3000SW column and these estimated molecular weights were more than 300,000 daltons. The data demonstrated the existence of at least two forms of big-big hPRL in the serum and indicated that radioactive big-big hPRL may be different from these hPRLs in the serum.

In patients with C1-C2 instability, not only cervical flexion but also cervical retraction constantly led to both maximal C1-C2 flexion and subluxation. In some patients with severe C1-C2 instability, protrusion also resulted in C1-C2 subluxation, even though the C1-C2 was maximally extended.

1 We investigated the ability of a newly synthesized sugar derivative, OJ-R9188, {N-(2-tetradecylhexadecanoyl)-O-(L-alpha-fucofuranosyl)-D-seryl}-L-glutamic acid 1-methylamide 5-L-arginine salt, to block binding of selectins to their ligands in vitro and inhibit the in®ltration of leukocytes in vivo. 2 OJ-R9188 prevented the binding of human E-, P-and L-selectin-IgG fusion proteins to immobilized sialyl Lewis x (sLe x )-pentasaccharide glycolipid, with IC 50 values of 4.3, 1.3, and 1.2 mM, respectively.3 In a mouse model of thioglycollate-induced peritonitis, OJ-R9188 at 10 mg kg 71 , i.v. inhibited neutrophil accumulation in the peritoneal cavity. In the IgE-mediated skin reaction, OJ-R9188 at 3 and 10 mg kg 71 , i.v. signi®cantly inhibited extravasation of neutrophils and eosinophils into the in¯ammatory sites and at 10 mg kg 71 , i.v. also inhibited in®ltration caused by picryl chlorideinduced delayed-type hypersensitivity in mice. These results suggest that OJ-R9188 may be a useful selectin blocker, with activity against human and mouse E-, P-and L-selectins in vitro and in vivo, and that blocking selectin-sLe x binding is a promising strategy for the treatment of allergic skin diseases.