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Notes: Recombinant human (rh) bone morphogenetic protein-2 (BMP-2) stimulates osteoblastic differentiation in cells isolated from human periodontal ligament (HPLC), and this action of rhBMP-2 may be modulated by prostaglandins (PGs), which are local regulatory factors in the bone metabolism. In the present study, we investigated the effect of prostaglandin E2 (PGE2) on rhBMP-2-stimulated osteoblastic differentiation in cultured HPLC. rhBMP-2 (500 ng/ml)-stimulated alkaline phosphatase (ALPase) activity was enhanced by simultaneous treatment with low concentrations (10−10-10−8 M) of PGE2, whereas a high concentration (10−6 M) of PGE2 suppressed it. rhBMP-2 did not induce cyclo-oxygenase-2 (COX-2) mRNA expression or subsequent PGE2 production, whereas it remarkably suppressed rhIL-1β-induced COX-2 mRNA expression and PGE2 production. The rhBMP-2 action on osteoblastic differentiation in HPLC was also enhanced by co-treatment with 0.25 to 25 ng/ml of rh interleukin-1β (IL-1β). The ALPase activity stimulated by simultaneous treatment with rhBMP-2 and rhIL-1β was partially inhibited by addition of 10−6 M of indomethacin, which completely inhibited rhIL-lβ-induced PGE2 production. These results reveal that PGE2 at different concentrations exerts a biphasic effect on BMP-2-stimulated osteoblastic differentiation in HPLC, BMP-2 inhibits IL-1β-induced PGE2 production through suppressing COX-2 expression, and the BMP-2-stimulated osteoblastic differentiation may be enhanced by the endogenous PGE2 induced by BMP-2 and IL-1β. These suggest that BMP-2 action on osteoblastic differentiation in HPLC may be modulated by PGE2 in autocrine and paracrine fashions.

Notes: Abstract The Tokaido “east coast road” has been the main road of Japan since Mediaeval times, and the journey from Tokyo at one end to Kyoto or Osaka at the other, which used to take a fortnight, can now be completed in about three hours by ‘bullet train’, and an even faster linear-motor car is likely to be in operation in the near future. Already during the 18. cent., Edo (Tokyo) was the largest city in the world, with a population over a million, and the rapid urbanization of Japan's population since Meiji times, and particularly during the post-WW II period, has been quite unprecendented. In 1950, the median size of place was 13,000 and by 1975 it was 140,000. About 60 million lived in the Tokaido zone. The Kanto, Nobi and Osaka plains, adjacent to the good harbours of Tokyo, Ise and Osaka bays, enjoying the relatively mild climate of the Pacific coast, and being within 600 km of each other, have been the focii of urban and industrial development in Japan. The emergence of Tokaido megalopolis was boosted by capital investment in this zone, and was contingent upon the industriousness and high level of education of the people. The concept of megalopolis in Japan is popularly associated with rapid urbanization, poly-nuclear and linear form, and concentration of population, capital and information, all of which elements are typified by the Tokaido zone. The linear ‘megalopolis pattern’ has been postulated as a more efficient growth form for high-dense society than the radial ‘metropolitan pattern’. It has even been suggested that megalopolis is a concept perceived by the intellect, its physical structure determined by information networks, metropolis being perceived by the eye and its physical structure being determined by transport and energy networks. Quite irrespective of the concept of megalopolis, there can be no denying that Japan's society is a ‘high-dense’ society. In 1975, 57% of the population lived in Densely Inhabited Districts (DIDs) at minimum densities of 40 persons per hectare, and these DIDs covered only 2.2% of the land area of Japan. The current trend is for more and more people to live in DIDs, but for overall DID densities to decrease. During the past 25 years, there has been a huge influx of population into the Tokaido zone, and while until 1960 the greatest increases were in the three main metropolitan centres, as these became saturated, rapid urbanization spread into the neighbouring prefectures. Since the mid-sixties, the central metropolitan wards have begun to lose residents, but the daytime population has continued to increase, giving rise to increasingly complex commuting patterns. To give an example, the commuting field of Yokohama includes almost all the prefectures of Tokaido megalopolis. Like the image of megalopolis itself, life in Tokaido megalopolis has its good and bad aspects. Although per capita space in dwellings is increasing somewhat, housing is extremely expensive and people commute long distances. Incomes are high but environmental problems persist. There is a ‘U-turn’ phenomenon, but metropolitan suburbs remain a popular choice of residence. Central management functions and knowledge and information oriented occupations are predominantly concentrated in Tokyo and Osaka, the two main nodes of Tokaido megalopolis. In the intermediate cities, new employment opportunities are stimulated by the expansion of second-level managerial functions. The transport and communications networks of Tokaido are becoming congested as mobility and information flow increase. Planning in the eighties will be affected by the switch from industries dependent on raw materials to knowledge intensive industries; from investment in production to investment in public facilities and pollution control. Within Tokaido megalopolis, there is room for local governments to expand efforts to improve the existing situation, and at its fringes to avert some of the less desirable consequences of rapid urbanization.

Notes: Abstract The present study evaluated the role of nitric oxide in the regulation of duodenal motility and pancreatic exocrine secretion in conscious sheep. Intravenous infusions of nitric oxide synthase inhibitors, Nω-nitro-l-arginine-methyl ester (l-NAME) and Nω-nitro-l-arginine, induced clusters of duodenal contractions like phase III of migrating motor complexes and simultaneously inhibited flow rate, bicarbonate ion and enzyme outputs of pancreatic juice. The effects of l-NAME were inhibited by simultaneous infusion of l-arginine, but not altered by adrenergic blockade using a combined infusion of phentolamine and propranolol. Inhibition of the pancreatic secretion occurred in coincidence with initiation of the duodenal contractions, while the pancreatic secretion was not inhibited when the premature duodenal contractions were abolished by the l-arginine infusion. The initiation of the cluster of duodenal contractions by l-NAME was not abolished by background infusion of atropine, whereas the amplitude of contractions was significantly inhibited by atropine. These results suggest that intrinsic nitric oxide plays a crucial role in the regulation of duodenal tone and maintenance of continuous secretion by the exocrine pancreas in sheep. These results also implied that inhibition of pancreatic exocrine secretion by the nitric oxide synthase inhibitor is presumably mediated in part through the contractile effect on the duodenum.