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During an investigation of the factors affecting the reaction of 2′,3′-O-isopropylidene nucleosides with phosphoryl chloride, trialkyl phosphates were found to be powerful accelerators and useful solvents for the phosphorylation. The addition of a trialkyl phosphate to a large excess of phosphoryl chloride was markedly effective in promoting the phosphorylation; further, the lower alkyl phosphates, such as trimethyl and triethyl phosphates, were able to replace the excessive amount of phosphoryl chloride as solvents. When unprotected nucleosides were treated with phosphoryl chloride in trimethyl phosphate, the corresponding 5′-phosphates were mainly produced, together with a small amount of highly-phosphorylated products, in good yields. On the contrary, the treatment of 5′-O-acetyl nucleosides in a similar manner gave the corresponding 2′(or 3′)-nucleotides in low yields. The formation of the 2′(or 3′)-phosphate was strongly inhibited by the addition of a small amount of water to the reaction mixture. Thus, the selective phosphorylation of unprotected nucleosides to the 5′-nucleotides in a one-step procedure was accomplished.

Calcitonin gene-related peptide (CGRP) is thought to be a prominent neuropeptide in cardiovascular regulation and neuroimmune modulation. There are two isoforms of CGRP (␣CGRP and ␤CGRP), and the main CGRP receptors are probably composed of a calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP)1. However, the physiological functions of CGRP that are mediated through the CLR/RAMP1 receptors remain to be clarified. For an improved understanding of the functions, we generated mice deficient in RAMP1, a specific subunit of CGRP receptors, by a conditional gene-targeting technique. The RAMP1-deficient mice (RAMP1 ؊/؊ ) exhibited high blood pressure, with no changes in heart rate. ␣CGRP was found to have a potent vascular relaxant activity compared with ␤CGRP in the artery of the WT (RAMP1 ؉/؉ ) mice. The activities of both CGRP isoforms were remarkably suppressed in the arteries of the RAMP1 ؊/؊ mice. The LPS-induced inflammatory responses of the RAMP1 ؊/؊ mice revealed a transient and significant increase in the serum CGRP levels and high serum levels of proinflammatory cytokines compared with the RAMP1 ؉/؉ mice. ␣CGRP and ␤CGRP equally suppressed the production of TNF-␣ and IL-12 in bone marrow-derived dendritic cells stimulated with lipopolysaccharide. Their inhibitory effects were not observed in the bone marrow-derived dendritic cells of the RAMP1 ؊/؊ mice. These results indicate that CGRP signaling through CLR/RAMP1 receptors plays a crucial role in the regulation of both blood pressure by vascular relaxation and proinflammatory cytokine production from dendritic cells.gene-disrupted mice ͉ calcitonin gene-related peptide ͉ adrenomedullin ͉ neuropeptide ͉ dendritic cells C alcitonin gene-related peptide (CGRP) is a 37-aa neuropeptide that is produced in the neural body of dorsal root ganglion cells and released from sensory nerve endings. There are two isoforms of CGRP: ␣ and ␤ in rats and mice and I and II in humans. These differ in their peptide sequences by 1 aa (rats) and 3 aa (mice and humans) of the 37 aa (1). ␣CGRP is produced mainly in the nervous system by the tissue-specific alternative splicing of the primary RNA transcript of the calcitonin/CGRP gene. On the other hand, ␤CGRP is produced not only in the neuronal tissues but also in the enteric nerves of the intestine (2) and in immune cells such as T cells (3). Pharmacologically, ␣CGRP is known to have the most potent vasodilatory activity (4). Most blood vessels are surrounded by a dense perivascular CGRPergic neural network, suggesting the physiological importance of CGRP in vasodilatory regulation (5). ␣CGRP also contributes to local neurogenic inflammation and nociception (6). Moreover, the functions of immune cells such as macrophages (7,8), Langerhans cells (8), and T cells (9, 10) are modulated by ␣CGRP. However, the precise functional differences between ␣CGRP and ␤CGRP remain unclear.Historically, CGRP receptors have been classified into two classes: CGRP 1 and CGRP 2 receptors. The CGRP 1 receptors are m...

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Vitamin D deficiency exists in patients with Crohn's disease in Japan. 25-OHD levels should be assessed in patients who have had Crohn's disease for a long time (>15 years) and who have been in the active stage of the disease for long periods.

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Some cutaneous inflammations are induced by percutaneous exposure to foreign Ags, and many chemical mediators regulate this inflammation process. One of these mediators, calcitonin gene-related peptide (CGRP), is a neuropeptide released from nerve endings in the skin. CGRP binds to its receptors composed of receptor activity-modifying protein 1 and calcitonin receptor-like receptor to modulate immune cell function. We show that CGRP regulates skin inflammation under physiological conditions, using contact hypersensitivity (CHS) models of receptor activity-modifying protein 1–deficient mice. CGRP has different functions in CHS responses mediated by Th1 or Th2 cells; it inhibits Th1-type CHS, such as 2,4,6-trinitrochlorobenzene–induced CHS, but promotes Th2-type CHS, such as FITC-induced CHS. CGRP inhibits the migration of Langerin+ dermal dendritic cells to the lymph nodes in 2,4,6-trinitrochlorobenzene–induced CHS, and upregulates IL-4 production of T cells in the draining lymph nodes in FITC-CHS. These findings suggest that CGRP regulates several types of CHS reactions under physiological conditions and plays an important role in cutaneous immunity.

We have developed a real-time, dynamic holographic material that exhibits rapid colouration upon irradiation with UV light and successive fast thermal bleaching within tens of milliseconds at room temperature. Photochromic polymer films were prepared by a simple solution-casting method from the benzene solution of the mixture of the photochromic molecule, poly(ethyl acrylate), and poly(phenoxyethyl acrylate). The real-time control of holographic images using the photochromic polymer film yields a speed equivalent to the time resolution of the human eye. This new type of dynamic holographic material based on fast photochromism opens up an exciting new area of research in the future development of a large dynamic 3D display.