We have developed a new strategy for the generation of phosphenium dication equivalents from readily available phosphinic acids and Tf 2 O. The in situ-generated dication equivalents can be readily coupled with simple (hetero)biaryls to form the corresponding dibenzophospholes directly. This protocol can also be applied to the concise synthesis of six-and seven-membered phosphacycles as well as the largely π-extended heteroacene derivatives, which are of great interest in the field of organic functional materials.

A phosphenium-cation-mediated formal [3+2]-cycloaddition reaction of internal alkynes is reported. The reaction proceeds under metal-free conditions to give the corresponding C-P rearranged benzophospholes regioselectively, even when ortho- and para-substituted arylphosphine oxides are starting substrates. Mechanistic studies by P{ H} NMR analysis suggest an involvement of three-membered phosphirenium cation species and C-P rearrangement prior to a ring closure for benzophosphole skeleton formation.

A Tf2O-mediated intramolecular phospha-Friedel–Crafts-type reaction of secondary biarylphosphine oxides has been developed. The reaction is promoted simply by Tf2O to form the corresponding dibenzophospholes under metal-free conditions. The starting substrates are readily available and easy-to-handle phosphine oxides, and the regioselectivity is controlled by the innate electronic nature. Thus, this newly developed protocol can provide concise and complementary approach to the highly π-conjugated dibenzophospholes of potent interest in material chemistry.

Autosomal dominant hypocalcemia can be caused by activating mutations of the calcium-sensing receptor (CaSR) gene. We experienced two patients (proband and her daughter) with hypocalcemia caused by a missense mutation of the CaSR gene. The proband, aged 25, showed hypocalcemia and hypoparathyroidism from infancy. She had been diagnosed as having idiopathic hypoparathyroidism and had been treated with calcitriol. She gave birth to a female infant at age 24 years. Her daughter was found to have hypocalcemia (Ca, 6.6 mg/dl), without seizure or tetany, when she was 7 months old. DNA analysis of their CaSR genes showed a novel heterozygous mutation at codon 129 (TGC-to-AGC) with substitution of cysteine for serine (C129S). Familial examination revealed that this mutation had occurred de-novo in the proband. Wild-type and mutant (C129S) CaSR cDNA were transfected into HEK293 cells, and intracellular calcium concentrations were measured with a fluorescent calcium indicator. HEK cells transfected with the C129S mutant CaSR gene showed a larger increase in intracellular calcium concentration in response to the change in the extracellular calcium concentration than HEK cells transfected with the wild-type receptor. We conclude that the C129S mutation in the CaSR gene observed in these patients causes autosomal dominant hypocalcemia.

This study provides an analysis of the clinical efficacy of influenza vaccination in a large cohort of nursing home residents in JAPAN: Annual influenza vaccine administration requires the attention of all nursing home attendants, physicians, and public health organizations.

A palladium-catalysed C–H arylation of benzophospholes with aryl halides has been developed. The reaction with aryl iodides and bromides proceeds well even under phosphine ligand-free Pd(OAc)2 catalysis whereas the Pd(PCy3)2...

Vitamin K deficiency is a relatively common condition in neonates. However, the role of vitamin K in neonatal bone metabolism remains to be determined. Osteocalcin (OC) is the most abundant noncollagenous protein in bone, and is regulated to be ␥-carboxylated by vitamin K. In this study, we measured ␥-carboxylated osteocalcin (Gla-OC) and non-or undercarboxylated osteocalcin (Glu-OC) separately, and examined the effects of vitamin K on osteocalcin metabolism. Eighteen full-term healthy neonates were enrolled in this study. In the cord and d-5 blood samples, the OC levels were determined by three different methods to examine the intact OC by immunoradiometric assay (IRMA), Gla-OC, and Glu-OC. Serum vitamin K fractions, hepaplastin test, and type 1 procollagen carboxyl extension peptide were also determined. Urine samples were also collected from the first voiding and on d 5 to determine urinary pyridinoline, deoxypyridinoline, and ␥-carboxylated glutamic acid. Serum levels of phylloquinone (PK) and menaquinone (MK)-4 increased on d 5 following vitamin K administration and increased intake in breast milk and/or formula. The OC levels determined by IRMA did not change between cord and d-5 blood samples, but the Gla-OC level increased remarkably and Glu-OC reduced to a negligible level. OC in cord blood is mainly Glu-OC, and Glu-OC is replaced with Gla-OC within 5 d of life after vitamin K supplement. The IRMA assay fails to distinguish Gla-OC from Glu-OC and caution is needed to estimate bone turnover with this method in the perinatal period. Natural vitamin K is composed of PK and MK. MK is further divided according to the length of its side chain. The main circulating vitamin K in human serum is PK and MK-7 (1). Vitamin K acts as a co-factor for ␥-carboxylase, known as a key enzyme for producing competent coagulation factors in the liver. Its deficiency is a relatively common condition in neonates and has long been a major cause of serious bleeding diseases in newborn babies. Neonatal vitamin K deficiency may be attributed to the following causes: the human placenta has a limited capacity to transfer vitamin K (2); and maternal breast milk contains a low level of vitamin K, especially in the early phase of lactation (3). Based on these facts, prophylactic administration of vitamin K to newborns has been recommended in many countries, though dosages and schedules of supplement differ among those countries. A number of studies have reported that vitamin K supplementation successfully decreased the incidence of neonatal intracranial hemorrhage and melena (4 -6).Another important substrate of ␥-carboxylase is OC, produced in osteoblasts. OC is the most abundant noncollagenous protein in bone, containing 49 amino acid residues. It is often used as a marker of osteoblastic activity and bone formation (7). OC has an affinity with calcium hydroxyapatite but does not bind to it until the OC becomes ␥-carboxylated in the osteoblasts (8). Vitamin K is essential for the ␥-carboxylation in three glutamate residues of the OC p...

In order to examine the effects of long-term hospitalization during pregnancy on vitamin D metabolism in pregnant women and neonates, we measured the serum 25-hydroxyvitamin D (25OHD) levels in pregnant women, as well as measuring 25OHD levels in cord blood and breast milk. In pregnant women hospitalized for longer than 1 month, the serum 25OHD levels were decreased at delivery compared with those in control subjects (10.9 +/- 2.6 ng/l vs 19.5 +/- 4.9 ng/l; P < 0.01). Although the levels of 25OHD in the cord blood were not significantly different between the long-term hospitalized and control pregnant women in this study (9.36 +/- 1.7 ng/l vs 11.1 +/- 3.0 ng/l), the 25OHD concentrations in the cord blood were significantly lower than the maternal levels in both groups; the ratios of the levels in cord blood to sera in the long-term hospitalized women and control subjects were 82.1% and 60.3%, respectively. Long maternal hospitalization does not always cause neonatal vitamin D deficiency, but could be one of its major risk factors. Therefore, sufficient sunlight exposure and intake of sufficient vitamin D are considered to be important to prevent vitamin D deficiency in long-term hospitalized pregnant women as well as their babies.