Thyroid hormones play important roles in bone growth, development, and turnover. To exert its biological activity, T(4) needs to be converted to T(3) by iodothyronine deiodinase. In human thyroid gland as well as rat brown adipose tissue, type 2 iodothyronine deiodinase (D2) expression is regulated by a TSH receptor-cAMP-mediated mechanism. TSH receptor knockout mice demonstrated the direct effects of TSH on bone via TSH receptors found on osteoblast and osteoclast precursors. In the present study we investigated the possible expression and function of iodothyronine deiodinase and TSH receptors in human osteoblast-like osteosarcoma (SaOS-2) cells and normal human osteoblast (NHOst) cells. Iodothyronine deiodinase activity was detected in SaOS-2 cells and NHOst cells, and all of the characteristics of deiodinating activity were compatible with those of D2. Northern analysis demonstrated D2 mRNA expression in SaOS-2 cells and NHOst cells. D2 mRNA levels as well as D2 activities were rapidly increased by dibutyryl cAMP or forskolin in SaOS-2 cells and NHOst cells. TSH receptor mRNA was demonstrated in SaOS-2 cells and NHOst cells, and D2 mRNA and D2 activity were stimulated by TSH in both cells. In addition, all T(3) receptor isoforms were detected by RT-PCR in SaOS-2 cells and NHOst cells. The present results indicate the expression of functional TSH receptors and D2 in human osteoblasts and suggest previously unrecognized roles of TSH receptors and local T(3) production by D2 in the pathophysiology of human osteoblasts.

Juglans mandshurica MAXIM. var. sieboldiana MAKINO (Juglandaceae, Japanese name: Onigurumi), a walnut tree, is widely planted in Japan. Several parts of this plant have been used in folk medicines and the fruit has been used for the treatment of chilblains and athlete's foot.1) As far as we know, there is no report regarding the chemical constituents of the fruit of this plant distributed in Japan, though the isolation of several naphthalenyl glucosides, a-tetralonyl glucosides, and a phenolbutyric acid glucoside from J. mandshurica MAXIM. collected from a mountain area of Wuchang, Heilongjiang Province, China has been reported in the literature. (isosclerone, 4-6) regiolone 7,8) ) by comparing the spectral data and the optical rotation, with those reported in the literature, however, chiral HPLC analysis of 1 showed two peaks (1a: [a] D ϩ24.5°, 1b: [a] D Ϫ26.0°, the ratio of ca. 5 : 1). From their sign of the optical rotations 2,4-13) and comparison of the circular dichroism (CD) data ( Fig. 1) with those of 4S-and 4R-configured isosclerone 4,13) and analogous compounds, 9,12,14) the absolute configurations at C-4 in 1a and 1b were determined to be S and R, respectively. This deduction was further supported by application of the exciton chirality method (see Experimental).15) Consequently, the absolute structures of 1a and 1b were concluded to be (4S) [4][5][6][7][8] C-NMR signal at C-1 of 2 was shifted by Ϫ7.8 ppm in comparison with that of 1. These features suggested that 2 was 5-hydroxy-4-methoxy-a-tetralone. This deduction was supported by 1 Hdetcted heteronuclear multiple bond correlation (HMBC) experiment (Fig. 2). The optical rotation of 2 was almost zero and chiral HPLC analysis (see Experimental) indicated that 2 existed as a racemate (2a, 2b; the ratio of ca. 1 : 1). As can be seen in Fig. 3, the CD Cotton effects of 2a and 2b were strongly dominated by the conformation of the cyclohexenone ring and the sign of the Cotton effect in the p→p* region may be attributed to the axial-chirality effect of axial (and/or quasi-axial) H or a substituent at the a-position, adjacent to the carbonyl group. 16,17) Namely, the conformation of the cyclohexenone ring was determined as half-chair or sofa form on the basis of the nuclear Overhauser enhancement spectroscopy (NOESY) correlation [H-4/one of the methylene protons at C-2 (d 2.58)] and the coupling constant of H-4 (dd, Jϭ10.2, 4.4 Hz). The CD spectra of 2a and 2b showed strongly positive (De ϩ5.8 at 221 nm) and negative (De Ϫ6.1 at 220 nm) Cotton effects, suggesting one of the methylene protons (d 2.58) at C-2 had b-and a-quasi-axial orientations with respect to the cyclohexenone ring, respectively (Fig. 4) new a a-tetralones, (4S)-and (4R)-5-hydroxy-4-methoxy-a a-tetralones and (4S)-and (4R)-5,8-dihydroxy-4-methoxy-a a-tetralones were isolated, together with five known ones, (4S)-and (4R)-4,8-dihydroxy-a a-tetralones, (4S)-4,8-dihydroxy-5-methoxy-a a-tetralone and (4S)-and (4R)-4-hydroxy-a a-tetralones, from the fruit of Juglans mandshurica MAXIM. var. s...

To investigate whether age at onset of steroid-sensitive nephrotic syndrome (SSNS) is predictive of subsequent relapses, or influences outcome, we retrospectively studied 60 patients who were under 10 years of age at onset and were followed for over 10 years. They were divided into three groups according to age at diagnosis: group 1-3 (1.0-3.9 years at onset, n=24), group 4-6 (4.0-6.9 years at onset, n=22), and group 7-9 (7.0-9.9 years at onset, n=14). In the 51 patients with long-term remission, defined as remaining relapse-free over 3 years, the total number of relapses was significantly more in group 1-3 (n=18) than in group 4-6 (n=19), and the interval between onset and long-term remission was significantly longer. Group 4-6 and group 7-9 had fewer patients with active disease at 10 years, follow-up than group 1-3, as assessed by the Kaplan-Meier method. These data suggest that the age at onset of SSNS influences the clinical course (i.e., frequency of relapses) and the time to reach long-term remission. An age of less than 4 years at onset of SSNS is associated with greater likelihood for frequent relapses and a greater time interval to attain long-term remission.

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