bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Properties of a Bismethano-bridged Bisdehydro[21]annulenone. Conformation in Solution and in the Crystalline State
Authors: Higuchi Hiroyuki , Kiyoto Seiken , Sakon Chiaki , Hiraiwa Naoki , Asano Kaori , Ojima Juro , Inoue Katsuya , Yamamoto Gaku 
Published: April 2006

Abstract
A bismethano-bridged bisdehydro[21]annulenone, tricyclo[15.4.1.16,11]tricosa-6,8,10,12,15,17,19,21-octaene-2,4-diyn-14-one, was synthesized. X-ray crystallography reveals the syn orientation of the two methano bridges. Two conformers are present in solution in a 97:3 ratio, the major isomer being the one existing in the crystalline state. Paratropicity of this compound in CDCl3 and in CF3CO2D is discussed.
An Efficient Triple Allylation of 1,3,5-Triazine by Means of Tin Reagent. Facile Synthesis of syn,syn-2,4,6-Trifunctionalized 1,3,5-Triazacyclohexanes
Authors: Yamaguchi Ryohei , Kobayashi Seiichi , Kozima Sinpei 
Published: April 2006

Abstract
An efficient triple addition of allyl groups to 1,3,5-triazine has bee carried out by means of an allyltin reagent to give 2,4,6-trially-1,3,5-triazacyclohexanes in high yields. Epoxidation and hydroxylation of the syn,syn-stereoisomer afford geometrically interesting syn,syn-trifunctionalized 1,3,5-triazacyclohexane derivatives.
Diastereoselective Addition of α-Sulfinyl Ester Enolate with Benzaldimines Possessing an Electron Withdrawing Group at the Nitrogen Atom
Authors: Shimizu Makoto , Kooriyama Yuuji , Fujisawa Tamotsu 
Published: April 2006

Abstract
The reaction of optically pure α-sulfinyl ester enolate with benzaldimines possessing an electron withdrawing group at the nitrogen atom gave β-amino ester in both enantiomeric forms in satisfactory optical and chemical yields (up to 94%ee), in which the changeover of the diastereofacial selectivity was induced by suitable choice of the protecting group at the nitrogen and the use of additives.
A New Lipobetaine from the Red Alga Neodilsea yendoana
Authors: Ishida Ryoichi , Matsuo Yoshihide , Suzuki Minoru , Sato Atsushi , Matsumoto Takeshi 
Published: April 2006

Abstract
A new icosanoid lipobetaine has been isolated from a red alga and its structure has been determined to be (2S)-2-[(3S)-3-[(5Z,8Z,11Z,14Z,17Z)-5,8,11,14,17-icosapentaenoyloxy]-(8Z,11Z,14Z)-8,11,14-icosatnenoylamino]-5-trimethylammoniopentanoate, mainly on the basis of NMR spectral and chemical means.
Synthesis of [5-Bipyridylalanyl2,2′]gramicidin S and Its Complexation with Divalent Metal Ions
Authors: Nishino Norikazu , Arai Toru , Hayashida Jun , Ogawa Hiroaki I , Yamamoto Hitoshi , Yoshikawa Susumu 
Published: April 2006

Abstract
A gramicidin S (GS) analog ([Bpa2,2′]GS), in which the Orn residues are replaced by l-5-bipyridylalanines, was synthesized by the solid-phase-synthesis and cyclization-cleavage method. The analog formed stable 1:1 complexes with transition metal ions such as Co2+, Ni2+, Cu2+, and Zn2+ in CH3OH without significant conformational change as shown by the 1H-NMR and circular dichroism analyses. These peptide-metal complexes are water-soluble and will be used in various models of artificial metalloproteins based on the β-sheet structure.
Cyclical Intravenous Pamidronate Treatment Affects Metaphyseal Modeling in Growing Patients With Osteogenesis Imperfecta
Authors: Land Christof , Rauch Frank , Glorieux Francis H 
Published: April 2006

Abstract
This analysis of 50 growing patients with osteogenesis imperfecta revealed that 2-4 years of pamidronate treatment lead to abnormalities in the shape of the distal femoral metaphyses.
Introduction: Cyclical intravenous pamidronate therapy is of clinical benefit in children and adolescents with moderate to severe osteogenesis imperfecta (OI) but might interfere with the shaping of long bone metaphyses during growth.
Materials and Methods: We evaluated the distal femur in 50 growing children with moderate to severe OI (mean age, 6.7 ± 3.4 years; 26 girls) who had received 2-4 years of pamidronate therapy (annual dose, 9 mg/kg body weight). The mediolateral width of the distal femoral growth plate and of the metaphysis, as well as the ratio between these two measures (called metaphyseal index), were determined on lower limb radiographs.
Results: Compared with untreated OI patients who were matched for OI type and age, pamidronate-treated patients had similar growth plate width but wider metaphyses, resulting in a 26% higher metaphyseal index (p &lt; 0.001). Apart from the effect on bone shape, each pamidronate cycle induces a transverse line in metaphyses that are adjacent to active growth plates. Analyses of these transverse lines revealed that they persist for an average time of ∼4 years, with a range from 2 to 8 years.
Conclusions: Pamidronate interferes with the process of periosteal resorption that is normally responsible for shaping the distal femoral metaphysis. Pamidronate-induced transverse lines disappear with time, supporting the view that these lines represent horizontal trabeculae that undergo remodeling. There is no evidence at present that these treatment induced morphological changes have any clinical implications.
Vertebral Deformities and Functional Impairment in Men and Women
Authors: Burger H. , Van Daele P. L. A. , Grashuis K. , Hofman A. , Grobbee D. E. , Schütte H. E. , Birkenhäger J. C. , Pols H. A. P. 
Published: April 2006

Abstract
The objective of this study was to assess the prevalence and health effects of vertebral deformities in men and women. The study was carried out as part of the cross-sectional baseline phase of The Rotterdam Study, a prospective population-based cohort study of residents aged 55 years or over of a district of Rotterdam, The Netherlands. The prevalence of vertebral deformities according to a modification of the Eastell method and concomitant functional impairment were assessed in a random sample of 750 men and 750 women. The prevalence of moderate (grade I) vertebral deformities was 8 and 7% in men and women, respectively. For severe deformities (grade II), these percentages were 4 and 8%. In men, the prevalence of both moderate and severe deformities increased with age. In women, however, the prevalence of moderate vertebral deformities remained constant, opposite to a marked increase in severe deformities. Moderate vertebral deformity was significantly associated with impaired rising in men only. Severe vertebral deformity was associated with a significantly increased risk of general disability and the use of a walking aid in both men and women, impaired bending in men, and impaired rising in women. It is concluded that (1) vertebral deformities are only slightly less common in men than in women from the general population and (2) severe progression with age occurs in women only and (3) severe vertebral deformity is, particularly in men, related to functional impairment.
Skeletal Integrity in Men Chronically Treated with Suppressive Doses of L-Thyroxine
Authors: Marcocci Claudio , Golia Franco , Vignali Edda , Pinchera Aldo 
Published: April 2006

Abstract
We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 ± 6 μg, and the cumulative dose of LT4 was 673 ± 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 ± 0.12 vs. 1.168 ± 0.15; femoral neck 0.979 ± 0.13 vs. 1.001 ± 0.13; Ward's triangle 0.854 ± 0.17 vs. 0.887 ± 0.15; and trocanther 0.852 ± 0.13 vs. 0.861 ± 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.
Analysis of Osteocalcin Expression in Transgenic Mice Reveals a Species Difference in Vitamin D Regulation of Mouse and Human Osteocalcin Genes
Authors: Clemens Thomas L. , Tang Hui , Maeda Shigeto , Kesterson Robert A. , Demayo Francesco , Pike J. Wesley , Gundberg Caren M. 
Published: April 2006

Abstract
A line of transgenic mice expressing a human osteocalcin genomic fragment (hOClocus) and a murine MC3T3-E1 cell line containing a stably integrated human osteocalcin promoter construct have been developed to characterize the osteogenic and hormonal regulation of human osteocalcin in vivo and in vitro. In this study, we used these models to demonstrate a species difference in the regulation of the mouse and human osteocalcin genes by vitamin D. Repeated administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to mice carrying the hOClocus transgene resulted in striking increases in serum human osteocalcin, whereas serum mouse osteocalcin levels were unchanged after 24 h and only modestly increased 48 h after the second dose of hormone. 1,25(OH)2D3 increased human calvarial mRNA expression by 1.8-fold and slightly decreased mouse osteocalcin mRNA levels by approximately 1.2-fold. Furthermore, treatment of primary calvarial osteoblasts from these mice with 1,25(OH)2D3 increased human osteocalcin production but inhibited mouse osteocalcin protein accumulation. To investigate further the mechanism for the apparent species difference in vitamin D3 induction of mouse and human osteocalcin, we examined the effect of 1,25(OH)2D3 in an MC3T3-E1 cell line (MC4) containing a stably integrated 3900 bp osteocalcin promoter-luciferase construct. Treatment of MC4 cells with ascorbic acid resulted in parallel increases of the endogenous mouse osteocalcin protein and luciferase reporter activity over a 12-day period. Continuous exposure of MC4 cells to 1,25(OH)2D3 resulted in time-and dose-dependent increases in the activity of the phOC3900 luciferase construct. By contrast, the hormone had no effect on mouse osteocalcin protein concentrations and inhibited its induction by ascorbic acid. However, when cells were treated acutely with 1,25(OH)2D3 at later times during growth in ascorbic acid, the induction of mouse osteocalcin protein was only partially inhibited. In conclusion, our results indicate that common osteogenic signals regulate both mouse and human osteocalcin gene expression, but the mouse gene is resistant to induction by vitamin D. This species difference in vitamin D regulation of osteocalcin appears to result from the failure of 1,25(OH)2D3 to transcriptionally activate the mouse osteocalcin gene.
Total Body Bone Mineral Density in Young Children: Influence of Head Bone Mineral Density
Authors: Taylor Arlene , Konrad Patricia T. , Norman Michael E. , Harcke H. Theodore 
Published: April 2006

Abstract
Dual-energy X-ray absorptiometry (DXA) with its short scan time, low radiation dose, and high precision and accuracy have made this technique particularly suitable for measuring total body bone mineral density (TBMD) in children. Other published reports have related TBMD to age in children 2–18 years of age. However, in young normal children aged 2–9 years (51 girls, 43 boys), we found that regression equations for TBMD with age as the predictor did not explain enough of the variance to warrant their use for predicting TBMD (adjusted R2 0.47, females; 0.41, males). Subtotal BMD (TBMD − head BMD) is predicted better by age because of a possibly invalid adult algorithm for head BMD (adjusted R2 0.73, females; 0.71, males).
The Effect of Aging on Bone Formation in Porous Hydroxyapatite: Biochemical and Histological Analysis
Authors: Inoue K. , Ohgushi H. , Yoshikawa T. , Okumura M. , Sempuku T. , Tamai S. , Dohi Y. 
Published: April 2006

Abstract
The effect of aging on osteoblastic differentiation of marrow stromal stem cells was examined. Porous hydroxyapatite (HA) disks were soaked in cells suspensions of bone marrow cells from young (8 weeks) and old rats (60 weeks) and then implanted subcutaneously in syngeneic young and old rats. The bone marrow/HA composites were harvested 8 weeks later, and the contents of bone Gla protein (BGP) and alkaline phosphatase (ALP) activity in them were determined. Histologically, bone formation could be detected in all the composites in young recipient rats; however, some old bone marrow/HA composites in old recipients did not show bone formation and the bone volume in the young bone marrow/HA composites was greater than in the old bone marrow/HA composites. The ratios of ALP activities of young bone marrow/HA composites to old bone marrow/HA composites in young and old recipients were about five times and four times, respectively. The ratios of BGP contents of young bone marrow/HA to old bone marrow/HA composite in young and old recipients were about nine and eight times, respectively. The results suggest that the decreased bone formation observed in old bone marrow cells was due to a smaller population of stromal cells and/or decreased capacity of differentiation of stromal stem cells into osteogenic cells.
The Vitamin D Receptor Gene Start Codon Polymorphism: A Functional Analysis of FokI Variants
Authors: Gross Coleman , Krishnan Aruna V. , Malloy Peter J. , Eccleshall T. Ross , Zhao Xiao-Yan , Feldman David 
Published: April 2006

Abstract
The vitamin D receptor (VDR) gene contains a start codon polymorphism (SCP) which is three codons upstream of a second start site (ATG). The SCP genotype can be determined with the restriction enzyme FokI, where “f” indicates the presence of the restriction site and the first ATG, while “F” indicates its absence. Recent evidence suggests that the ff genotype is correlated with lower bone mineral density (BMD) in some populations. The SCP results in alternate VDRs that differ structurally, with the F variant (F-VDR) being three amino acids shorter than the f variant (f-VDR). To determine whether there are functional differences between the f-VDR and the F-VDR, we studied the two VDR forms expressed in COS-7 cells. The proteins were distinguishable from one another on Western blots by their different mobilities, confirming the larger size of f-VDR. Ligand binding studies showed no significant differences between the affinities of the two VDR forms for [3H]-1,25-dihydroxyvitamin D3 ([3H]-1,25(OH)2D3) (Kd = 131 ± 78 pM, f-VDR; Kd = 237 ± 190 pM, F-VDR; p = 0.24); however, a 2-fold difference in affinity can not be discriminated by this method. There were no differences in the abilities of the two receptor forms to bind DNA as determined by electrophoretic mobility shift assays. The ability of the two VDR forms to transactivate target genes was investigated using three different vitamin D responsive luciferase reporter constructs: 24-hydroxylase, osteocalcin, and osteopontin. In these transactivation experiments, 1,25(OH)2D3 dose-response (0.1–10 nM) curves revealed that the ED50 values for transactivation were indistinguishable between the two VDR forms. Additionally, cultured human fibroblasts with FF,Ff, and ff genotypes had similar sensitivity to 1,25(OH)2D3 with respect to the induction of 24-hydroxylase mRNA. In summary, we were unable to detect significant differences in ligand affinity, DNA binding, or transactivation activity between f-VDR and F-VDR forms. We must emphasize, however, that the sensitivity of the methods used limits our ability to detect minor differences in VDR affinity and function. In conclusion, we cannot define a mechanism whereby the SCP in the VDR might contribute to population differences in BMD.
Responses of Trabecular and Cortical Bone Turnover and Bone Mass and Strength to Bisphosphonate YH529 in Ovariohysterectomized Beagles with Calcium Restriction
Authors: Yoshida Yasushi , Moriya Atsuko , Kitamura Kazuyuki , Inazu Mizuho , Okimoto Nobukazu , Okazaki Yuichi , Nakamura Toshitaka 
Published: April 2006

Abstract
Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3–6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4–6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4–6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4–6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4–6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.
Osteoclast Differentiation Requires Ascorbic Acid
Authors: Ragab Ashraf A. , Lavish Sandra A. , Banks Michael A. , Goldberg Victor M. , Greenfield Edward M. 
Published: April 2006

Abstract
Osteoclast differentiation assays are usually conducted in alpha minimal essential medium (α-MEM). We reasoned that determining which components of this media are critical for osteoclast differentiation might provide insight into the mechanisms that regulate osteoclast differentiation. This study demonstrates that ascorbic acid is the crucial component of α-MEM that stimulates differentiation of murine osteoclasts in cocultures with murine mesenchymal support cells. Thus, supplementation with ascorbic acid allows osteoclast differentiation to occur in basal MEM media as well as in RPMI-1640 and basal media Eagle (BME) media. The conclusion that osteoclast differentiation is stimulated by ascorbic acid was obtained whether osteoclast differentiation was induced by 1,25-dihydroxyvitamin D3 or parathyroid hormone, whether ST2 or CIMC-2 cells were used as mesenchymal support cells, and whether osteoclast precursors were obtained from spleen or bone marrow. Time course studies revealed that although ascorbic acid only modestly increases the rate at which osteoclast precursors begin to express tartrate-resistant acid phosphatase, it strongly increases the rate at which precursors fuse into mature, multinucleated cells. Moreover, ascorbic acid strongly increases the life span of both osteoclasts and their precursors. The increases in precursor formation, fusion, and life span induced by ascorbic acid are together responsible for the stimulation of osteoclast differentiation by ascorbic acid. Given the known effects of ascorbic acid on differentiation of mesenchymal cells, it may stimulate osteoclast differentiation indirectly by regulating the differentiation state of the mesenchymal cells that support osteoclast differentiation.
Gender Differences in Insulin-like Growth Factor and Bone Mineral Density Association in Old Age: The Rancho Bernardo Study
Authors: Barrett-Connor Elizabeth , Goodman-Gruen Deborah 
Published: April 2006

Abstract
Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as evidenced by in vitro and animal studies. In clinical studies, the age-related decrease in IGF-I parallels the age-related decrease in bone mineral density (BMD), but several age-adjusted cross-sectional studies show no consistent association of IGF-I and BMD. We report here a cross-sectional study of serum IGF-I and BMD levels in 483 men and 455 postmenopausal women not using estrogen; subjects were 55 years of age and older, community-dwelling, ambulatory, and unselected for bone density. IGF-I was measured by a highly specific radioimmunoassay. BMD was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry. Men had higher IGF-I and BMD levels than women. In age-adjusted and age-stratified models, IGF-I was associated with BMD only in women (test for interaction, p &lt; 0.0001). Gender differences persisted in gender-specific multiple regression analyses adjusted for age, body mass index, thiazide diuretic use, current smoking, alcohol intake, physical activity, and weight change; IGF-I was significantly associated with BMD at the spine (p = 0.0001) and hip (p = 0.02) in women, but not in men (p's &gt; 0.6). Circulating estradiol levels were not associated with IGF-I levels in either gender; testosterone was inversely associated with IGF-I and only in men. This striking gender difference has not been described previously. Its etiology is unknown. The answer could lead to improved understanding of gender differences in osteoporosis and in response to treatment with IGF-I or growth hormone.