bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor Tyrosine Kinases Inhibit Bone Morphogenetic Protein-Smad Responsive Promoter Activity and Differentiation of Murine MC3T3-E1 Osteoblast-like Cells
Authors: Nakayama Konosuke , Tamura Yasuhiro , Suzawa Miyuki , Harada Shun-Ichi , Fukumoto Seiji , Kato Mitsuyasu , Miyazono Kohei , Rodan Gideon A , Takeuchi Yasuhiro , Fujita Toshiro 
Published: April 2006

Abstract
Growth factors such as fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) that activate extracellular signal-regulated kinases (ERKs) through receptor tyrosine kinases (RTKs) stimulate proliferation but suppress differentiation of osteoblasts. To study the mechanism of this inhibitory action of these growth factors on osteoblastic differentiation, we evaluated Smad1 transactivity in MC3T3-E1 osteoblast-like cells by reporters of promoter activity of mouse Smad6, an early response gene to bone morphogenetic proteins (BMPs). FGF-2 and EGF inhibited alkaline phosphatase activity and Smad6 promoter activity stimulated by BMP-2. Overexpression of constitutively active MEK by adenovirus mimicked, but that of dominant negative Ras or treatment with a MEK1 inhibitor, PD098059, reversed, the inhibitory effects of these growth factors on both activities. These effects are mediated by BMP-responsive elements (BMPREs) on Smad6 promoter, because an artificial reporter driven by three tandem BMPREs gave similar results, and these effects were all abolished when the BMPREs were mutated. RTK-ERK activation inhibited the promoter activity even when BMP signal was mediated by a mutant Smad1, which lacks phosphorylation sites by ERKs, or by a Smad1 fused to Gal4 DNA binding domain, which constitutively localizes in the nucleus. These results show that the RTK-Ras-ERK pathway suppresses BMP signal by interfering with Smad1 transactivity. Because direct phosphorylation of Smad1 by ERKs is not required for the inhibition, other transcriptional factors that are phosphorylated by ERKs might be involved in the regulation of osteoblastic differentiation by ERKs.
Effect of 8-Month Vertical Whole Body Vibration on Bone, Muscle Performance, and Body Balance: A Randomized Controlled Study
Authors: Torvinen Saila , Kannus Pekka , Sievänen Harri , Järvinen Tero AH , Pasanen Matti , Kontulainen Saija , Nenonen Arja , Järvinen Teppo LN , Paakkala Timo , Järvinen Markku , Vuori Ilkka 
Published: April 2006

Abstract
Recent animal studies have given evidence that vibration loading may be an efficient and safe way to improve mass and mechanical competence of bone, thus providing great potential for preventing and treating osteoporosis. Randomized controlled trials on the safety and efficacy of the vibration on human skeleton are, however, lacking. This randomized controlled intervention trial was designed to assess the effects of an 8-month whole body vibration intervention on bone, muscular performance, and body balance in young and healthy adults. Fifty-six volunteers (21 men and 35 women; age, 19-38 years) were randomly assigned to the vibration group or control group. The vibration intervention consisted of an 8-month whole body vibration (4 min/day, 3-5 times per week). During the 4-minute vibration program, the platform oscillated in an ascending order from 25 to 45 Hz, corresponding to estimated maximum vertical accelerations from 2g to 8g. Mass, structure, and estimated strength of bone at the distal tibia and tibial shaft were assessed by peripheral quantitative computed tomography (pQCT) at baseline and at 8 months. Bone mineral content was measured at the lumbar spine, femoral neck, trochanter, calcaneus, and distal radius using DXA at baseline and after the 8-month intervention. Serum markers of bone turnover were determined at baseline and 3, 6, and 8 months. Five performance tests (vertical jump, isometric extension strength of the lower extremities, grip strength, shuttle run, and postural sway) were performed at baseline and after the 8-month intervention. The 8-month vibration intervention succeeded well and was safe to perform but had no effect on mass, structure, or estimated strength of bone at any skeletal site. Serum markers of bone turnover did not change during the vibration intervention. However, at 8 months, a 7.8% net benefit in the vertical jump height was observed in the vibration group (95% CI, 2.8-13.1%; p = 0.003). On the other performance and balance tests, the vibration intervention had no effect. In conclusion, the studied whole body vibration program had no effect on bones of young, healthy adults, but instead, increased vertical jump height. Future human studies are needed before clinical recommendations for vibration exercise.
Smoking May Impair the Bone Protective Effects of Nutritional Calcium: A Population-Based Approach
Authors: Sirola Joonas , Kröger Heikki , Honkanen Risto , Sandini Lorenzo , Tuppurainen Marjo , Jurvelin Jukka S , Saarikoski Seppo 
Published: April 2006

Abstract
Postmenopausal women were randomly selected to investigate the effects of smoking on prevention of bone loss with nutritional calcium. DXA was performed twice, and smoking and calcium intake habits were inquired through the mail in 954 women. Smoking dampened the bone protective effects of nutritional calcium. This may reflect the pathophysiology underlying smoking-induced bone loss postmenopause.
This study evaluated the effect of smoking on the bone protective properties of nutritional calcium. Of the random sample of 954 peri- and postmenopausal women selected from the Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort (n = 13,100) in Kuopio, Finland, 182 had smoked at some time (ever smokers) and 772 had never smoked. Women were divided in tertiles according to self-reported dairy nutritional calcium intake (mg/day): &lt;648 (1st), 648-927 (2nd), &gt;927 (3rd). Bone mineral density at lumbar spine (LS) and femoral neck (FN) was measured with DXA at baseline in 1989-1991 and at the 5-year follow-up in 1994-1997. In a linear regression model, nutritional calcium intake did not predict annual bone loss in smokers. These results were similar in the subanalysis on 71 current smokers (at both baseline and 5-year measurements) and on 85 past smokers. In never smokers, a statistically significant linear trend was observed between calcium intake and annual bone loss at LS, but at FN only after adjustment for age, weight, hormone replacement therapy (HRT), and other covariates. In analysis of covariance (ANCOVA), no differences in bone loss rate were observed between calcium intake tertiles among smokers. In nonsmokers, the annual bone loss rate was lower in the second (−0.41%) and the third (−0.35%) tertile compared with the first tertile (−0.61%) at LS (p &lt; 0.05) and lower in the third tertile (−0.55%) than in first tertile (−0.72%) at FN after adjustment for age, weight, HRT, and other covariates (p &lt; 0.05). When smokers were added to the nonsmoker group, the differences in bone loss rate between calcium intake tertiles disappeared. In addition, in ANCOVA, the term of interaction between smoking and calcium intake was statistically significant at LS only. In conclusion, smoking seems to impair the bone protective effects of nutritional calcium in postmenopausal women, more clearly in LS than FN.
The Food and Drug Administration's Osteoporosis Guidance Document: Past, Present, and Future
Authors: Colman Eric G 
Published: April 2006

Abstract
In December 1979, the Food and Drug Administration's (FDA) Division of Metabolic and Endocrine Drug Products issued its Guidelines for the Clinical Evaluation of Drugs Used in the Treatment of Osteoporosis. The Guidance Document recommended study designs, patient populations for study, and techniques for evaluating skeletal mass and fracture frequency that were considered central to showing the efficacy and safety of drugs used to treat and prevent postmenopausal osteoporosis (PMO). In this paper, I discuss the evolution of the Osteoporosis Guidance as it relates to the pharmaceutical industry's efforts to develop effective and safe anti-osteoporosis drugs. Current regulatory policy on osteoporosis drugs and thoughts on the future direction of the Osteoporosis Guidance are also provided.
Is It Ethical to Conduct Placebo-Controlled Clinical Trials in the Development of New Agents for Osteoporosis? An Industry Perspective
Authors: Rosenblatt Michael 
Published: April 2006

Abstract
To represent industry on the topic of this conference, position papers were obtained from six pharmaceutical and biotechnology companies. Despite their holding a wide range of positions in the market with regard to prevention and treatment of osteoporosis, all companies were unanimous in their concerns about the ability to conduct randomized placebo-controlled clinical trials (PCTs) in the future. The clinical research environment contains conflicting directives. Regulatory agencies strongly prefer (even insist on) PCTs as a requirement for drug approval, while many physicians, human studies institutional review boards, and informed patients believe that it is no longer ethical to place osteoporotic patients on placebo because effective therapies are now available. PCTs offer the best means of calibrating the absolute efficacy of a new agent and identifying its side effects against a “neutral” background. Are comparison-controlled clinical trials (CCTs) using an approved drug the answer? No. Examples are given that illustrate that such trials require very large numbers of patients to show “non-inferiority” (approximately 15,000-20,000) or “superiority” (approximately 30,000) compared with an existing approved therapy. Such studies are not only impractical, but also accumulate a greater number of fractures during the course of clinical research in both the new treatment and control (active comparator) groups than would occur in PCTs. Total adverse experiences and exposure of patients to investigational agents is considerably greater when CCTs rather than PCTs are used. Based on this analysis, industry recommends that regulatory approval of new agents for osteoporosis be based on (1) conduct of PCTs in patients at low risk for fracture (e.g., T-score &lt; −2.5 and no previous osteoporotic fracture); (2) use of bone mineral density as an end-point for the indication “to preserve or improve bone mass”; (3) a 2-year, rather than 3-year, trial period; (4) demonstration of no adverse effect on bone quality preclinically; (5) extrapolation of clinical trial results to higher risk patients; (6) an option for the sponsor to perform additional fracture end-point studies postapproval to obtain an indication for “treatment to reduce the risk of fractures specifically in the spine, hip, or both”; and (7) the option to file for a “prevention” claim before a “treatment” claim.
Serum FGF23 Levels in Normal and Disordered Phosphorus Homeostasis
Authors: Weber Thomas J , Liu Shiguang , Indridason Olafur S , Quarles L Darryl 
Published: April 2006

Abstract
We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia.
Introduction: Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin.
Methods: Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis.
Results and Conclusions: FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p &lt; 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = −0.60) and calcium and phosphorus (Ca × P) product (r = −0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca × P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.
Comparison of Three Bone Ultrasounds for the Discrimination of Subjects With and Without Osteoporotic Fractures Among 7562 Elderly Women
Authors: Krieg MA , Cornuz J , Ruffieux C , Sandini L , Büche D , Dambacher MA , Hartl F , Häuselmann HJ , Kraenzlin M , Lippuner K , Neff M , Pancaldi P , Rizzoli R , Tanzi F , Theiler R , Tyndall A , Wimpfheimer K , Burckhardt P 
Published: April 2006

Abstract
Bone ultrasound measures (QUSs) can assess fracture risk in the elderly. We compared three QUSs and their association with nonvertebral fracture history in 7562 Swiss women 70–80 years of age. The association between nonvertebral fracture was higher for heel than phalangeal QUS.
Introduction: Because of the high morbidity and mortality associated with osteoporotic fractures, it is essential to detect subjects at risk for such fractures with screening methods. Because quantitative bone ultrasound (QUS) discriminated subjects with osteoporotic fractures from controls in several cross-sectional studies and predicted fractures in prospective studies, QUS could be more practical than DXA for screening.
Material and Methods: This cross-sectional and retrospective multicenter (10 centers) study was performed to compare three QUSs (two heel ultrasounds: Achilles+ [GE-Lunar] and Sahara [Hologic]; the phalanges: ultrasound DBM sonic 1200 [IGEA]) for determining by logistic regression nonvertebral fracture odds ratio (OR) in a sample of 7562 Swiss women, 75.3 ± 3.1 years of age. The two heel QUSs measured the broadband ultrasound attenuation (BUA) and the speed of sound (SOS). In addition, Achilles+ calculated the stiffness index (SI) and the Sahara calculated the quantitative ultrasound index (QUI) from BUA and SOS. The DBM sonic 1200 measured the amplitude-dependent SOS (AD-SOS).
Results: Eighty-six women had a history of atraumatic hip fracture after the age of 50, 1594 had a history of forearm fracture, and 2016 had other nonvertebral fractures. No fracture history was reported by 3866 women. Discrimination for hip fracture was higher than for the other nonvertebral fractures. The two heel QUSs had a significantly higher discrimination power than the QUSs of the phalanges, with standardized ORs, adjusted for age and body mass index, ranging from 2.1 to 2.7 (95% CI = 1.6, 3.5) compared with 1.4 (95% CI = 1.1, 1.7) for the AD-SOS of DBM sonic 1200.
Conclusion: This study showed a high association between heel QUS and hip fracture history in elderly Swiss women. This could justify integration of QUS among screening strategies for identifying elderly women at risk for osteoporotic fractures.
Omega-3 Fatty Acids Improve Recovery, whereas Omega-6 Fatty Acids Worsen Outcome, after Spinal Cord Injury in the Adult Rat
Authors: King Von R. , Huang Wenlong L. , Dyall Simon C. , Curran Olimpia E. , Priestley John V. , Michael-Titus Adina T. 
Published: April 2006

Spinal cord injury (SCI) is a cause of major neurological disability, and no satisfactory treatment is currently available. Evidence suggests that polyunsaturated fatty acids (PUFAs) could target some of the pathological mechanisms that underlie damage after SCI. We examined the effects of treatment with PUFAs after lateral spinal cord hemisection in the rat. The ω-3 PUFAs α-linolenic acid and docosahexaenoic acid (DHA) injected 30 min after injury induced significantly improved locomotor performance and neuroprotection, including decreased lesion size and apoptosis and increased neuronal and oligodendrocyte survival. Evidence showing a decrease in RNA/DNA oxidation suggests that the neuroprotective effect of ω-3 PUFAs involved a significant antioxidant function. In contrast, animals treated with arachidonic acid, an ω-6 PUFA, had a significantly worse outcome than controls. We confirmed the neuroprotective effect of ω-3 PUFAs by examining the effects of DHA treatment after spinal cord compression injury. Results indicated that DHA administered 30 min after spinal cord compression not only greatly increased survival of neurons but also resulted in significantly better locomotor performance for up to 6 weeks after injury.This report shows a striking difference in efficacy between the effects of treatment with ω-3 and ω-6 PUFAs on the outcome of SCI, with ω-3 PUFAs being neuroprotective and ω-6 PUFAs having a damaging effect. Given the proven clinical safety of ω-3 PUFAs, our observations show that these PUFAs have significant therapeutic potential in SCI. In contrast, the use of preparations enriched in ω-6 PUFAs after injury could worsen outcome after SCI.
Menge aller robust stabilisierenden PID-Regler: Methodik und Software (Teil II) (The Set of All Robust Stabilizing PID Controllers: Methods and Software (Part II))
Authors: Bajcinca Naim , Hulin Thomas 
Published: April 2006

Abstract
Dieser Aufsatz befasst sich mit der Berechnung der Menge aller stabilisierenden PID-Regler im zeitdiskreten Bereich. Dem Verfahren liegt die im ersten Teil vorgestellte Entkopplung von Reglerparametern zugrunde, die für zeitdiskrete Systeme in einem rotierten Parameterraum stattfindet. Die resultierenden stabilen Gebiete setzen sich aus konvexen polygonalen Schnitten zusammen. Die Entwurfsmethodik kann in zwei Unterprobleme aufgeteilt werden, erstens die Bestimmung von Intervallen, für die stabile Polygone existieren, und zweitens die Berechnung dieser Polygone. Diese Veröffentlichung stellt Lösungsansätze für beide Probleme vor.
A Comparison of U.S. and Chinese Sorghum Germplasm for Early Season Cold Tolerance
Authors: Franks Cleve D. , Burow Gloria B. , Burke John J. 
Published: April 2006

ABSTRACTEarly season cold tolerance in grain sorghum [Sorghum bicolor (L.) Moench] is a desirable trait for extending its production range and minimizing risks associated with early spring plantings. Ten Chinese Kaoliang accessions were compared with 10 U.S. inbred parental lines and 10 U.S. commercial hybrids for a range of cold tolerance traits under laboratory, growth chamber, and field settings. Chinese lines were superior to both the inbred and hybrid classes in laboratory germination rates and field‐based rates of emergence. In the growth chamber assays, Kaoliangs were not significantly different than U.S. hybrids for most traits measured at either of the two temperature treatments (12 and 24°C), with the exception of shoot length, for which the Chinese germplasm was higher. At the cooler temperature, Kaoliangs were significantly greater than U.S. inbreds for only fresh shoot weight; when tested at the warmer temperature, Kaoliangs had higher dry root weight, fresh and dry shoot weights, and fresh and dry whole plant weights, relative to the U.S. inbred class. The U.S. hybrids had greater total plot weight and final stand counts in the field than Kaoliangs, which were likewise higher than U.S. inbreds for both of these traits. Chinese accessions from this working group would serve as a source of favorable genes primarily for tolerance to low temperatures during the germination and emergence phase of growth in the breeding of cold tolerance sorghum lines.
New Japanese Theatre
Authors: Goodman David 
Published: April 2006

When European theatre was introduced to Japan, Kabuki (including its bastard offspring Shimpa—Kabuki-style modern theatre) was practically the only theatre there was, and it consequently became the referent for all theatrical endeavor. Kabuki actors and Kabuki language, Kabuki gestures and Kabuki notions—there was nothing else. When in the early 1920s Aoyama Sugisaku directed a play using the vernacular, he was met with praise from some quarters, contempt from others, but amazement from all. It was thus natural for Osanai Kaoru to see Kabuki as a vehicle for modern theatre. In a lecture delivered in Moscow, Osanai declared:The future of Japanese theatre will see a synthesis of all Asian art traditions, including those of India, China, Siam, and the islands of the South Pacific, as well as further incorporating the European dramatic tradition. New art will have to be created from these materials.
The Body Training of Moshe Feldenkrais
Authors: Linklater Kristin 
Published: April 2006

In October, 1971, Moshe Feldenkrais came to the United States to give seminars in body training at the Esalen Institute, at Carnegie Mellon, and at the School of the Arts at New York University. The interest shown in his work by these institutions reflects an important change of emphasis in the area of movement training for actors.The choice, put simply, is between training the body to perform skillfully as a well-exercised, aesthetically pleasing physical instrument, and freeing the body of its habitual tensions and programmed patterns of behavior so that it can respond uninhibitedly to impulse, and genuinely reflect individual imagination and emotion.There is a trend away from the use of the formal disciplines of ballet, modern dance and classical mime as exercises. Actors are turning to Yoga classes, are being Rolf’d, are taking Alexander classes and T’ai Chi.
Notes: ‘64–‘74
Authors: Childs Lucinda 
Published: April 2006

When the appearance of work changes radically, one generally can also assume that the underlying concerns governing the work have shifted. While the hypothesis of that statement definitely applies to my work, the conclusion does not, and I find myself reflecting on aspects of continuity rather than discontinuity, particularly with regard to the involvement of the spectator.In 1964, one of my dances took place on a street in lower Manhattan. It was observable to an audience from the windows of a loft located on the opposite side of the street. The dance was entirely based on its found surroundings, and performers, myself and one other, essentially blended in with the other activity that was going on in the street. From time to time, however during the six-minute duration of the dance, we were engaged in pointing out various details and/or irregularities in the facades of the buildings: lettering and labels, the assorted content of displays in the store fronts (sheets, pillow cases, etc.).