bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteopontin-Deficiency Suppresses Growth of B16 Melanoma Cells Implanted in Bone and Osteoclastogenesis in Co-Cultures
Authors: Ohyama Yoshio , Nemoto Hiroyuki , Rittling Susan , Tsuji Kunikazu , Amagasa Teruo , Denhardt David T , Nifuji Akira , Noda Masaki 
Published: April 2006

Abstract
Tumor metastasis and invasion to bone is one of major medical issues in our modern societies. Osteopontin deficiency decreased tumor invasion in bone based on knockout mouse study. In bone, osteopontin is a positive factor to increase tumor invasion.
Introduction: Osteopontin is an arginine-glycine-aspartate (RGD)-containing protein and is recognized by integrin family members. Osteopontin promotes cell attachment to bone, where it is abundantly present. Because osteopontin levels were reported to be elevated in patients bearing highly metastatic tumors, this molecule has been implicated in the metastasis of tumors. However, the effect of osteopontin on the invasion of tumor cells in bone microenvironment has not been clear. The purpose of this paper is to elucidate the effect of host osteopontin on the behavior of tumor cells in bone.
Materials and Methods: Bone marrow ablation was conducted in the femora of mice, and B16 melanoma cells were injected directly into the ablated bone marrow space of the osteopontin-deficient and wildtype mice.
Result: Invasion foci of B16 melanoma cells in the cortical bone was observed 7 weeks after tumor cell implantation. The number of the foci was 5-fold less in osteopontin-deficient mice compared with that in wildtype mice. In wildtype mice, trabecular bone formation was not observed in the ablated marrow space where tumor cells were injected. In contrast, significant levels of trabecular bone were observed in the marrow space of osteopontin-deficient mice even after tumor cells were injected. To examine cellular mechanisms underlying these observations, co-cultures of bone marrow cells and B16 cells were conducted. While the presence of B16 cells promoted TRACP+ cell development in wildtype bone marrow cells, such enhancement in TRACP+ cell formation by the co-cultures with B16 cells was reduced in the case of bone marrow cells from osteopontin-deficient mice.
Conclusions: Osteopontin deficiency reduced the bone loss caused by tumor cell implantation into the bone marrow space.
Vitamin D Receptor Expression in Human Muscle Tissue Decreases With Age
Authors: Bischoff-Ferrari HA , Borchers M , Gudat F , Dürmüller U , Stähelin HB , Dick W 
Published: April 2006

Abstract
Intracellular 1,25-dihydroxyvitamin D receptor (VDR) is expressed in human skeletal muscle tissue. However, it is unknown whether VDR expression in vivo is related to age or vitamin D status, or whether VDR expression differs between skeletal muscle groups.
Introduction: We investigated these factors and their relation to 1,25-dihydroxyvitamin D receptor (VDR) expression in freshly removed human muscle tissue.
Materials and Methods: We investigated biopsy specimens of the gluteus medius taken at surgery from 20 female patients undergoing total hip arthroplasty (mean age, 71.6 ± 14.5; 72% &gt; 65 years) and biopsy specimens of the transversospinalis muscle taken at surgery from 12 female patients with spinal operations (mean age, 55.2 ± 19.6; 28% &gt; 65 years). The specimens were obtained by immunohistological staining of the VDR using a monoclonal rat antibody to the VDR (Clone no. 9A7). Quantitative VDR expression (number of VDR positive nuclei) was assessed by counting 500 nuclei per specimen and person. Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were assessed at day of admission to surgery.
Results: All muscle biopsy specimens stained positive for VDR. In the univariate analyses, increased age was associated with decreased VDR expression (r = 0.5: p = 0.004), whereas there were no significant correlations between VDR expression and 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels. VDR expression did not differ between patients with hip and spinal surgery. In the multivariate analysis, older age was a significant predictor of decreased VDR expression after controlling biopsy location (gluteus medius or the transversospinalis muscle), and 25-hydroxyvitamin D levels (linear regression analysis: β-estimate = −2.56; p = 0.047).
Conclusions: Intranuclear immunostaining of the VDR was present in muscle biopsy specimens of all orthopedic patients. Older age was significantly associated with decreased VDR expression, independent of biopsy location and serum 25-hydroxyvitamin D levels.
Fanconi's Syndrome in HIV+ Adults: Report of Three Cases and Literature Review
Authors: Earle Karen E , Seneviratne Tara , Shaker Joseph , Shoback Dolores 
Published: April 2006

Abstract
We diagnosed Fanconi's syndrome (phosphate depletion and dysfunction of the renal tubules) in three HIV+ patients. This was temporally related to their HIV treatment. Physicians caring for patients with HIV should recognize the association of this rare syndrome with antiretroviral medications and monitor their patients carefully.
Introduction: Fanconi's syndrome is caused by increased excretion of phosphate, glucose, amino acids, and other intermediary metabolites, and can result in osteomalacia.
Materials and Methods: We diagnosed this syndrome in three HIV+ patients.
Results: The first was a 43-year-old woman referred for multiple painful stress fractures. She demonstrated hypophosphatemia, metabolic acidosis, phosphaturia, glucosuria, and generalized aminoaciduria. These abnormalities resolved with oral phosphate replacement and discontinuation of the antiretroviral medication tenofovir. The second patient was a 39-year-old man with hypophosphatemia and bone pain. His symptoms improved with discontinuation of adefovir and supplementation of phosphate, potassium, and calcitriol. The third patient was a 48-year-old man who presented with symptomatic tetany caused by hypocalcemia (total serum calcium of 6.5 mg/dl [8.5–10.5 mg/dl]). Nine months before presentation, he had been treated with cidofovir for retinitis caused by cytomegalovirus. With calcium, phosphate, potassium, and calcitriol therapy, his laboratory abnormalities improved substantially, although he continues to require daily electrolyte replacement.
Conclusions: Each patient demonstrated generalized renal tubular dysfunction temporally related to treatment with antiretroviral drugs. The mechanism responsible for these abnormalities is not known; however, physicians caring for patients with HIV disease should recognize the association of Fanconi's syndrome with antiretroviral medications and monitor susceptible patients to prevent potential skeletal and neuromuscular complications.
Identification of Novel Target Genes of the Bone-Specific Transcription Factor Runx2
Authors: Stock Michael , Schäfer Henning , Fliegauf Manfred , Otto Florian 
Published: April 2006

Abstract
Fifteen putative transcriptional target genes regulated by the osteogenic transcription factor Runx2 were identified by cDNA microarray and differential hybridization techniques. Expression pattern and regulation of one gene, Pttg1ip, was analyzed in detail.
Introduction: The transcription factor Runx2 is a key regulator of osteoblast development and plays a role in chondrocyte maturation. The identification of transcriptional target genes of Runx2 may yield insight into how osteoblastic differentiation is achieved on a molecular level.
Materials and Methods: Using a differential hybridization technique (selective amplification through biotin and restriction-mediated enrichment [SABRE]) and cDNA microarray analysis, 15 differentially expressed genes were identified using mRNA from C3H 10T1/2 cells with constitutive and inducible overexpression of Runx2.
Results and Conclusions: Among the 15 genes identified, 4 encode the extracellular matrix proteins Ecm1, Mgp, Fbn5, and Osf-2, three represent the transcription factors Esx1, Osr1, and Sox9, whereas others were Ptn, Npdc-1, Hig1, and Tem1. The gene for Pttg1ip was upregulated in Runx2-expressing cells. Pttg1ip is widely expressed during development, but at highest levels in limbs and gonads. The Pttg1ip promoter binds Runx2 in a sequence specific manner, and Runx2 is able to transactivate the Pttg1ip promoter in MC3T3-E1 cells. Therefore, Pttg1ip is likely to be a novel direct transcriptional target gene of Runx2. In conclusion, the genes identified in this study are important candidates for mediating Runx2 induced cellular differentiation.
Direct Transformation from Quiescence to Bone Formation in the Adult Periosteum Following a Single Brief Period of Bone Loading
Authors: Pead Matthew J. , Skerry Timothy M. , Lanyon Lance E. 
Published: April 2006

Abstract
The concept of resorption preceding formation in a coupled response is well established as the normal sequence of remodeling in adult bone. So prevalent is this concept, however, that the idea of the direct activation of osteogenic modeling in normal adult bone is often ignored. This experiment documents the direct transformation of the normal, quiescent, adult periosteum to active bone formation. The osteogenic stimulus was provided by a single short period of dynamic loading. Periosteal activation and the production of new bone within 5 days of loading was unaccompanied by resorption or the presence of osteoclasts. We therefore conclude that an adult resting periosteum can become directly converted to formation as a physiologic response to an appropriate osteogenic stimulus without the need for resorption. To distinguish this process from remodeling we suggest it be called renewed modeling. It is notable that a single short exposure to an “osteogenic” loading regime can influence the full cascade of cellular events between quiescence and active bone formation.
The Biphosphonate Aledronate (MK-217) Inhibits Bone Loss due to Ovariectomy in Rats
Authors: Seedor JG , Quartuccio HA , Thompson DD 
Published: April 2006

Abstract
Estrogen deficiency in mammals is known to increase bone turnover and result in reduced bone mass. The bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphophonic acid disodium salt, alendronate (MK-217), is a potent inhibitor of bone resorption and was evaluated in this study for its ability to inhibit bone loss following ovariectomy in rats. Alendronate was administered sc in doses of 0.0, 0.056, 0.28, 1.40, and 7.0 mg P/kg/month, divided into two, four, or eight monthly subcutaneous injections for each dose, to female Sprague-Dawley rats (250–280 g) that underwent bilateral ovariectomy. Rats were sacrificed 12 weeks postovariectomy, the femora ashed, and the tibiae prepared for static and dynamic histomorphometric analyses.
Femoral bone mass in vehicle-treated rats was reduced by 12% 12 weeks after ovariectomy compared to the nonovariectomized control group. In MK-217-treated rats femoral bone mass was significantly increased in a dose-dependent manner compared to either ovariectomized or nonovariectomized controls. Histomorphometric analysis showed significant increases in tibial trabecular bone volume with no decrease in osteoclast number. Doses delivered twice per month or eight times per month were equally effective in achieving the peak bone volume 12 weeks after ovariectomy.
In conclusion, alendronate (MK-217) was effective in inhibiting bone loss due to estrogen deficiency in rats, and the magnitude of its effect was related primarily to the total amount of compound administered rather than the frequency of its administration.
Familial Aggregation of Paget's Disease of Bone
Authors: Siris Ethel S. , Ottman Ruth , Flaster Edith , Kelsey Jennifer L. 
Published: April 2006

Abstract
This epidemiologic study of Paget's disease of bone used data from 788 cases and 387 spouse controls to investigate the following: (1) the extent to which this disorder aggregates in families; (2) the cumulative incidence of the disease in first-degree relatives of patients throughout life; and (3) the influence of age at diagnosis (&lt;55 versus 55+ years) and presence of bone deformity in the case on risk of Paget's disease in relatives.
A positive family history in parents or siblings was reported by 12.3% of cases and 2.1% of controls. The rate of Paget's disease was approximately seven times as high in relatives of cases as in relatives of controls, and this increased rate did not differ according to gender of case or control or gender of relatives. Cumulative incidence of Paget's disease to age 90 was much higher in relatives of cases (8.9 ± 1.0% SEM) than in relatives of controls (1.8 ± 0.9% SEM). Among relatives of cases, cumulative risk was highest when the case had both early age at diagnosis and bone deformity (20.7 ± 3.6% SEM) compared with risk when the case had early age at diagnosis but not bone deformity (10.8 ± 3.2% SEM), bone deformity but not early age at diagnosis (5.8 ± 1.3% SEM), or neither bone deformity nor early age at diagnosis (3.6 ± 0.8% SEM). Risk in siblings of cases was higher when a parent was affected (22.1 ± 8.0% SEM) than when both parents were unaffected (6.7 ± 1.1% SEM).
These findings suggest that first-degree relatives of patients with Paget's disease have increased risk of developing the disorder, especially if the affected relatives have early age at diagnosis or deforming bone disease.
Isolation and Purification of Osteocytes
Authors: van der Plas A , Nijweide P. J. 
Published: April 2006

Abstract
An isolation method for osteocytes is described. After removal of the periostea, bone cells were isolated from calvariae of 18-day-old chicken embryos by alternating treatments with collagenase and EDTA. Osteocytes were purified from the heterogeneous bone cell population with the help of the osteocyte-specific MAb OB 7.3 bound to protein G-conjugated magnetic beads. The purity of the osteocyte population ultimately obtained was more than 95%. Osteocytes were found to adhere rapidly to glass or plastic substrates. They showed numerous processes of various types. These processes could branch and make contact with those of other osteocytes. After 1–2 days of culture, the isolated osteocytes formed a network of apparently interconnected cell processes very similar to the osteocyte network in bone.
An Uncoupling Agent Containing Strontium Prevents Bone Loss by Depressing Bone Resorption and Maintaining Bone Formation in Estrogen-Deficient Rats
Authors: Marie Pierre J. , Hott Monique , Modrowski Dominique , de Pollak Cinderella , Guillemain Joel , Deloffre Pascale , Tsouderos Yannis 
Published: April 2006

Abstract
Trabecular bone loss in estrogen deficiency is associated with enhanced bone resorption with a smaller increase in bone formation. We previously reported that low doses of strontium can increase trabecular bone volume in rodents by affecting bone resorption and formation. In this study we determined the effect of a new divalent strontium salt (S12911) on bone loss induced by E2 deficiency. Sprague-Dawley female rats (230 g, n = 15–25 per group) were sham operated or ovariectomized (OVX) and treated with 17β-estradiol (E2, 10 μg/kg/day, sc) or S12911 by gavage at the dose of 77, 154, or 308 mg/kg/day or the vehicle. Treatment for 60 days with S12911 resulted in a dose-dependent increase in plasma, urine, and bone strontium concentrations without any deleterious effect on total or skeletal growth. OVX rats were osteopenic compared to sham rats as shown by decreased femoral dry bone weight and mineral content measured on bone ash and by DXA. Treatment of OVX rats with S12911 prevented bone loss as bone ash and bone mineral content were restored to the values in sham rats. Trabecular bone volume measured by histomorphometry on the tibial metaphysis was decreased by 46% in OVX rats and was corrected by E2. Treatment of OVX rats with S12911 increased the trabecular bone volume by 30–36%. Histomorphometric indices of bone resorption (osteoclast surface and number) were increased in OVX rats and were reduced by S12911 to the levels in sham rats. In contrast to this inhibitory effect on bone resorption, the osteoid surface, osteoblast surface, mineral apposition rate, and bone formation rate were as high in OVX rats treated with S12911 as in untreated OVX rats. In addition, plasma osteocalcin (OC) and alkaline phosphatase (ALP) levels remained elevated or were further increased in OVX rats treated with S12911. In contrast, treatment with E2 reduced both bone resorption and formation and plasma ALP and OC to the levels in sham rats. The data indicate that the divalent strontium salt S12911 is acting as an uncoupling agent that can prevent the femoral osteopenia and partially prevent the trabecular bone loss in E2-deficient rats by inhibiting bone resorption without reducing bone formation.
Stretch-Induced PTH-Related Protein Gene Expression in Osteoblasts
Authors: Chen Xuesong , Macica Carolyn M , Ng Kong Wah , Broadus Arthur E 
Published: April 2006

Abstract
Mechanical forces play a critical role in regulating skeletal mass and structure. We report that mechanical loading induces PTHrP in osteoblast-like cells and that TREK-2 stretch-activated potassium channels seem to be involved in this induction. Our data suggest PTHrP as a candidate endogenous mediator of the anabolic effects of mechanical force on bone.
Introduction: Mechanical force has anabolic effects on bone. The PTH-related protein (PTHrP) gene is known to be mechanically inducible in smooth muscle cells throughout the organism, and N-terminal PTH and PTHrP products have been reported to have anabolic effects in bone. We explored the idea that PTHrP might be a candidate mediator of the effects of mechanical force on bone.
Materials and Methods: Mechanical loading was applied by swelling osteoblast-like cells in hypotonic solution and/or by application of cyclical stretch through a FlexerCell apparatus. RNase protection assay and real-time quantitative PCR analysis were used to assay PTHrP gene expression.
Results and Conclusion: Stretching UMR201-10B osteoblast-like cells by swelling in hypotonic solutions rapidly increased PTHrP mRNA. This induction was insensitive to gadolinium and nifedipine, to the removal of extracellular calcium, and to depletion of endoplasmic reticulum calcium, indicating that neither stretch-activated cation channels, L-type calcium channels, nor ER calcium is involved in the induction of PTHrP. The TREK family potassium channels are activated by both stretch and intracellular acidosis, and we identified these channels in osteoblast-like cells by PCR. Intracellular acidification increased PTHrP mRNA expression in UMR-201-10B cells, and siRNA targeted against the TREK-2 gene reduced endogenous TREK-2 expression and dampened PTHrP mRNA induction. Cyclical stretch also induced PTHrP in UMR-201-10B osteoblast-like cells and in MLO-A5 post-osteoblast-pre-osteocyte cells, the latter a stage in the osteoblastic differentiation program that is likely to be a key target of force in vivo. Our evidence suggests PTHrP as a candidate mediator of the anabolic effects of mechanical force on bone.
Multiplex Ligation-Dependent Probe Amplification for Rapid Detection of Proteolipid Protein 1 Gene Duplications and Deletions in Affected Males and Carrier Females with Pelizaeus–Merzbacher Disease
Authors: Warshawsky Ilka , Chernova Olga B , Hübner Christian A , Stindl Reinhard , Henneke Marco , Gal Andreas , Natowicz Marvin R 
Published: April 2006

Abstract
Background: Pelizaeus–Merzbacher disease is a rare X-linked neurodegenerative disorder caused by sequence variations in the proteolipid protein 1 gene (PLP1). PLP1 gene duplications account for ∼50%–75% of cases and point variations for ∼15%–20% of cases; deletions and insertions occur infrequently. We used multiplex ligation-dependent probe amplification (MLPA) to detect PLP1 gene alterations, especially gene duplications and deletions.
Methods: We performed MLPA on 102 samples from individuals with diverse PLP1 gene abnormalities and from controls, including 50 samples previously characterized for the PLP1 gene by quantitative PCR but which were anonymized for prior results and sex.
Results: All males with PLP1 gene duplications (n = 13), 1 male with a triplication, 2 males with whole gene deletions, and all controls (n = 72) were unambiguously assigned to their correct genotype. Of 4 female carriers tested by MLPA and quantitative PCR, 3 were duplication carriers by both methods, and 1 was a triplication carrier by MLPA and a duplication carrier by quantitative PCR. For 1 sample with a partial deletion, MLPA showed exon 3 deleted but PCR showed exons 3 and 4 deleted. Sequence analysis of 2 samples with reduced dosage for exons 3 and 5 revealed point variations overlapping the annealing site for the corresponding MLPA probe. The precision of MLPA analysis was excellent and comparable to or better than quantitative PCR, with CVs of 4.3%–9.8%.
Conclusions: MLPA is a rapid and reliable method to determine PLP1 gene copies. Samples with partial PLP1 gene dosage alterations require confirmation with a non-MLPA method.
Usability von Smart Home User Interfaces — Herausforderungen und Lösungsansätze (Smart Home Usability — Challenges and Solutions)
Authors: Ringbauer Brigitte , Heidmann Frank 
Published: April 2006

Zusammenfassung
Die ubiquitäre technologische Unterstützung eines generationenübergreifenden Lebens und Arbei-tens im intelligenten Haus der Zukunft ist seit einigen Jahren ein zentrales Anwendungsfeld der Mensch-Computer-Kooperation. Dabei nimmt die Benutzungsschnittstelle als zentrales Akzeptanzkriterium für Smart Home Applikationen kontinuierlich an Bedeutung zu. Die Weiterentwicklung der IuK-Technologien in Kombination mit intelligenter Sensorik und die zunehmende Vernetzung der häuslichen Umgebung bringt Chancen für Verbesserungen im Sicherheits-, Komfort- und Umweltbereich. Ob es um umfassende und verlässliche Alarmfunktionen, ressourcensparende Gebäudetechnik oder eine technologische Unterstützung für ältere Menschen und Pflegebedürftige im häuslichen Umfeld geht — die intelligente Haustechnik bietet viele Vorteile. Dem enormen Potential für eine weit reichende Komfortsteigerung steht zurzeit noch eine Vielzahl von Hindernissen gegenüber. Die Komplexität der Bedienung des Gesamtsystems steigt durch einen höheren Grad an Vernetzung und Automatisierungsmöglichkeiten. Ebenso ist die Kompatibilität verschiedener Systeme noch nicht in befriedigendem Maße gegeben. Der Beitrag stellt ausgewählte Smart Home Projekte in Deutschland vor und definiert Qualitäts-kriterien für eine einfache Bedienung integrierter Benutzungsschnittstellen.