bluuebunny/crossref_metadata_2025_split huggingface dataset:
Volumetric bone mineral density and bone structure in childhood chronic kidney disease
Authors: Wetzsteon Rachel J , Kalkwarf Heidi J , Shults Justine , Zemel Babette S , Foster Bethany J , Griffin Lindsay , Strife C Frederic , Foerster Debbie L , Jean-Pierre Darlene K , Leonard Mary B 
Published: May 2011

AbstractChronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (vBMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomographic scans were obtained in 156 children with CKD [69 stages 2 to 3, 51 stages 4 to 5, and 36 stage 5D (dialysis)] and 831 healthy participants aged 5 to 21 years. Sex-, race-, and age- or tibia length–specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with a higher TrabBMD Z-score in younger participants (p &lt; .001) compared with healthy children; this association was attenuated in older participants (interaction p &lt; .001). Mean CortArea Z-score was lower (p &lt; .01) in CKD 4–5 [−0.49, 95% confidence interval (CI) −0.80, −0.18)] and CKD 5D (−0.49, 95% CI −0.83, −0.15) compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD Z-score (p &lt; .01), and this association was significantly attenuated in older participants (interaction p &lt; .05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (serum C-terminal telopeptide of type 1 collagen) were associated with lower CortBMD and CortArea Z-scores and greater EndoC Z-score (r = 0.18–0.36, all p ≤ .02). CortBMD Z-score was significantly lower in CKD participants with PTH levels above versus below the upper limit of the Kidney Disease Outcome Quality Initiative (KDOQI) CKD stage-specific target range: −0.46 ± 1.29 versus 0.12 ± 1.14 (p &lt; .01). In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible. © 2011 American Society for Bone and Mineral Research
Stronger bone correlates with African admixture in African-American women
Authors: Chen Zhao , Qi Lihong , Beck Thomas J , Robbins John , Wu Guanglin , Lewis Cora E , Cauley Jane A , Wright Nicole C , Seldin Michael F 
Published: May 2011

Abstract
Osteoporosis affects all populations, but the risk for low bone density and fracture varies greatly by self-reported race and ethnicity. In this article, the relationship between measured percent African admixture and hip structural geometry, estimated from the hip structural analysis (HSA) program, was examined in a subcohort of the Women's Health Initiative (WHI). The study sample included 793 African-American women and 8559 non-Hispanic white women. All the participants were postmenopausal, between the ages of 50 and 79 years, at the time of recruitment and were followed for up to 9 years. Bone density and hip geometry were assessed using dual-energy X-ray absorptiometry. African admixture was measured for African Americans using genetic ancestry informative markers. Multiple regression and mixed-effects models were used for cross-sectional and longitudinal analyses, respectively. Covariates assessed from questionnaires and physical measurements were included in the analysis to control for possible confounding effects. The study results show significant correlations between percent of African admixture and HSA assessments. In comparison with non-Hispanic white women, significantly greater bone strength, as indicated by higher hip bone mineral density and stronger hip geometry, in women with higher African admixture was observed. However, women with higher percent African admixture had larger reductions in bone strength than non-Hispanic white women during the follow-up. © 2011 American Society for Bone and Mineral Research
The renin-angiotensin system, blood pressure, and heart structure in patients with hereditary vitamin D–resistance rickets (HVDRR)
Authors: Tiosano Dov , Schwartz Yitzchak , Braver Yulia , Hadash Amir , Gepstein Vardit , Weisman Yosef , Lorber Avraham 
Published: May 2011

Abstract
Vitamin D deficiency has been linked to hypertension and an increased prevalence of cardiovascular risk factors and disease. Studies in vitamin D receptor knockout (VDR KO) mice revealed an overstimulated renin-angiotensin system (RAS) and consequent high blood pressure and cardiac hypertrophy. VDR KO mice correspond phenotypically and metabolically to humans with hereditary 1,25-dihydroxyvitamin D–resistant rickets (HVDRR). There are no data on the cardiovascular system in human HVDRR. To better understand the effects of vitamin D on the human cardiovascular system, the RAS, blood pressure levels, and cardiac structures were examined in HVDRR patients. Seventeen patients (9 males, 8 females, aged 6 to 36 years) with hereditary HVDRR were enrolled. The control group included age- and gender-matched healthy subjects. Serum calcium, phosphorous, creatinine, 25-hydroxyvitamin D [25(OH)D],1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathyroid hormone (PTH), plasma rennin activity (PRA), aldosterone, angiotensin II (AT-II), and angiotensin-converting enzyme (ACE) levels were determined. Ambulatory 24-hour blood pressure measurements and echocardiographic examinations were performed. Serum calcium, phosphorus, and alkaline phosphatase values were normal. Serum 1,25(OH)2D3 and PTH but not PRA and ACE levels were elevated in the HVDRR patients. AT-II levels were higher than normal in the HVDRR patients but not significantly different from those of the controls. Aldosterone levels were normal in all HVDRR patients. No HVDRR patient had hypertension or echocardiographic pathology. These findings reveal that 6- to 36-year-old humans with HVDRR have normal renin and ACE activity, mild but nonsignificant elevation of AT-II, normal aldosterone levels, and no hypertension or gross heart abnormalities. © 2011 American Society for Bone and Mineral Research
FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH
Authors: Yuan Quan , Sato Tadatoshi , Densmore Michael , Saito Hiroaki , Schüler Christiane , Erben Reinhold G , Lanske Beate 
Published: May 2011

Abstract
Parathyroid hormone (PTH) is widely recognized as a key regulator of mineral ion homeostasis. Daily intermittent administration of PTH is the only currently available anabolic therapy for bone disorders such as osteoporosis. Recent studies have shown that PTH increases transcription and secretion of fibroblast growth factor 23 (FGF-23), another important regulator of phosphate homeostasis and skeletal metabolism. However, the full relationship between PTH and FGF-23 is largely unknown. This study evaluated the effect of FGF-23/Klotho signaling on the phosphaturic and anabolic functions of PTH. Eight-day-old wild-type (WT) Fgf23−/− and Kl−/− mice were injected with 100 µg/kg PTH(1–34) or vehicle daily for a 2-week-period and then euthanized. Intermittent injection of PTH successfully reduced the serum phosphate levels and reversed the hyperphosphatemia of Fgf23−/− and Kl−/− mice. Bone changes were analyzed in the distal femur metaphysis by peripheral quantitative computed tomography (pQCT), micro–computed tomography (µCT), and histomorphometry. PTH treatment induced substantial increases in bone mineral density (BMD) and trabecular bone volume in each mouse genotype. Expression of osteoblastic marker genes, including Runx2, Col1, Alp, Ocn, and Sost, was similarly altered. In addition, primary osteoblasts were isolated and treated with 100 nM PTH in vitro. PTH treatment similarly induced cAMP accumulation and phosphorylation of ERK1/2 and CREB in the osteoblasts from each genotype. Taken together, our results demonstrate that FGF-23/Klotho signaling is not essential for the phosphaturic and anabolic functions of PTH, suggesting that PTH can function as a therapeutic agent to improve the skeletal quality of patients even in the presence of abnormal serum FGF-23 levels. © 2011 American Society for Bone and Mineral Research
The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase‐D toxin
Authors: Chaves‐Moreira Daniele , Souza Fernanda N. , Fogaça Rosalvo T.H. , Mangili Oldemir C. , Gremski Waldemiro , Senff‐Ribeiro Andrea , Chaim Olga M. , Veiga Silvio S. 
Published: May 2011

AbstractBrown spider venom phospholipase‐D belongs to a family of toxins characterized as potent bioactive agents. These toxins have been involved in numerous aspects of cell pathophysiology including inflammatory response, platelet aggregation, endothelial cell hyperactivation, renal disorders, and hemolysis. The molecular mechanism by which these toxins cause hemolysis is under investigation; literature data have suggested that enzyme catalysis is necessary for the biological activities triggered by the toxin. However, the way by which phospholipase‐D activity is directly related with human hemolysis has not been determined. To evaluate how brown spider venom phospholipase‐D activity causes hemolysis, we examined the impact of recombinant phospholipase‐D on human red blood cells. Using six different purified recombinant phospholipase‐D molecules obtained from a cDNA venom gland library, we demonstrated that there is a correlation of hemolytic effect and phospholipase‐D activity. Studying recombinant phospholipase‐D, a potent hemolytic and phospholipase‐D recombinant toxin (LiRecDT1), we determined that the toxin degrades synthetic sphingomyelin (SM), lysophosphatidylcholine (LPC), and lyso‐platelet‐activating factor. Additionally, we determined that the toxin degrades phospholipids in a detergent extract of human erythrocytes, as well as phospholipids from ghosts of human red blood cells. The products of the degradation of synthetic SM and LPC following recombinant phospholipase‐D treatments caused hemolysis of human erythrocytes. This hemolysis, dependent on products of metabolism of phospholipids, is also dependent on calcium ion concentration because the percentage of hemolysis increased with an increase in the dose of calcium in the medium. Recombinant phospholipase‐D treatment of human erythrocytes stimulated an influx of calcium into the cells that was detected by a calcium‐sensitive fluorescent probe (Fluo‐4). This calcium influx was shown to be channel‐mediated rather than leak‐promoted because the influx was inhibited by L‐type calcium channel inhibitors but not by a T‐type calcium channel blocker, sodium channel inhibitor or a specific inhibitor of calcium activated potassium channels. Finally, this inhibition of hemolysis following recombinant phospholipase‐D treatment occurred in a concentration‐dependent manner in the presence of L‐type calcium channel blockers such as nifedipine and verapamil. The data provided herein, suggest that the brown spider venom phospholipase‐D‐induced hemolysis of human erythrocytes is dependent on the metabolism of membrane phospholipids, such as SM and LPC, generating bioactive products that stimulate a calcium influx into red blood cells mediated by the L‐type channel. J. Cell. Biochem. 112: 2529–2540, 2011. © 2011 Wiley‐Liss, Inc.
BMP‐2 suppresses renal interstitial fibrosis by regulating epithelial–mesenchymal transition
Authors: Yang Yu‐Lin , Ju Hong‐Zen , Liu Shu‐Fen , Lee Tao‐Chen , Shih Yuan‐Wei , Chuang Lea‐Yea , Guh Jinn‐Yuh , Yang Ya‐Ying , Liao Tung‐Nan , Hung Tsung‐Jen , Hung Min‐Yuan 
Published: May 2011

AbstractDysregulation of epithelial‐to‐mesenchymal transition (EMT) may contribute to renal fibrogenesis. Our previous study indicated that bone morphogenetic protein‐2 (BMP‐2) significantly reversed transforming growth factor (TGF)‐β1‐induced renal interstitial fibrosis. In this study, we examined the underlying mechanism and elucidate the regulation of EMT process under BMP‐2 treatment. Cultured renal interstitial fibroblast (NRK‐49F) was treated with TGF‐β1 (10 ng/ml) with or without BMP‐2 (10–250 ng/ml) for 24 h. The expression of α‐smooth muscle actin (α‐SMA), E‐cadherin, fibronectin, or Snail transcriptional factors was analyzed by immunofluorescence staining or Western blotting. Cell migration was analyzed by wound‐healing assay. NRK‐49F treated with TGF‐β1 induced significant EMT including upregulatioin of α‐SMA, fibronectin, and snail proteins and down‐regulation of E‐cadherin. Interestingly, co‐treatment with BMP‐2 dose‐dependently reversed TGF‐β1‐induced cellular fibrosis, cell migration, and above EMT change. The above effect was closely correlated with Snail since BMP‐2 dose‐ and time‐course dependently induced a significant decrease in the level of Snail. Moreover, Snail siRNA significantly reversed TGF‐β1‐induced increases in the level of α‐SMA and fibronectin (intracellular and extracellular). We suppose that BMP‐2 have the potential to attenuate TGF‐β1‐induced renal interstitial fibrosis by attenuating Snail expression and reversing EMT process. J. Cell. Biochem. 112: 2558–2565, 2011. © 2011 Wiley‐Liss, Inc.
Alkaline stress‐induced autophagy is mediated by mTORC1 inactivation
Authors: Suk Jinkyu , Kwak Sang Su , Lee Jae Ho , Choi Ji Hye , Lee Sang‐Hee , Lee Dong Hwan , Byun Boohyeong , Lee Geon‐Hyoung , Joe Cheol O. 
Published: May 2011

AbstractThe activation of autophagic pathway by alkaline stress was investigated. Various types of mammalian cells were subjected to alkaline stress by incubation in bicarbonate buffered media in humidified air containing atmospheric 0.04% CO2. The induction of autophagy following alkaline stress was evaluated by assessing the conversion of cytosolic LC3‐I into lipidated LC3‐II, the accumulation of autophagosomes, and the formation of autolysosomes. Colocalization of GFP‐LC3 with endolysosomal marker in HeLa GFP‐LC3 cells undergoing autophagic process by alkaline stress further demonstrates that autophagosomes triggered by alkaline stress matures into autolysosomes for the lysosome dependent degradation. We found that the inactivation of mTORC1 is important for the pathway leading to the induction of autophagy by alkaline stress since the expression of RhebQ64L, a constitutive activator of mTORC1, downregulates the induction of autophagy after alkaline stress in transfected human 293T cells. These results imply that activation of autophagic pathway following the inactivation of mTORC1 is important cellular events governing alkaline stress‐induced cytotoxicity and clinical symptoms associated with alkalosis. J. Cell. Biochem. 112: 2566–2573, 2011. © 2011 Wiley‐Liss, Inc.
The role of Lrp5/6 in cardiac valve disease: LDL‐density‐pressure theory
Authors: Rajamannan Nalini M. 
Published: May 2011

AbstractAtherosclerosis and osteoporosis are the leading causes of mortality and morbidity in the World. Recent epidemiologic studies have demonstrated that these disease processes develop in parallel. Evidence indicates that hyperlipidemia plays a paradoxical role in both disease processes. However, the mechanism is not understood. This prospectus hypothesizes the role of lipids activate atherosclerosis within the bone and the heart to initiate the development of diseases in both of these tissues. The Prospectus on the Lrp 5/6 receptors provides a foundation for the mechanisms involved in the Lrp5/6 mediated disease biology. The LDL‐Density‐Pressure theory: the Role of Lrp5/6 provides a biological and a hemodynamic approach towards understanding the development of valvular heart disease and the implications in the field of bone molecular biology. This prospectus will review the current literature, provide a basis for the development of valve disease and indicate future therapeutic pathways for this disease process in the future. J. Cell. Biochem. 112: 2222–2229, 2011. © 2011 Wiley‐Liss, Inc.
Dispositional optimism buffers combat veterans from the negative effects of warzone stress on mental health symptoms and work impairment
Authors: Thomas Jeffrey L. , Britt Thomas W. , Odle‐Dusseau Heather , Bliese Paul D. 
Published: May 2011

AbstractThe study examined dispositional optimism s role in buffering the effect of warzone stress on mental health symptoms and mental health symptoms on work impairment. A total of 2,439 soldiers from an active‐duty brigade combat team were surveyed following a 12‐month deployment to Iraq. Posttraumatic stress disorder (PTSD) symptoms, depression symptoms, combat exposure, deployment demands, and work impairment were measured. Soldiers higher in dispositional optimism showed weaker relationships between combat exposure and PTSD symptoms, and between deployment demands and PTSD and depression symptoms. Dispositional optimism also buffered mental health symptom effects on work impairment. Dispositional optimism may protect soldiers from warzone stress and mental health symptoms. Potential mechanisms explaining how dispositional optimism may serve as a protective factor are discussed. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–15, 2011.
Employee voice behavior: A meta‐analytic test of the conservation of resources framework
Authors: Ng Thomas W. H. , Feldman Daniel C. 
Published: May 2011

SummaryAlthough voice (i.e. expressing change‐oriented ideas and suggestions) has frequently been investigated as a way for workers to reciprocate to their employers for the positive treatment they receive, much less is known about how workers use voice to deal with stress. This study takes a conservation of resources perspective to examine the relationships among workplace stress, voice behavior, and job performance. We first examined the strength of relationships of three major groups of workplace stressors and strains (job based, social based, and organization based) with voice behavior. We then examined the relationships of voice behavior with performance variables (e.g. in‐role performance and creativity) to investigate how voice may help workers preserve or accumulate resources to enhance their performance. The meta‐analytic findings presented here provide support for a negative relationship between workplace stress and voice and a positive relationship between voice behavior and performance outcomes. Copyright © 2011 John Wiley & Sons, Ltd.
Antitumor effects of telomerase inhibitor TMPyP4 in osteosarcoma cell lines
Authors: Fujimori Jun , Matsuo Toshihiro , Shimose Shoji , Kubo Tadahiko , Ishikawa Masakazu , Yasunaga Yuji , Ochi Mitsuo 
Published: May 2011

AbstractTelomere studies in carcinomas have been extensively reported for prognostic utility and effective methods for targeting telomerase therapy has been described, but efficacy of telomerase inhibitor remained unknown in sarcoma cells. In this study, we investigated the effects of telomerase inhibitor cationic porphyrin TMPyP4 on telomerase activity, telomere length, cell growth, and apoptosis in osteosarcoma cell lines. TMPyP4 significantly inhibited telomerase activity in telomerase positive HOS and Saos‐2, but not in MG‐63. TMPyP4 significantly induced telomere shortening, and inhibition of the cell growth in HOS and Saos‐2 with over 17% apoptosis rates. In terms of MG‐63, TMPyP4 did not induce inhibition of both telomerase activity and cell growth, although it induced significant telomere shortening. Telomere length after treatment was 5.60 kb in HOS, 4.00 kb in Saos‐2, and 9.89 kb in MG‐63. These results may suggest that both telomerase activity loss and sufficient telomere shortening are necessary to inhibit cell growth in telomerase positive osteosarcoma cells. TMPyP4 did not induced telomere shortening but significantly inhibited the growth with 22.6% apoptosis rate in telomerase negative with extremely longer telomere‐U2OS, may indicating the antitumor effect of TMPyP4 may be related to DNA damage including telomere dysfunction through G‐quadruplex stabilization, independent on telomere length. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:1707–1711, 2011
Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model
Authors: Hsu Wellington K. , Polavarapu Mahesh , Riaz Rehan , Roc Gilbert C. , Stock Stuart R. , Glicksman Zachary S. , Ghodasra Jason H. , Hsu Erin L. 
Published: May 2011

AbstractThe use of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix®; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber‐based collagen scaffold in a rodent spine fusion model. Thirty‐six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 µg rhBMP‐2 on ACS (positive control), TrioMatrix®, Grafton® (Osteotech, Inc., Eatontown, NJ), and DBX® (Synthes, Inc., West Chester, PA). Both TrioMatrix® and rhBMP‐2‐treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton®, and DBX® groups. Notably, the use of TrioMatrix® as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP‐2 group. T2‐weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP‐2; this response was significantly reduced with the use of TrioMatrix®. Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost‐effective bone graft substitute that could be useful in spine fusions where BMP‐2 is contraindicated. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1812–1819, 2011
Calcification in human intervertebral disc degeneration and scoliosis
Authors: Hristova Gergana I. , Jarzem Peter , Ouellet Jean A. , Roughley Peter J. , Epure Laura M. , Antoniou John , Mwale Fackson 
Published: May 2011

AbstractCalcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs (IVDs). The purpose of this study was to assess the calcification potential of IVDs in degenerative disc disease (DDD) and adolescent idiopathic scoliosis (AIS). For this purpose, 34 IVDs from 16 adult patients with DDD and 25 IVDs from 9 adolescent patients with AIS were obtained at surgery. The concave and convex parts of the scoliotic discs were analyzed separately. Von Kossa staining was performed to visualize calcium deposits, while type X collagen (COL X) expression associated with endochondral ossification was measured by immunohistochemistry. Alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential. Results showed the presence of calcium deposits and COL X in degenerative and scoliotic IVDs, but not in control discs, and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs. The results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in AIS discs might reflect a premature degenerative process. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1888–1895, 2011