bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proximal Femur Mechanical Adaptation to Weight Gain in Late Adolescence: A Six-Year Longitudinal Study
Authors: Petit Moira A , Beck Thomas J , Hughes Julie M , Lin Hung-Mo , Bentley Christy , Lloyd Tom 
Published: October 2007

Abstract
The effect of weight gain in late adolescence on bone is not clear. Young women who consistently gained weight (n = 23) from 17 to 22 yr of age had increased BMD but a lack of subperiosteal expansion compared with stable weight peers (n = 48). Bone strength increased appropriately for lean mass in both groups but decreased relative to body weight in weight gainers, suggesting increased bone fragility in weight gainers.
Introduction: Weight gain leading to obesity often starts in adolescence, yet little is known about its effects on bone. We used longitudinal data to examine the effects of weight gain in late adolescence (from 17 to 22 yr of age) on proximal femur BMD, geometry, and estimates of bending strength.
Materials and Methods: Participants were classified as either weight gainers (WG, n = 23) or stable weight (SW, n = 48) using a random coefficients model. Weight gainers had positive increases in weight (p &lt; 0.05) at each clinic visit from age 17 onward. Proximal femur DXA scans (Hologic QDR 2000) taken annually from 17 to 22 yr of age were analyzed for areal BMD (g/cm2), subperiosteal width (cm), and bone cross-sectional area (CSA) at the proximal femoral shaft. Cortical thickness was measured, and section modulus (Z, cm3) was calculated as a measure of bone bending strength. Total body lean (g) and fat (g) mass were measured from DXA total body scans.
Results: Over ages 17–22, height remained stable in both groups. Weight remained static in the SW group but increased 14% on average in the WG group (p &lt; 0.05). After controlling for age 17 baseline values, WG had higher BMD (+2.6%), thicker cortices (+3.6%), and greater bone CSA (+2.3%). Increased BMD did not translate to greater increases in bone bending strength (Z). The SW group achieved similar gains in Z by greater subperiosteal expansion. Bone strength index (SI = Z/height) normalized for body weight remained constant in the SW group but decreased significantly in the WG group. In contrast, SI normalized to lean mass did not change over time in either group. Other variables including physical activity, nutrition, and hormone levels (estradiol, testosterone, cortisol) did not differ significantly between groups.
Conclusions: These data suggest that weight gain in late adolescence may inhibit the periosteal expansion known to normally occur throughout life in long bones, resulting in decreased bone strength relative to body weight.
Factors Affecting Short-Term Bone Density Precision Assessment and the Effect on Patient Monitoring
Authors: Leslie William D 
Published: October 2007

Abstract
The most widely used procedure for performing a BMD reproducibility assessment (same-technologist with simple repositioning on the same day) systematically underestimates precision error and will lead to over categorization of change in a large fraction of monitored patients.
Introduction: The most common procedure for establishing the least significant change (LSC) to monitor bone mineral density (BMD) with DXA is for the same technologist to perform repeat subject scans on the same day with simple repositioning. The objective of the current report is to determine how the reproducibility scanning procedure impacts on the precision assessment and categorization of change in routine clinical practice.
Materials and Methods: The study population was drawn from the database of the Manitoba Bone Density Program which includes all clinical DXA test results for the Province of Manitoba, Canada. All patients who had baseline and follow up total spine (L1–4) and the total hip BMD measurements on the same instrument up to March 31, 2007 were included as the ‘clinical monitoring population’ (N = 5048 scan-pairs). BMD precision was assessed in a convenience sample of patients who were agreeable to undergoing a repeat assessment (50% performed on the same day with repositioning, 68% by different technologists) (N = 331 spine and 328 hip scan-pairs).
Results: Precision error was greater when the scan-pairs were acquired on different days than on the same day for both the total spine (p &lt; .001) and total hip (p &lt; .01). No other factor was consistently associated with precision error. The reference LSC (different days and different technologists) categorized the smallest fraction of the monitored population with change, whereas other combinations gave a significant rate of over categorization (up to 19.3% for the lumbar spine and up to 18.3% for the total hip).
Conclusions: The most widely procedure for performing a BMD reproducibility assessment (same-technologist with simple repositioning on the same day) systematically underestimates precision error and will lead to over categorization of change in a large fraction of monitored patients.
A Population-Based Assessment of Rates of Bone Loss at Multiple Skeletal Sites: Evidence for Substantial Trabecular Bone Loss in Young Adult Women and Men
Authors: Riggs B Lawrence , Melton L Joseph , Robb Richard A , Camp Jon J , Atkinson Elizabeth J , McDaniel Lisa , Amin Shreyasee , Rouleau Peggy A , Khosla Sundeep 
Published: October 2007

Abstract
Using QCT, we made a longitudinal, population-based assessment of rates of bone loss over life at the distal radius, distal tibia, and lumbar spine. Cortical bone loss began in perimenopause in women and later in life in men. In contrast, trabecular bone loss began in young adulthood in both sexes.
Introduction: Although conventional wisdom holds that bone loss begins at menopause in women and later in life in men, this has not been examined longitudinally in population-based studies using precise technology capable of distinguishing cortical and trabecular bone.
Materials and Methods: In an age- and sex-stratified population sample (n = 553), we measured volumetric BMD (vBMD) of trabecular and cortical bone by QCT annually for up to 3 yr at the distal radius (DR) and distal tibia (DT) (n = 552) and trabecular vBMD at baseline and 3 yr at the lumbar spine (LS) (n = 474).
Results: Substantial cortical bone loss began in middle life in women but began mainly after age 75 in men. In contrast, substantial trabecular bone loss began in young adult women and men at all three skeletal sites and continued throughout life with acceleration during perimenopause in women. Women experienced 37% and men experienced 42% of their total lifetime trabecular bone loss before age 50 compared with 6% and 15%, respectively, for cortical bone. Median rates of change in trabecular bone (%/yr) were −0.40, −0.24, and −1.61 in young adult women and −0.38, −0.40, and −0.84 in young adult men at the DR, DT, and LS, respectively (all p &lt; 0.001). The early trabecular bone loss did not consistently correlate with putative causal factors, except for a trend with IGF-related variables at DT in women. However, in postmenopausal women and, to a lesser extent, in older men, higher rates of cortical and trabecular bone loss were associated with lower levels of biologically-active sex steroids and with higher levels of follicle-stimulating hormone and bone turnover markers.
Conclusions: The late onset of cortical bone loss is temporally associated with sex steroid deficiency. However, the early-onset, substantial trabecular bone loss in both sexes during sex steroid sufficiency is unexplained and indicates that current paradigms on the pathogenesis of osteoporosis are incomplete.
Renal Dysfunction Is a Confounder for Plasma Natriuretic Peptides in Detecting Heart Dysfunction in Uremic and Idiopathic Dilated Cardiomyopathies
Authors: Codognotto Marta , Piccoli Antonio , Zaninotto Martina , Mion Monica , Plebani Mario , Vertolli Ugo , Tona Francesco , Ruzza Luisa , Barchita Agata , Boffa Giovanni M 
Published: October 2007

AbstractBackground: The diagnostic value of natriuretic peptides in uremic cardiomyopathy has not been defined, nor has the effect of a hemodialysis (HD) session on peptides.Methods: We performed an observational study of 100 white adult outpatients in New York Heart Association class I–II, with neither diabetes nor ischemic heart disease, 50 of whom had idiopathic dilated cardiomyopathy (DCM) and 50 of whom had uremic cardiomyopathy and were undergoing HD. We measured plasma N-terminal proB-type natriuretic peptide (NT-proBNP), BNP, and atrial natriuretic peptide (ANP) both before and after a dialysis session. Doppler echocardiograms were evaluated. We performed multiple regression analysis on the logarithm of peptide concentrations using clinical, laboratory, and echocardio-Doppler data as explanatory variables.Results: Mean peptide concentrations were higher in the HD group, with an HD:DCM ratio of 25 for NT-proBNP and 5 for BNP and ANP. Peptides were correlated with each other (r &gt; 0.85). After HD, NT-proBNP significantly increased by 14%, BNP decreased by 17%, and ANP decreased by 56%. Predialysis concentrations correlated with postdialysis values (r &gt; 0.85). A multiple regression equation significantly fitted the observed peptide concentrations, both pre- and postdialysis, using the same set of 4 variables: disease group (DCM or HD), diastolic pattern, left atrial volume, and body mass index.Conclusions: Renal dysfunction was a confounder for natriuretic peptides, which were present in higher concentrations in the uremic patients with milder cardiac dysfunction than in those with idiopathic DCM without renal dysfunction. Left diastolic function pattern and atrial volume were cardiac determinants of peptide concentrations in DCM and HD.
The behaviour of organic solvents containing C5-BTBP and CyMe4-BTBP at low irradiation doses
Authors: Retegan Teodora , Ekberg Christian , Englund Sofie , Fermvik Anna , Foreman M. R. S. , Skarnemark Gunnar 
Published: October 2007

Low doses of gamma radiation were given to four different solvents containing C5-BTBP and CyMe4-BTBP, each molecule dissolved both in cyclohexanone and hexanol. Four corresponding solvents were kept unirradiated and used as references for the extraction experiments. Multiple samples were taken from both the irradiated solutions and the reference solutions at certain time intervals. The samples were used in extraction experiments with the radionuclides 241Am and 152Eu. The protection against radiolysis of the extracting molecules by the diluent used for dissolution without adding a scavenger molecule was checked. The interplay between the diluent and the side group of the extracting molecule for protection against radiolysis was also studied by keeping the same type of core molecule for binding to the metal ions and varying the diluent and side group.
The results were unexpected. The presence of a cyclic molecule as both a side group or diluent seems to keep the extraction of europium almost unaffected by radiolysis, while americium behaves differently from solvent to solvent. The diluent alone does not protect the extracting molecule. In some of the studied systems there is a distinct change in the extraction behaviour of Am between the irradiated and reference solutions, an effect that is however only present at the beginning of the experimental series. At later times the difference in distribution ratios between the irradiated and reference solution is constant. This phenomenon is found only when the side group and diluent are structurally dissimilar.
Lysophosphatidic Acid Protects Mesenchymal Stem Cells Against Hypoxia and Serum Deprivation-Induced Apoptosis
Authors: Chen Jinghai , Baydoun Anwar R. , Xu Ruixia , Deng Linzi , Liu Xuebin , Zhu Weiquan , Shi Linhui , Cong Xiangfeng , Hu Shengshou , Chen Xi 
Published: October 2007

AbstractBone marrow-derived mesenchymal stem cells (MSCs) have shown great promise for cardiac repair. However, poor viability of transplanted MSCs within the ischemic heart has limited their therapeutic potential. Our previous studies have documented that hypoxia and serum deprivation (hypoxia/SD), induced MSCs apoptosis through the mitochondrial apoptotic pathway. Since serum lysophosphatidic acid (LPA) levels are known to be significantly elevated after acute myocardial infarction and that LPA enhanced survival of other cell systems, we embarked on determining whether LPA protects MSCs against hypoxia/SD-induced apoptosis. We have also investigated the potential mechanism(s) that may mediate such actions of LPA. All experiments were carried out on rat bone marrow MSCs. Apoptosis was induced by exposure of cells to hypoxia/SD in a sealed GENbox hypoxic chamber. Effects of LPA were investigated in the absence and presence of inhibitors that target either Giproteins, the mitogen activated protein kinases ERK1/2, or phosphoinositide 3-kinase (PI3K). The data obtained showed that hypoxia/SD-induced apoptosis was significantly attenuated by LPA through Gi-coupled LPA1 receptors linked to the downstream ERK1/2 and PI3K/Akt signaling pathways that function in parallel. Additional studies have demonstrated that hypoxia/SD-induced activation of mitochondrial dysfunction was virtually abolished by LPA treatment and that inhibition of the LPA1 receptor, Gi proteins, the PI3K/Akt pathway, or ERKs effectively reversed this protective action of LPA. Taken together, our findings indicate that LPA is a novel, potent survival factor for MSCs and this may prove to be of considerable therapeutic significance in terms of exploiting MSC-based therapy in the infracted myocardium.Disclosure of potential conflicts of interest is found at the end of this article.
Novel Effectors of Directed and Ngn3-Mediated Differentiation of Mouse Embryonic Stem Cells into Endocrine Pancreas Progenitors
Authors: Serafimidis Ioannis , Rakatzi Irini , Episkopou Vasso , Gouti Mina , Gavalas Anthony 
Published: October 2007

Abstract
The delineation of regulatory networks involved in early endocrine pancreas specification will play a crucial role in directing the differentiation of embryonic stem cells toward the mature phenotype of β cells for cell therapy of type 1 diabetes. The transcription factor Ngn3 is required for the specification of the endocrine lineage, but its direct targets and the scope of biological processes it regulates remain elusive. We show that stepwise differentiation of embryonic stem cells using successive in vivo patterning signals can lead to simultaneous induction of Ptf1a and Pdx1 expression. In this cellular context, Ngn3 induction results in upregulation of its known direct target genes within 12 hours. Microarray gene expression profiling at distinct time points following Ngn3 induction suggested novel and diverse roles of Ngn3 in pancreas endocrine cell specification. Induction of Ngn3 expression results in regulation of the Wnt, integrin, Notch, and transforming growth factor β signaling pathways and changes in biological processes affecting cell motility, adhesion, the cytoskeleton, the extracellular matrix, and gene expression. Furthermore, the combination of in vivo patterning signals and inducible Ngn3 expression enhances ESC differentiation toward the pancreas endocrine lineage. This is shown by strong upregulation of endocrine lineage terminal differentiation markers and strong expression of the hormones glucagon, somatostatin, and insulin. Importantly, all insulin+ cells are also C-peptide+, and glucose-dependent insulin release was 10-fold higher than basal levels. These data suggest that bona fide pancreas endocrine cells have been generated and that timely induction of Ngn3 expression can play a decisive role in directing ESC differentiation toward the endocrine lineage.
Disclosure of potential conflicts of interest is found at the end of this article.
Mesenchymal Stem Cells Cooperate with Bone Marrow Cells in Therapy of Diabetes
Authors: Urbán Veronika S. , Kiss Judit , Kovács János , Gócza Elen , Vas Virág , Monostori Ėva , Uher Ferenc 
Published: October 2007

AbstractSeveral recent studies have suggested that the adult bone marrow harbors cells that can influence β-cell regeneration in diabetic animals. Other reports, however, have contradicted these findings. To address this issue, we used an animal model of type 1 diabetes in which the disease was induced with streptozotocin in mice. Freshly prepared sex-mismatched bone marrow cells (BMCs) and syngeneic or allogeneic mesenchymal stem cells (MSCs) were concomitantly administrated into sublethally irradiated diabetic mice. Blood glucose and serum insulin concentrations rapidly returned to normal levels, accompanied by efficient tissue regeneration after a single injection of a mixture of 106 BMCs per 105 MSCs. Neither BMC nor MSC transplantation was effective alone. Successful treatment of diabetic animals was not due to the reconstitution of the damaged islet cells from the transplant, since no donor-derived β-cells were found in the recovered animals, indicating a graft-initiated endogenous repair process. Moreover, MSC injection caused the disappearance of β-cell-specific T lymphocytes from diabetic pancreas. Therefore, we suggest that two aspects of this successful treatment regimen operate in parallel and synergistically in our model. First, BMCs and MSCs induce the regeneration of recipient-derived pancreatic insulin-secreting cells. Second, MSCs inhibit T-cell-mediated immune responses against newly formed β-cells, which, in turn, are able to survive in this altered immunological milieu. Thus, the application of this therapy in human patients suffering from diabetes and/or other tissue destructive autoimmune diseases may be feasible.Disclosure of potential conflicts of interest is found at the end of this article.
Multipotent Stem Cells from Umbilical Cord: Cord Is Richer than Blood!
Authors: Secco Mariane , Zucconi Eder , Vieira Natassia M. , Fogaça Luciana L.Q. , Cerqueira Antonia , Carvalho Maria Denise F. , Jazedje Tatiana , Okamoto Oswaldo K. , Muotri Alysson R. , Zatz Mayana 
Published: October 2007

Abstract
The identification of mesenchymal stem cell (MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. Here, we compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors. Samples were processed simultaneously, under the same culture conditions. Although MSCs from blood were obtained from only 1 of the 10 samples, we were able to isolate large amounts of multipotent MSCs from all UC samples, which were able to originate different cell lineages. Since the routine procedure in UC banks has been to store the blood and discard other tissues, such as the cord and/or placenta, we believe our results are of immediate clinical value. Furthermore, the possibility of originating different cell lines from the UC of neonates born with genetic defects may provide new cellular research models for understanding human malformations and genetic disorders, as well as the possibility of testing the effects of different therapeutic drugs.
Disclosure of potential conflicts of interest is found at the end of this article.
Oct-4 Is Critical for Survival/Antiapoptosis of Murine Embryonic Stem Cells Subjected to Stress: Effects Associated with Stat3/Survivin
Authors: Guo Ying , Mantel Charlie , Hromas Robert A. , Broxmeyer Hal E. 
Published: October 2007

Abstract
Understanding survival/antiapoptosis of murine embryonic stem (ES) cells may enhance their clinical potential. We hypothesized that Oct-4 might be involved in survival of undifferentiated ES cells under stress. The Oct-4 tetracycline conditional knockout cell line ZHBtc4 was used to test this possibility, and apoptosis was induced by either etoposide, heat shock, or UV exposure. Apoptosis in Oct-4 knocked-down ES cells was significantly increased in response to all stress situations compared with parental cells. Oct-4 knockdown was not associated with changes in morphology or expression of Nanog, SSEA-1, KLF-4, or Sox2 within the time frame and culture conditions used, suggesting that enhanced sensitivity of these cells to apoptosis was not due to an overtly differentiated state of the cells. To address potential intracellular mediators, we focused on the inhibitor of apoptosis proteins family member Survivin, an antiapoptosis protein. The Survivin promoter was transfected into ES cells after knockdown of Oct-4. Survivin promoter activity was dramatically decreased in the Oct-4 knockdown cells. Western blots substantiated that Oct-4 knockdown ES cells had decreased Survivin protein expression. Since the Survivin promoter does not have binding sites for Oct-4, this suggested an indirect effect of Oct-4 on expression of Survivin. Leukemia inhibitory factor-induced signal transducer and activator of transcription-3 (STAT3) is responsible for ES cell survival, and STAT3 regulates Survivin expression in breast cancer cells. Western blot analysis showed that downregulated Oct-4 was associated with decreased phosphorylation of STAT3. Our results suggest that Oct-4 is essential for antiapoptosis of ES cells in response to stress, effects that may be mediated through the STAT3/Survivin pathway.
Disclosure of potential conflicts of interest is found at the end of this article.
Human Mesenchymal Stem Cells Inhibit Neutrophil Apoptosis: A Model for Neutrophil Preservation in the Bone Marrow Niche
Authors: Raffaghello Lizzia , Bianchi Giordano , Bertolotto Maria , Montecucco Fabrizio , Busca Alessandro , Dallegri Franco , Ottonello Luciano , Pistoia Vito 
Published: October 2007

AbstractMesenchymal stem cells (MSC) establish close interactions with bone marrow sinusoids in a putative perivascular niche. These vessels contain a large storage pool of mature nonproliferating neutrophils. Here, we have investigated the effects of human bone marrow MSC on neutrophil survival and effector functions. MSC from healthy donors, at very low MSC:neutrophil ratios (up to 1:500), significantly inhibited apoptosis of resting and interleukin (IL)-8-activated neutrophils and dampened N-formyl-l-methionin-l-leucyl-l-phenylalanine (f-MLP)-induced respiratory burst. The antiapoptotic activity of MSC did not require cell-to-cell contact, as shown by transwell experiments. Antibody neutralization experiments demonstrated that the key MSC-derived soluble factor responsible for neutrophil protection from apoptosis was IL-6, which signaled by activating STAT-3 transcription factor. Furthermore, IL-6 expression was detected in MSC by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Finally, recombinant IL-6 was found to protect neutrophils from apoptosis in a dose-dependent manner. MSC had no effect on neutrophil phagocytosis, expression of adhesion molecules, and chemotaxis in response to IL-8, f-MLP, or C5a. These results support the following conclusions: (a) in the bone marrow niche, MSC likely protect neutrophils of the storage pool from apoptosis, preserving their effector functions and preventing the excessive or inappropriate activation of the oxidative metabolism, and (b) a novel mechanism whereby the inflammatory potential of activated neutrophils is harnessed by inhibition of apoptosis and reactive oxygen species production without impairing phagocytosis and chemotaxis has been identified.Disclosure of potential conflicts of interest is found at the end of this article.