bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systemic provascular response in bone marrow to musculoskeletal trauma in mice
Authors: Laing A. J. , Dillon J. P. , Condon E.T. , Coffey J. C. , Street J. T. , Wang J. H. , McGuinness A. J. , Redmond H. P. 
Published: January 2007

Post-natal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells migrate, differentiate and incorporate into the nacent endothelium and thereby contribute to physiological and pathological neurovascularisation, has stimulated much interest. Its contribution to neovascularisation of tumours, wound healing and revascularisation associated with ischaemia of skeletal and cardiac muscles is well established. We evaluated the responses of endothelial precursor cells in bone marrow to musculoskeletal trauma in mice.Bone marrow from six C57 Black 6 mice subjected to a standardised, closed fracture of the femur, was analysed for the combined expression of cell-surface markers stem cell antigen 1 (sca-1+) and stem cell factor receptor, CD117 (c-kit+) in order to identify the endothelial precursor cell population. Immunomagnetically-enriched sca-1+mononuclear cell (MNCsca-1+) populations were then cultured and examined for functional vascular endothelial differentiation. Bone marrow MNCsca-1+,c-kit+counts increased almost twofold within 48 hours of the event, compared with baseline levels, before decreasing by 72 hours.Sca-1+mononuclear cell populations in culture from samples of bone marrow at 48 hours bound together Ulex Europus-1, and incorporated fluorescent 1,1′-dioctadecyl- 3,3,3,’3′-tetramethylindocarbocyanine perchlorate-labelled acetylated low-density lipoprotein intracellularily, both characteristics of mature endothelium.Our findings suggest that a systemic provascular response of bone marrow is initiated by musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of neovascularisation and the healing of fractures.
Development of genu varum in achondroplasia
Authors: Lee S. T. , Song H. R. , Mahajan R. , Makwana V. , Suh S. W. , Lee S. H. 
Published: January 2007

Genu varum in the achondroplastic patient has a complex and multifactorial aetiology. There is little mention in the literature of the role of fibular overgrowth. Using the ratio of fibular to tibial length as a measurement of possible fibular overgrowth, we have related it to the development of genu varum. Full-length standing anteroposterior radiographs of 53 patients with achondroplasia were analysed. There were 30 skeletally-immature and 23 skeletally-mature patients. Regression analysis was performed in order to determine if there was a causal relationship between fibular overgrowth and the various indices of alignment of the lower limb. Analysis showed that the fibular to tibial length ratio had a significant correlation with the medial proximal tibial angle and the mechanical axial deviation in the skeletally-immature group. We conclude that there is a significant relationship between fibular overgrowth and the development of genu varum in the skeletally-immature achondroplastic patient.
An in vitro study demonstrating that haematomas found at the site of human fractures contain progenitor cells with multilineage capacity
Authors: Oe K. , Miwa M. , Sakai Y. , Lee S. Y. , Kuroda R. , Kurosaka M. 
Published: January 2007

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells. Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.
Operative delay for fracture of the hip
Authors: Von Meibom N. , Gilson N. , Dhapre A. , Davis B. 
Published: January 2007

We undertook a simultaneous prospective two-centre study to examine why patients with fractures of the proximal femur experience a delay in undergoing surgery. At centre 1, 23 of 105 patients (22%) suffered an avoidable delay, 18 (78%) because of a lack of theatre capacity while at centre 2, 71 of 130 patients (55%) had an avoidable delay, with 54 (76%) because of this cause. Miscellaneous reasons such as poor ward management, co-existing medical conditions, and lack of equipment were responsible for the remainder of the delays. Without a substantial increase in operating capacity for acute trauma, it will not be possible to comply with guidelines which recommend surgical treatment within 24 hours in elderly and vulnerable patients.
The effect of surgical approach on blood flow to the femoral head during resurfacing
Authors: Khan A. , Yates P. , Lovering A. , Bannister G. C. , Spencer R. F. 
Published: January 2007

We determined the effect of the surgical approach on perfusion of the femoral head during hip resurfacing arthroplasty by measuring the concentration of cefuroxime in bone samples from the femoral head. A total of 20 operations were performed through either a transgluteal or an extended posterolateral approach. The concentration of cefuroxime in bone was significantly greater when using the transgluteal approach (mean 15.7 mg/kg; 95% confidence interval 12.3 to 19.1) compared with that using the posterolateral approach (mean 5.6 mg/kg; 95% confidence interval 3.5 to 7.8; p < 0.001). In one patient, who had the operation through a posterolateral approach, cefuroxime was undetectable. Using cefuroxime as an indirect measure of blood flow, the posterolateral approach was found to be associated with a significant reduction in the blood supply to the femoral head during resurfacing arthroplasty compared with the transgluteal approach.
Amino-Terminal Pro–Brain Natriuretic Peptide, Brain Natriuretic Peptide, and Troponin T for Prediction of Mortality in Acute Heart Failure
Authors: Sakhuja Rahul , Green Sandy , Oestreicher Eveline M , Sluss Patrick M , Lee-Lewandrowski Elizabeth , Lewandrowski Kent B , Januzzi James L 
Published: January 2007

Abstract
Background: Combining testing for natriuretic peptides [amino-terminal pro–brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP)] and cardiac troponin T (cTnT) may help predict mortality in patients with acute heart failure (HF).
Methods: We studied 209 patients with acute HF at an urban academic center and used ROC curves and multivariate analyses to examine the relationship of outcome to natriuretic peptide and cTnT concentrations at presentation.
Results: Higher concentrations of natriuretic peptides and cTnT at presentation were predictors of death at 60 days and 1 year (P &lt;0.001 and P &lt;0.01, respectively, at both time points). Optimal cutoff points for NT-proBNP, BNP, and cTnT for predicting death by 60 days or 1 year were 5562 and 3174 ng/L, 428 and 352 ng/L, and 0.01 and 0.01 μg/L, respectively. Most decedents demonstrated increased concentrations of both natriuretic peptides and cTnT and had a 25% mortality rate at the 60-day time point (P &lt;0.001). Mortality rates were low (&lt;4%) among patients with either no increase or an increase in only 1 marker. Decedents with increases in both a natriuretic peptide and cTnT at presentation had the highest death rate at 1 year (45%, P &lt;0.001). This combination was strongly predictive of death [NT-proBNP plus cTnT: hazard ratio (HR), 7.66; 95% confidence interval (CI), 3.06–17.8; BNP plus cTnT: HR, 6.82; 95% CI, 2.99–16.5].
Conclusions: A dual-marker strategy incorporating a natriuretic peptide and cTnT is superior to either marker alone for estimating short- and longer-term risk in patients with acute HF.
Cystatin C and Estimates of Renal Function: Searching for a Better Measure of Kidney Function in Diabetic Patients
Authors: Pucci Laura , Triscornia Stefano , Lucchesi Daniela , Fotino Carmen , Pellegrini Giovanni , Pardini Ennia , Miccoli Roberto , Del Prato Stefano , Penno Giuseppe 
Published: January 2007

Abstract
Background: Early identification of impairment in renal function is crucial in diabetic patients. Serum cystatin C may be the most sensitive indicator of glomerular filtration rate (GFR) in the clinical setting.
Methods: We compared cystatin C with creatinine, the Cockcroft-Gault (C-G) formula, and the Modification of Diet in Renal Disease (MDRD) study equation for the assessment of early decreased renal function in 288 diabetic patients (125 type 1, 163 type 2) with renal impairment [GFR: 4–222 mL · min−1 · (1.73 m2)−1]. Relationships of cystatin C, creatinine, and iohexol clearance were linearized by plotting their reciprocals in a simple regression model. Diagnostic efficiency was calculated from ROC curves.
Results: In this study population, cystatin C (P = 0.0013) was better correlated with GFR (r = 0.857) than were creatinine (r = 0.772), C-G (r = 0.750), and MDRD (r = 0.806), a result replicated in patients with normal renal function (P = 0.023, type 1; P = 0.011, type 2), but not in those with decreased GFR. Mean cystatin C concentrations showed step-by-step statistically significant increases as GFR decreased, allowing very early detection of reduction in renal function. At 90 mL · min−1 · (1.73 m2)−1 and 75 mL · min−1 · (1.73 m2)−1 cut-points, diagnostic efficiencies of cystatin C (89% and 92%) were better than those of the other variables (79%–82% and 85%–86%, respectively; P = 0.01).
Conclusions: All data supported the value of serum cystatin C compared with conventional estimates based on serum creatinine measurement for detecting very early reduction of renal function. Use of cystatin C to measure renal function will optimize early detection, prevention, and treatment strategies for diabetic nephropathy.
Cell-Free Fetal DNA in Amniotic Fluid: Unique Fragmentation Signatures in Euploid and Aneuploid Fetuses
Authors: Lapaire Olav , Bianchi Diana W , Peter Inga , O’Brien Barbara , Stroh Helene , Cowan Janet M , Tantravahi Umadevi , Johnson Kirby L 
Published: January 2007

Abstract
Background: Circulating cell-free fetal deoxyribonucleic acids (cffDNA) are novel biomarkers with many clinical applications. Amniotic fluid (AF) is a rich source of cffDNA. We investigated the biophysical characteristics of cffDNA in AF, hypothesizing that they would differ from cffDNA in maternal plasma.
Methods: We obtained 10 mL of fresh AF supernatant from women carrying euploid fetuses (n = 39) and aneuploid fetuses (n = 4). To test the effects of storage and karyotype, samples from euploid fetuses (n = 19) and aneuploid fetuses with trisomies 21 (n = 16), 18 (n = 9), or 13 (n = 3); triploidy (n = 4); or monosomy X (n = 2) were frozen at −80 °C. AF cffDNA was characterized by real-time quantitative PCR amplification of glyceraldehyde-3-phosphate dehydrogenase, gel electrophoresis, and analysis of the DNA fragmentation signature.
Results: We observed a significant correlation of concentration with gestational age for fresh AF cffDNA from euploid fetuses (R2 = 0.77, P &lt;0.0001) but not for frozen cffDNA (P = 0.63). The median amount of cffDNA in frozen euploid samples was significantly lower than in fresh samples (P &lt;0.0001). After adjustment for gestational age, there was a statistically significant decrease in the median amount of cffDNA in frozen aneuploidy samples compared with frozen euploid samples (P = 0.0005). Analysis of the cffDNA size distribution showed different and qualitatively unique patterns for each karyotype.
Conclusions: Gestational age, karyotype, and sample storage time affect concentrations and fragment size of AF cff DNA. These effects may be attributable to fundamental differences in tissue sources, excretion modes, or kinetic pathways. Characteristic signature patterns for each common aneuploidy offer the possibility of using DNA fragmentation analysis as a means of triaging AF samples.
Stem/Progenitor Cell-Like Properties of Desmoglein 3dim Cells in Primary and Immortalized Keratinocyte Lines
Authors: Wan Hong , Yuan Ming , Simpson Cathy , Allen Kirsty , Gavins Felicity N.E. , Ikram Mohammed S. , Basu Subham , Baksh Nuzhat , O'Toole Edel A. , Hart Ian R. 
Published: January 2007

Abstract
We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more “stem/progenitor cell-like” phenotype. Here, we have confirmed that Dsg3dim cells derived from cultured primary human adult keratinocytes have comparability with α6bri/CD71dim stem cells in terms of colony-forming efficiency. Moreover, these Dsg3dim cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3bri cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3dim cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3bri and sorted control cells. Dsg3dim HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3dim and Dsg3bri populations. Taken together our data indicate that Dsg3dim populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features.
Disclosure of potential conflicts of interest is found at the end of this article.
Human AB Serum and Thrombin-Activated Platelet-Rich Plasma Are Suitable Alternatives to Fetal Calf Serum for the Expansion of Mesenchymal Stem Cells from Adipose Tissue
Authors: Kocaoemer Asli , Kern Susanne , Klüter Harald , Bieback Karen 
Published: January 2007

Abstract
MSCs are currently in focus regarding their clinical potential in cell therapy and tissue engineering. However, most isolation and expansion protocols for clinical-scale production of MSCs use fetal calf serum (FCS) as a supplement, which poses a potential risk for infections as well as immunological reactions. To find a suitable FCS substitute, we investigated the effects of pooled human AB serum (AB-HS) and thrombin-activated platelet-rich plasma (tPRP) on adipose tissue MSCs (AT-MSCs) with FCS as the standard control medium. AT-MSCs of 10 donors were cultured under three different conditions: (a) 10% FCS, (b) 10% AB-HS, and (c) 10% tPRP. Colony-forming units, cumulative population doubling rates, and differentiation capacity toward the adipogenic and osteogenic lineages were assessed, along with immunophenotype. We demonstrated that AB-HS and tPRP provide a significantly higher proliferative effect on AT-MSCs than does FCS. In the first six passages, AB-HS and tPRP MSCs exhibited a fold expansion of 66.6 ± 15.7 and 68.1 ± 6.7, respectively, compared with 24.4 ± 0.7 for FCS. Differentiation capacity was preserved throughout long-term culture. Immunophenotype was characteristic for MSCs and comparable for all culture conditions with the exception of a distinct CD45-/CD14-positive side population for AB-HS and tPRP that tended to diminish with prolonged culture. We showed that pooled human AB serum and thrombin-activated platelet-rich plasma are alternatives to FCS for AT-MSCs. These human sources are better characterized regarding potential infectious threats, while providing a higher proliferation rate and retaining differentiation capacity and mesenchymal stem cell marker expression throughout long-term culture.
Disclosure of potential conflicts of interest is found at the end of this article.
Severe Hypoxia Defines Heterogeneity and Selects Highly Immature Progenitors Within Clonal Erythroleukemia Cells
Authors: Giuntoli Serena , Rovida Elisabetta , Gozzini Antonella , Barbetti Valentina , Cipolleschi Maria Grazia , Olivotto Massimo , Dello Sbarba Persio 
Published: January 2007

Abstract
We showed that resistance to severe hypoxia defines hierarchical levels within normal hematopoietic populations and that hypoxia modulates the balance between generation of progenitors and maintenance of hematopoietic stem cells (HSC) in favor of the latter. This study deals with the effects of hypoxia (0.1% oxygen) in vitro on Friend's murine erythroleukemia (MEL) cells, addressing the question of whether a clonal leukemia cell population comprise functionally different cell subsets characterized by different hypoxia resistance. To identify leukemia stem cells (LSC), we used the Culture Repopulating Ability (CRA) assay we developed to quantify in vitro stem cells capable of short-term reconstitution (STR). Hypoxia strongly inhibited the overall growth of MEL cell population, which, despite its clonality, comprised progenitors characterized by markedly different hypoxia-resistance. These included hypoxia-sensitive colony-forming cells and hypoxia-resistant STR-type LSC, capable of repopulating secondary liquid cultures of CRA assays, confirming what was previously shown for normal hematopoiesis. STR-type LSC were found capable not only of surviving in hypoxia but also of being mostly in cycle, in contrast with the fact that almost all hypoxia-surviving cells were growth-arrested and with what we previously found for HSC. However, quiescent LSC were also detected, capable of delayed culture repopulation with the same efficiency as STR-like LSC. The fact that even quiescent LSC, believed to sustain minimal residual disease in vivo, were found within the MEL cells indicates that all main components of leukemia cell populations may be present within clonal cell lines, which are therefore suitable to study the sensitivity of individual components to treatments.
Disclosure of potential conflicts of interest is found at the end of this article.
Differential Developmental Ability of Embryos Cloned from Tissue-Specific Stem Cells
Authors: Inoue Kimiko , Noda Shinichi , Ogonuki Narumi , Miki Hiromi , Inoue Shinichi , Katayama Kazufumi , Mekada Kazuyuki , Miyoshi Hiroyuki , Ogura Atsuo 
Published: January 2007

Abstract
Although cloning animals by somatic cell nuclear transfer is generally inefficient, the use of certain nuclear donor cell types may significantly improve or deteriorate outcomes. We evaluated whether two multipotent stem cell lines produced in vitro—neural stem cells (NSCs) and mesenchymal stem cells (MSCs)—could serve as nuclear donors for nuclear transfer cloning. Most (76%) NSC-derived embryos survived the two-cell–to–four-cell transition, the stage when the major zygotic gene activation occurs. Consistent with this observation, the expression patterns of zygotically active genes were better in NSC-derived embryos than in fibroblast clone embryos, which arrested at the two-cell stage more frequently. Embryo transfer experiments demonstrated that at least some of these NSC embryos had the ability to develop to term fetuses (1.6%, 3/189). In contrast, embryos reconstructed using MSCs showed a low rate of in vitro development and never underwent implantation in vivo. Chromosomal analysis of the donor MSCs revealed very frequent aneuploidy, which probably impaired the potential for development of their derived clones. This is the first demonstration that tissue-specific multipotent stem cells produced in vitro can serve as donors of nuclei for cloning mice; however, these cells may be prone to chromosomal aberrations, leading to high embryonic death rates. We found previously that hematopoietic stem cells (HSCs) are very inefficient donor cells because of their failure to activate the genes essential for embryonic development. Taken together, our data led us to conclude that tissue-specific stem cells in mice, namely NSCs, MSCs, and HSCs, exhibited marked variations in the ability to produce cloned offspring and that this ability varies according to both the epigenetic and genetic status of the original genomes.
Disclosure of potential conflicts of interest is found at the end of this article.
Src as a therapeutic target in anti-hormone/anti-growth factor-resistant breast cancer
Authors: Hiscox Stephen , Morgan L , Green Tim , Nicholson Robert I 
Published: January 2007

Endocrine therapy is the treatment of choice in hormone receptor-positive breast cancer. However, the effectiveness of anti-hormone drugs, such as tamoxifen, is limited because of the development of resistance, ultimately leading to disease progression and patient mortality. Using in vitro cell models of anti-hormone resistance, we have previously demonstrated that altered growth factor signalling contributes to an endocrine insensitive phenotype. Significantly, our recent studies have revealed that the acquisition of endocrine resistance in breast cancer is accompanied by a greatly enhanced migratory and invasive phenotype. Furthermore, therapeutic intervention using anti-growth factor monotherapies, despite an initial growth suppressive phase, again results in the development of a resistant state and a further augmentation of their invasive phenotype.
Using the dual specific Src/Abl kinase inhibitor, AZD0530, we have highlighted a central role for Src kinase in promoting the invasive phenotype that accompanies both anti-hormone and anti-growth factor resistance. Importantly, the use of Src inhibitors in combination with anti-growth factor therapies appears to be additive, producing a marked inhibitory effect on cell growth, migration and invasion and ultimately prevents the emergence of a resistant phenotype. These observations suggest that the inhibition of Src activity may present a novel therapeutic intervention strategy, particularly when used as an adjuvant in endocrine-resistant breast disease, with the potential to delay or prevent the acquisition of subsequent resistance to anti-growth factor therapies.