bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Role for γ-Secretase in the Formation of Primitive Streak-like Intermediates from ES Cells in Culture
Authors: Hughes James N. , Dodge Natasha , Rathjen Peter D. , Rathjen Joy 
Published: September 2009

Abstract
γ-Secretase is a membrane-associated protease with multiple intracellular targets, a number of which have been shown to influence embryonic development and embryonic stem (ES) cell differentiation. This paper describes the use of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) to evaluate the role of γ-secretase in the differentiation of pluripotent stem cells to the germ lineages. The addition of DAPT did not prevent the formation of primitive ectoderm-like cells from ES cells in culture. In contrast, the addition of DAPT during primitive ectoderm-like cell differentiation interfered with the ability of both serum and BMP4 to induce a primitive streak-like intermediate and resulted in the preferential formation of neurectoderm. Similarly, DAPT reduced the formation of primitive streak-like intermediates from differentiating human ES cells; the culture conditions used resulted in a population enriched in human surface ectoderm. These data suggest that γ-secretase may form part of the general pathway by which mesoderm is specified within the primitive streak. The addition of an E-cadherin neutralizing antibody was able to partially reverse the effect of DAPT, suggesting that DAPT may be preventing the formation of primitive streak-like intermediates and promoting neurectoderm differentiation by stabilizing E-cadherin and preventing its proteolysis.
Disclosure of potential conflicts of interest is found at the end of this article.
MPR1 as a novel selection marker in Saccharomyces cerevisiae
Authors: Ogawa‐Mitsuhashi Kaoru , Sagane Koji , Kuromitsu Junro , Takagi Hiroshi , Tsukahara Kappei 
Published: September 2009

AbstractL‐Azetidine‐2‐carboxylic acid (AZC) is a toxic four‐membered ring analogue of L‐proline that is transported into cells by proline transporters. AZC and L‐proline in the cells are competitively incorporated into nascent proteins. When AZC is present in a minimum medium, misfolded proteins are synthesized in the cells, thereby inhibiting cell growth. The MPR1 gene has been isolated from the budding yeast Saccharomyces cerevisiae Σ1278b as a multicopy suppressor of AZC‐induced growth inhibition. MPR1 encodes a novel acetyltransferase that detoxifies AZC via N‐acetylation. Since MPR1 is absent in the laboratory strain of S. cerevisiae S288C, it could be a positive selection marker that confers AZC resistance in the S288C background strains. To examine the usefulness of MPR1, we constructed some plasmid vectors that harboured MPR1 under the control of various promoters and introduced them into the S288C‐derived strains. The expression of MPR1 conferred AZC resistance that was largely dependent on the expression level of MPR1. In an additional experiment, the galactose‐inducible MPR1 and ppr1+, the fission yeast Schizosaccharomyces pombe homologue of MPR1, were used for gene disruption by homologous recombination, and here AZC‐resistant colonies were also successfully selected. We concluded that our MPR1–AZC system provides a powerful tool for yeast transformation. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of bone chip orientation on quantitative estimates of changes in bone mass using digital subtraction radiography
Authors: Mol André , Dunn Stanley M. 
Published: September 2009

Objectives:  To assess the effect of the orientation of arbitrarily shaped bone chips on the correlation between radiographic estimates of bone loss and true mineral loss using digital subtraction radiography.Methods:  Twenty arbitrarily shaped bone chips (dry weight 1–10 mg) were placed individually on the superior lingual aspect of the interdental alveolar bone of a dry dentate hemi‐mandible. After acquiring the first baseline image, each chip was rotated 90 degrees and a second radiograph was captured. Follow‐up images were created without the bone chips and after rotating the mandible 0, 1, 2, 4, and 6 degrees around a vertical axis. Aluminum step tablet intensities were used to normalize image intensities for each image pair. Follow‐up images were registered and geometrically standardized using projective standardization. Bone chips were dry ashed and analyzed for calcium content using atomic absorption.Results:  No significant difference was found between the radiographic estimates of bone loss from the different bone chip orientations (Wilcoxon: P > 0.05). The correlation between the two series of estimates for all rotations was 0.93 (Spearman: P < 0.05). Linear regression analysis indicated that both correlates did not differ appreciably (

and

).Conclusion:  It is concluded that the spatial orientation of arbitrarily shaped bone chips does not have a significant impact on quantitative estimates of changes in bone mass in digital subtraction radiography. These results were obtained in the presence of irreversible projection errors of up to six degrees and after application of projective standardization for image reconstruction and image registration.
Root surface debridement and endotoxin removal
Authors: Cadosch J. , Zimmermann U. , Ruppert M. , Guindy J. , Case D. , Zappa U. 
Published: September 2009

Objective:  This study assessed associations between the number of standardized scaling strokes and the reduction of endotoxin on the root surface.Background:  Therapy of periodontally involved teeth attempts removal of accretions by scaling and root planing. The amount of mechanical therapy required to free the root surface from etiologic factors remains unknown.Methods:  Twenty‐four extracted human caries‐free single rooted teeth with at least 5 mm attachment loss were used. A region of interest (ROI) which contained subgingival calculus was defined on the root surface of each tooth. Standardized force instrumentation was applied using a force‐measuring curet. Fifty working strokes were applied to every ROI. Forces applied were recorded. The force recordings were converted from Millivolts into Newtons (N). After every unit of 5 strokes, presence of calculus was evaluated and scaling debris was collected. Endotoxin concentration was determined in the debris samples.Results:  The endotoxin values for strokes 1–5 were statistically significantly greater than the values from all other stroke intervals. Complete calculus removal occured after a mean of 9.3 strokes. The endotoxin concentration reached a minimal level with concentrations of 0.03–0.306 EU/ml after calculus removal was complete.Conclusion:  These findings suggest that completion of calculus removal coincides with endotoxin levels associated with clinically healthy teeth.
Effect of soluble receptors to interleukin‐1 and tumor necrosis factor alpha on experimentally induced root resorption in rats
Authors: Zhang Dongliang , Goetz Werner , Braumann Bert , Bourauel Christoph , Jaeger Andreas 
Published: September 2009

Objective:  In this study, the role of the inflammatory cytokines interleukin‐1 (IL‐1) and tumor necrosis factor alpha (TNFα) in the course of mechanically induced root resorption was investigated.Methods:  Mechanical induction of root resorption was performed on the upper left first molars in 18 male Wistar rats according to the method of Nakane and Kameyama. Starting on day minus 1, six animals received daily intraperitoneal injections of 2 ml of 1 µg/ml soluble receptors to IL‐1 (sIL‐1RII) and another six animals were administered the same dose of soluble receptors to TNFα (sTNFα‐RI). Six animals served as a control. On d 7 the left maxillae were prepared for histological and morphometric analysis of the extent of the root resorption that had developed.Results:  The qualitative and quantitative results demonstrated that in both receptor groups the amount of root resorption was significantly reduced. Especially following systemic application of sTNFα‐RI, root resorption was nearly completely prevented.Conclusions:  Our results indicate that IL‐1 and more particularly TNFα are important for the induction and the further process of mechanically induced root resorption in the rat.
Unique genes induced by mechanical stress in periodontal ligament cells
Authors: Myokai Fumio , Oyama Masataka , Nishimura Fusanori , Ohira Taisuke , Yamamoto Tadashi , Arai Hideo , Takashiba Shogo , Murayama Yoji 
Published: September 2009

Objectives:  The aim of this study is to isolate mechanical stress‐induced genes (MSGens) from human periodontal ligament (PDL) cells and to analyze profiles of the mRNA expression of these genes.Background:  Differential expression of genes in PDL cells under physiological stress such as occlusal force is thought to be orchestrated not only for the remodeling of PDL itself but also for the repair and regeneration of periodontal tissues. However, little is known about the genes expressed in PDL cells under mechanical stress.Methods:  The cDNA from mechanical stress‐applied human PDL cells was subtracted against the cDNA from static control cells. The subtracted cDNA was amplified by polymerase chain reaction (PCR) and cloned for further analysis.Results:  Among 68 independent clones isolated, 15 contained DNA fragments greater than 250 bp. Reverse Northern analysis revealed a marked induction of MSGen‐15 and MSGen‐28 mRNA expression in the mechanical stress‐applied cells. However, little difference in the magnitude of expression for the other MSGens was detected between the stress‐applied cells and the control cells. After nucleotide sequencing and the analysis of homology with known genes, five clones were identified; ribosomal protein S27 (MSGen‐9), MRG 15 (MSGen‐15), androgen‐binding protein (MSGen‐18), cathepsin H (MSGen‐28), and cytochrome c (MSGen‐47). Interestingly, it has been reported that MRG 15 is a novel transcription factor involved in the regulation of cell growth and senescence. The remaining 10 clones, classified into six sequence types, had no significant homology with any known genes.Conclusions:  These results suggest that many known and unknown genes are expressed in response to mechanical stress in PDL cells, and that a transcription factor, MRG 15, may be responsible for molecular events in PDL cells under mechanical stress.
Effect of Emdogain® on human periodontal fibroblasts in an in vitro wound‐healing model
Authors: Rincon J. C. , Haase H. R. , Bartold P. M. 
Published: September 2009

Objective:  The aim of this study was to evaluate the influence of Emdogain® (EMD) on cultured gingival fibroblasts, periodontal ligament fibroblasts and dermal fibroblasts, using an in vitro model of wound healing.Background:  Enamel matrix derivative has been demonstrated to promote periodontal regeneration. However, the precise mechanisms by which this agent acts are still unclear.Methods:  The effect of EMD on proliferation of the cells was studied using subconfluent cultures of gingival fibroblasts and periodontal ligament fibroblasts. The cells were made quiescent overnight and then stimulated with various concentrations of EMD (10, 50, 100 and 150 μg/ml) for 24 h. Negative and positive controls were cells cultured in media containing 0.2% and 10% fetal calf serum (FCS). The DNA synthesis was measured by the cellular uptake of [3H]thymidine. For in vitro wounding the cells were cultured, wounded and stimulated with 0.2% FCS, 10% FCS and EMD at a concentration of 20 μg/ml. The percentage of wound fill after treatment was measured after d 1, 4, 6, 12 and 16. The proliferation of cells was also calculated by the extent of incorporation of crystal violet.Results:  The results demonstrated that cells in vitro fill an empty space by a combination of proliferation and cell migration. The most rapid closure of a wound area occurred where both proliferation and migration can occur as was seen when wounded cultures were maintained in 10% FCS or at a concentration of 20 μg/ml EMD which promoted proliferation.Conclusions:  Therefore, EMD appears to exert an influence on cells that is compatible with improved wound healing.
The herpesvirus–Porphyromonas gingivalis–periodontitis axis
Authors: Slots J. , Kamma J.J. , Sugar C. 
Published: September 2009

Objectives and background:  Members of the herpesvirus family have accumulated considerable support for a role in severe types of periodontitis. This study aimed to examine whether human cytomegalovirus (HCMV), Epstein–Barr virus type 1 (EBV‐1) or herpes simplex virus (HSV) together with the major periodontopathic bacterium Porphyromonas gingivalis might interact in the pathogenesis of periodontal breakdown.Methods:  Sixteen subjects each contributed paper point samples from two progressing and two stable periodontitis lesions, as determined by ongoing loss of probing attachment. Polymerase chain reaction methodology was used to identify subgingival herpesviruses, P. gingivalis and other bacterial pathogens. Chi‐squared tests and multivariate logistic regression were employed to identify statistical associations between herpesviruses, periodontopathic bacteria and clinical variables.Results:  HCMV and HSV were both significant predictors of the presence of subgingival P. gingivalis. In turn, P. gingivalis was positively associated with periodontitis active disease, probing attachment level, probing pocket depth, gingival bleeding upon probing and patient age. EBV‐1 was not linked to P. gingivalis, although the virus was predictive of periodontitis active disease. The periodontitis disease risk associated with herpesvirus–P. gingivalis combinations depended on both site‐specific and subject‐specific factors.Conclusion:  The present data of aggressive periodontitis implicate HCMV, HSV and P. gingivalis as either cofactors in its etiology or triggers of relapses. Further studies are needed to determine the spectrum of periodontopathogenicity of herpesviruses and effective management of these viruses in periodontal sites.
The effects of enamel matrix derivative (EMD) on osteoblastic cells in culture and bone regeneration in a rat skull defect
Authors: Yoneda Satoshi , Itoh Daisuke , Kuroda Shinji , Kondo Hisatomo , Umezawa Akihiro , Ohya Keiichi , Ohyama Takashi , Kasugai Shohei 
Published: September 2009

Objective:  Enamel matrix derivative (EMD) has been clinically used to promote periodontal tissue regeneration. The purpose of the present study is to clarify EMD affects on osteoblastic cells and bone regeneration.Materials and Methods:  Mouse osteoblastic cells (ST2 cells and KUSA/A1 cells) are used in culture experiments. After cells were treated with EMD, cell growth was evaluated with DNA measurement, 5‐bromo‐2′‐deoxyurydine (BrdU) incorporation assay. Measurement of alkaline phosphatase (ALP) activity and mineralized‐nodule (MN) formation, Northern blotting analysis and zymography are also performed. In addition, EMD was applied to a rat skull defect and the defect was radiographically and histologically evaluated 2 weeks after the application.Results:  EMD did not stimulate ST2 cell growth; however, it enhanced KUSA/A1 cell proliferation. Although EMD stimulated ALP activity in both the cells, ALP activity in KUSA/A1 cells was affected to a much greater degree. Corresponding to the increase in ALP activity, MN formation in KUSA/A1 cells was enhanced by EMD. EMD stimulated osteoblastic phenotype expression of KUSA/A1 cells such as type I collagen, osteopontin, transforming growth factor beta 1 and osteocalcin. EMD treatment also stimulated matrix metalloproteinase production in KUSA/A1 cells. Although the effects of EMD on osteoblastic cells depend on cell type, the overall effect of EMD on osteoblastic cells is stimulatory rather than inhibitory. Finally, EMD application to a rat skull defect accelerated new bone formation.Conclusion:  These results indicate that EMD affects osteoblastic cells and has potential as a therapeutic material for bone healing.
Povidone‐iodine as a periodontal pocket disinfectant
Authors: Hoang T. , Jorgensen M. G. , Keim R. G. , Pattison A. M. , Slots J. 
Published: September 2009

Objectives and background: Povidone‐iodine [polyvinylpyrrolidone‐iodine complex (PVP‐iodine)] might constitute a valuable adjunct to current periodontal therapy because of its broad‐spectrum antimicrobial activity, low potential for developing resistance and adverse reactions, wide availability, ease of use, and low financial cost. This investigation employed a randomized, split‐mouth study design to determine the microbiological and clinical effects of 10% PVP‐iodine subgingival irrigation in periodontitis lesions showing radiographic evidence of subgingival calculus.Methods: Sixteen adults having at least one periodontal pocket of 6 mm or more in each quadrant of the dentition and harboring one or more periodontopathic bacteria participated in the study. In each subject, a study site in each quadrant was randomly chosen to receive either subgingival irrigation with 10% PVP‐iodine together with scaling and root planing, scaling and root planing alone, subgingival irrigation with 10% PVP‐iodine, or subgingival irrigation with sterile saline. Prior to therapy and at 5 weeks post‐treatment, microbiological culture was carried out without knowledge of the clinical status or the type of treatment rendered. A blinded clinical examiner determined presence of dental plaque, probing pocket depth, and gingival bleeding on probing. Microbiological and clinical data were analyzed using a repeated measures analysis of variance and Kruskal–Wallis rank test with the Tukey and Mann–Whitney post hoc tests.Results: At 5 weeks post‐treatment, subgingival irrigation with PVP‐iodine together with scaling and root planing caused a 95% or greater reduction in total pathogen counts in 44% of pockets having ≥ 6 mm depth whereas scaling and root planing alone, povidone‐iodine irrigation alone and water irrigation alone caused 95% reduction of total pathogens only in 6–13% of similar study sites (P = 0.02). Reduction in mean pocket depth was 1.8 mm for the PVP‐iodine/scaling and root planing group, 1.6 mm for the scaling and root planing group, and 0.9 mm for the PVP‐iodine and the saline monotherapy groups, with statistical significance reached for the scaling and root planing group vs. the PVP‐iodine group (P = 0.04) and for the scaling and root planing group vs. the saline group (P = 0.02). Reduction in visible dental plaque, which ranged from 38% to 62%, showed no significant differences among treatment groups.Conclusions: The addition of subgingival PVP‐iodine irrigation to conventional mechanical therapy may be a cost‐effective means of reducing total counts of periodontal pathogens and helping control periodontal disease. However, subgingival irrigation with PVP‐iodine without concomitant mechanical debridement might not improve microbiological and clinical variables in comparison with saline irrigation, at least not in sites with radiographic evidence of subgingival calculus.
Interleukin‐1β, clinical parameters and matched cellular‐histopathologic changes of biopsied gingival tissue from periodontitis patients
Authors: Hou Lein‐Tuan , Liu Cheing‐Meei , Liu Bu‐Yuan , Lin Shih‐Jung , Liao Chia‐Shih , Rossomando Edward F. 
Published: September 2009

Objective:  The aim of the present study was to investigate whether interleukin (IL)‐1β in diseased tissues adjacent to periodontal pockets can reflect the degree of inflammation and destruction of these tissues pathologically.Background:  IL‐1β‐dependent mechanisms have been strongly implicated in contributing to inflammation and destruction of bone and attachment loss, which are characteristic features of periodontal disease. This biochemical mediator released during pro‐inflammatory processes has not been objectively integrated with clinical and histopathologic features of periodontal disease.Methods:  Periodontitis‐affected inflamed tissue and clinically nonaffected healthy gingivae were harvested from 14 periodontal patients, respectively. The severity of tissue inflammation was illustrated by clinical parameters and cellular histologic changes and quantified by histometric assessments. IL‐1β in these extracted specimens was measured with an enzyme‐linked immunosorbent assay (ELISA) technique. Pathogenic roles that IL‐1β plays in gingival inflammation and pathologic tissue changes in tissue sections were analyzed statistically.Results:  The overall total tissue IL‐1β, tissue concentration of IL‐1β, and percentage of inflammatory cell infiltration (PICI) determined from diseased gingivae were obviously higher than those of controls from both healthy sites of periodontitis and non‐periodontitis subjects. With increasing gingival index (GI), plaque index (PlI), and probing depth (PD), there was a marked elevation in total tissue IL‐1β. Total tissue IL‐1β was significantly correlated with GI, PlI, the PICI, and tissue alterations. Polymorphonuclear leukocytes (PMNs) and monocyte‐macrophage cells seemed to predominate in heavily infiltrated areas of diseased gingiva. These cell types were confirmed by immunocytochemical localization with either monoclonal mouse antihuman neutrophil elastase antibody or monoclonal mouse antihuman macrophage (CD68) antibody, respectively. Total tissue IL‐1β and the PICI were also elevated in diseased gingivae near deeper PD, while neither total IL‐1β nor tissue concentration was statistically correlated with PD. Thus, correlation analysis indicates that IL‐1β level in inflamed periodontal tissues correlates highly with clinical parameters (GI and PlI) and PICI (the degree of inflammation).Conclusions:  These observations suggest that IL‐1β plays a significant role in the pathogenic mechanisms of periodontal tissue destruction, and that measurement of tissue IL‐1β would be a valuable aid and useful for diagnostic markers of periodontal diseases.
A life course approach to women’s reproductive health
Authors: Rich-Edwards Janet , Morton Susan 
Published: September 2009

AbstractThis chapter explores the emerging evidence that adult reproductive function is shaped by intergenerational, in utero, and childhood factors, as well as adult environment. It opens with a discussion of early life factors that shape women's reproductive health, with a focus on determinants of pregnancy outcome. It then presents evidence that the gynecological and obstetric health status of young women reveals latent chronic disease processes.
A life course approach to musculoskeletal ageing: muscle strength, osteoporosis, and osteoarthritis
Authors: Bassey Joan , Sayer Avan Aihie , Cooper Cyrus , Cauley Jane 
Published: September 2009

AbstractThis chapter reviews the development and aging of three key components of the musculoskeletal system (muscle, bone, and cartilage), and considers their consequences for adult disease. Musculoskeletal disorders are an important cause of morbidity and functional impairment in the general population. They are strongly age-related, and tend to occur more frequently among women than men. For the three important causes of musculoskeletal disability(age-related declines in muscle strength; osteoporosis; and osteoarthritis) evidence now exists to suggest aetiological factors acting throughout the life course.