bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating monocytes have the capacity to be transdifferentiated into keratinocyte‐like cells
Authors: Medina Abelardo , Brown Erin , Carr Nicholas , Ghahary Aziz 
Published: March 2009

ABSTRACTTransdifferentiation is a process in which the original commitment of a cell is changed to give rise to unexpected peripheral mature cells. Our previous report showed that circulating stem cells can generate keratinocyte‐like cells (KLCs). However, it remains to be determined whether or not other peripheral blood mononuclear cells (PBMC) subsets have the potential to follow the same cell fate. In this study, the cell transdifferentiation of circulating CD14+ monocytes into KLCs and their regulatory effect on matrix metalloproteinase‐1 (MMP‐1) expression in dermal fibroblasts were evaluated. The results showed that monocytes isolated from peripheral blood mononuclear cells have the capacity to generate KLCs. These transdifferentiated cells exhibited, along with a keratinocyte‐like morphology, a characteristic profile consisting in stratifin+, cytokeratins+ (types I and II), CD14low, and involucrin+ on day 21 in culture. Similar to keratinocyte‐conditioned media, KLC‐derived conditioned media were able to induce an increase in the MMP‐1 expression in dermal fibroblasts. This effect was significantly reduced by using 14‐3‐3 protein‐depleted KLC‐conditioned media. Our findings show the potential transdifferentiation of circulating CD14+ monocytes into KLCs and their regulatory effect on MMP‐1 expression in dermal fibroblasts.
Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis
Authors: Timmers Michael S. , Graafland Niels , Bernards Alexandra T. , Nelissen Rob G. H. H. , Van Dissel Jaap T. , Jukema Gerrolt N. 
Published: March 2009

ABSTRACTIn a retrospective, case–control cohort study an assessment was made of the clinical outcome of patients with osteomyelitis treated with a new modality of negative pressure wound therapy, so called negative pressure instillation therapy. In this approach, after surgical debridement, a site of osteomyelitis is treated with negative pressure of at least 300 mmHg applied through polyvinyl alcohol dressing. The polyvinyl alcohol foam is irrigated through the tubes three times a day with a polyhexanide antiseptic solution. In 30 patients (14 males; mean age 52 [range, 26–81]) admitted between 1999 and 2003 with osteomyelitis of the pelvis or lower extremity, we assessed time to wound closure, number of surgical procedures and rate of recurrence of infection as well as need for rehospitalizations. For comparison, a control group of 94 patients (males, 58; mean age 47 [range, 9–85]), matched for site and severity of osteomyelitis, was identified in hospital records between 1982 and 2002. These patients underwent standard surgical debridement, implantation of gentamicin polymethylmethacrylate beads and long‐term intravenous antibiotics. In the Instillation group the rate of recurrence of infection was 3/30 (10%), whereas 55/93 (58.5%) of the controls had a recurrence (p<0.0001). Moreover, in those treated with instillation the total duration of hospital stay was shorter and number of surgical procedures smaller as compared with the controls (all p<0.0001). We conclude that in posttraumatic osteomyelitis negative pressure instillation therapy reduces the need for repeated surgical interventions in comparison with the present standard approach.
Effects of negative pressure wound therapy on cellular energetics in fibroblasts grown in a provisional wound (fibrin) matrix
Authors: McNulty Amy K. , Schmidt Marisa , Feeley Teri , Villanueva Patricia , Kieswetter Kris 
Published: March 2009

ABSTRACTNegative pressure wound therapy (NPWT) using reticulated open cell foam dressing (ROCF) is effective for treatment of recalcitrant wounds; however, the effects of this therapy on cellular metabolism remain to be elucidated. The effect of two different subatmospheric pressure applications on the cell energetics of human fibroblasts grown in a 3D fibrin matrix was studied using two different pressure‐manifolding materials, an ROCF or gauze under suction (GUS). It was found that levels of cytochrome c oxidase, energy charge, and adenosine triphosphate/adenosine diphosphate were significantly increased following the application of NPWT using ROCF vs. GUS (p<0.05). Increases in these parameters likely reflect an improved energetic status. In addition, levels of transforming growth factor‐β and platelet‐derived growth factor (α and β isoforms) were significantly increased (80 and 53%, respectively; p<0.05) over static control cultures following treatment with NPWT using ROCF but not following GUS. These growth factors are known to be important during wound healing. Clearly, both the material used as the dressing to manifold the subatmospheric pressure and the pressure used have a dramatic effect on cellular response.
The spatio‐temporal dynamics of ligament healing
Authors: Chamberlain Connie S. , Crowley Erin , Vanderby Ray 
Published: March 2009

ABSTRACTLigament injury commonly occurs with no effective treatment to restore its original state. Numerous studies have examined wound healing after injury, reporting a provisional matrix and scar formation within the wound. Few studies however report the inflammatory, proliferative, and remodeling process during ligament healing in a spatio‐temporal manner. Our goal was then to more completely elucidate this process in a rat medial collateral ligament (MCL) healing model. In this study, medial collateral ligaments were surgically transected and allowed to heal. At 1, 3, 5, 7, 9, 11, 14, and 28 days postinjury ligaments were collected and examined with microangiography or immunohistochemistry. We demonstrate that neutrophils and mitotic cells peak between 1 and 5 days postinjury. The majority of factors crest between 5 and 9 days postinjury, including circulating macrophages, resident macrophages, T lymphocytes, hematopoietic cells, vascular endothelial growth factor, and blood vessels. The apoptotic cells predominate from day 9 to the end of the study (day 28). Initially, most assayed markers localize to the epiligament and to granulation tissue at the site of damage. Later, the healing region with its granulation tissue and cells continues to expand into the uninjured tissue. From these results, we have expanded current descriptions of ligament healing and offer a more complete representation of the healing process.
Real Options, Product Market Competition, and Asset Returns
Authors: AGUERREVERE FELIPE L. 
Published: March 2009

ABSTRACTWe study how competition in the product market affects the link between firms' real investment decisions and their asset return dynamics. In our model, assets in place and growth options have different sensitivities to market wide uncertainty. The strategic behavior of market participants influences the relative importance of these components of firm value. We show that the relationship between the degree of competition and assets' expected rates of return varies with product market demand. When demand is low, firms in more competitive industries earn higher returns, whereas when demand is high firms in more concentrated industries earn higher returns.
Income Risk and Portfolio Choice: An Empirical Study
Authors: ANGERER XIAOHONG , LAM POK‐SANG 
Published: March 2009

ABSTRACTThis paper investigates the relationship between portfolio choice and labor income risk in the National Longitudinal Survey of Youth 1979 Cohort. Permanent income risk (variability of shocks to income that have permanent effect) significantly reduces the share of risky assets in the household's portfolio, while transitory income risk (variability of shocks with no lasting effect) does not. This result provides strong evidence that households' portfolio choices respond to labor income risks in a manner consistent with economic theory.
Long‐Term Clinical Follow‐up after Sirolimus‐Eluting Stent versus Bare Metal Stent Implantation in Patients with Acute Coronary Syndrome
Authors: OGITA MANABU , NAKAMURA TOMOHIRO , FUJIWARA NAOKI , SAKAKURA KENICHI , FUNAYAMA HIROSHI , SUGAWARA YOSHITAKA , KUBO NORIFUMI , AKO JUNYA , MOMOMURA SHINICHI 
Published: March 2009

Background and Objective: Drug‐eluting stents have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) compared with bare metal stents (BMSs); however, the long‐term efficacy of sirolimus‐eluting stent (SES) implantation in patients with acute coronary syndrome (ACS) has not been well established. We have investigated the long‐term clinical outcome of SES in patients with ACS.
Methods: Consecutive 245 patients with ACS treated by primary stenting within 24 hours after onset were enrolled. There were 128 patients treated with SES and 117 patients were treated with BMS. We evaluated the incidence of major cardiac events (MACE; total death, nonfatal myocardial infarction, TVR) at 3 years, comparing with 8‐month clinical outcome.
Results: Eight‐month clinical follow‐up shows a significantly lower incidence of TVR in the SES group, 3.1% in the SES group versus 9.4% in the BMS group (P = 0.04). At 3‐year clinical follow‐up, there was no significant difference in the rate of TVR between the two groups, 8.4% versus 12.4% (P = 0.37). Cumulative incidence of total MACE was 9.2% in the SES group compared with 15.9% in the BMS group (P = 0.18). Only one case of stent thrombosis was observed in the SES (late thrombosis), while two cases of stent thrombosis occurred in the BMS group (late and very late thrombosis; P = 0.55).
Conclusion: SES implantation in patients with ACS is associated with favorable long‐term clinical outcome with no excess of late stent thrombosis. Further long‐term clinical follow‐up will be warranted to confirm the safety and efficacy of SES.
Drug Delivery at the Aortic Valve Tissues of Healthy Domestic Pigs with a Paclitaxel‐Eluting Valvuloplasty Balloon
Authors: SPARGIAS KONSTANTINOS , MILEWSKI KRZYSTOF , DEBINSKI MARCIN , BUSZMAN PIOTR P , COKKINOS DENNIS V , POGGE REMBERT , BUSZMAN PAWEL 
Published: March 2009

Background: Restenosis occurs invariably within 1 year following balloon valvulopasty in aortic valve stenosis. The mechanism of restenosis seems to involve a dynamic cellular component that could be a target for drug inhibition. We investigated the feasibility of local drug delivery at the aortic valve tissues of healthy pigs with a paclitaxel‐eluting balloon.
Methods: Aortic valvuloplasty was performed in eight anesthetized domestic pigs using paclitaxel‐eluting balloons (3 μg/mm2 balloon surface area). They were assigned to two or four times 15‐second balloon inflations and were sacrificed 30 minutes after final balloon inflation.
Results: The aortic annulus to balloon diameter ratio was 1.15 ± 0.07. The mean paclitaxel concentration in the aortic valve leaflets was 0.91 ± 1.36 μg/mL (0.34 ± 0.05 μg/mL in the two‐inflation group, 1.48 ± 1.86 μg/mL in the four‐inflation group, P = 0.23). The percentage of the total paclitaxel dose recovered in the aortic valve leaflets was 18 ± 11−6% (13 ± 6−6% and 25 ± 14−6% in the two‐ and four‐inflation group, P = 0.16).
Conclusion: Local drug delivery at the aortic valve leaflets of healthy pigs with a paclitaxel‐eluting balloon is feasible and concentrations within the therapeutic window are detected 30 minutes after the procedure. The antirestenotic potential of this treatment should be studied.
Modulation of suicidal erythrocyte cation channels by an AMPA antagonist
Authors: Föller Michael , Mahmud Hasan , Gu Shuchen , Kucherenko Yuliya , Gehring Eva‐Maria , Shumilina Ekaterina , Floride Elisa , Sprengel Rolf , Lang Florian 
Published: March 2009

AbstractIn neurons alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors are heteromeric cation channels composed of different sub‐units, including GluA1‐GluA4. When expressed without GluA2, AMPA receptors function as Ca2+‐permeable cation channels. In erythrocytes, activation of Ca2+‐permeable cation channels triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with subsequent exposure of phosphatidylserine at the cell surface. Activators of the channels and thus eryptosis include removal of extracellular Cl− (replaced by gluconate) and energy depletion (removal of glucose). The present study explored whether GluA1 is expressed in human erythrocytes and whether pharmacological AMPA receptor inhibition modifies Ca2+ entry and suicidal death of human erythrocytes. GluA1 protein abundance was determined by confocal microscopy, phosphatidylserine exposure was estimated from annexin V binding, cell volume from forward scatter in FACS analysis, cytosolic Ca2+ concentration from Fluo3 fluorescence and channel activity by whole‐cell patch‐clamp recordings. As a result, GluA1 is indeed expressed in the erythrocyte cell membrane. The AMPA receptor antagonist NBQX (1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxo‐benzo[f]quinoxaline‐7‐sulfonamide) inhibited the cation channels following Cl− removal and the eryptosis following Cl− removal or energy depletion. The present study reveals a novel action of AMPA receptor antagonists and raises the possibility that GluA1 or a pharmacologically related protein participates in the regulation of Ca2+ entry into and suicidal death of human erythrocytes.
Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells
Authors: Preynat‐Seauve Olivier , de Rham Casimir , Tirefort Diderik , Ferrari‐Lacraz Sylvie , Krause Karl‐Heinz , Villard Jean 
Published: March 2009

AbstractNeural progenitor cells (NPC) of foetal origin or derived from human embryonic stem cells (HESC) have the potential to differentiate into mature neurons after transplantation into the central nervous system, opening the possibility of cell therapy for neurodegenerative disorders. In most cases, the transplanted NPC are genetically unrelated to the recipient, leading to potential rejection of the transplanted cells. Very few data provide reliable information as to the potential immune response of allogeneic neural progenitors derived from HESC. In this study, we analyzed in vitro the allogeneic immune response of T lymphocytes and natural killer (NK) cells to NPC derived from HESC or of foetal origin. We demonstrate that NPC induce T‐cell stimulation and a strong NK cytotoxic response. NK‐cell activity is unrelated to MHC‐I expression but driven by the activating NKG2D receptor. Cyclosporine and dexamethasone previously used in clinical studies with foetal NPC did not only fail to prevent NK alloreactivity but strongly inhibited the terminal maturation from NPC into mature neurons. We conclude that allogenic transplantation of NPC in the central nervous system will most likely require an immunosuppressive regimen targeting allogenic T and NK cells, whereas possible interference with the differentiation of NPC needs to be carefully evaluated.
Topical application of green and white tea extracts provides protection from solar‐simulated ultraviolet light in human skin
Authors: Camouse Melissa M. , Domingo Diana Santo , Swain Freddie R. , Conrad Edward P. , Matsui Mary S. , Maes Daniel , Declercq Lieve , Cooper Kevin D. , Stevens Seth R. , Baron Elma D. 
Published: March 2009

Background:  Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties.Aims:  We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation‐induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis.Methods:  Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene.Results:  Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1. There was no significant difference in the levels of protection afforded by the two agents. Hence, both green tea and white tea are potential photoprotective agents that may be used in conjunction with established methods of sun protection.
Putative signaling action of amelogenin utilizes the Wnt/β‐catenin pathway
Authors: Matsuzawa M. , Sheu T.‐J. , Lee Y.‐J. , Chen M. , Li T.‐F. , Huang C. T. , Holz J. D. , Puzas J. E. 
Published: March 2009

Background and Objective:  While it has long been known that amelogenin is essential for the proper development of enamel, its role has generally been seen as structural in nature. However, our new data implicate this protein in the regulation of cell signaling pathways in periodontal ligament cells and osteoblasts. In this article we report the successful purification of a recombinant mouse amelogenin protein and demonstrate that it has signaling activity in isolated mouse calvarial cells and human periodontal ligament cells.Material and Methods:  To determine the regulatory function of canonical Wnt signaling by amelogenin, we used TOPGAL transgenic mice. These mice express a β‐galactosidase transgene under the control of a LEF/TCF and β‐catenin‐inducible promoter. To investigate in greater detail the molecular mechanisms involved in the β‐catenin signaling pathway, isolated osteoblasts and periodontal ligament cells were exposed to full‐length recombinant mouse amelogenin and were evaluated for phenotypic changes and β‐catenin signaling using a TOPFLASH construct and the LacZ reporter gene.Results:  In these in vitro models, we showed that amelogenin can activate β‐catenin signaling.Conclusion:  Using the TOPGAL transgenic mouse we showed that amelogenin expression in vivo is localized mainly around the root, the periodontal ligament and the alveolar bone.
The effect of Porphyromonas gingivalis infection on cytokine levels in type 2 diabetic mice
Authors: Nishihara R. , Sugano N. , Takano M. , Shimada T. , Tanaka H. , Oka S. , Ito K. 
Published: March 2009

Background and Objective:  Several studies have shown that diabetes mellitus increases the severity of periodontitis. Conversely, periodontitis has been shown to have an impact on diabetes, although the underlying mechanisms of this are unclear. The aim of this study was to compare the inflammatory response to Porphyromonas gingivalis infection in normal and diabetic mice.Material and Methods:  Porphyromonas gingivalis were inoculated adjacent to the periosteum, at a point on the midline of the skull located between the ears, in C57BL/6 (normal) and KKAy (diabetic) mice. After induction, the levels of tumor necrosis factor‐α, interleukin‐6 and adiponectin in the mice were measured using real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay.Results:  The KKAy mice showed significant increases in blood glucose, serum tumor necrosis factor‐α and interleukin‐6 levels after inoculation with Porphyromonas gingivalis, and a significant decrease in adiponectin to 35.7%. Similar results were observed at the mRNA level in liver and visceral adipose tissue.Conclusion:  These observations suggest that tumor necrosis factor‐α, interleukin‐6 and adiponectin are an integral part of the link between diabetes mellitus and Porphyromonas gingivalis infection.
The use of live‐animal micro‐computed tomography to determine the effect of a novel phospholipase A2 inhibitor on alveolar bone loss in an in vivo mouse model of periodontitis
Authors: Cantley M. D. , Bartold P. M. , Marino V. , Reid R. C. , Fairlie D. P. , Wyszynski R. N. , Zilm P. S. , Haynes D. R. 
Published: March 2009

Background and Objective:  Live‐animal micro‐computed tomography is a new and promising technique that can be used to quantify changes in bone volume for periodontal disease models. The major aim of this study was to develop the methodology of live‐animal micro‐computed tomography and to determine the effect of a novel secretory phospholipase A2 inhibitor on alveolar bone loss.Material and Methods:  Periodontitis was induced in mice by oral infection with Porphyromonas gingivalis over a period of 13 wk, and live‐animal micro‐computed tomography scans were taken at different time‐points to determine bone volume changes with disease progression. This enabled conclusions to be made as to when treatment was most likely to be effective. In addition, the model was used to investigate a novel drug, the secretory phospholipase A2 inhibitor, KHO64, and its potential ability to inhibit osteoclast bone resorption and treat periodontitis.Results:  The results from live‐animal micro‐computed tomography scans revealed greater, statistically significant, bone volume loss in diseased mice compared with normal mice (p < 0.05). This corresponded to a larger area from the cemento–enamel junction to the alveolar bone crest, as assessed by stereo imaging (p < 0.001). These techniques can therefore detect and quantify alveolar bone loss. Both methods revealed that KHO64 had no significant effect on the volume of bone resorption.Conclusion:  Live‐animal micro‐computed tomography is a robust, reproducible technique that clearly demonstrates significant time‐dependent changes in alveolar bone volume in a small‐animal model of periodontitis.
Porphyromonas gingivalis fimbriae‐dependent interleukin‐6 autocrine regulation by increase of gp130 in endothelial cells
Authors: Ho Y‐S. , Lai M‐T. , Liu S‐J. , Lin C‐T. , Naruishi K. , Takashiba S. , Chou H‐H. 
Published: March 2009

Background and Objective:  Local persistent infection by Porphyromonas gingivalis leads to inflammatory systemic diseases, such as atherosclerosis. We have reported previously that avirulent P. gingivalis fimbriae‐dependent invasion into endothelial cells might be involved in progression of atherosclerosis. Although interleukin‐6 (IL‐6) regulates progression of atherosclerosis, little is known about the relationship of P. gingivalis fimbriae‐dependent invasion to IL‐6 regulation in endothelial cells.Material and Methods:  We examined the secretion of IL‐6 and the expression of the IL‐6 signal transducer gp130 in human umbilical vein endothelial cells (HUVEC) infected with the wild‐type FDC381 strain of P. gingivalisand a fimbriae‐deficient mutant (fimA) by enzyme‐linked immunosorbent assay, quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and flow cytometry (fluorescence‐activated cell sorting, FACS) analysis.Results:  Coculture of HUVEC with P. gingivalis resulted in increase of IL‐6 secretion at 24 h postinfection. Interestingly, the increase was inhibited significantly in HUVEC infected with the P. gingivalis fimA mutant. In addition, the increase of IL‐6 secretion induced by P. gingivalis infection was significantly impaired by the meiosis specific kinase 1 inhibitor, PD98059, or the nuclear factor κB inhibitor, Bay11‐7082. Furthermore, we demonstrated that gp130 expression increased with P. gingivalis infection. Importantly, gp130 expression was significantly impaired by P gingivalis fimA mutant infection compared with wild‐type P. gingivalis infection, as assessed by both quantitative RT‐PCR and FACS analysis.Conclusion:  Our findings indicate that P. gingivalis fimbriae are important factors in the autocrine regulation of IL‐6, by increasing gp130 in endothelial cells.