bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant radiotherapy for cutaneous melanoma
Authors: Mendenhall William M. , Amdur Robert J. , Grobmyer Stephen R. , George Thomas J. , Werning John W. , Hochwald Steven N. , Mendenhall Nancy P. 
Published: February 2008

AbstractThe purpose of the current study was to discuss the efficacy of adjuvant radiotherapy (RT) in the treatment of melanoma by reviewing the pertinent literature. The risk of locoregional recurrence after surgery alone for locally advanced melanoma is relatively high. The likelihood of a positive sentinel lymph node biopsy (SLNB) exceeds 20% for melanomas >2 mm thick and approximately ≥20% of those patients with positive SLNB will be found to have residual positive lymph nodes on completion lymph node dissection. Patients with positive regional lymph nodes have an approximately ≥20% risk of regional recurrence after surgery alone, particularly if multiple lymph nodes are involved and/or extracapsular extension is present. Postoperative adjuvant RT results in locoregional control rates of 85% to 90% or higher in high‐risk patients with a modest risk of complications. The impact of adjuvant RT on survival is likely minimal. Cancer 2008. © 2008 American Cancer Society.
Identification of molecular markers of bipolar cells in the murine retina
Authors: Kim Douglas S. , Ross Sarah E. , Trimarchi Jeffrey M. , Aach John , Greenberg Michael E. , Cepko Constance L. 
Published: February 2008

AbstractRetinal bipolar neurons serve as relay interneurons that connect rod and cone photoreceptor cells to amacrine and ganglion cells. They exhibit diverse morphologies essential for correct routing of photoreceptor cell signals to specific postsynaptic amacrine and ganglion cells. The development and physiology of these interneurons have not been completely defined molecularly. Despite previous identification of genes expressed in several bipolar cell subtypes, molecules that mark each bipolar cell type still await discovery. In this report, novel genetic markers of murine bipolar cells were found. Candidates were initially generated by using microarray analysis of single bipolar cells and mining of retinal serial analysis of gene expression (SAGE) data. These candidates were subsequently tested for expression in bipolar cells by RNA in situ hybridization. Ten new molecular markers were identified, five of which are highly enriched in their expression in bipolar cells within the adult retina. Double‐labeling experiments using probes for previously characterized subsets of bipolar cells were performed to identify the subtypes of bipolar cells that express the novel markers. Additionally, the expression of bipolar cell genes was analyzed in Bhlhb4 knockout retinas, in which rod bipolar cells degenerate postnatally, to delineate further the identity of bipolar cells in which novel markers are found. From the analysis of Bhlhb4 mutant retinas, cone bipolar cell gene expression appears to be relatively unaffected by the degeneration of rod bipolar cells. Identification of molecular markers for the various subtypes of bipolar cells will lead to greater insights into the development and function of these diverse interneurons. J. Comp. Neurol. 507:1795–1810, 2008. © 2008 Wiley‐Liss, Inc.
Distribution of the protein IMPACT, an inhibitor of GCN2, in the mouse, rat, and marmoset brain
Authors: Bittencourt Simone , Pereira Catia M. , Avedissian Marcelo , Delamano Arthur , Mello Luiz E. , Castilho Beatriz A. 
Published: February 2008

AbstractIMPACT is an inhibitor of GCN2, a kinase that phosphorylates the alpha subunit of the translation initiation factor 2 (eIF2α). GCN2 has been implicated in regulating feeding behavior and learning and memory in mice. IMPACT is highly abundant in the brain, suggesting its relevance in the control of GCN2 activation in the central nervous system. We describe here the distribution of IMPACT in the brain of rodents (mice and rats) and of a primate (marmoset) using highly specific antibodies raised against the mouse IMPACT protein. Neurons expressing high levels of IMPACT were found in most areas of the brain. In the hippocampal formation the lack of IMPACT in the dentate gyrus granule cells was striking. The hypothalamus is exceptionally rich in neurons expressing high levels of IMPACT, particularly in the suprachiasmatic nucleus. The only exception to this pattern was the ventromedial nucleus. The thalamic neurons are mostly devoid of IMPACT, with the exception of the paraventricular, reuniens and reticular nuclei, and intergeniculate leaf. The brainstem displayed high levels of IMPACT. For the marmoset, IMPACT expression in the brain is not as prominent when compared to other organs. In the marmoset brain the pattern of IMPACT expression was similar to rodents in most areas, except for the very strong labeling of the Purkinje cells, the lack of IMPACT‐positive neurons in the nucleus reuniens, and weak labeling of interneurons in the hippocampus. GCN1, the activator of GCN2 to which IMPACT binds, is widely distributed in all neuronal populations, and all IMPACT‐positive cells were also GCN1‐positive. The data presented herein suggest that IMPACT may be involved in biochemical homeostatic mechanisms that would prevent GCN2 activation and therefore ATF4 (CREB‐2) synthesis in neurons. J. Comp. Neurol. 507:1811–1830, 2008. © 2008 Wiley‐Liss, Inc.
Three‐dimensional free surface flow simulation of segregating dense suspensions
Authors: Ilinca F. , Hétu J.‐F. 
Published: February 2008

AbstractThis paper presents a 3D numerical solution algorithm for the simulation of free surface flows of dense suspensions including particle migration phenomena. Segregation of the solid phase in processes such as powder injection molding and molding of semi‐solid materials affects the rheology of the mixture and therefore the filling pattern. Segregation affects also the final properties and characteristics of such molded parts as a non‐uniform particles distribution leads to non‐uniform shrinkage, warpage and non‐uniform mechanical properties. In this paper, particle migration is modeled using the diffusion flux model of Phillips et al. (Phys. Fluids A 1992; 4:30–40) and is extended to address 3D mold filling problems. The solution algorithm is validated against flow problems for which experimental and numerical data are available: circular Couette flow, piston‐driven flow and sudden contraction–expansion flow. The particle migration model is then used to simulate mold filling problems in which the piston movement in the sleeve is known to induce particle migration before the material enters the cavity. An arbitrary Lagrangian–Eulerian (ALE) formulation is developed and combined to a level‐set front capturing method to simulate the piston movement and the evolution of the free surface in molding simulations. The ALE formulation is first compared with an Eulerian solution for the case of the piston‐driven flow problem. The approach is then applied to injection molding problems to study the evolution of particle distributions during molding and in the final molded parts. Copyright © 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Reactive polyurethane carbon nanotube foams and their interactions with osteoblasts
Authors: Verdejo Raquel , Jell Gavin , Safinia Laleh , Bismarck Alexander , Stevens Molly M. , Shaffer Milo S.P. 
Published: February 2008

AbstractThe remarkable intrinsic properties of carbon nanotubes, including their high mechanical strength, electrical conductivity, and nanoscale 3D architecture, create promising opportunities for the use of nanotube composites in a number of fields, particularly for composites in which conventional fillers cannot be accommodated. In the current study, 3D polyurethane (PU) nanocomposite foams were developed, and their potential biomedical applications were investigated. Multiwalled carbon nanotubes (CNTs) were synthesized by chemical vapor deposition and, following suitable chemical modification, uniformly distributed within the walls of PU foams produced by direct reaction. Although the loading fraction was too low to observe significant mechanical effects, CNT incorporation improved the wettability of the nanocomposite surfaces in a concentration‐dependent manner, supporting the claim that the nanotubes are active at the pore surface. Studies of bone cell interactions with the nanocomposite foams revealed that increasing CNT loading fraction did not cause osteoblast cytotoxicity nor have any detrimental effects on osteoblast differentiation or mineralization. The application of “fixed” or embedded CNTs in nondegradable scaffolds is likely advantageous over “loose” or unattached CNTs from a toxicological point of view. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Effects of bone morphogenetic protein on neonatal rat calvarial osteoblast‐like cells: An in vitro study
Authors: Aybar Buket , Emes Yusuf , Atalay Belir , Vural Pervin , Kaya A. Selhan , Eren Selame N. , İşsever Halim , Bilir Ayhan 
Published: February 2008

AbstractBone morphogenetic proteins (BMPs) are factors that promote osteoblastic differentiation and osteogenesis. The aim of this study was to examine the behavior of neonatal rat calvarial osteoblast cells cultured on different concentrations of BMP graft materials. Fifty thousand cells per milliliter were seeded and cultured on graft materials for 24 and 48 h. Different concentrations of BMPs (combination of BMPs numbered from 1 to 14) were supplemented to the medium. To evaluate cellular proliferation and differentiation, specimens were examined for DNA synthesis, alkaline phosphatase (ALP) activity, cell numbers, and viability of the cells. Further, transforming growth factor‐β1 (TGF‐β1) and lactate dehydrogenase (LDH) levels were investigated. Morphological appearance of the specimens at 24 and 48 h of incubation was evaluated using scanning electron microcopy. Evaluations of DNA synthesis, cell count, and cell viability data revealed that a significant difference existed at 24 and 48 h (p < 0.05). The TGF‐β1 and ALP analysis showed only a significant difference between the groups at the end of 24 h (p < 0.05). Regarding the lactate dehydrogenase activity there was not any significant difference at 24 and 48 h (p > 0.05). No morphological differences were observed in cell morphology on BMP graft material and the control group. These results indicate that BMPs have an inductive effect on osteoblast differentiation and a possible inhibitory effect in the early phases of cell proliferation. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice
Authors: Uluçkan Özge , Eagleton Mark C. , Floyd Desiree H. , Morgan Elizabeth A. , Hirbe Angela C. , Kramer Matthew , Dowland Nikki , Prior Julie L. , Piwnica‐Worms David , Jeong Soon Seog , Chen Ridong , Weilbaecher Katherine 
Published: February 2008

AbstractPlatelets contribute to the development of metastasis, the most common cause of mortality in cancer patients, but the precise role that anti‐platelet drugs play in cancer treatment is not defined. Metastatic tumor cells can produce platelet αIIbβ3 activators, such as ADP and thromboxane A2 (TXA2). Inhibitors of platelet β3 integrins decrease bone metastases in mice but are associated with significant bleeding. We examined the role of a novel soluble apyrase/ADPase, APT102, and an inhibitor of TXA2 synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of experimental bone metastases. We found that treatment with ASA and APT102 in combination (ASA + APT102), but not either drug alone, significantly decreased breast cancer and melanoma bone metastases in mice with fewer bleeding complications than observed with αIIbβ3 inhibition. ASA + APT102 diminished tumor cell induced platelet aggregation but did not directly alter tumor cell viability. Notably, APT102 + ASA treatment did not affect initial tumor cell distribution and similar results were observed in β3−/− mice. These results show that treatment with ASA + APT102 decreases bone metastases without significant bleeding complications. Anti‐platelet drugs such as ASA + APT102 could be valuable experimental tools for studying the role of platelet activation in metastasis as well as a therapeutic option for the prevention of bone metastases. J. Cell. Biochem. 104: 1311–1323, 2008. © 2008 Wiley‐Liss, Inc.
Cold‐triggered/heat‐destroyed emulsions composed of phospholipids and triacylglycerols as thermal history indicators for cold‐chain distribution systems
Authors: Nagata Kohdai , Mizoguchi Tatsuya , Kitsunai Makoto , Hirose Kumi , Hirasawa Akira , Chiba Kazuhiro 
Published: February 2008

AbstractBACKGROUND: Recently, cold‐chain distribution systems have come to play important roles in worldwide food processing/storage/transportation networks. To ensure the maintenance of the quality and safety of foods, it is necessary to develop thermal history indicators for products involved in cold‐chain distribution systems. To provide a record of the occurrence of a high‐temperature event during a cold‐chain system, a temperature‐related phase change in a material within the indicator is needed to indicate that the high‐temperature event occurred. Preferentially, for safety, the materials of the indicators should be edible and easy to handle. It should be possible to store the indicators at ambient temperature before use, and they should be triggered automatically just by cooling at the start of a cold‐chain system. Furthermore, if the indicator is heated even once during the cold‐chain distribution system, its appearance must be irreversibly altered to provide evidence of the high‐temperature experience.RESULTS: Based on the edible materials composed of lyso‐lecithin (15 g), lecithin (2 g), triacylglycerol (150 g), and water, we successfully constructed a stable emulsion that could be triggered just by cooling to 4 °C or lower for more than 12 h. After triggering, it was immediately destroyed by heating up to 20 °C or higher. Furthermore, the mechanism of cold‐triggering and heat‐destruction has been studied by nuclear magnetic resonance.CONCLUSION: The cold‐triggered/heat‐destroyed emulsion should be applied as a new thermal history indicator that can be automatically triggered just by cooling down and irreversibly change its appearance after a high‐temperature experience in cold‐chain distribution systems. Copyright © 2008 Society of Chemical Industry
Endotoxemia does not limit energy supply in exercising rat skeletal muscle
Authors: Giannesini Benoit , Izquierdo Marguerite , Dalmasso Christiane , Fur Yann Le , Cozzone Patrick J. , Verleye Marc , Guern Marie‐Emmanuelle Le , Gillardin Jean‐Marie , Bendahan David 
Published: February 2008

AbstractAlthough depletion in high‐energy phosphorylated compounds and mitochondrial impairment have been reported in septic skeletal muscle at rest, their impact on energy metabolism has not been documented during exercise. In this study we aimed to investigate strictly gastrocnemius muscle function non‐invasively, using magnetic resonance techniques in endotoxemic rats. Endotoxemia was induced by injecting animals intraperitoneally at t0 and t0 + 24 h with Klebsiella pneumoniae lipopolysaccharides (at 3 mg kg−1). Investigations were performed at t0 + 48 h during a transcutaneous electrical stimulation protocol consisting of 5.7 min of repeated isometric contractions at a frequency of 3.3 HZ. Endotoxin treatment produced a depletion in basal phosphocreatine content and a pronounced reduction in oxidative adenosine triphosphate (ATP) synthesis capacity, whereas the resting ATP concentration remained unchanged. During the stimulation period, endotoxemia caused a decrease in force‐generating capacity that was fully accounted for by the loss of muscle mass. It further induced an acceleration of glycolytic ATP production and an increased accumulation of adenosine diphosphate (ADP, an important mitochondrial regulator) that allowed a near‐normal rate of oxidative ATP synthesis. Finally, endotoxemia did not affect the total rate of ATP production or the ATP cost of contraction throughout the whole stimulation period. These data demonstrate that, in an acute septic phase, metabolic alterations in resting muscle do not impact energy supply in exercising muscle, likely as a result of adaptive mechanisms. Muscle Nerve, 2008
A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra‐tumoral genetic heterogeneity and new genetic changes on recurrence
Authors: Jones AM , Mitter R , Springall R , Graham T , Winter E , Gillett C , Hanby AM , Tomlinson IPM , Sawyer EJ 
Published: February 2008

AbstractThe aims of this study were to identify genetic changes associated with malignant progression of the fibroepithelial neoplasms, phyllodes tumours of the breast (PTs), and to ascertain whether genetic progression occurs when PTs recur locally. A further aim was to assess whether the genetic data support the classification of these tumours into three subtypes, benign, borderline and malignant. 126 PTs (37 benign, 41 borderline, 48 malignant) were analysed by either array‐CGH or the Illumina Goldengate assay. The large‐scale genetic changes associated with malignant/borderline phenotypes were + 1q, + 5p, + 7, + 8, − 6, − 9p, − 10p and − 13. Cluster analysis of the array‐CGH data supported the division of malignant and borderline PTs into two separate groups, one comprising almost all malignant lesions and the other, benign and borderline tumours. Interstitial deletions of 9p21 that involved the p16INK4a locus were present in many malignant/borderline PTs, and some of these appeared to cause homozygous loss. Loss of expression of p16INK4a was found frequently and this was associated with 9p deletion; we also identified one p16INK4a mutation and evidence of methylation of p16INK4a in malignant PTs. Our evidence shows that inactivation of this gene is important in the development of malignant PTs. In selected PTs, multiple areas of stroma were isolated and analysed separately by array‐CGH. We found considerable intra‐tumoral genetic heterogeneity. Analysis of paired primary and recurrent tumours showed that recurrent tumours often acquired new genetic changes; in particular, benign tumours tended to acquire changes characteristic of the malignant/borderline phenotype. We believe it likely that unfavourable sub‐clones not easily identified by histology account for the unpredictable clinical behaviour of these tumours. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The RNA‐binding and adaptor protein Sam68 modulates signal‐dependent splicing and transcriptional activity of the androgen receptor
Authors: Rajan P , Gaughan L , Dalgliesh C , El‐Sherif A , Robson CN , Leung HY , Elliott DJ 
Published: February 2008

AbstractThe RNA‐binding protein Sam68 has been reported to be up‐regulated in clinical cases of prostate cancer (PCa), where it is thought to contribute to cell proliferation and survival. Consistent with this, we observed over‐expression of Sam68 in a panel of clinical prostate tumours as compared with benign controls. Since Sam68 is implicated in a number of signalling pathways, we reasoned that its role in PCa may involve modulation of the androgen receptor (AR) signalling cascade, which drives the onset and progression of PCa. We found that Sam68 interacts with the AR in vivo in LNCaP cells, and is dynamically recruited to androgen response elements within the promoter region of the prostate‐specific antigen (PSA) gene. Based on its known functions and nuclear location, Sam68 might either: (a) co‐regulate AR‐dependent transcription positively or negatively; or (b) modulate AR‐dependent alternative splicing by enhancing incorporation of a Sam68‐responsive exon transcribed under the control of an androgen‐responsive promoter. We tested these possibilities using functional assays. Both wild‐type Sam68 protein and the Sam68V229F mutant, which is impaired in RNA binding, functioned as a ligand‐dependent AR co‐activator on an androgen‐regulated reporter gene. In contrast, splicing of a Sam68‐responsive variable exon, transcribed under control of an androgen‐responsive promoter, was strongly repressed in the presence of AR and androgens. This splicing inhibition was reversed by ectopic expression of Sam68 but enhanced by Sam68V229F. These results demonstrate that Sam68 has separable effects on AR‐regulated transcriptional activity and alternative splicing, both of which may affect PCa phenotypes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Functional and phenotypic characteristics of testicular macrophages in experimental autoimmune orchitis
Authors: Rival C , Theas MS , Suescun MO , Jacobo P , Guazzone V , van Rooijen N , Lustig L 
Published: February 2008

AbstractTesticular inflammation with compromised fertility can occur despite the fact that the testis is considered an immunoprivileged organ. Testicular macrophages have been described as cells with an immunosuppressor profile, thus contributing to the immunoprivilege of the testis. Experimental autoimmune orchitis (EAO) is a model of organ‐specific autoimmunity and testicular inflammation. EAO is characterized by an interstitial inflammatory mononuclear cell infiltration, damage of the seminiferous tubules and germ cell apoptosis. Here we studied the phenotype and functions of testicular macrophages during the development of EAO. By stereological analysis, we detected an increased number of resident (ED2+) and non‐resident (ED1+) macrophages in the testicular interstitium of rats with orchitis. We showed that this increase was mainly due to monocyte recruitment. The in vivo administration of liposomes containing clodronate in rats undergoing EAO led to a reduction in the number of testicular macrophages, which correlated with a decreased incidence and severity of the testicular damage and suggests a pathogenic role of macrophages in EAO. By immunohistochemistry and flow cytometry we detected an increased number of testicular macrophages expressing MHC class II, CD80 and CD86 costimulatory molecules in rats with orchitis. Also, testicular macrophages from rats with EAO showed a higher production of IFNγ (ELISA). We conclude that testicular macrophages participate in EAO development, and the ED1+ macrophage subset is the main pathogenic subpopulation. They stimulate the immune response through the production of pro‐inflammatory cytokines and antigen presentation and thus activation of T cells in the target organ. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.