bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions
Authors: Comeau Wendy , Gibb Robbin , Hastings Erica , Cioe Jan , Kolb Bryan
Published: February 2008

We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90‐day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion‐induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 134–146, 2008.
Physiological responses to social and physical challenges in children: Quantifying mechanisms supporting social engagement and mobilization behaviors
Authors: Heilman Keri J. , Bal Elgiz , Bazhenova Olga V. , Sorokin Yevgeniya , Perlman Susan B. , Hanley Mary C. , Porges Stephen W.
Published: February 2008

Physiological response patterns to laboratory‐based social and physical challenges were investigated in 37 typically‐developing 3‐ to 5‐year‐old children. The study was conducted to determine whether the response profiles during each challenge were similar and whether individual differences in the response profiles to the challenges were correlated. Results demonstrated challenge specific physiological response strategies. In response to the social challenge, respiratory sinus arrhythmia and heart period increased and motor activity decreased. In contrast, in response to the physical challenge, respiratory sinus arrhythmia and heart period decreased and motor activity increased. Neither challenge reliably elicited changes in salivary cortisol. Only heart period responses were correlated between the challenges. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 171–182, 2008.
Understanding language and cognitive deficits in very low birth weight children
Authors: Ortiz‐Mantilla Silvia , Choudhury Naseem , Leevers Hilary , Benasich April A.
Published: February 2008

Very‐low‐birth‐weight infants are at much higher risk for cognitive and language delays but the nature of such deficits is not clearly understood. Given increasing rates of prematurity and infants born very‐low‐birth‐weight, examination of mechanisms that underlie poorer developmental outcome is essential. We investigated language and cognitive abilities in very‐low and normal birth‐weight infants to determine whether performance differences were due to poorer global cognitive performance or to deficits in specific processing abilities. Thirty‐two very‐low and 32 normal birth‐weight infants received visual and auditory‐visual habituation recognition‐memory tasks, and standardized language and cognitive assessments. Very‐low‐birth‐weight infants performed more poorly on visual and auditory‐visual habituation tasks and scored lower than controls on cognitive and language measures. These findings suggest that differences in language abilities in very‐low‐birth‐weight children may be part of a global deficit that impacts many areas of cognitive functioning rather than a specific impairment in rapid auditory processing. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 107–126, 2008.
Adrenocortical and behavioral attunement in parents with 1‐year‐old infants
Authors: van Bakel Hedwig J. A. , Riksen‐Walraven J. Marianne
Published: February 2008

Sethre‐Hofstad et al. [2002, Psychoneuroendocrinology 27:731–747] found that behaviorally well‐attuned or sensitive parents showed better physiological attunement with their 2‐ to 4‐year‐old toddlers' adrenocortical responses to a potentially challenging task than less sensitive parents. In the present study we aimed to replicate this finding in a sample of 83 parents with 15‐month‐old infants. Parental and infant cortisol responses were assessed using saliva samples collected before and 21 min after the child's confrontation with a stranger and a moving robot. Infant behaviors reflecting distress/uncertainty during the stranger‐robot session were rated from videotape. Parental sensitivity was observed during a parent–infant teaching episode. Our findings replicate those of Sethre‐Hofstad et al. [2002, Psychoneuroendocrinology 27:731–747] by showing correlated parent–infant cortisol responses for sensitive parents but not for less sensitive parents. Furthermore, sensitive parents cortisol responses were associated with their children's distress/uncertainty during the stranger‐robot episode, whereas this was not true for less sensitive parents. Results indicate an important connection between behavior and physiology in parent–infant interactions that deserve more research. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 196–201, 2008.
Preobesity in the infant OLETF rat: The role of suckling
Authors: Schroeder Mariana , Lavi‐Avnon Yael , Zagoory‐Sharon Orna , Moran Timothy H. , Weller Aron
Published: February 2008

The Otsuka Long Evans Tokushima Fatty (OLETF) rat model of obesity, which lacks CCK1 receptors, has been extensively investigated over the last decade. We have recently focused on the early developmental stages of this strain, finding that OLETF pups are heavier than controls from birth and hyperphagic already from postnatal (PN) Day 2. OLETF mothers present differential maternal behavior patterns and increased nursing time and frequency, which might contribute to the preobese characteristics of the pups. The present investigation examined the pups' ability to gain weight from the nursing episodes. First, we measured the pups' weight gain from one nursing bout from their own dam. Next we examined the pups' weight gain after a feeding competition test with control pups from foster dams of both strains. OLETF pups gained more weight than controls from their own dams on PN Week 1 due to a higher suckling rate (and/or efficacy) and on PN Week 3 due to increased nursing time. When competing with control pups, OLETF pups gained significantly more weight after the same nursing bout, regardless of the strain of the mother. Body mass index (BMI) was significantly higher in OLETF pups compared to controls. The maternal parameters assessed from the experiment were latencies to pup retrieval and to nursing, and nursing duration; differences were only observed in nursing time. OLETF dams increased their average nursing time over the PN weeks, while control dams decreased their nursing time toward weaning. The results suggest an important contribution of OLETF pups toward their own preobese development. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 202–202, 2008.
IRAK‐4 kinase activity is required for IRAK‐4‐dependent innate and adaptive immune responses
Authors: Lye Elizabeth , Dhanji Salim , Calzascia Thomas , Elford Alisha R. , Ohashi Pamela S.
Published: February 2008

Interleukin‐1 receptor‐associated kinase (IRAK)‐4 is a serine‐threonine kinase that plays an important role in innate and adaptive immune responses. While the requirement of IRAK‐4 kinase activity has been studied in the context of IL‐1R signaling, it is not clear whether IRAK‐4 requires its kinase function for all of its roles in the immune system. IRAK‐4 kinase‐dead knock‐in (IRAK‐4KD/KD) mice were generated to further elucidate whether IRAK‐4 kinase activity is required for IRAK‐4 to induce cytokine production. IRAK‐4KD/KD mice were impaired in their ability to produce cytokines in response to in vivo challenge with lipopolysaccharide (LPS), a potent TLR4 ligand. Cytokine production was also reduced in macrophages and dendritic cells from IRAK‐4KD/KD mice in response to LPS and other TLR ligands. In addition, adaptive immune responses were impaired in IRAK‐4KD/KD mice. Although in vitro T cell proliferation in response to TCR activation was unaffected in IRAK‐4‐deficient mice, in vivo T cell responses to lymphocytic choriomeningitits virus infection were significantly impaired in IRAK‐4‐knockout mice or mice expressing the kinase‐dead mutant of IRAK‐4. Collectively, these results indicate that IRAK‐4 kinase activity is required for IRAK‐4‐dependent signaling in innate and adaptive immunity.
Tripeptidyl peptidase II is dispensable for the generation of both proteasome‐dependent and proteasome‐independent ligands of HLA‐B27 and other class I molecules
Authors: Marcilla Miguel , Villasevil Eugenia M. , de Castro José Antonio López
Published: February 2008

A significant fraction of the HLA‐B27‐bound peptide repertoire is resistant to proteasome inhibitors. The possible implication of tripeptidyl peptidase II (TPPII) in generating this subset was analyzed by quantifying the surface re‐expression of HLA‐B*2705 after acid stripping in the presence of two TPPII inhibitors, butabindide and Ala‐Ala‐Phe‐chloromethylketone. Neither decreased HLA‐B27 re‐expression under conditions in which TPPII activity was largely inhibited. This was in contrast to a significant effect of the proteasome inhibitor epoxomicin. The failure of TPPII inhibition to decrease surface re‐expression was not limited to HLA‐B27, since it was also observed in several HLA‐B27‐negative cell lines, including Mel JuSo. Actually, HLA class I re‐expression in Mel JuSo cells increased as a function of butabindide concentration, which is consistent with an involvement of TPPII in destroying HLA class I ligands. Inhibition of TPPII with small interfering RNA also failed to decrease the surface expression of HLA class I molecules on 143B cells. Our results indicate that TPPII is dispensable for the generation of proteasome‐dependent HLA class I ligands and, without excluding its role in producing some individual epitopes, this enzyme is not involved to any quantitatively significant extent, in generating the proteasome‐independent HLA‐B27‐bound peptide repertoire.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200838181
Immunomodulation by herpesvirus U51A chemokine receptorviaCCL5 and FOG‐2 down‐regulation plus XCR1 and CCR7 mimicry in human leukocytes
Authors: Catusse Julie , Spinks Jenny , Mattick Claire , Dyer Angela , Laing Ken , Fitzsimons Carlos , Smit Martine J. , Gompels Ursula A.
Published: February 2008

Human herpesvirus‐6A (HHV‐6A) betachemokine‐receptor U51A binds inflammatory modulators CCL2, CCL5, CCL11, CCL7, and CCL13. This unique specificity overlaps that of human chemokine receptors CCR1, CCR2, CCR3, and CCR5. In model cell lines, expression leads to CCL5 down‐regulation with both constitutive and inducible signaling. Here, immunomodulation pathways are investigated in human leukocytes permissive for infection. Constitutive signaling was shown using inositol phosphate assays and inducible calcium signaling by response to CCL2, CCL5 and CCL11. Constitutive signaling targets were examined using an immune response‐related microarray and RT‐PCR, showing down‐regulation of CCL5 and FOG‐2, a hematopoietic transcriptional repressor. By RT‐PCR and siRNA reversion, CCL5 and FOG‐2 were shown down‐regulated, during peak U51A expression post infection. Two further active ligands, XCL1 and CCL19, were identified, making U51A competitor to their human receptors, XCR1 and CCR7, on T lymphocytes, NK and dendritic cells. Finally, U51A‐expressing cell lines and infectedex vivoleukocytes, showed migration towards chemokine‐gradients, and chemokine internalization. Consequently, U51A may affect virus dissemination or host transmission by chemotaxis of infected cells to sites of chemokine secretion specific for U51A (for example the lymph node or lung, by CCL19 or CCL11, respectively) and evade immune‐effector cells by chemokine diversion and down‐regulation, affecting virus spread and inflammatory pathology.
Intradermal NKT cell activation during DNA priming in heterologous prime‐boost vaccination enhances T cell responses and protection against Leishmania
Authors: Dondji Blaise , Deak Eszter , Goldsmith‐Pestana Karen , Perez‐Jimenez Eva , Esteban Mariano , Miyake Sachiko , Yamamura Takashi , McMahon‐Pratt Diane
Published: February 2008

Heterologous prime‐boost vaccination employing DNA‐vaccinia virus (VACV) modality using the Leishmania homologue of receptors for activated C kinase (LACK) (p36) antigen has been shown to elicit protective immunity against both murine cutaneous and visceral leishmaniasis. However, DNA priming is known to have limited efficacy; therefore in the current study the effect of NKT cell activation using α‐galactosyl‐ceramide (αGalCer) during intradermal DNAp36 priming was examined. Vaccinated mice receiving αGalCer + DNAp36 followed by a boost with VVp36 appeared to be resolving their lesions and had at ten‐ to 20‐fold higher reductions in parasite burdens. NKT cell activation during αGalCer + DNAp36 priming resulted in higher numbers of antigen‐reactive effector CD4+ and CD8+ T cells producing granzyme and IFN‐γ, with lower levels of IL‐10. Although immunodepletion studies indicate that both CD4 and CD8 T cells provide protection in the vaccinated mice, the contribution of CD4+ T cells was significantly increased in mice primed with DNAp36 together with αGalCer. Notably 5 months after boosting, mice vaccinated with DNAp36 + αGalCer continued to show sustained and heightened T cell immune responses. Thus, heterologous prime‐boost vaccination using αGalCer during priming is highly protective against murine cutaneous leishmaniasis, resulting in the heightened activation and development of CD4 and CD8 T cells (effector and memory T cells).
Type I interferon‐dependent and ‐independent expression of tripartite motif proteins in immune cells
Authors: Rajsbaum Ricardo , Stoye Jonathan P. , O'Garra Anne
Published: February 2008

The tripartite motif (TRIM) proteins are important in a variety of cellular functions additional to anti‐viral activity. We systematically analysed mRNA expression of representative TRIM molecules in mouse macrophages, myeloid and plasmacytoid dendritic cells, and a selection of CD4+ T cell subsets. We defined four clusters of TRIM genes based on their selective expression in these cells. The first group of TRIM genes was preferentially expressed in CD4+ T cells and contained the COS‐FN3 motif previously shown to be involved in protein interactions. Additional TRIM genes were identified that showed up‐regulation in macrophages and dendritic cells upon influenza virus infection in a type I IFN‐dependent manner, suggesting that they have anti‐viral activity. In support of this notion, a subset of these TRIM molecules mapped to mouse chromosome 7, syntenic to human chromosome 11, where TRIM family members such as TRIM5, shown to have anti‐viral activity, are localized. A distinct group of TRIM was constitutively expressed in plasmacytoid dendritic cells independently of viral infection or signalling through the type I IFN receptor. Our findings on expression and regulation of TRIM genes in cells of the immune system that have different effector functions in innate and adaptive immune responses, may provide leads for determining functions of this diverse family of molecules.
Role of tripeptidyl peptidase II in MHC class I antigen processing – the end of controversies?
Authors: Endert Peter van
Published: February 2008

Peptide ligands presented by MHC class I molecules are generated in a cascade of proteolytic events starting with the proteasome in the cytosol and frequently terminating with trimming aminopeptidases in the endoplasmic reticulum. Several cytosolic proteases can carry out intermediate proteolytic steps between these start and endpoints. Among these, tripeptidyl peptidase II (TPP II), an exceptionally large homo‐oligomeric protease, has been proposed to be involved in the generation of many or most MHC class I ligands by cleaving long precursor peptides. In this issue of the European Journal of Immunology, the effect of pharmacological or genetic TPP II inhibition on peptide loading of HLA‐B27 and other HLA class I molecules is examined, and no evidence for a role of TPP II in this process is detected. Although further studies using more efficient inhibitors and focusing on HLA class I alleles such as HLA‐A3 are warranted, these results, together with other recently published data, suggest that the role of TPP II in MHC class I processing may be much more limited than previously appreciated.

See accompanying article: http://dx.doi.org/10.1002/eji200737444
Synthesis and Structural Characterization of New Rhodium‐Tin Heterodimetallic Complexes
Authors: Kilian Michaela , Wadepohl Hubert , Gade Lutz H.
Published: February 2008

Reaction of the triamidostannates(II) MeSi{SiMe2N(p‐tol)}3SnLi(OEt2) (1a) and MeSi{SiMe2N(3,5‐xyl)}3SnLi(OEt2) (1b) with 1/2 molar equiv. of [RhCl(diolefin)]2 (diolefin = COD, NBD) and phosphanes, phosphites or isonitriles (“L”) gave the square‐planar complexes [MeSi{SiMe2NAryl}3SnRh(L)(diolefin)] (Aryl = 3,5‐xyl, p‐tol) in which thestannates are directly bonded to rhodium through Rh–Sn bonds. In contrast, the analogous transformation of 1b with 1/2 equiv. of [RhCl(C2H4)2]2 and PiPr3 in toluene did not lead to a square‐planar bisethylene complex [MeSi{SiMe2N(3,5‐xyl)}3SnRh(C2H4)2(PiPr3)] but the brown 18e π‐arene complex [MeSi{SiMe2N(3,5‐xyl)}3SnRh(PiPr3)(η6‐toluene)] (6). Equilibria of the square planar diolefin complexes with π‐arene systems such as 6 were observed upon their dissolution in toluene.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
CuI–Br Oligomers and Polymers Involving Cu–S(cystamine) Bonds
Authors: Louvain Nicolas , Mercier Nicolas , Kurmoo Mohamedally
Published: February 2008

The syntheses, crystal structures, and thermal properties of five cuprous bromides derived from cystamine, [NH3(CH2)2SS(CH2)2NH3]2+, here denoted by (SS), are reported. Whereas (SS)2Cu4Br8 (1) is a polar tetramer and (SS)2Cu2Br6 (2) consists of [(SS)Cu2Br6]2– dimers, α1‐(SS)Cu2Br4 (3), (SS)Cu3Br5 (4), and α2‐(SS)Cu2Br4 (5) are polymers; 3 and 5 are one‐dimensional and 4 has a corrugated 2D network. All the compounds contain corner‐shared tetrahedra with Cu–Br–Cu connections, and in some cases, edge‐shared with double bromine bridges. The copper coordination is tetrahedral, either CuBr4 or CuBr3S, except in one case, in which trigonal geometry was encountered. Compounds 1, 2, and 4, which are synthesized at 50 °C, display Cu–S bonds with the cystamine through either one or both sulfur atoms. On the other hand, 3 and 5, which are synthesized at 80 °C, do not have any. There is a high tendency to form hydrogen bonds between the polar ammonium heads of the cystamine with the bromine atoms. The range of phases experienced in this system is related to the bifunctional nature of cystamine, which is characterized by its primary ammonium ends and its disulfide bridge, and to the subtle competition between Br– and S–S ligands towards the CuI ions, which appears to be controllable by temperature. The presence of both chiral M‐ and P‐helicoidal conformers of cystamine in 1–5 results in racemic compounds adopting centrosymmetric structures for 1, 3, 4, and 5 but 2 adopts a noncentrosymmetric structure (P212121) resulting from the coordination of copper ions to one conformer; the other conformer is noncoordinated and acts as the counterion.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Further characterization of the binding of heparin to granulocyte colony‐stimulating factor: Importance of sulfate groups
Authors: Liang Aiye , Liu Xiaojun , Du Yuguang , Wang Keyi , Lin Bingcheng
Published: February 2008

Heparin mediates fundamental biological mechanisms through interaction with proteins. Previously, we have shown that standard heparin binds to granulocyte colony‐stimulating factor (G‐CSF) with an affinity of 4.8×105 M−1. To further study the structural features in heparin that are responsible for this interaction, we studied the bindings of G‐CSF and N‐desulfated and 2,3‐O‐desulfated heparin by CZE. Results showed that the N‐desulfated heparin had a similar affinity for G‐CSF ((5.4 ± 0.9)×105 M−1), but the 2,3‐O‐desulfated heparin had a 1000‐fold lower affinity ((3.4 ± 1.2)×102 M−1) in comparison to standard heparin. The results showed that 2,3‐O‐sulfate groups are more important than N‐sulfate groups in heparin–G‐CSF interaction.
Two‐level finite element method with a stabilizing subgrid for the incompressible Navier–Stokes equations
Authors: Nesliturk A. I. , Aydın S. H. , Tezer‐Sezgin M.
Published: February 2008

We consider the Galerkin finite element method for the incompressible Navier–Stokes equations in two dimensions. The domain is discretized into a set of regular triangular elements and the finite‐dimensional spaces employed consist of piecewise continuous linear interpolants enriched with the residual‐free bubble functions. To find the bubble part of the solution, a two‐level finite element method with a stabilizing subgrid of a single node is described, and its application to the Navier–Stokes equation is displayed. Numerical approximations employing the proposed algorithm are presented for three benchmark problems. The results show that the proper choice of the subgrid node is crucial in obtaining stable and accurate numerical approximations consistent with the physical configuration of the problem at a cheap computational cost. Copyright © 2008 John Wiley & Sons, Ltd.
A pseudospectral Fourier method for a 1D incompressible two‐fluid model
Authors: Holmås H. , Clamond D. , Langtangen H. P.
Published: February 2008

This paper presents an accurate and efficient pseudospectral (PS) Fourier method for a standard 1D incompressible two‐fluid model. To the knowledge of the authors, it is the first PS method developed for the purpose of modelling waves in multiphase pipe flow. Contrary to conventional numerical methods, the PS method combines high accuracy and low computational costs with flexibility in terms of handling higher order derivatives and different types of partial differential equations. In an effort to improve the description of the stratified wavy flow regime, it can thus serve as a valuable tool for testing out new two‐fluid model formulations. The main part of the algorithm is based on mathematical reformulations of the governing equations combined with extensive use of fast Fourier transforms. All the linear operations, including differentiations, are performed in Fourier space, whereas the nonlinear computations are performed in physical space. Furthermore, by exploiting the concept of an integrating factor, all linear parts of the problem are integrated analytically. The remaining nonlinear parts are advanced in time using a Runge–Kutta solver with an adaptive time step control. As demonstrated in the results section, these steps in sum yield a very accurate, fast and stable numerical method. A grid refinement analysis is used to compare the spatial convergence with the convergence rates of finite difference (FD) methods of up to order six. It is clear that the exponential convergence of the PS method is by far superior to the algebraic convergence of the FD schemes. Combined with the fact that the scheme is unconditionally linearly stable, the resulting increase in accuracy opens for several orders of magnitude savings in computational time. Finally, simulations of small amplitude, long wavelength sinusoidal waves are presented to illustrate the remarkable ability of the PS method to reproduce the linear stability properties of the two‐fluid model. Copyright © 2008 John Wiley & Sons, Ltd.
Activated Notch1 maintains the phenotype of radial glial cells and promotes their adhesion to laminin by upregulating nidogen
Authors: Li Hedong , Chang Yu‐Wen , Mohan Kriti , Su Hui‐Wen , Ricupero Christopher L. , Baridi Ajoeb , Hart Ronald P. , Grumet Martin
Published: February 2008

Radial glia are neural stem cells that exist only transiently during central nervous system (CNS) development, where they serve as scaffolds for neuronal migration. Their instability makes them difficult to study, and therefore we have isolated stabilized radial glial clones from E14.5 cortical progenitors (e.g., L2.3) after expression of v‐myc. Activated Notch1 intracellular region (actNotch1) promotes radial glia in the embryonic mouse forebrain (Gaiano et al., (2000), and when it was introduced into E14.5 cortical progenitors or radial glial clone L2.3, the cells exhibited enhanced radial morphology and increased expression of the radial glial marker BLBP. A representative clone of L2.3 cells expressing actNotch1 called NL2.3‐4 migrated more extensively than L2.3 cells in culture and in white matter of the adult rat spinal cord. Microarray and RT‐PCR comparisons of mRNAs expressed in these closely related clones showed extensive similarities, but differed significantly for certain mRNAs including several cell adhesion molecules. Cell adhesion assays demonstrated significantly enhanced adhesion to laminin of NL2.3‐4 by comparison to L2.3 cells. The laminin binding protein nidogen was the most highly induced adhesion molecule in NL2.3‐4, and immunological analyses indicated that radial glia synthesize and secrete nidogen. Adhesion of NL2.3‐4 cells to laminin was inhibited by anti‐nidogen antibodies and required the nidogen binding region in laminin, indicating that nidogen promotes cell adhesion to laminin. The combined results indicate that persistent expression of activated Notch1 maintains the phenotype of radial glial cells, inhibits their differentiation, and promotes their adhesion and migration on a laminin/nidogen complex. © 2008 Wiley‐Liss, Inc.
Steroid hormone receptor expression and function in microglia
Authors: Sierra Amanda , Gottfried‐Blackmore Andres , Milner Teresa A. , McEwen Bruce S. , Bulloch Karen
Published: February 2008

Steroid hormones such as glucocorticoids and estrogens are well‐known regulators of peripheral immune responses and also show anti‐inflammatory properties in the brain. However, the expression of steroid hormone receptors in microglia, the pivotal immune cell that coordinates the brain inflammatory response, is still controversial. Here we use real time RT‐PCR to show that microglia, isolated from adultfms‐EGFP mice by FACS, express glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and estrogen receptor alpha (ERα). GR was the most abundant steroid hormone receptor transcript in microglia. The presence of GR and ERα immunoreactivity was further confirmedin vivoat the ultrastructural level. To understand the role of steroid hormone receptors during the inflammation process, we evaluated the expression of steroid hormone receptors after inflammatory challenge and found a significant down‐regulation of GR, MR, and ERα in microglia. Finally, we tested the immunomodulatory properties of estrogens and glucocorticoids. Estradiol benzoate did not have any significant impact on the inflammatory profile ofex vivosorted microglia, either in resting conditions or after challenge. Furthermore, corticosterone was a more consistent anti‐inflammatory agent than 17β‐estradiolin vitro. Our results support the hypothesis that adult microglia are a direct target of steroid hormones and that glucocorticoids, through the predominant expression of GR and MR, are the primary steroid hormone regulators of microglial inflammatory activity. The down‐regulation of steroid hormone receptors after LPS challenge may serve as a prerequisite to suppressing the anti‐inflammatory actions of endogenous steroid hormones on the immune system, and contribute to a sustained activation of microglia. © 2008 Wiley‐Liss, Inc.
Mapping a multidimensional emotion in response to television commercials
Authors: Morris Jon D. , Klahr Nelson J. , Shen Feng , Villegas Jorge , Wright Paul , He Guojun , Liu Yijun
Published: February 2008

Unlike previous emotional studies using functional neuroimaging that have focused on either locating discrete emotions in the brain or linking emotional response to an external behavior, this study investigated brain regions in order to validate a three‐dimensional construct – namely pleasure, arousal, and dominance (PAD) of emotion induced by marketing communication. Emotional responses to five television commercials were measured with Advertisement Self‐Assessment Manikins (AdSAM®) for PAD and with functional magnetic resonance imaging (fMRI) to identify corresponding patterns of brain activation. We found significant differences in the AdSAM scores on the pleasure and arousal rating scales among the stimuli. Using the AdSAM response as a model for the fMRI image analysis, we showed bilateral activations in the inferior frontal gyri and middle temporal gyri associated with the difference on the pleasure dimension, and activations in the right superior temporal gyrus and right middle frontal gyrus associated with the difference on the arousal dimension. These findings suggest a dimensional approach of constructing emotional changes in the brain and provide a better understanding of human behavior in response to advertising stimuli. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Alveolar soft part sarcoma of the larynx: A case report of an unusual location with immunohistochemical and ultrastructural analyses
Authors: Kusafuka Kimihide , Muramatsu Koji , Yabuzaki Tsugumi , Ishiki Hiroto , Asano Rie , Kamijo Tomoyuki , Iida Yoshiyuki , Ebihara Mitsuru , Onitsuka Testuro , Kameya Toru
Published: February 2008

Background

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal neoplasm of uncertain origin. In this article, we report a case of ASPS occurring in the larynx, an extremely rare location for this rather unusual tumor.

Methods and Results

The patient was a 34‐year‐old Japanese woman who requested an examination for hoarseness. The tumor showed a proliferation of large polygonal cells with periodic‐acid‐Schiff–positive diastase‐resistant intracytoplasmic granules, arranged in an alveolar growth pattern. The cytoplasm of the tumor cells was eosinophilic. Tumor cells were positive for vimentin and titin. Nuclear immunoreactivity for TFE3 was observed, and the Ki‐67 labeling index was 14.7%. Ultrastructurally, electron‐dense rod‐shaped crystals were infrequently observed in the cytoplasm. This case was finally diagnosed as ASPS of the larynx.

Conclusion

We discuss the histogenesis and differential diagnosis of ASPS with immunohistochemical and ultrastructural findings. TFE3 immunohistochemistry was found to be a very useful marker for the diagnosis of ASPS. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
N2‐N3 neck nodal control without planned neck dissection for clinical/radiologic complete responders—Results of Trans Tasman Radiation Oncology Group Study 98.02
Authors: Corry June , Peters Lester , Fisher Richard , Macann Andrew , Jackson Michael , McClure Bev , Rischin Danny
Published: February 2008

Background

The aim of this study was to determine the incidence of isolated nodal failure in patients with N2/3 disease who achieved a complete clinical and radiological response (CR) at 12 weeks postchemoradiation, when no planned neck dissection was performed.

Methods

We analyzed the nodal response and subsequent neck control of 102 patients with initial N2/3 disease treated on the Trans Tasman Radiation Oncology Group 98.02 study.

Results

With a median 4.3 years follow‐up, the patterns of first failure in the CR patients were local 4%, local and nodal 2%, distant 28%, and locoregional plus distant (within 1 month) 6%.There were no patients who had only neck failure.

Conclusion

Patients in this trial with N2/3 disease who obtained a clinical and radiological complete response to chemoradiation had a zero incidence of isolated neck failure without a planned neck dissection. The continued use of planned neck dissections in this patient subset cannot be justified. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Using fluorodeoxythymidine to monitor anti‐EGFR inhibitor therapy in squamous cell carcinoma xenografts
Authors: Atkinson David M. , Clarke Michelle J. , Mladek Ann C. , Carlson Brett L. , Trump David P. , Jacobson Mark S. , Kemp Brad J. , Lowe Val J. , Sarkaria Jann N.
Published: February 2008

Background

3′‐18F‐fluoro‐3′‐deoxy‐fluorothymidine (18F‐FLT), a nucleoside analog, could monitor effects of molecularly targeted therapeutics on tumor proliferation.

Methods

We tested whether 18F‐FLT positron emission tomography (PET) uptake changes are associated with antitumor effects of erlotinib in A431 xenografts or cetuximab in SCC1 xenografts.

Results

Compared with pretreatment FLT PET scans, 3 days of erlotinib in A431 reduced the standardized uptake value (SUV) by 18%, whereas placebo increased SUV by 1% (p = .005). One week of cetuximab in SCC1 reduced SUV by 62%, whereas placebo reduced SUV by 16% (p = .005). FLT uptake suppression following anti–epidermal growth factor receptor (EGFR) treatment was associated with reduced tumor thymidine kinase‐1 (TK1) activity. In vitro TK1 knockdown studies confirmed the importance of TK1 activity on intracellular FLT accumulation suppression.

Conclusions

18F‐FLT PET imaging detects tumor responses to EGFR‐inhibitors within days of starting therapy. This technique may identify patients likely to benefit from EGFR‐inhibitors early in their treatment course. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Oral primary angiosarcoma of the lower lip mucosa: Report of a case in a 15‐year‐old boy
Authors: Arribas‐Garcia Ignacio , Domínguez Manuel Fernández , Alcalá‐Galiano Andrea , García Antonio Fernández , Valls Julio Castedo , De Rasche Enrique Niembro
Published: February 2008

Background.

Angiosarcomas are rare soft tissue malignant tumors with dismal prognosis. Head and neck involvement is uncommon (5%) and usually affects the scalp or facial skin.

Methods and Results.

We present the case of an inferior lip mucosal low‐grade angiosarcoma in a 15‐year‐old boy treated exclusively with surgery. One and a half years after treatment, the patient was free of signs of recurrence. Prompt and accurate diagnosis with adequate imaging modalities and multidisciplinary treatment are crucial for optimal management of these neoplasms.

Conclusion.

Lip mucosal involvement is exceptional with only a few cases described in the literature, all in patients older than 60 years To our knowledge, this is the youngest patient ever reported. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Vidian nerve schwannoma with middle cranial fossa extension resected via a maxillary swing approach
Authors: Honda Keigo , Asato Ryo , Tanaka Shinzo , Endo Tsuyoshi , Nishimura Kazunari , Ito Juichi
Published: February 2008

Background.

Vidian nerve schwannoma is an extremely rare type of facial nerve schwannoma. To the best of our knowledge, only 1 case has been reported.

Methods.

We report an additional case of vidian nerve schwannoma with middle cranial fossa extension in a 49‐year‐old Japanese woman. The surgical approaches for infratemporal fossa schwannomas are reviewed, and the maxillary swing approach we used is described.

Results.

We adopted a maxillary swing approach combined with endonasal endoscopic techniques for the resection of the lesion. Gross total resection was achieved without sacrificing the trigeminal nerves or the facial motor nerves. The postoperative course was uneventful.

Conclusion.

Vidian nerve schwannoma is located in the retromaxillary space. It can grow silently until it involves the median skull base extensively. The maxillary swing approach was useful in this case. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Comparison of 2D fiber network orientation measurement methods
Authors: Sander E. A. , Barocas V. H.
Published: February 2008

The mechanical properties of tissues, tissue analogs, and biomaterials are dependent on their underlying microstructure. As such, many mechanical models incorporate some aspect of microstructure, but a robust protocol for characterizing fiber architecture remains a challenge. A number of image‐based methods, including mean intercept length (MIL), line fraction deviation (LFD), and Fourier transform methods (FTM), have been applied to microstructural images to describe material heterogeneity and orientation, but a performance comparison, particularly for fiber networks, has not been conducted. In this study, we constructed 40 two‐dimensional test images composed of simulated fiber networks varying in fiber number, orientation, and anisotropy index. We assessed the accuracy of each method in measuring principal direction (θ) and anisotropy index (α). FTM proved to be the superior method because it was more reliable in measurement accuracy (Δθ = 2.95° ± 6.72°, Δα = 0.03 ± 0.02), faster in execution time, and flexible in its application. MIL (Δθ = 6.23° ± 10.68°, Δα = 0.08 ± 0.06) was not significantly less accurate than FTM but was much slower. LFD (Δθ = 9.97° ± 11.82°, Δα = 0.24 ± 0.13) consistently underperformed. FTM results agreed qualitatively with fibrin gel SEM micrographs, suggesting that FTM can be used to obtain image‐based statistical measurements of microstructure. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res 2009
Molecularly designed surfaces for blood deheparinization using an immobilized heparin‐binding peptide
Authors: Martins M. Cristina L. , Curtin Scott A. , Freitas Sidónio C. , Salgueiro Pedro , Ratner Buddy D. , Barbosa Mário A.
Published: February 2008

Systemic heparinization, used during haemodialysis to prevent blood clotting on the extracorporeal circuit, leads to a high incidence of hemorrhagic complications. The adverse reactions associated with heparin neutralization using protamine sulphate justify the development of an alternative system for blood deheparinization. The main objective of this work is to design nanostructured surfaces with the capacity to bind heparin from blood in a selective way. A heparin‐binding polypeptide, composed of L‐lysine and L‐leucine (pKL), was synthesized and immobilized, in different concentrations, onto self‐assembled monolayers (SAMs) terminated with tetra(ethylene‐glycol) (EG4 SAMs). Immobilization was performed using a fixed concentration of pKL after surface activation to different degrees using a range of CDI (N,N′‐carbonyldiimidazole) concentrations. Results demonstrated that the presence of pKL increases heparin adsorption to EG4‐SAMs, independently of the pKL concentration and the way of immobilization (adsorption or covalent bound). Selectivity towards heparin was successfully achieved on SAMs with low concentrations of immobilized pKL (9–17% of pKL). Surfaces were characterized using ellipsometry, contact angle measurements, Fourier transform infrared reflection absorption spectroscopy (IRAS), atomic force microscopy, and X‐ray photoelectron spectroscopy. Heparin adsorption was assessed using IRAS and N‐sulphonate‐35S‐heparin. Therefore, this study could give a good contribution for the design of blood deheparinization devices. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Functional and phenotypic characterization of human keratinocytes expanded in microcarrier culture
Authors: Borg Danielle J. , Dawson Rebecca A. , Leavesley David I. , Hutmacher Dietmar W. , Upton Zee , Malda Jos
Published: February 2008

Skin cells for transplantation are routinely prepared by growing patient keratinocytes in a semi‐defined cocktail of growth factors, including serum and feeder cells. However, these reagents require substantial risk remediation and can contribute to transplant rejection. Microcarrier culture is an emerging technology that may allow the elimination of feeder cells whilst facilitating expansion of cultured keratinocytes. However, the behavior of keratinocytes in microcarrier culture and the potential of these cells to form an epidermis have been poorly defined. We characterized freshly isolated human keratinocytes cultured on CultiSpher‐G® microcarriers in the absence of murine feeder cells and assessed the potential of the keratinocytes to form an epidermis in an in vitro model. In a single passage, keratinocytes multiplied 44.9‐fold in microcarrier‐bioreactor culture in 17 days, whereas two‐dimensional cultures reached confluence in 9 days and only expanded 7.4‐fold. Histological characterization of keratinocytes on the microcarriers revealed that the cells were randomly distributed within these porous structures, however, not all pores contained cells. High‐resolution microcomputed tomography imaging of the microcarriers confirmed limited interconnectivity of the pores. Immunoreactivity of specific epidermal markers was confirmed during cell expansion via immunohistochemistry. Despite the expression of differentiation markers, microcarrier‐expanded keratinocytes retained the capacity to form an epidermis, as was evaluated using an in vitro human skin equivalent model. The epidermis formed by microcarrier‐expanded keratinocytes in this model exhibited morphology similar to native skin. Significantly, the microcarrier technique successfully eliminates the need for a feeder cell layer and hence facilitates development of an improved culture system. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Analysis of the osteoinductive capacity and angiogenicity of an in vitro generated extracellular matrix
Authors: Pham Quynh P. , Kasper F. Kurtis , Mistry Amit S. , Sharma Upma , Yasko Alan W. , Jansen John A. , Mikos Antonios G.
Published: February 2008

In this study, the osteoinductive potential of an in vitro generated extracellular matrix (ECM) deposited by marrow stromal cells seeded onto titanium fiber mesh scaffolds and cultured in a flow perfusion bioreactor was investigated. Culture periods of 8, 12, and 16 days were selected to allow for different amounts of ECM deposition by the cells as well as ECM with varying degrees of maturity (Ti/ECM/d8, Ti/ECM/d12, and Ti/ECM/d16, respectively). These ECM‐containing constructs were implanted intramuscularly in a rat animal model. After 56 days, histologic analysis of retrieved constructs revealed no bone formation in any of the implants. Surrounding many of the implants was a fibrous capsule, which was often interspersed with fat cells. Within the pore spaces, the predominant tissue response was the presence of blood vessels and young fibroblasts or fat cells. The number of blood vessels on a per area basis calculated from a histomorphometric analysis increased as a function of the amount of ECM within the implanted constructs, with a significant difference between Ti/ECM/d16 and plain Ti constructs. These results indicate that although an in vitro generated ECM alone may not induce bone formation at an ectopic site, its use may enhance the vascularization of implanted constructs. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res 2009
Genotoxicity and cytotoxicity in multiple organs induced by titanium miniplates in Wistar rats
Authors: Piozzi Rodrigo , Ribeiro Daniel Araki , Padovan Luís Eduardo Marques , Filho Hugo Nary , Matsumoto Mariza Akemi
Published: February 2008

Internal fixture materials are currently used as metallic biomaterials in rehabilitation of human body. Nevertheless, metal release due to corrosion phenomena appears to play a crucial role for human health. Thus, the goal of the present study was to evaluate whether liver, kidney, and lung are particularly sensitive organs for DNA damaging and cytotoxicity following implantation of internal fixture materials composed by titanium alloy in vivo. A total of 18 rats underwent surgical titanium miniplates in their tibias, being randomly distributed into three groups: 30 days, 90 days, and 180 days after implantation. A total of six animals served as negative control (animals that not received any implant). After experimental design, the lung, liver, and kidney were removed for histopatological and genotoxic analysis as depicted by H.E. stain and single cell gel (comet) assay, respectively. No significant statistically differences (p > 0.05) for DNA damaging were found to all experimental groups when compared to negative control for all organs evaluated. In addition, no remarkable morphological alterations were detected under histopathological analysis. Taken together, such results suggest that titanium miniplates are neither able to induce DNA damage in multiple organs nor to cause some abnormalities in lung, liver, and kidney. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res 2009
Antibacterial properties of Ag (or Pt)‐containing calcium phosphate coatings formed by micro‐arc oxidation
Authors: Song Won‐Hoon , Ryu Hyun Sam , Hong Seong‐Hyeon
Published: February 2008

Silver (or platinum)‐containing calcium phosphate (hydroxyapatite (HA) and tricalcium phosphate (α‐TCP)) coatings on titanium substrates were formed by micro‐arc oxidation (MAO) and their in vitro antibacterial activity and in vitro cytotoxicity were evaluated. MAO was performed in an electrolytic solution containing β‐glycerophosphate disodium salt pentahydrate (β‐GP) and calcium acetate monohydrate (CA), and Ag and Pt were introduced in the form of AgNO3 (or CH3COOAg) and H2PtCl6, respectively. The MG63 and human osteosarcoma (HOS) cell lines were used to investigate the proliferation and differentiation behavior of the cells, respectively, whereas two strains of bacteria, Staphylococcus aureus and Escherichia coli, were used to evaluate the antibacterial activity of the coatings. The phase, morphology, and Ag content of the coatings were strongly dependent on the applied voltage and Ag precursor concentration. HA and α‐TCP phases were detected in the coatings oxidized above 400 V and the presence of Ag was confirmed by EDS. While the coatings with a high content of Ag were cytotoxic and those obtained in the Pt‐containing electrolyte had no apparent antibacterial activity, the calcium phosphate coatings obtained in the low Ag concentration electrolyte exhibited in vitro antibacterial activity but no cytotoxicity. Thus, biocompatible calcium phosphate coatings on Ti implants with antibacterial activity can be achieved by one‐step MAO. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Method for predicting sorption of small drug molecules onto polylactide
Authors: Karst David , Yang Yiqi
Published: February 2008

A method has been developed to predict the percent sorption of small drug molecules onto polylactide (PLA). In this method, molecular modeling is first used to calculate the interaction energy between the adsorbate and PLA. Alternatively, the adsorbate‐PLA interaction energy can be calculated by summing the adsorbate functional group contributions to the interaction energy. These functional group contributions have been found in this study. The adsorbate‐PLA interaction energy is then substituted into a linear equation to predict the natural log of the sorption equilibrium constant, and the percent sorption is obtained from this value. This linear equation has been developed based on experimental sorption data for dyes on PLA. The predicted percent sorption of two small drugs on PLA has been verified with experimental data. Our method possibly could be used to select appropriate drugs for use in controlled release studies involving PLA. This method also could be used to calculate the functional group contributions to the interaction energies between other drugs and polymers and to predict their percent sorption onto those polymers, which could be used to select drugs suitable for controlled release studies involving those polymers. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009