bluuebunny/crossref_metadata_2025 huggingface dataset:
Elastin‐derived peptides: Matrikines critical for glioblastoma cell aggressiveness in a 3‐D system
Authors: Coquerel Bérénice , Poyer Florent , Torossian Frédéric , Dulong Virginie , Bellon Georges , Dubus Isabelle , Reber Annie , Vannier Jean‐Pierre
Published: April 2009

In the most common primary brain tumors, malignant glioma cells invade the extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which is mainly composed of hyaluronan (HA) along with the elastin present in the basement membrane of blood vessels. To determine the role of ECM components in the invasive capacity of glioma cell lines, we developed a 3‐D cell‐culture system, based on a hydrogel in which HA can be coreticulated with kappa‐elastin (HA‐κE). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of κE and a related, specific peptide (VGVAPG)3. In addition, MMP‐2 secretion increased and MMP‐12 synthesis occurred. Extracellular injections of κE or (VGVAPG)3 provoked a pronounced and dose‐dependent increase in [Ca2+]i. κE significantly enhanced the expression of the genes encoding elastin‐receptor and tropoelastin. We propose the existence of a positive feedback loop in which degradation of elastin generates fragments that stimulate synthesis of tropoelastin followed by further degradation as well as migration and proliferation of the very cells responsible for degradation. All steps in this ECM‐based loop could be blocked by the addition of either of the EBP antagonists, lactose, and V‐14 peptide, suggesting that the loop itself should be considered as a new therapeutic target. © 2009 Wiley‐Liss, Inc.
Post‐traumatic stress disorder and prediction of aggression in persons with dementia
Authors: Ball Valdesha L. , Hudson Sonora , Davila Jessica , Morgan Robert , Walder Annette , Graham David P. , Snow Andrea L. , Kunik Mark E.
Published: April 2009

Objective

This prospective cohort study evaluated the potential of increased aggression in patients with dementia who had a preexisting diagnosis of post‐traumatic stress disorder (PTSD) compared with those without a diagnosis of PTSD.

Methods

Patients more than 60 years of age with newly diagnosed dementia between 2001 and 2004 were identified from the Michael E. DeBakey Veterans Affairs (VA) Medical Center in Houston, TX. Among these patients, we identified patients with a preexisting diagnosis of PTSD. The proportions of patients who became aggressive within 2 years of enrollment were compared in patients with and without PTSD. Fisher's exact tests were used to compare differences in the number of PTSD patients with and without aggression.

Results

A total of 215 patients were identified with newly diagnosed dementia. Ten were found to have a diagnosis of PTSD, and 205 did not. Eighty‐four (41%) of the 205 were found to be aggressive. Among the 10 patients with a diagnosis of PTSD, 4 (40%) were aggressive.

Conclusion

There was no evidence to support an increased risk of aggression in patients with a coexisting diagnosis of dementia and PTSD. Copyright © 2009 John Wiley & Sons, Ltd.
Detection of event‐related modulations of oscillatory brain activity with multivariate statistical analysis of MEG data
Authors: Soto Juan L.P. , Pantazis Dimitrios , Jerbi Karim , Lachaux Jean‐Phillipe , Garnero Line , Leahy Richard M.
Published: April 2009

We describe a method to detect brain activation in cortically constrained maps of current density computed from magnetoencephalography (MEG) data using multivariate statistical inference. We apply time–frequency (wavelet) analysis to individual epochs to produce dynamic images of brain signal power on the cerebral cortex in multiple time–frequency bands. We form vector observations by concatenating the power in each frequency band, and fit them into separate multivariate linear models for each time band and cortical location with experimental conditions as predictor variables. The resulting Roy's maximum root statistic maps are thresholded for significance using permutation tests and the maximum statistic approach. A source is considered significant if it exceeds a statistical threshold, which is chosen to control the familywise error rate, or the probability of at least one false positive, across the cortical surface. We compare and evaluate the multivariate approach with existing univariate approaches to time–frequency MEG signal analysis, both on simulated data and experimental data from an MEG visuomotor task study. Our results indicate that the multivariate method is more powerful than the univariate approach in detecting experimental effects when correlations exist between power across frequency bands. We further describe protectedF‐tests and linear discriminant analysis to identify individual frequencies that contribute significantly to experimental effects. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
The fMRI success rate of children and adolescents: Typical development, epilepsy, attention deficit/hyperactivity disorder, and autism spectrum disorders
Authors: Yerys Benjamin E. , Jankowski Kathryn F. , Shook Devon , Rosenberger Lisa R. , Barnes Kelly Anne , Berl Madison M. , Ritzl Eva K. , VanMeter John , Vaidya Chandan J. , Gaillard William D.
Published: April 2009

Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18‐year‐old had a significantly greater scan success rate than 4‐ to 6‐year‐old; adolescents (13‐ to 18‐year‐old) demonstrated greater scan success rates than 7‐ to 9‐year‐old. Success rate for completing an entire battery of experimental runs (n = 2–6), varied between 50–59% for patient populations and 69% for TYP (79% when excluding 4‐ to 6‐year‐old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20–30% more children should be recruited in these patient groups, but only 10–20% for TYP for research studies. Studies with 4‐ to 6‐year‐olds may require 20–40% additional participants; studies with 10‐ to 18‐year‐olds may require 10–15% additional participants. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Dynamic Granger–Geweke causality modeling with application to interictal spike propagation
Authors: Lin Fa‐Hsuan , Hara Keiko , Solo Victor , Vangel Mark , Belliveau John W. , Stufflebeam Steven M. , Hämäläinen Matti S.
Published: April 2009

A persistent problem in developing plausible neurophysiological models of perception, cognition, and action is the difficulty of characterizing the interactions between different neural systems. Previous studies have approached this problem by estimating causal influences across brain areas activated during cognitive processing using structural equation modeling (SEM) and, more recently, with Granger–Geweke causality. While SEM is complicated by the need for a priori directional connectivity information, the temporal resolution of dynamic Granger–Geweke estimates is limited because the underlying autoregressive (AR) models assume stationarity over the period of analysis. We have developed a novel optimal method for obtaining data‐driven directional causality estimates with high temporal resolution in both time and frequency domains. This is achieved by simultaneously optimizing the length of the analysis window and the chosen AR model order using the SURE criterion. Dynamic Granger–Geweke causality in time and frequency domains is subsequently calculated within a moving analysis window. We tested our algorithm by calculating the Granger–Geweke causality of epileptic spike propagation from the right frontal lobe to the left frontal lobe. The results quantitatively suggested that the epileptic activity at the left frontal lobe was propagated from the right frontal lobe, in agreement with the clinical diagnosis. Our novel computational tool can be used to help elucidate complex directional interactions in the human brain. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Optical flow approaches to the identification of brain dynamics
Authors: Lefèvre Julien , Baillet Sylvain
Published: April 2009

The superior temporal resolution of magneto‐ and electroencephalography (MEEG) provides unique insight into the dynamics of brain function. The analysis of the spatial dimensions of MEEG recordings can take a multiplicity of approaches: from the original scalp recordings to the identification of their generators through localizing or imaging techniques. Overall, both MEEG native or imaging data may be considered as multidimensional structures with potentially dense information contents. Quantitative analysis of the spatiotemporal flow of information conveyed by MEEG begins with a feature‐extraction problem, thereby leading to improved insight in the multidimensional structure of brain dynamics. In this contribution, we approach this endeavor by suggesting that brain dynamic features from local through global spatial scales may be identified using the previously‐introduced technique of surface‐based optical flow. We illustrate this assertion by the quantitative analysis of time‐resolved sequences of brain activity through the identification of episodes of relative topographical stability. In that respect, we revisit the concept of brain microstates with a new approach and distinct operational hypotheses. Local dynamic features from a variety of brain systems may also be explored through this methodology, as illustrated by experimental data on fast responses in the visual system as revealed by MEEG source imaging. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
EEG source imaging with spatio‐temporal tomographic nonnegative independent component analysis
Authors: Valdés‐Sosa Pedro A. , Vega‐Hernández Mayrim , Sánchez‐Bornot José Miguel , Martínez‐Montes Eduardo , Bobes María Antonieta
Published: April 2009

This article describes a spatio‐temporal EEG/MEG source imaging (ESI) that extracts a parsimonious set of “atoms” or components, each the outer product of both a spatial and a temporal signature. The sources estimated are localized as smooth, minimally overlapping patches of cortical activation that are obtained by constraining spatial signatures to be nonnegative (NN), orthogonal, sparse, and smooth‐in effect integrating ESI with NN‐ICA. This constitutes a generalization of work by this group on the use of multiple penalties for ESI. A multiplicative update algorithm is derived being stable, fast and converging within seconds near the optimal solution. This procedure, spatio‐temporal tomographic NN ICA (STTONNICA), is equally able to recover superficial or deep sources without additional weighting constraints as tested with simulations. STTONNICA analysis of ERPs to familiar and unfamiliar faces yields an occipital‐fusiform atom activated by all faces and a more frontal atom that only is active with familiar faces. The temporal signatures are at present unconstrained but can be required to be smooth, complex, or following a multivariate autoregressive model. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Comparing MEG and fMRI views to naming actions and objects
Authors: Liljeström Mia , Hultén Annika , Parkkonen Lauri , Salmelin Riitta
Published: April 2009

Most neuroimaging studies are performed using one imaging method only, either functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG). Information on both location and timing has been sought by recording fMRI and EEG, simultaneously, or MEG and fMRI in separate sessions. Such approaches assume similar active areas whether detected via hemodynamic or electrophysiological signatures. Direct comparisons, after independent analysis of data from each imaging modality, have been conducted primarily on low‐level sensory processing. Here, we report MEG (timing and location) and fMRI (location) results in 11 subjects when they named pictures that depicted an action or an object. The experimental design was exactly the same for the two imaging modalities. The MEG data were analyzed with two standard approaches: a set of equivalent current dipoles and a distributed minimum norm estimate. The fMRI blood‐oxygen‐level dependent (BOLD) data were subjected to the usual random‐effect contrast analysis. At the group level, MEG and fMRI data showed fairly good convergence, with both overall activation patterns and task effects localizing to comparable cortical regions. There were some systematic discrepancies, however, and the correspondence was less compelling in the individual subjects. The present analysis should be helpful in reconciling results of fMRI and MEG studies on high‐level cognitive functions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Dynamical MEG source modeling with multi‐target Bayesian filtering
Authors: Sorrentino Alberto , Parkkonen Lauri , Pascarella Annalisa , Campi Cristina , Piana Michele
Published: April 2009

We present a Bayesian filtering approach for automatic estimation of dynamical source models from magnetoencephalographic data. We apply multi‐target Bayesian filtering and the theory of Random Finite Sets in an algorithm that recovers the life times, locations and strengths of a set of dipolar sources. The reconstructed dipoles are clustered in time and space to associate them with sources. We applied this new method to synthetic data sets and show here that it is able to automatically estimate the source structure in most cases more accurately than either traditional multi‐dipole modeling or minimum current estimation performed by uninformed human operators. We also show that from real somatosensory evoked fields the method reconstructs a source constellation comparable to that obtained by multi‐dipole modeling. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Predicting stimulus‐rate sensitivity of human somatosensory fMRI signals with MEG
Authors: Nangini Cathy , Hlushchuk Yevhen , Hari Riitta
Published: April 2009

With increasing stimulus rate (SR), cortical EEG and MEG responses typically decrease in amplitude whereas BOLD fMRI signals increase. To address this discrepancy, we predicted BOLD responses with squared MEG waveforms using a recently proposed energy‐density model. Tactile stimuli were delivered to finger tips at SRs of 1, 4, or 10 Hz in successive 25‐s blocks, and brain signals were detected from area 3b of the primary somatosensory cortex of nine healthy adults using a 306‐channel whole‐scalp neuromagnetometer and a 3‐T fMRI magnet. The main MEG deflections decreased in amplitude as a function of SR, whereas the BOLD signals increased from 1‐ to 4‐Hz SR, with no further change at 10 Hz. MEG energy densities, obtained over the whole stimulus train and convolved with different hemodynamic response functions, predicted both the shape and amplitude of the BOLD signals well, and incorporation of nonlinear terms into the model did not offer any further advantage. Thus, squared MEG waveforms obtained over the entire stimulus train provided an appropriate estimate of area 3b neuronal activity associated with the BOLD signal. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Sources of auditory brainstem responses revisited: Contribution by magnetoencephalography
Authors: Parkkonen Lauri , Fujiki Nobuya , Mäkelä Jyrki P.
Published: April 2009

Auditory brainstem responses provide diagnostic value in pathologies involving the early parts of the auditory pathway. Despite that, the neural generators underlying the various components of these responses have remained unclear. Direct electrical recordings in humans are possible only in limited time periods during surgery and from small regions of the diseased brains. The evidence of the generator sites is therefore fragmented and indirect, based strongly on lesion studies and animal models. Source modeling of EEG has been limited to grand averages across multiple subjects. Here, we employed magnetoencephalography (MEG) to shed more light on the neural origins of the auditory brainstem responses (ABR) and to test whether such deep brain structures are accessible by MEG. We show that the magnetic counterparts of the electric ABRs can be measured in 30 min and that they allow localization of some of the underlying neural sources in individual subjects. Many of the electric ABR components were present in our MEG data; however, the morphologies of the magnetic and electric responses were different, indicating that the MEG signals carry information complementary to the EEG data. The locations of the neural sources corresponding to the magnetic ABR deflections ranged from the auditory nerve to the inferior colliculus. The earliest cortical responses were detectable at the latency of 13 ms. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Clinical applications of magnetoencephalography
Authors: Stufflebeam Steven M. , Tanaka Naoaki , Ahlfors Seppo P.
Published: April 2009

Magnetoencephalography (MEG), in which magnetic fields generated by brain activity are recorded outside of the head, is now in routine clinical practice throughout the world. MEG has become a recognized and vital part of the presurgical evaluation of patients with epilepsy and patients with brain tumors. We review investigations that show an improvement in the postsurgical outcomes of patients with epilepsy by localizing epileptic discharges. We also describe the most common clinical MEG applications that affect the management of patients, and discuss some applications that are close to having a clinical impact on patients. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Synthetic approach for novel bis(α‐aminophosphonic acid) derivatives of chromone containing 1,2,4,3‐triazaphosphole moieties
Authors: Ali Tarik E. , Halacheva Silvia S.
Published: April 2009

Terephthalic acid hydrazide (1) was reacted with phenylphosphonic dichloride to yield bis(1,3,4,2‐oxadiazaphosphole) derivative 3, which was condensed with α‐aminophosphonic acid derivative 4 to afford bis[(1,2,4,3‐triazaphospholyl)(chromonyl)methylphosphonic acid] derivative 5. The addition of diethyl phosphite to Schiff bases 9 and 10 derived from the condensation of bis(4‐amino‐1,2,4,3‐triazaphosphole) derivative 6 or bis(4‐phosphorylamino‐1,2,4,3‐triazaphosphole) derivative 7 with 3‐formyl‐6‐methylchromone (8) yielded bis[(1,2,4,3‐triazaphospholyl)(chromonyl)aminomethylphosphonate] derivative 11 and bis[(1,2,4,3‐triazaphospholyl)(chromonyl)phosphorylamino‐methylphosphonate] derivative 12, respectively. The structures of all products were established by elemental analysis and spectral data. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:117–122, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20520
True identity by immunohistochemistry and molecular morphology of undifferentiated malignancies of the head and neck
Authors: Carbone Antonino , Gloghini Annunziata , Rinaldo Alessandra , Devaney Kenneth O. , Tubbs Raymond , Ferlito Alfio
Published: April 2009

Although conventional squamous carcinomas can often be recognized with little difficulty by experienced pathologists, it remains a fact that a substantial number of head and neck malignancies are capable of posing real challenges to the diagnostic pathologist. Those head and neck tumors showing the least kinship with normal host tissues—that is, the undifferentiated malignancies—are a particular problem and an approach to dealing with them is traced out below. As a matter of basic light microscopy, these tumors can usually be relegated to 1 of 4 categories: small round cell tumors, spindle cell tumors, large polygonal cell (epithelioid) tumors, and pleomorphic tumors. Once they have been so subclassified, these lesions can then be studied by immunohistochemistry and, when necessary, by molecular methods as well. Immunohistochemistry often permits these tumors to be assigned to a particular tissue type, specifically, epithelial, mesenchymal, lymphoid, or melanocytic. Application of additional immunohistochemical antibodies, in turn, can permit further refinement of this impression (eg, allowing distinction of a neuroendocrine tumor from a carcinoma). In selected instances, molecular techniques (such as in situ hybridization) may be employed both for diagnostic as well as for prognostic purposes. It should be borne in mind, however, that the pathologist's diagnosis will sometimes only be as good as the clinical information provided, which is why the diagnosis of undifferentiated malignancies of the head and neck truly is a multifaceted process, demanding the close cooperation of pathologists, clinicians, and radiologists. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Primary laryngeal lymphoma: Report of 3 cases and review of the literature
Authors: Markou Konstantinos , Goudakos John , Constantinidis John , Kostopoulos Ioannis , Vital Victor , Nikolaou Angelos
Published: April 2009

Background

Extranodal lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The aim of this study was to report the experience of our department in the management of these aggressive lesions, as they require special diagnostic and therapeutic attention.

Methods

The case records of 3 patients with the diagnosis of lymphoma involving the larynx were retrospectively reviewed.

Results

The histopathological diagnosis revealed 1 case of marginal zone lymphoma mucosa‐associated lymphoid tissue type, 1 case of T‐lymphoblastic lymphoma, and 1 case of a rare coexistence of in situ squamous cell carcinoma with an isolated intravascular (angioimmunoblastic) lymphoma of peripheral T‐cell origin. Details of the presentation, diagnostic procedures, treatment, and outcome of these patients were presented.

Conclusions

Primary laryngeal lymphoma is a rare entity. Early symptoms are subtle and nonspecific, and confirmation of the diagnosis is often difficult. Because of the rarity of this tumor type, the optimal management remains controversial and it seems that should be managed not as a distinct disease entity but as an unusual presentation of non‐Hodgkin lymphoma, according to the recent treatment trends. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Mechanisms of resistance to EGFR inhibitors in head and neck cancer
Authors: Cooper Jonathan B. , Cohen Ezra Eddy Wyssam
Published: April 2009

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that activates multiple signaling pathways, including phosphatidylinositol‐3‐kinase/v‐AKT murine thymoma viral oncogene homolog protein (Akt), has long been a target of novel therapies. Despite universal EGFR expression in head and neck squamous cell carcinoma (HNSCC), the majority of patients do not respond to EGFR inhibitors. This review focuses on mechanisms of resistance to these agents in HNSCC, and how these may be unique when compared with other malignancies such as non‐small cell lung and colorectal cancers. Published studies and abstracts reveal that there are likely several mechanisms underlying resistance, suggesting that different strategies will be required to improve efficacy of EGFR inhibitors in HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Acupuncture for radiation‐induced xerostomia in patients with cancer: A pilot study
Authors: Garcia M. Kay , Chiang Joseph S. , Cohen Lorenzo , Liu Meide , Palmer J. Lynn , Rosenthal David I. , Wei Qi , Tung Samuel , Wang Congjun , Rahlfs Thomas , Chambers Mark S.
Published: April 2009

Background

This pilot study evaluated if acupuncture can alleviate radiation‐induced xerostomia among patients with cancer. Secondary objectives were to assess the effects of acupuncture on salivary flow and quality of life (QOL).

Methods

Nineteen patients received acupuncture twice a week for 4 weeks.

Results

Xerostomia inventory (XI) and patient benefit questionnaire (PBQ) scores were significantly better after acupuncture on weeks 4 and 8 than at baseline (XI: p = .0004 and .0001; PBQ: p = .0004 and .0011, respectively). For QOL at weeks 4 and 8, there was a significant difference for questions related to head/neck cancer (p = .04 and .006, respectively). At week 8, there was a significant difference in physical well‐being (p = .04). At weeks 5 and 8, there were significant differences in the total score (p = .04 and .03, respectively).

Conclusions

Acupuncture was effective for radiation‐induced xerostomia in this small pilot study. Further research is needed. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Comparative study on chronic tissue damage after cordectomies using either CO2 laser or microdissection electrodes
Authors: Zapater Enrique , Frías Soledad , Pérez Ana , Basterra Jorge
Published: April 2009

Background.

This study compared the chronic damage to laryngeal soft tissues produced by microdissection electrodes and a CO2 laser after cordectomies.

Methods.

We included patients who were operated on to treat T1 glottic carcinomas and needed a second laryngeal surgery. We examined specimens from 6 patients each operated on with a CO2 laser or microdissection electrodes. The specimens were processed using Masson trichrome. We studied the grade and level of collagenization and analyzed relationships with age, interval between surgical procedures, and device.

Results.

Control samples showed low collagenization. Second samples showed moderate collagenization, which was similar regardless of whether microdissection electrodes or a CO2 laser was used. A relationship was observed between the level of collagenization and interval between surgeries, irrespective of the surgical procedure used.

Conclusions.

The chronic vocal fold tissue damage produced by a CO2 laser and microdissection electrodes was similar. In our series, the vocal fold scar was completed between weeks 12 and 20. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase #
Authors: Yano Masahiko , Ikeda Masanori , Abe Ken-ichi , Kawai Yoshinari , Kuroki Misao , Mori Kyoko , Dansako Hiromichi , Ariumi Yasuo , Ohkoshi Shougo , Aoyagi Yutaka , Kato Nobuyuki
Published: April 2009

Recently, we reported that β-carotene, vitamin D2, and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti-HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved in their anti-HCV activities. However, the molecular mechanism by which oxidative stress induces anti-HCV status remains unknown. Oxidative stress is also known to activate extracellular signal-regulated kinase (ERK). Therefore, we hypothesized that oxidative stress induces anti-HCV status via the mitogen activated protein kinase (MAPK)/ERK kinase (MEK)–ERK1/2 signaling pathway. In this study, we found that the MEK1/2-specific inhibitor U0126 abolished the anti-HCV activities of the three nutrients in a dose-dependent manner. Moreover, U0126 significantly attenuated the anti-HCV activities of polyunsaturated fatty acids, interferon-γ, and cyclosporine A, but not statins. We further demonstrated that, with the exception of the statins, all of these anti-HCV nutrients and reagents actually induced activation of the MEK–ERK1/2 signaling pathway, which was inhibited or reduced by treatment not only with U0126 but also with vitamin E. We also demonstrated that phosphorylation of ERK1/2 by cyclosporine A was attenuated with N-acetylcysteine treatment and led to the negation of inhibition of HCV RNA replication. We propose that a cellular process that follows ERK1/2 phosphorylation and is specific to oxidative stimulation might lead to down-regulation of HCV RNA replication. Conclusion: Our results demonstrate the involvement of the MEK–ERK1/2 signaling pathway in the anti-HCV status induced by oxidative stress in a broad range of anti-HCV reagents. This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication. (Hepatology 2009.)
Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C #
Authors: Vanni Ester , Abate Maria Lorena , Gentilcore Elena , Hickman Ingrid , Gambino Roberto , Cassader Maurizio , Smedile Antonina , Ferrannini Ele , Rizzetto Mario , Marchesini Giulio , Gastaldelli Amalia , Bugianesi Elisabetta
Published: April 2009

Chronic hepatitis C (CHC) has been associated with type 2 diabetes and insulin resistance, but the extent of impairment in insulin action, the target pathways involved, and the role of the virus per se have not been defined. In this study, we performed a euglycemic hyperinsulinemic clamp (1 mU · minute−1 · kg−1) coupled with infusion of tracers ([6,6-2H2]glucose, [2H5]glycerol) and indirect calorimetry in 14 patients with biopsy-proven CHC, who were selected not to have any features of the metabolic syndrome, and in seven healthy controls. We also measured liver expression of inflammatory cytokines/mediators and tested their association with the metabolic parameters. Compared to controls, in patients with CHC: (1) total glucose disposal (TGD) during the clamp was 25% lower (P = 0.003) due to impaired glucose oxidation (P = 0.0002), (2) basal endogenous glucose production (EGP) was 20% higher (P = 0.011) and its suppression during the clamp was markedly reduced (P = 0.007), and (3) glycerol appearance was not different in the basal state or during the clamp, but lipid oxidation was less suppressed by insulin (P = 0.004). Lipid oxidation was higher in patients with CHC who had more steatosis and was directly related to EGP, TGD, and glucose oxidation. The decreased insulin-stimulated suppression of EGP was associated with increased hepatic suppressor of cytokine signaling 3 (SOCS3; P < 0.05) and interleukin-18 (P < 0.05) expression. Conclusion: Hepatitis C infection per se is associated with peripheral and hepatic insulin resistance. Substrate competition by increased lipid oxidation and possibly enhanced hepatic expression of inflammatory cytokines/mediators could be involved in the defective glucose regulation. (Hepatology 2009.)
The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders #
Authors: Keitel Verena , Cupisti Kenko , Ullmer Christoph , Knoefel Wolfram T. , Kubitz Ralf , Häussinger Dieter
Published: April 2009

TGR5 (Gpbar-1) is a plasma membrane-bound, G protein–coupled receptor for bile acids. TGR5 messenger RNA (mRNA) has been detected in many tissues, including rat cholangiocytes and mouse gallbladder. A role for TGR5 in gallstone formation has been suggested, because TGR5 knockout mice did not develop gallstones when fed a lithogenic diet. In this study, expression and localization of TGR5 was studied in human gallbladders. TGR5 mRNA and protein were detected in all 19 gallbladders. Although TGR5 mRNA was significantly elevated in the presence of gallstones, no such relation was found for TGR5 protein levels. In order to study the localization of TGR5 in human gallbladders, a novel antibody was generated. The receptor was localized in the apical membrane and the rab11-positive recycling endosome of gallbladder epithelial cells. Furthermore, the TGR5 staining colocalized with the cyclic adenosine monophosphate–regulated chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) and the apical sodium-dependent bile salt uptake transporter, suggesting a functional coupling of TGR5 to bile acid uptake and chloride secretion. Stimulation with bile acids significantly increased cyclic adenosine monophosphate concentration in human gallbladder tissue. Incubation of gallbladder epithelial cells with a TGR5 agonist led to a rise ofN-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE)-fluorescence, suggestive of a decrease in intracellular chloride concentration. The TGR5 agonist–dependent increase in MQAE-fluorescence was absent in TGR5 knockout mice or in the presence of a CFTR inhibitor, indicating that TGR5 mediates chloride secretion via activation of CFTR. The presence of the receptor in both the plasma membrane and the recycling endosome indicate that TGR5 can be regulated by translocation.Conclusion:The data suggest a role for TGR5 in bile acid–induced fluid secretion in biliary epithelial cells. (Hepatology 2009.)
Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus #
Authors: Aly Hussein Hassan , Qi Yue , Atsuzawa Kimie , Usuda Nobuteru , Takada Yasutsugu , Mizokami Masashi , Shimotohno Kunitada , Hijikata Makoto
Published: April 2009

We developed an in vitro system that can be used for the study of the life cycle of a wide variety of blood-borne hepatitis C viruses (HCV) from various patients using a three-dimensional hollow fiber culture system and an immortalized primary human hepatocyte (HuS-E/2) cell line. Unlike the conventional two-dimensional culture, this system not only enhanced the infectivity of blood-borne HCV but also supported its long-term proliferation and the production of infectious virus particles. Both sucrose gradient fractionation and electron microscopy examination showed that the produced virus-like particles are within a similar fraction and size range to those previously reported. Infection with different HCV strains showed strain-dependent different patterns of HCV proliferation and particle production. Fluctuation of virus proliferation and particle production was found during prolonged culture and was found to be associated with change in the major replicating virus strain. Induction of cellular apoptosis was only found when strains of HCV-2a genotype were used for infection. Interferon-alpha stimulation also varied among different strains of HCV-1b genotypes tested in this study. Conclusion: These results suggest that this in vitro infection system can reproduce strain-dependent events reflecting viral dynamics and virus-cell interactions at the early phase of blood-borne HCV infection, and that this system can allow the development of new anti-HCV strategies specific to various HCV strains. (Hepatology 2009.)
Field study of macropore flow processes using tension infiltration of a dye tracer in partially saturated soils
Authors: Cey Edwin E. , Rudolph David L.
Published: April 2009

Macropores are important preferential pathways for the migration of water and contaminants through the vadose zone. The objective of this study was to examine small‐scale preferential flow processes during infiltration in macroporous, low permeability soils. A series of tension infiltration tests were conducted using Brilliant Blue dye tracer at two field sites in southwestern Ontario, Canada. The maximum applied pressure head was varied for each test and the resulting dye stain patterns and macropore networks were characterized by excavation, mapping, photography, and image analysis. Worm burrows were the dominant macropore type, with average macropore densities exceeding 400 m−2 and peak densities of more than 750 m−2 at 30 cm depth at both sites. Flow in macropores became significant at infiltration pressures > − 3 cm, with corresponding increases in infiltration rate, soil water content variability (spatially and temporally), and depth of dye staining. The results demonstrated clear evidence for partially saturated macropore flow under porewater tension conditions and the associated importance of macropore–matrix interaction in controlling this flow. Field observations of transient infiltration showed that film and rivulet flow along macropores yielded vertical flow velocities exceeding 40 m d−1. Simple calculations showed that film flow along the walls and corners of irregularly shaped macropores could explain the observed results. Copyright © 2009 John Wiley & Sons, Ltd.
Regulation of HSP70 on activating macrophages using PDT‐induced apoptotic cells
Authors: Zhou Feifan , Xing Da , Chen Wei R.
Published: April 2009

Although anti‐tumor immunological responses have been mainly associated with necrosis, apoptosis‐associated immune responses have been recently suggested as well. In this study, we investigated anti‐tumor immune responses and regulatory mechanisms of HSP70 using apoptotic cells induced by photodynamic therapy (PDT). The relationships between HSP70 release, HSP70 translocation and macrophage responses were studied using confocal fluorescence microscopy, FACS and ELISA. Macrophages incubated with apoptotic cells as well as necrotic tumor cells showed a high level of TNFα secretion. Apoptotic cells but not the apoptotic cell supernatants induced TNFα secretion. During both necrosis and apoptosis processes, the TNFα production was diminished drastically when HSP70 or TLR‐2 was inhibited. After the PDT treatment, cytoplasmic HSP70 was released from the necrotic cells, while HSP70 rapidly translocated to the surface of the apoptotic cells. Furthermore, the TNFα secretion and the tumor cytotoxicity of splenocytes from mice immunized with apoptotic cells appeared similar to that of splenocytes immunized with necrotic cells. Our in vitro and in vivo results show that apoptosis can potentially have higher impact in inducing immunological responses, hence clarifying the immunological regulatory mechanisms of HSP70 under cell apoptosis and necrosis induced by PDT treatment. These findings could lead to an optimal PDT treatment based on immunological responses. © 2009 UICC
Predicting nominal exchange rate movements using skewness information from options prices
Authors: Ratcliff Ryan
Published: April 2009

This paper uses a measure of the relative price of out‐of‐the‐money (OTM) European put and call currency options to forecast daily movements in the dollar/euro exchange rate over the period of January 2002–June 2004. As these OTM options are pure bets on future movements of the exchange rate, their relative price contains information about the market's estimate of the relative probabilities of appreciation or depreciation of the euro over the life of the options. Forecasts that include the relative price of the OTM options offer significantly better out‐of‐sample predictions of tomorrow's exchange rate than either the simple random walk or an interest rate parity model. These results offer new insight into the puzzle of the day‐to‐day volatility of currency prices that should be driven by slow‐moving macro fundamentals. Copyright © 2009 John Wiley & Sons, Ltd.
Photonics‐based In Vivo total hemoglobin monitoring and clinical relevance
Authors: McMurdy John , Jay Gregory , Suner Selim , Crawford Gregory
Published: April 2009

Anemia is a serious disorder which, as a result of antiquated invasive blood testing, is undiagnosed in millions of people in the U.S. As a result of the clinical need, many technological solutions have been proposed to measure total blood hemoglobin, and thus diagnose anemia, noninvasively. Because hemoglobin is the strongest chromophore in tissue, spectroscopic methods have been the most prevalently investigated. Difficulties in extracting a quantitative estimation of hemoglobin based on tissue absorption include variability in the absorption spectra of hemoglobin derivatives, interference from other tissue chromophores, and interpatient physiological variations affecting the effective optical pathlength of light propagating in tissue. In spite of these challenges, studies with a high degree of correlation between in vitro and in vivo measured total hemoglobin have been disclosed using variants of transmission and diffuse reflection spectroscopy in assorted physiological locations. A review of these technologies and the relevant advantages/disadvantages are presented here. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of different modifications of a calcium phosphate bone cement on adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells
Authors: Vater Corina , Lode Anja , Bernhardt Anne , Reinstorf Antje , Heinemann Christiane , Gelinsky Michael
Published: April 2009

Collagen and noncollagenous proteins of the extracellular bone matrix are able to stimulate bone cell activities and bone healing. The modification of calcium phosphate bone cements used as temporary bone replacement materials with these proteins seems to be a promising approach to accelerate new bone formation. In this study, we investigated adhesion, proliferation, and osteogenic differentiation of human bone marrow stromal cells (hBMSC) on Biocement D/collagen composites which have been modified with osteocalcin and O‐phospho‐L‐serine. Modification with osteocalcin was carried out by its addition to the cement precursor before setting as well as by functionalization of the cement samples after setting and sterilization. hBMSC were cultured on these samples for 28 days with and without osteogenic supplements. We found a positive impact especially of the phosphoserine‐modifications but also of both osteocalcin‐modifications on differentiation of hBMSC indicated by higher expression of the osteoblastic markers matrix metalloproteinase‐13 and bone sialo protein II. For hBMSC cultured on phosphoserine‐containing composites, an increased proliferation has been observed. However, in case of the osteocalcin‐modified samples, only osteocalcin adsorbed after setting and sterilization of the cement samples was able to promote initial adhesion and proliferation of hBMSC. The addition of osteocalcin before setting results in a finer microstructure but the biological activity of osteocalcin might be impaired due to the sterilization process. Thus, our data indicate that the initial adhesion and proliferation of hBMSC is enhanced rather by the biological activity of osteocalcin than by the finer microstructure. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Effects of cholesterol‐bearing pullulan (CHP)‐nanogels in combination with prostaglandin E1 on wound healing
Authors: Kobayashi Hiroshi , Katakura Osamu , Morimoto Nobuyuki , Akiyoshi Kazunari , Kasugai Shohei
Published: April 2009

The cholesterol‐bearing pullulan (CHP)‐nanogels are able to trap hydrophobic drugs or proteins inside the nanogels, which is potential in application to drug delivery system and tissue engineering. On the other hand, prostaglandin E1 (PGE1) plays important roles in wound healing and PGE1 ointment has been clinically used to treat chronic skin ulcers and wounds. The purpose of this study is to evaluate effects of CHP nanogels in combination with prostaglandin E1 on wound healing in full thickness skin defect model. A square skin defect (1 × 1 cm2) of full thickness was created on the dorsal of Wistar rats. The wound was treated with CHP nanogels without PGE1 (CHP group) or CHP nanogels containing with PGE1 (CHP/PGE1 group) or PGE1 ointment (PGE1 ointment group). In both CHP/PGE1 and PGE1 ointment groups, ∼6 μg of PGE1 was applied to each wound. In the control group, the wound was untreated. The wound was evaluated in measuring wound area and histologically. In CHP/PGE1 group, the rate of wound size reduction was significantly higher than the ones of other groups. Histologically, CHP/PGE1 promoted neoepithelialization, neovascularization, and wound closure compared to the other treatments. These results suggest that CHP in combination with PGE1 can promote wound healing, which confirms the efficiency of CHP nanogels‐based drug delivery system. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
In vivo and in vitro evaluation of gelation and hemostatic properties of a novel tissue‐adhesive hydrogel containing a cross‐linkable polymeric micelle
Authors: Murakami Yoshihiko , Yokoyama Masayuki , Nishida Hiroshi , Tomizawa Yasuko , Kurosawa Hiromi
Published: April 2009

There is a clinical requirement for a local hemostat that arrests bleeding from both suture holes and cross‐sectional surfaces of parenchymatous organs. A novel tissue‐adhesive hydrogel was prepared that contains a cross‐linkable polymeric micelle consisting of poly(ethylene glycol)‐poly(DL‐lactide) block polymers, and, by means of a rheometer, the factors that affect the hydrogel's gelation properties was clarified. The storage modulus and the gelation time greatly depended on both the pH and the concentrations of both the polymeric micelle and polyallylamine solutions. Furthermore, the hemostatic potential of the hydrogel in a mouse hemostasis model was evaluated under optimal conditions as determined by the rheometer. The average amount of bleeding from the mouse liver was 172.9 mg (S.D. 69.7 mg, N = 7) in the control experiments, whereas it was 20.1 mg (s.d. 13.2, N = 7) when the hydrogel was applied to the wound (p = 0.002). The result demonstrated that the novel synthetic hydrogel possessed a significant hemostatic potential as a local hemostat. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
In situ preparation and characterization of a novel gelatin/poly(D,L‐lactide)/hydroxyapatite nanocomposite
Authors: Zheng Xiaotong , Zhou Shaobing , Xiao Yu , Yu Xiongjun , Feng Bo
Published: April 2009

A novel biodegradable polymer–ceramic nanocomposite was prepared using the in situ preparation method, which consisted of gelatin (gel), poly(D,L‐lactide) (PDLLA), and hydroxyapatite (HA) nanofibers. In this article, the HA nanofibers with length/diameter (L/D) ratio of 19.8 in gel/PDLLA/HA nanocomposites were synthesized and precipitated in polymeric matrix by one‐step hydrothermal mineralization. The crystalline phases, structural morphology, mechanical characterization, and chemical interaction of gel/PDLLA/HA nanocomposites were investigated by X‐ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive X‐ray spectroscopy, mechanical test, and Fourier transform infrared spectroscopy. The results showed that the crystalline HA nanofibers were uniformly mineralized in gel and PDLLA matrix and the interaction between Ca2+ in HA (nanofibers and negative‐charged functional groups in gel and PDLLA molecular chains was formed. Thus, the schematic model of two polymeric chains bridged by inorganic nanofibers was designed on the basis of the experimental results. Moreover, it can clearly explain why the mechanical properties of gel/PDLLA/HA nanocomposites turned strong. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
A complete solution to the existence problem for 1‐rotational k‐cycle systems of Kv
Authors: Wu Shung‐Liang , Buratti Marco
Published: April 2009

The necessary and sufficient conditions for the existence of a 1‐rotational k‐cycle system of the complete graph Kv are established. The proof provides an algorithm able to determine, directly and explicitly, an odd k‐cycle system of Kv whenever such a system exists. © 2009 Wiley Periodicals,
Inc. J Combin Designs 17: 283–293, 2009
Generalized Hadamard matrices whose transposes are not generalized Hadamard matrices
Authors: Craigen R. , de Launey W.
Published: April 2009

In answer to “Research Problem 16” in Horadam's recent book Hadamard matrices and their applications, we provide a construction for generalized Hadamard matrices whose transposes are not generalized Hadamard matrices. © 2009 Wiley Periodicals,
Inc. J Combin Designs 17: 456–458, 2009