bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mouse embryonic stem cell model of Schwann cell differentiation for studies of the role of neurofibromatosis type 1 in Schwann cell development and tumor formation
Authors: Roth Therese M. , Ramamurthy Poornapriya , Ebisu Fumi , Lisak Robert P. , Bealmear Beverly M. , Barald Kate F. 
Published: June 2007

AbstractThe neurofibromatosis Type 1 (NF1) gene functions as a tumor suppressor gene. One known function of neurofibromin, the NF1 protein product, is to accelerate the slow intrinsic GTPase activity of Ras to increase the production of inactive rasGDP, with wide‐ranging effects on p21ras pathways. Loss of neurofibromin in the autosomal dominant disorder NF1 is associated with tumors of the peripheral nervous system, particularly neurofibromas, benign lesions in which the major affected cell type is the Schwann cell (SC). NF1 is the most common cancer predisposition syndrome affecting the nervous system. We have developed an in vitro system for differentiating mouse embryonic stem cells (mESC) that are NF1 wild type (+/+), heterozygous (+/−), or null (−/−) into SC‐like cells to study the role of NF1 in SC development and tumor formation. These mES‐generated SC‐like cells, regardless of their NF1 status, express SC markers correlated with their stage of maturation, including myelin proteins. They also support and preferentially direct neurite outgrowth from primary neurons. NF1 null and heterozygous SC‐like cells proliferate at an accelerated rate compared to NF1 wild type; this growth advantage can be reverted to wild type levels using an inhibitor of MAP kinase kinase (Mek). The mESC of all NF1 types can also be differentiated into neuron‐like cells. This novel model system provides an ideal paradigm for studies of the role of NF1 in cell growth and differentiation of the different cell types affected by NF1 in cells with differing levels of neurofibromin that are neither transformed nor malignant. © 2007 Wiley‐Liss, Inc.
α7β1 integrin is a receptor for laminin‐2 on Schwann cells
Authors: Chernousov Michael A. , Kaufman Stephen J. , Stahl Richard C. , Rothblum Katrina , Carey David J. 
Published: June 2007

AbstractThe Schwann cell basal lamina acts as an organizer of peripheral nerve tissue and influences many aspects of cell behavior during development and regeneration. A principal component of the Schwann cell basal lamina is laminin‐2. This study was undertaken to identify Schwann cell receptors for laminin‐2. We found that among several Schwann cell integrins that can potentially interact with laminin‐2, only α7β1 bound to laminin‐2‐Sepharose. Dystroglycan, a non‐integrin Schwann cell receptor for laminin‐2 identified previously, was also found to bind to laminin‐2‐Sepharose. Antibody to the α7 integrin subunit partially inhibited Schwann cell adhesion to laminin‐2. Small interfering RNA‐mediated suppression of either α7 integrin or dystroglycan expression decreased adhesion and spreading of Schwann cells on laminin‐2, whereas knocking down both proteins together inhibited adhesion and spreading on laminin‐2 almost completely. α7 integrin and dystroglycan both colocalized with laminin‐2 containing basal lamina tubes in differentiating neuron–Schwann cell cocultures. The α7β1 integrin also coprecipitates with focal adhesion kinase in differentiating cocultures. These findings strongly suggest that α7β1 integrin is a Schwann cell receptor for laminin‐2 that provides transmembrane linkage between the Schwann cell basal lamina and cytoskeleton. © 2007 Wiley‐Liss, Inc.
Phenotypic characterization of neural stem cells from human fetal spinal cord: Synergistic effect of LIF and BMP4 to generate astrocytes
Authors: Weible Michael W. , Chan‐Ling Tailoi 
Published: June 2007

AbstractIf cell based therapy for spinal cord injury is to become a reality, greater insights into the biology of human derived spinal cord stem cells are a prerequisite. Significant species differences and regional specification of stem cells necessitates determining the effects of growth factors on human spinal cord stem cells. Fetal spinal cords were dissociated and expanded as neurospheres in medium with bone morphogenetic protein 4 (BMP4), leukemia inhibitory factor (LIF) or BMP4 and LIF. First‐generation neurospheres comprised a heterogeneous population of neural cell types and after plating emergent cells included neurons, oligodendrocytes and GFAP+ cells which coexpressed stem cells markers and those of the neuronal lineage and were thus identified as GFAP+ neural precursor cells (NPC). When plated, neurospheres maintained in BMP4 demonstrated a reduced proportion of emergent oligodendrocytes from 13 to 4%, whereas LIF had no statistically significant effect on cell type distribution. Combining BMP4 and LIF reduced the proportion of oligodendrocytes to 3% and that of neurons from 37 to 16% while increasing the proportion of GFAP+ NPC from 45 to 79%. After 10 passages in control media aggregates gave rise to multiple neural phenotypes and only continued passage of neurospheres in the presence of BMP4 and LIF resulted in unipotent aggregates giving rise to only astrocytes. These results provide a means of obtaining pure populations of human spinal‐cord derived astrocytes, which could be utilized for further studies of cell replacement strategies or in vitro evaluation of therapeutics. © 2007 Wiley‐Liss, Inc.
Electromagnetic source imaging: Backus–Gilbert resolution spread function‐constrained and functional MRI‐guided spatial filtering
Authors: Wan Xiaohong , Sekiguchi Atsushi , Yokoyama Satoru , Riera Jorge , Kawashima Ryuta 
Published: June 2007

AbstractElectromagnetic source imaging techniques are usually limited by their low spatial resolution, even though these techniques have high temporal resolution. Our heuristic analysis shows that the spatial ambiguity of electromagnetic source localization arises from interference from other sources. In this paper, we suggest a new inverse solution based on the principle of spatial filtering to effectively suppress the interference from other sources, especially from the far sources. By means of this approach, functional MRI information can also be effectively integrated into the inverse solution to further improve spatial accuracy of source localization. Most importantly, the results of source localization by this approach are not significantly biased by incompatible fMRI information. Our simulations and experimental results using electroencephalography based on a realistic head model show that the Backus–Gilbert resolution spread function‐constrained and functional MRI‐guided spatial filtering suggested in this paper provide high spatial accuracy and resolution of source localization, even in the presence of multiple simultaneously active sources. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
A meta‐analytic study of changes in brain activation in depression
Authors: Fitzgerald Paul B. , Laird Angela R. , Maller Jerome , Daskalakis Zafiris J. 
Published: June 2007

AbstractObjective: A large number of studies with considerably variable methods have been performed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta‐analytic technique to synthesise the results of much of this research. Methods: Three separate quantitative meta‐analytical studies were conducted using the Activation Likelihood Estimation technique. Analysis was performed on three types of studies: (1) those conducted at rest comparing brain activation in patients with depression and controls; (2) those involving brain changes following antidepressant treatment; and (3) those comparing brain activation patterns induced by the induction of positive or negative emotion in patients with depression compared with controls. Results: There appears to be a complex series of areas of the brain implicated in the pathophysiology of depression although limited overlap was found across imaging paradigms. This included a network of regions including frontal and temporal cortex as well as the insula and cerebellum that are hypoactive in depressed subjects and in which there is increase in activity with treatment. There was a corresponding set of subcortical and limbic regions in which opposite changes were found. Conclusions: There is limited overlap between the brain regions identified using differing imaging methods. The most consistently identified regions include areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia and cerebellum. Further research is required to identify if different imaging methods are identifying complementary networks that are equally involved in the disorder. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
fMRI reveals that non‐local processing in ventral retinotopic cortex underlies perceptual grouping by temporal synchrony
Authors: Caplovitz Gideon P. , Barroso Diego J. , Hsieh Po‐Jang , Tse Peter U. 
Published: June 2007

AbstractWhen spatially separated objects appear and disappear in a synchronous manner, they perceptually group into a single global object that itself appears and disappears. We employed functional magnetic resonance imaging (fMRI) to identify brain regions involved in this type of perceptual grouping. Subjects viewed four chromatically‐defined disks (one per visual quadrant) that flashed on and off. We contrasted %BOLD signal changes between blocks of synchronously flashing disks (Grouping) with blocks of asynchronously flashing disks (no‐Grouping). Results: A region of interest analysis revealed %BOLD signal change in the Grouping condition was significantly greater than in the no‐Grouping condition within retinotopic areas V2, V3, and V4v. Within a single quadrant of the visual field, the spatio‐temporal information present in the image was identical across the two stimulus conditions. As such, the two conditions could not be distinguished from each other on the basis of the rate or pattern of flashing within a single visual quadrant. The observed results must therefore arise through nonlocal interactions between or within these retinotopic areas, or arise from outside these retinotopic areas. Furthermore, when V2 and V3 were split into ventral and dorsal sub‐ROIs, ventral retinotopic areas V2v and V3v preferentially differentiated between the two conditions whereas the corresponding dorsal areas V2d and V3d did not. In contrast, within hMT+, %BOLD signal was significantly greater in the no‐Grouping condition. Conclusion: Nonlocal processing within, between, or to ventral retinotopic cortex at least as early as V2v, and including V3v, and V4v, underlies perceptual grouping via temporal synchrony. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Ranking and averaging independent component analysis by reproducibility (RAICAR)
Authors: Yang Zhi , LaConte Stephen , Weng Xuchu , Hu Xiaoping 
Published: June 2007

AbstractIndependent component analysis (ICA) is a data‐driven approach that has exhibited great utility for functional magnetic resonance imaging (fMRI). Standard ICA implementations, however, do not provide the number and relative importance of the resulting components. In addition, ICA algorithms utilizing gradient‐based optimization give decompositions that are dependent on initialization values, which can lead to dramatically different results. In this work, a new method, RAICAR (Ranking and Averaging Independent Component Analysis by Reproducibility), is introduced to address these issues for spatial ICA applied to fMRI. RAICAR utilizes repeated ICA realizations and relies on the reproducibility between them to rank and select components. Different realizations are aligned based on correlations, leading to aligned components. Each component is ranked and thresholded based on between‐realization correlations. Furthermore, different realizations of each aligned component are selectively averaged to generate the final estimate of the given component. Reliability and accuracy of this method are demonstrated with both simulated and experimental fMRI data. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery
Authors: Wen Wei-Hong , Liu Jia-Yun , Qin Wei-Jun , Zhao Jing , Wang Tao , Jia Lin-Tao , Meng Yan-Ling , Gao Hui , Xue Cai-Fang , Jin Bo-Quan , Yao Li-Bo , Chen Si-Yi , Yang An-Gang 
Published: June 2007

Abstract

RNA interference is highly effective at inhibiting HBV gene expression and replication. However, before small interfering RNA (siRNA) can be used in the clinic, it is essential to develop a system to target their delivery. Antibody-mediated delivery is a novel approach for targeting siRNA to appropriate cells. In this report, we asked whether this siRNA delivery strategy would be effective against HBV. Of 5 candidates, a specific siRNA that effectively inhibited HBV gene expression and replication was determined. Two fusion proteins, s-tP and sCκ-tP, were constructed to contain a single chain of the human variable fragment, scFv, against hepatitis B surface antigen (HBsAg), a truncated protamine (tP), and in the case of sCκ-tP, a constant region of the κ chain (Cκ). S-tP and sCκ-tP were developed to provide targeted delivery of the siRNA, siRNA expressing cassettes (SEC), and siRNA-producing plasmids. Fluorescein isothiocyanate-siRNA, fluorescein isothiocyanate-SEC, and plasmid DNA were specifically delivered into HBsAg-positive cells using the sCκ-tP fusion protein, and effectively inhibited HBV gene expression and replication. HBV gene expression was also inhibited by siRNA or siRNA-producing plasmids in HBV transgenic mice.

Conclusion:

Our results describe a potential method for the targeted delivery of siRNA or siRNA-producing plasmids against HBV, using anti-HBsAg fusion proteins. (HEPATOLOGY 2007;46:84–94.)
A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes
Authors: Fraser Abigail , Ebrahim Shah , Davey Smith George , Lawlor Debbie A. 
Published: June 2007

Abstract

Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (

P

for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women.

Conclusion:

elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population. (HEPATOLOGY 2007;46:158–165.)
Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver
Authors: Patel Rushang D. , Hollingshead Brett D. , Omiecinski Curtis J. , Perdew Gary H. 
Published: June 2007

Abstract

The aryl-hydrocarbon receptor (AhR) is a basic helix-loop-helix/Per-Arnt-Sim transcription factor that can be activated by exogenous as well as endogenous ligands. AhR is traditionally associated with xenobiotic metabolism. In an attempt to identify novel target genes, C57BL/6J mice were treated with β-naphthoflavone (BNF), a known AhR ligand, and genome-wide expression analysis studies were performed using high-density microarrays. Constitutive androstane receptor (CAR) was found to be one of the differentially regulated genes. Real-time quantitative polymerase chain reaction (qPCR) verified the increase in CAR messenger RNA (mRNA) level. BNF treatment did not increase CAR mRNA in AhR-null mice. Time-course studies in mice revealed that the regulation of CAR mRNA mimicked that of

Cyp1A1

, a known AhR target gene. To demonstrate that the increase in CAR mRNA translates to an increase in functional CAR protein, mice were sequentially treated with BNF (6 hours) followed by the selective CAR agonist, TCPOBOP (3 hours). qPCR revealed an increase in the mRNA level of

Cyp2b10

, previously known to be regulated by CAR. This also suggests that CAR protein is present in limiting amounts with respect to its transactivation ability. Finally, CAR was also up-regulated in primary human hepatocytes in response to AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a]pyrene.

Conclusion:

This study identifies a mode of up-regulating CAR and potentially expands the role of AhR in drug metabolism. This study also demonstrates

in vivo

up-regulation of CAR through chemical exposure. (HEPATOLOGY 2007;46:209–218.)
Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor β signaling, promoting cirrhosis and hepatocellular carcinoma
Authors: Matsuzaki Koichi , Murata Miki , Yoshida Katsunori , Sekimoto Go , Uemura Yoshiko , Sakaida Noriko , Kaibori Masaki , Kamiyama Yasuo , Nishizawa Mikio , Fujisawa Junichi , Okazaki Kazuichi , Seki Toshihito 
Published: June 2007

Abstract

Many patients with chronic hepatitis caused by hepatitis C virus (HCV) infection develop liver fibrosis with high risk for hepatocellular carcinoma (HCC), but the mechanism underling this process is unclear. Conversely, transforming growth factor beta (TGF-β) activates not only TGF-β type I receptor (TβRI) but also c-Jun N-terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Whereas the TβRI/pSmad3C pathway suppresses epithelial cell growth by upregulating p21WAF1 transcription, JNK/pSmad3L-mediated signaling promotes extracellular matrix deposition, partly, by upregulating plasminogen activator inhibitor 1 (PAI-1). We studied the domain-specific Smad3 phosphorylation in biopsy specimens representing chronic hepatitis, cirrhosis, or HCC from 100 patients chronically infected with HCV, and correlated Smad3 phosphorylation with clinical course. As HCV-infected livers progressed from chronic hepatitis through cirrhosis to HCC, hepatocytic pSmad3L/PAI-1 increased with fibrotic stage and necroinflammatory grade, and pSmad3C/p21WAF1 decreased. Of 14 patients with chronic hepatitis C with strong hepatocytic pSmad3L positivity, 8 developed HCC within 12 years; only 1 of 12 showing little pSmad3L positivity developed HCC. We further sought molecular mechanisms

in vitro

. JNK activation by the pro-inflammatory cytokine interleukin-1β stimulated the pSmad3L/PAI-1 pathway in facilitating hepatocytic invasion, in the meantime reducing TGF-β-dependent tumor-suppressive activity by the pSmad3C/p21WAF1 pathway.

Conclusion:

These results indicate that chronic inflammation associated with HCV infection shifts hepatocytic TGF-β signaling from tumor-suppression to fibrogenesis, accelerating liver fibrosis and increasing risk for HCC. (HEPATOLOGY 2007;46:48–57.)
Telangiectatic adenoma
Authors: Paradis Valérie , Champault Axelle , Ronot Maxime , Deschamps Lydia , Valla Dominique-Charles , Vidaud Dominique , Vilgrain Valérie , Belghiti Jacques , Bedossa Pierre 
Published: June 2007

Abstract

What were previously called telangiectatic focal nodular hyperplasias are in fact true adenomas with telangiectatic features (TAs) without overt characterized genetic abnormalities. The aim of our study was to review a surgical series of TAs in order to describe clinical, biological, and radiological findings of these lesions and to evaluate their outcomes. From January 1996 to November 2005, 284 patients with benign hepatocellular nodules underwent surgical resection at Beaujon Hospital. Among them, 32 TAs from 27 patients were diagnosed. Ninety-two percent of the patients were women. Mean age was 38 years (range 17–63). Mean body mass index was 28 (range 18–49), with 16 patients being overweight. Symptoms revealed lesions in 10 patients. In 13 patients, TA was associated with another benign liver lesion. Mean size of the TAs was 5 cm (range 1–17 cm). Histological analysis showed cellular atypias in 6 cases (19%), steatosis in 17 cases (53%), vascular changes in 19 cases (59%), and significant inflammatory infiltrate in 29 cases (91%). In 1 case, the TA had foci of well-differentiated hepatocellular carcinoma. In 18 of the 26 cases (69%), adjacent liver showed significant steatosis. Serum biomarkers of inflammation were increased in 90% of patients (19 of 22). After surgical resection, inflammatory marker levels returned to normal values in all patients tested.

Conclusion:

This study has shown that TAs occur in a characteristic background of overweight patients and are often associated with a biological inflammatory syndrome. Moreover, a TA may progress to malignancy. (HEPATOLOGY 2007;46:140–146.)
Development and validation of a disease-targeted quality of life instrument in chronic hepatitis B
Authors: Spiegel Brennan M. R. , Bolus Roger , Han Steven , Tong Myron , Esrailian Eric , Talley Jennifer , Tran Tram , Smith Jason , Karsan Hetal A. , Durazo Francisco , Bacon Bruce , Martin Paul , Younossi Zobair , Hwa-Ong Siew , Kanwal Fasiha 
Published: June 2007

Abstract

Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test–retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test–retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health.

Conclusion

: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials. (HEPATOLOGY 2007;46:113–121.)