bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic performance of wood‐frame houses in south‐western British Columbia
Authors: Goda Katsuichiro , Atkinson Gail M.
Published: November 2010

The seismic performance of conventional wood‐frame structures in south‐western British Columbia is analytically investigated through incremental dynamic analysis by utilizing available UBC‐SAWS models, which were calibrated based on experimental test results. To define an adequate target response spectrum that is consistent with information from national seismic hazard maps, record selection/scaling based on the conditional mean spectrum (CMS) is implemented. Furthermore, to reflect complex seismic hazard contributions from different earthquake sources (i.e. crustal events, interface events, and inslab events), we construct CMS for three earthquake types, and use them to select and scale an adequate set of ground motion records for the seismic performance evaluation. We focus on the impacts of adopting different record selection criteria and of using different shear‐wall types (Houses 1–4; in terms of seismic resistance, House 1>House 2>House 3>House 4) on the nonlinear structural response. The results indicate that the record selection procedures have significant influence on the probabilistic relationship between spectral acceleration at the fundamental vibration period and maximum inter‐story drift ratio, highlighting the importance of taking into account response spectral shapes in selecting and scaling ground motion records. Subjected to ground motions corresponding to the return period of 2500 years, House 1 is expected to experience very limited extent of damage; Houses 2 and 3 may be disturbed by minor damage; whereas House 4 may suffer from major damage occasionally. Finally, we develop statistical models of the maximum inter‐story drift ratio conditioned on a seismic intensity level for wood‐frame houses, which is useful for seismic vulnerability assessment. Copyright © 2010 John Wiley & Sons, Ltd.
A fundamental dual‐zone continuum theory for dynamic soil–structure interaction
Authors: Pak Ronald Y. S. , Ashlock Jeramy C.
Published: November 2010

A continuum theory for an improved characterization of dynamic soil–structure interaction in the framework of three‐dimensional elastodynamics is presented. Effective in demonstrating the importance of integrating free‐field and near‐field effects under general soil and foundation conditions, a compact two‐zone delineation of the soil medium is proposed as a quintessential mechanics perspective for this class of problems. Sufficient to deliver a practical resolution of some perennial analytical and experimental conflicts, a fundamental formulation commensurate to a gradated unification of the homogenization approach and any sole free‐field inhomogeneous representation is developed and implemented computationally. Specialized to the problem of a rigid circular footing on sand, a nominal set of dynamic contact stress distributions and related impedance functions by the dual‐zone theory is included for theoretical and engineering evaluation. Through its comparison with benchmark analytical solutions and relevant physical measurements, the usage of the underlying conceptual platform as an advanced yet practical foundation for general dynamic soil–structure interaction is illustrated. Copyright © 2010 John Wiley & Sons, Ltd.
Germline polymorphisms in genes involved in the CD44 signaling pathway are associated with clinical outcome in localized gastric adenocarcinoma
Authors: Winder Thomas , Ning Yan , Yang Dongyun , Zhang Wu , Power Derek G , Bohanes Pierre , Gerger Armin , Wilson Peter M. , Lurje Georg , Tang Laura H , Shah Manish , Lenz Heinz‐Josef
Published: November 2010

The cluster of differentiation 44 (CD44) signaling pathway is crucial in cancer‐cell growth, invasion, proliferation and metastasis. CD44 is a transmembrane receptor for hyaluronan and osteopontin, and has recently attracted attention as a gastric cancer stem cell marker. Previous studies showed that polymorphisms in the CD44 gene can influence both human cancer survival and determine cellular response to cytotoxic chemotherapeutics. In addition, CD44 protein overexpression has been associated with poor prognosis in gastric adenocarcinoma (GA). We tested the hypothesis whether polymorphisms involved in the CD44 pathway will predict clinical outcome in patients with localized GA. Either blood or formalin‐fixed paraffin‐embedded (FFPE) tissues were obtained from 137 patients with localized GA at University of Southern California and Memorial Sloan‐Kettering Cancer Center medical facilities. DNA was isolated and polymorphisms within the CD44 pathway were determined by PCR‐RFLP technique. In univariate analysis CD44 rs187116 and CD44 rs7116432 were significantly associated with time to tumor recurrence (TTR) and overall survival (OS). After adjusting for covariates, patients harboring at least one G allele of CD44 rs187116 remained significantly associated with TTR (adjusted p = 0.009) and OS (adjusted p = 0.045). Further, patients harboring CD44 T‐A haplotype were at the lowest risk of developing tumor recurrence (HR: 0.255; 95% CI: 0.11–0.591; adjusted p = 0.001) and death (HR 0.198; 95% CI: 0.07–0.563; adjusted p = 0.002). These results provide the first evidence that CD44 polymorphisms predict clinical outcome in patients with localized GA. This may help to identify localized GA patients at high risk for tumor recurrence.
Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors
Authors: Trujillo Kristina A. , Heaphy Christopher M. , Mai Minh , Vargas Keith M. , Jones Anna C. , Vo Phung , Butler Kimberly S. , Joste Nancy E. , Bisoffi Marco , Griffith Jeffrey K
Published: November 2010

Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT‐PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient‐matched, tumor‐adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN‐1 and TAHN‐5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra‐lobular fibroblasts expressing MMP2, SPARC, TGF‐β3, which are inducers of EMT, were both prevalent in TAHN‐1 tissues, sparse in TAHN‐5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α‐smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN‐1 tissues. These results identify cellular processes that are differentially activated between TAHN‐1 and TAHN‐5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors.
Metabolic syndrome and mammographic density: The Study of Women's Health Across the Nation
Authors: Conroy Shannon M. , Butler Lesley M. , Harvey Danielle , Gold Ellen B. , Sternfeld Barbara , Greendale Gail A. , Habel Laurel A.
Published: November 2010

The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In our study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression and mixed models to examine the cross‐sectional and longitudinal associations of the MetS and components of the MetS to percent MD in 790 premenopausal and early perimenopausal women enrolled in the Study of Women's Health Across the Nation (SWAN). In cross‐sectional analyses adjusted for body mass index (BMI), modest inverse associations were observed between percent MD and the MetS [β = −2.5, standard error (SE) = 1.9, p = 0.19], abdominal adiposity (β = −4.8, SE = 1.9, p = 0.01) and raised glucose (β = −3.7, SE = 2.4, p = 0.12). In longitudinal models adjusted for covariates including age and BMI, abdominal adiposity (β = 0.34, SE = 0.17, p = 0.05) was significantly positively associated with slower annual decline in percent MD with time. In conclusion, our results do not support the hypothesis that the MetS increases breast cancer risk via a mechanism reflected by an increase in percent MD.
The calcium-sensing receptor mediates bone turnover induced by dietary calcium and parathyroid hormone in neonates
Authors: Shu Lei , Ji Ji , Zhu Qi , Cao Guofan , Karaplis Andrew , Pollak Martin R , Brown Edward , Goltzman David , Miao Dengshun
Published: November 2010

We have investigated, in neonates, whether the calcium-sensing receptor (CaR) mediates the effects of dietary calcium on bone turnover and/or modulates parathyroid hormone (PTH)–induced bone turnover. Wild-type (WT) pups and pups with targeted deletion of the Pth (Pth–/–) gene or of both Pth and CaR (Pth–/–CaR–/–) genes were nursed by dams on a normal or high-calcium diet. Pups nursed by dams on a normal diet received daily injections of vehicle or of PTH(1–34) (80 µg/kg) for 2 weeks starting from 1 week of age. In pups receiving vehicle and fed by dams on a normal diet, trabecular bone volume, osteoblast number, type 1 collagen–positive area, and mineral apposition rate, as well as the expression of bone-formation-related genes, all were reduced significantly in Pth–/– pups compared with WT pups and were decreased even more dramatically in Pth–/–CaR–/– pups. These parameters were increased in WT and Pth–/– pups but not in Pth–/–CaR–/– pups fed by dams on a high-calcium diet compared with pups fed by dams on a normal diet. These parameters also were increased in WT, Pth–/–, and Pth–/–CaR–/– pups following exogenous PTH treatment; however, the percentage increase was less in Pth–/–CaR–/– pups than in WT and Pth–/– pups. In vehicle-treated pups fed by dams on either the normal or high-calcium diet and in PTH-treated pups fed by dams on a normal diet, the number and surfaces of osteoclasts and the ratio of RANKL/OPG were reduced significantly in Pth–/– pups and less significantly in Pth–/–CaR–/– pups compared with WT pups. These parameters were further reduced significantly in WT and Pth–/– pups from dams fed a high-calcium diet but did not decrease significantly in similarly treated Pth–/–CaR–/– pups, and they increased significantly in PTH-treated pups compared with vehicle-treated, genotype-matched pups fed by dams on the normal diet. These results indicate that in neonates, the CaR mediates alterations in bone turnover in response to changes in dietary calcium and modulates PTH-stimulated bone turnover. © 2011 American Society for Bone and Mineral Research.
Involvement of calcitonin and its receptor in the control of calcium-regulating genes and calcium homeostasis in zebrafish (Danio rerio)
Authors: Lafont Anne-Gaëlle , Wang Yi-Fang , Chen Gen-Der , Liao Bo-Kai , Tseng Yung-Che , Huang Chang-Jen , Hwang Pung-Pung
Published: November 2010

Calcitonin (CT) is one of the hormones involved in vertebrate calcium regulation. It has been proposed to act as a hypocalcemic factor, but the regulatory pathways remain to be clarified. We investigated the CT/calcitonin gene–related peptide (CGRP) family in zebrafish and its potential involvement in calcium homeostasis. We identified the presence of four receptors: CTR, CRLR1, CRLR2, and CRLR3. From the phylogenetic analysis, together with the effect observed after CT and CGRP overexpression, we concluded that CTR appears to be a CT receptor and CRLR1 a CGRP receptor. The distribution of these two receptors shows a major presence in the central nervous system and in tissues involved in ionoregulation. Zebrafish embryos kept in high-Ca2+-concentration medium showed upregulation of CT and CTR expression and downregulation of the epithelial calcium channel (ECaC). Embryos injected with CT morpholino (CALC MO) incubated in high-Ca2+ medium, showed downregulation of CTR together with upregulation on ECaC mRNA expression. In contrast, overexpression of CT cRNA induced the downregulation of ECaC mRNA synthesis, concomitant with the downregulation in the calcium content after 30 hours postfertilization. At 4 days postfertilization, CT cRNA injection induced upregulation of hypercalcemic factors, with subsequent increase in the calcium content. These results suggest that CT acts as a hypocalcemic factor in calcium regulation, probably through inhibition of ECaC synthesis. © 2011 American Society for Bone and Mineral Research.
Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells
Authors: Cheng Ying-Hua , Chitteti Brahmananda R , Streicher Drew A , Morgan Joseph A , Rodriguez-Rodriguez Sonia , Carlesso Nadia , Srour Edward F , Kacena Melissa A
Published: November 2010

Osteoblasts (OBs) exert a prominent regulatory effect on hematopoietic stem cells (HSCs). We evaluated the difference in hematopoietic expansion and function in response to co-culture with OBs at various stages of development. Murine calvarial OBs were seeded directly (fresh) or cultured for 1, 2, or 3 weeks prior to seeding with 1000 Lin-Sca1 + cKit+ (LSK) cells for 1 week. Significant increases in the following hematopoietic parameters were detected when comparing co-cultures of fresh OBs to co-cultures containing OBs cultured for 1, 2, or 3 weeks: total hematopoietic cell number (up to a 3.4-fold increase), total colony forming unit (CFU) number in LSK progeny (up to an 18.1-fold increase), and percentage of Lin-Sca1+ cells (up to a 31.8-fold increase). Importantly, these studies were corroborated by in vivo reconstitution studies in which LSK cells maintained in fresh OB co-cultures supported a significantly higher level of chimerism than cells maintained in co-cultures containing 3-week OBs. Characterization of OBs cultured for 1, 2, or 3 weeks with real-time PCR and functional mineralization assays showed that OB maturation increased with culture duration but was not affected by the presence of LSK cells in culture. Linear regression analyses of multiple parameters measured in these studies show that fresh, most likely more immature OBs better promote hematopoietic expansion and function than cultured, presumably more mature OBs and suggest that the hematopoiesis-enhancing activity is mediated by cells present in fresh OB cultures de novo. © 2011 American Society for Bone and Mineral Research.
Ethanol‐induced redox imbalance in rat kidneys
Authors: Nechifor Marina Tamara , Dinu Diana
Published: November 2010

This study reports the effects of long‐term ethanol consumption on kidney redox status, in terms of enzymatic mechanisms involved in regulating the cytosolic [NADH]/[NAD+] balance. Wistar rats were treated with ethanol (2 g/kg body weight/24 h) via intragastric intubation for 10 and 30 weeks, respectively. Ethanol administration induced an enhancement of alcohol dehydrogenase activities and affected the capacity of the kidney to prevent NADH accumulation in the cytosol. After 10 weeks, the excess of NADH was balanced by increased activities of malate dehydrogenase and aspartate transaminase. In the event of a longer period of ethanol intake, the kidney was not able to balance the NADH excess, even though an increase in malate dehydrogenase, lactate dehydrogenase, aspartate transaminase, and alanine transaminase activities was noted. The electrophoretic analysis of alcohol dehydrogenase, lactate dehydrogenase, and malate dehydrogenase isoforms revealed differences between control and ethanol‐treated animals. The results suggest that rat kidneys have a multicomponent metabolic response to the same daily dose of ethanol that functions to maintain the redox status and which varies with the length of the administration period. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:224–230, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20379
Attachment style
Authors: Levy Kenneth N. , Ellison William D. , Scott Lori N. , Bernecker Samantha L.
Published: November 2010

Attachment theory, developed by Bowlby to explain human bonding, has profound implications for conducting and adapting psychotherapy. We summarize the prevailing definitions and measures of attachment style. We review the results of three meta‐analyses examining the association between attachment anxiety, avoidance, and security and psychotherapy outcome. Fourteen studies were synthesized, which included 19 separate therapy cohorts with a combined sample size of 1,467. Attachment anxiety showed a d of −.46 with posttherapy outcome, while attachment security showed a d of.37 association with outcome. Attachment avoidance was uncorrelated with outcome. The age and gender composition of the samples moderated the relation between attachment security and outcome: samples with a higher proportion of female clients and a higher mean age showed a smaller relation between security and outcome. We discuss the practice implications of these findings and related research on the link between attachment and the therapy relationship. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:193–203, 2011.
Religion and spirituality
Authors: Worthington Everett L. , Hook Joshua N. , Davis Don E. , McDaniel Michael A.
Published: November 2010

Many clients highly value religious and spiritual (R/S) commitments, and many psychotherapists have accommodated secular treatments to R/S perspectives. We meta‐analyzed 51 samples from 46 studies (N = 3,290) that examined the outcomes of religious accommodative therapies and nonreligious spirituality therapies. Comparisons on psychological and spiritual outcomes were made to a control condition, an alternate treatment, or a subset of those studies that used a dismantling design (similar in theory and duration of treatment, but including religious contents). Patients in R/S psychotherapies showed greater improvement than those in alternate secular psychotherapies both on psychological (d =.26) and on spiritual (d = .41) outcomes. Religiously accommodated treatments outperformed dismantling‐design alternative treatments on spiritual (d = .33) but not on psychological outcomes. Clinical examples are provided and therapeutic practices are recommended. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:204–214, 2011.
A hybrid model of social phobia: an analysis of social anxiety and related symptoms of anxiety
Authors: Gros Daniel F. , Simms Leonard J. , Antony Martin M.
Published: November 2010

The categorical underpinnings of the current diagnostic nomenclature have been the subject of repeated criticism. Recently, researchers have proposed several alternatives to the current system, including hybrid models of combined diagnostic categories and symptom dimensions. In the present study, we investigated the symptoms associated with a hybrid model of social phobia. The study included (a) the development of the initial set of symptom dimensions, generation of an item pool, and review by an expert panel, and (b) data collection and component analysis of the item pool to determine the structure of the symptoms. Six separate theoretically relevant symptom dimensions were identified. Implications of these findings on the development of a new hybrid model of social phobia were discussed. © 2010 Wiley Periodicals, Inc. J Clin Psychol 00:1–15, 2010.
A novel targeting modality for renal cell carcinoma: human osteocalcin promoter‐mediated gene therapy synergistically induced by vitamin C and vitamin D3
Authors: Johnson Nicole A. , Chen Bing‐Hung , Sung Shian‐Ying , Liao Chia‐Hui , Hsiao Wan‐Chi , W. K. Chung Leland , Hsieh Chia‐Ling
Published: November 2010

Background

Advanced renal cell carcinoma (RCC) frequently develops skeletal metastasis and is highly resistant to conventional therapies. We hypothesized that the osteocalcin (OC) promoter may be a promising gene delivery system for RCC targeted gene therapy because osteotropic tumors gain osteomimetic properties and thrive in the new environment by exhibiting a bone‐like gene expression profile. Human OC (hOC) expression is highly regulated by vitamins and hormone. In the present study, we tested the feasibility of vitamin‐regulatable hOC promoter for RCC‐specific transcriptional targeting, and examined the anti‐tumor effect of vitamins C and D3with hOC‐based adenoviral vectors towards RCC.

Methods

Real‐time reverse transcriptase‐polymerase chain reaction measured OC expression induced by vitamins C and D3, either alone or in combination, in RCC and normal human renal epithelial cells (HRE). The RCC‐cytotoxic effects of concomitant vitamins and hOC promoter‐based adenoviral vectors, Ad‐hOC‐TK and Ad‐hOC‐E1, were evaluated in both cell culture and a xenograft murine model.

Results

We found that high doses of vitamin C induced H2O2‐dependent apoptosis in RCC but not HRE. Treatment of RCC cells with combined vitamins C and D3treatment significantly increased OC promoter activity compared to single reagent treatment. Combined vitamin therapy reduced tumor size (85%) and complete tumor regression occurred in 38% of mice co‐administrated Ad‐hOC‐E1.

Conclusions

The results obtained in the present study demonstrate that vitamins C and D3synergized with the anti‐tumor effects of therapeutic genes driven by hOC promoter through direct cytotoxicity as well as transcriptional targeting. This combined gene therapy provides a promising modality for advanced RCC targeted therapy. Copyright © 2010 John Wiley & Sons, Ltd.
The ciliary smooth muscle electrotransfer: basic principles and potential for sustained intraocular production of therapeutic proteins
Authors: Touchard Elodie , Kowalczuk Laura , Bloquel Carole , Naud Marie‐Christine , Bigey Pascal , Behar‐Cohen Francine
Published: November 2010

Background

We have developed a nonviral gene therapy method based on the electrotransfer of plasmid in the ciliary muscle. These easily accessible smooth muscle cells could be turned into a biofactory for any therapeutic proteins to be secreted in a sustained manner in the ocular media.

Methods

Electrical conditions, design of electrodes, plasmid formulation, method and number of injections were optimized in vivo in the rat by localizing β‐galactosidase expression and quantifying reporter (luciferase) and therapeutic (anti‐tumor necrosis factor) proteins secretion in the ocular media. Anatomical measurements were performed via human magnetic resonance imaging to design a human eye‐sized prototype that was tested in the rabbit.

Results

In the rat, transscleral injection of 30 µg of plasmid diluted in half saline (77 mM NaCl) followed by application of eight square‐wave electrical pulses (15 V, 10 ms, 5.3 Hz) using two platinum/iridium electrodes, an internal wire and an external sheet, delivered plasmid efficiently to the ciliary muscle fibers. Gene transfer resulted in a long‐lasting (at least 5 months) and plasmid dose‐/injection number‐ dependent secretion of different molecular weight proteins mainly in the vitreous, without any systemic exposure. Because ciliary muscle anatomical measurements remained constant among ages in adult humans, an integrated device comprising needle‐electrodes was designed and manufactured. Its usefulness was validated in the rabbit.

Conclusions

Plasmid electrotransfer to the ciliary muscle with a suitable medical device represents a promising local and sustained protein delivery system for treating posterior segment diseases, avoiding repeated intraocular injections. Copyright © 2010 John Wiley & Sons, Ltd.
Transplantation of CTLA4Ig gene‐transduced adipose tissue‐derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis
Authors: Choi Eun Wha , Shin Il Seob , Lee Hee Woo , Park So Young , Park Ji Hyun , Nam Mi Hyun , Kim Jong Sung , Woo Sang Kyu , Yoon Eun Ji , Kang Sung Keun , Ra Jeong Chan , Youn Hwa Young , Hong Sung Hwa
Published: November 2010

Background

Autoimmune thyroiditis is one of common organ‐specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig gene‐transduced ATMSC on autoimmune thyroiditis.

Methods

Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene‐transduced human ATMSC (CTLA4Ig‐MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3‐week period. Blood and tissue samples were collected 1 week after the last cell transplantation.

Results

The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig‐MSC group was considerably lower than those in other groups. In culture supernatant of LPS‐stimulated spleen cells, both of the MSC‐treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig‐MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC‐treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down‐regulating Th1 cytokines.

Conclusion

Although CTLA4Ig‐MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig‐MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ‐specific autoimmune disease. Copyright © 2011 John Wiley & Sons, Ltd.
Imaging of the pleura
Authors: Helm Emma J. , Matin Tahreema N. , Gleeson Fergus V.
Published: November 2010

Pleural disease is a problem of global significance which causes significant morbidity and mortality. Pleural disease is usually first suspected on chest x‐ray but further imaging, often ultrasound, is usually required as part of the diagnostic work‐up. Complex imaging with computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)‐CT are less often performed but are routinely required in patients with mesothelioma and occasionally required in patients with pleural infection and other pleural diseases. Cross‐sectional imaging may be used to suggest the diagnosis of pleural disease, quantify disease severity, guide biopsy, and even predict prognosis. This review will focus on the contributions of CT, MRI, and PET to the management of pleural disease with discussion of their relative strengths and weaknesses. J. Magn. Reson. Imaging 2010;32:1275–1286. © 2010 Wiley‐Liss, Inc.
Imaging phenotypes of chronic obstructive pulmonary disease
Authors: Ley‐Zaporozhan Julia , van Beek Edwin J.R.
Published: November 2010

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. COPD is defined by irreversible airflow obstruction. It is a heterogeneous disease affecting the airways and/or the parenchyma with different severity during the course of the disease. These different aspects of COPD can be addressed by imaging using a combination of morphological and functional techniques. Computed tomography (CT) is the technique of choice for morphological imaging of the lung parenchyma and airways. This morphological information is to be accomplished by functional information about ventilation and perfusion, mainly provided by magnetic resonance imaging (MRI). The comprehensive diagnostic possibilities of CT complemented by MRI will allow for a more sensitive detection, phenotype‐driven characterization, and dedicated therapy monitoring of the disease. J. Magn. Reson. Imaging 2010;32:1340–1352. © 2010 Wiley‐Liss, Inc.
Computed tomography and magnetic resonance imaging of mediastinal tumors
Authors: Takahashi Koji , Al‐Janabi Nabaa Jaba
Published: November 2010

We describe the clinical, pathological, and imaging findings of mediastinal tumors with focus on thymic hyperplasia, thymic epithelial tumors, and germ cell tumors, malignant lymphoma, and various cystic masses. Chemical shift magnetic resonance imaging (MRI) is useful in characterization of the normal thymus and differentiation of hyperplastic thymus and thymic tumors. In contrast to noninvasive thymomas, invasive thymomas and thymic carcinomas show a more aggressive growth pattern. Local invasion and pleural spread are characteristic of invasive thymoma and mediastinal lymphadenopathy and distant metastasis suggest thymic carcinomas. Mature teratoma typically shows various computed tomography (CT) attenuation, and MR signal intensity depending on its contents and fat tissue and bone within the lesions are its characteristic findings. Seminomas typically have homogenous internal CT attenuation and MR signal intensity with minimal contrast enhancement. Nonseminomatous malignant germ cell tumors characteristically show prominent internal degenerative changes and invasion to the adjacent structures. In mediastinal lymphomas, a residual mass is common after treatment and MRI provides important information in distinguishing viable tumors from residual benign masses. Some mediastinal cysts may reveal high attenuation similar to solid lesions on CT depending on their contents and MRI can be useful in the differentiation of cystic masses from solid lesions. J. Magn. Reson. Imaging 2010;32:1325–1339. © 2010 Wiley‐Liss, Inc.
Lung perfusion measured using magnetic resonance imaging: New tools for physiological insights into the pulmonary circulation
Authors: Hopkins Susan R. , Prisk G. Kim
Published: November 2010

Since the lung receives the entire cardiac output, sophisticated imaging techniques are not required in order to measure total organ perfusion. However, for many years studying lung function has required physiologists to consider the lung as a single entity: in imaging terms as a single voxel. Since imaging, and in particular functional imaging, allows the acquisition of spatial information important for studying lung function, these techniques provide considerable promise and are of great interest for pulmonary physiologists. In particular, despite the challenges of low proton density and short T2* in the lung, noncontrast MRI techniques to measure pulmonary perfusion have several advantages including high reliability and the ability to make repeated measurements under a number of physiologic conditions. This brief review focuses on the application of a particular arterial spin labeling (ASL) technique, ASL‐FAIRER (flow sensitive inversion recovery with an extra radiofrequency pulse), to answer physiologic questions related to pulmonary function in health and disease. The associated measurement of regional proton density to correct for gravitational‐based lung deformation (the “Slinky” effect (Slinky is a registered trademark of Pauf‐Slinky incorporated)) and issues related to absolute quantification are also discussed. J. Magn. Reson. Imaging 2010;32:1287–1301. © 2010 Wiley‐Liss, Inc.
Magnetic resonance imaging and computed tomography developments in imaging of venous thromboembolism
Authors: van Langevelde Kirsten , Tan Melanie , Šrámek Alexandr , Huisman Menno V. , de Roos Albert
Published: November 2010

Venous thromboembolism (VTE) is a disease that causes high morbidity and mortality in the population. At present the first‐line imaging test for a suspected pulmonary embolism (PE) is computed tomography (CT) pulmonary angiography, and ultrasonography is widely used for the diagnosis of deep‐vein thrombosis (DVT). Although these modalities are proven to be safe and accurate, unresolved issues remain, such as whether CT scanning in patients with a suspected PE should be extended to the legs. Another issue is the diagnosis of recurrent DVT. Magnetic resonance imaging (MRI) offers a number of advantages in the imaging of VTE. Recent developments of scanning protocols with shorter acquisition times, sometimes complemented by navigator gating or making use of endogenous contrast, offer new perspectives for the use of MRI. This review provides an overview of state of the art MRI techniques for the diagnosis of PE and DVT. Furthermore, the use of new contrast agents such as fibrin labeling to detect thrombi are addressed. J. Magn. Reson. Imaging 2010;32:1302–1312. © 2010 Wiley‐Liss, Inc.
Image‐based modeling of lung structure and function
Authors: Tawhai Merryn H. , Lin Ching‐Long
Published: November 2010

The current state‐of‐the‐art in image‐based modeling allows derivation of patient‐specific models of the lung, lobes, airways, and pulmonary vascular trees. The application of traditional engineering analyses of fluid and structural mechanics to image‐based subject‐specific models has the potential to provide new insight into structure–function relationships in the individual via functional interpretation that complements imaging and experimental studies. Three major issues that are encountered in studies of airflow through the bronchial airways are the representation of airway geometry, the imposition of physiological boundary conditions, and the treatment of turbulence. Here we review some efforts to resolve each of these issues, with particular focus on image‐based models that have been developed to simulate airflow from the mouth to the terminal bronchiole, and subjected to physiologically meaningful boundary conditions via image registration and soft‐tissue mechanics models. J. Magn. Reson. Imaging 2010;32:1421–1431. © 2010 Wiley‐Liss, Inc.
Multimodality molecular imaging of the lung
Authors: Chen Delphine L. , Kinahan Paul E.
Published: November 2010

The continued progression of chronic lung disease despite current treatment options has led to the increasing evaluation of molecular imaging tools for diagnosis, treatment planning, drug discovery, and therapy monitoring. Concurrently the development of multimodality positron emission tomography (PET) / computed tomography (CT), single‐photon emission computed tomography (SPECT)/CT, and magnetic resonance imaging (MRI)/PET scanners has opened the potential for more sophisticated imaging biomarker probes. Here we review the potential uses of multimodality imaging tools, the established uses of molecular imaging in nononcologic lung pathophysiology and drug discovery, and some of the technical challenges in multimodality molecular imaging of the lung. J. Magn. Reson. Imaging 2010;32:1409–1420. © 2010 Wiley‐Liss, Inc.
Demonstration of the heterogeneous distribution of asthma in the lungs using CT and hyperpolarized helium‐3 MRI
Authors: Aysola Ravi , de Lange Eduard E. , Castro Mario , Altes Talissa A.
Published: November 2010

Asthma is a chronic inflammatory disease that affects both the large and small airways and results in bronchoconstriction, mucous hypersecretion, smooth muscle hypertrophy, and subepithelial fibrosis. To gain insight into the pathophysiology of asthma, chest computed tomography (CT) has been investigated as a noninvasive method to evaluate airway wall thickness of medium and large airways. Hyperpolarized gas MRI can assess the functional alterations of airflow within the lung resulting from the structural changes in the airways. In this article, we review the application of CT‐based techniques and hyperpolarized gas MRI to study structural and functional changes in asthma. From the result of studies with CT and hyperpolarized gas MRI, it is becoming apparent that asthma has a regional distribution within the lung, that is, some areas of the lung are more affected than others. Furthermore, there appears to be some persistence to this distribution which may explain the observed patterns of airway remodeling and provide targets for localized therapies such as local application of anti‐inflammatory agents or bronchial thermoplasty. Thus, cross sectional imaging in asthma is providing new insights into the pathophysiology of the disease and has the potential to become essential in the guidance of localized treatments. J. Magn. Reson. Imaging 2010;32:1379–1387. © 2010 Wiley‐Liss, Inc.
A matched case–control study of hepatitis B virus mutations in the preS and core promoter regions associated independently with hepatocellular carcinoma
Authors: Liu Shijian , Xie Jiaxin , Yin Jianhua , Zhang Hongwei , Zhang Qi , Pu Rui , Li Chengzhong , Ni Wu , Wang Hongyang , Cao Guangwen
Published: November 2010

This study aimed to determine hepatitis B virus (HBV) mutations associated independently with the risk of hepatocellular carcinoma (HCC), as adjusted with other mutations in the preS and core promoter regions of HBV genotypes B and C. One hundred and forty HBV‐infected patients with HCC and 280 HBV‐infected patients without HCC who had intact data of HBV genotyping and DNA sequencing in both regions were involved in this age‐, sex‐matched case–control study. Univariate and two‐step stepwise multivariate regression analyses were performed to determine factors associated with the risk of HCC. Of 39 mutations evaluated, 23 in genotype C and 6 in genotype B were associated with an increased risk of HCC in the univariate analysis. Multivariate analyses established that genotype C (adjusted odds ratio [AOR] = 3.3; 95% confidence interval [CI] = 1.1–9.8), viral load (≥104 copies/ml) (AOR = 2.4; 95% CI = 1.0–5.8), A2962G (AOR = 18.7; 95% CI = 7.5–46.7), preS2 start codon mutation (AOR = 12.5; 95% CI = 3.4–45.5), C105T (AOR = 0.1; 95% CI = 0.0–0.2), T1753V (AOR = 3.1; 95% CI = 1.1–9.2), and A1762T/G1764A (AOR = 2.9; 95% CI = 1.1–7.3) were associated independently with HCC, adjusted for factors including mutations in both regions. By using an estimating haplotype frequencies program, it was found that a haplotypic carriage with 105C and 2962G was significantly more frequent in the patients with HCC than in those without HCC and the frequency of haplotype 2962G‐preS2 start codon wildtype‐105C‐1762T/1764A was 47.9% in the patients with HCC and 4.3% in those without HCC. Conclusively, A2962G and T105C are novel factors associated independently with HCC. Further prospective studies are needed to confirm the role of these mutations in the development of HCC. J. Med. Virol. 83:45–53, 2011. © 2010 Wiley‐Liss, Inc.
Clinical and molecular characterization of a parechovirus type 1 outbreak in neonates in Croatia
Authors: Ljubin‐Sternak Sunčanica , Juretić Emilja , Šantak Maja , Pleša Mirna , Forčić Dubravko , Vilibić‐Čavlek Tatjana , Aleraj Borislav , Mlinarić‐Galinović Gordana
Published: November 2010

During July 2009 an outbreak in neonates represented with gastrointestinal and respiratory symptoms was observed at the Neonatal Postintensive Care Unit, Clinical Hospital Center, Zagreb. Human parechovirus type 1 (HPeV1) was isolated from seven patients, one of whom was asymptomatic. All but one were premature neonates with serious underlying conditions, and all recovered fully after several days. In order to characterize the HPeV1s, sequencing of the VP1/2A region was conducted on six isolates from the outbreak and four isolates detected in Croatia in 2008 and 2007. The analysis of sequence similarity showed that the nucleotide identity between the prototype strain (Harris) and HPeV1 isolated in Croatia was 76.5–77.5%. Croatian strains from 2007 and 2009 clustered together with strains from the Netherlands and Germany detected in 2003 and 2006, respectively, while strains from 2008 clustered with the strain from Finland detected in 2000. Change of the dominant strains each year may suggest antigenic variation as a result of viral response to specific immunity of the target population. J. Med. Virol. 83:137–141, 2011. © 2010 Wiley‐Liss, Inc.
Respiratory viruses in children admitted to hospital intensive care units: Evaluating the CLART® Pneumovir DNA array
Authors: Frobert Emilie , Escuret V. , Javouhey E. , Casalegno J.S , Bouscambert‐Duchamp M. , Moulinier C. , Gillet Y. , Lina B. , Floret D. , Morfin F.
Published: November 2010

Viruses play a significant part in children's respiratory infections, sometimes leading to hospitalization in cases of severe respiratory distress. The aim of this study was to investigate respiratory infections in children treated in a hospital intensive care unit (ICU). Assays were performed using the CLART® Pneumovir DNA array assay (Genomica, Coslada, Madrid, Spain), which makes it possible to detect 11 genus of respiratory viruses simultaneously. During the winter of 2008–2009, 73 respiratory specimens collected from 53 children under 2 years of age and admitted to an ICU were tested. At least one virus was detected in 78% (57/73) of the samples. The virological diagnosis was based on single infections in 65% (37/57) and on multiple infections in 35% (20/57) of cases. The array assay revealed respiratory syncytial virus (RSV) in 73.6% (42/57) of the samples and rhinovirus in 24.6% (14/57), either on their own or in co‐infections. All viruses identified in single and multiple infections were tested, taking into account clinical features, risk factors, and severity criteria. Children with no risk factors presented more multiple infections, up to 42% of cases, than children with at least one risk factor. RSV seemed to induce severe symptoms by itself as no difference in intubation needs was observed when RSV was detected on its own or in co‐infection. The CLART® Pneumovir DNA array was useful for examining severe viral respiratory infections, when other viruses than those detected by conventional methods could be involved, particularly in an ICU. J. Med. Virol. 83:150–155, 2011. © 2010 Wiley‐Liss, Inc.
Chronic liver disease and cirrhosis among patients with hepatitis B virus infection in northern Portugal with reference to the viral genotypes
Authors: Mota Ana , Areias Jorge , Cardoso Margarida Fonseca
Published: November 2010

The prevalence of infection with hepatitis B virus in Portugal is around 1% of the population; 20–30% of those infected typically develop cirrhosis. The study focuses on the epidemiological profile of patients with hepatitis B infection and liver damage, in particular, cirrhosis. Of the 358 individuals that comprised the study, a liver biopsy was performed in 249 to identify the presence of cirrhosis. Cirrhosis was observed in 59 patients (23.7%) The Child–Pugh classification was used to assess the prognosis of cirrhosis: 3 out of the 59 patients were classified as Child–Pugh grade C, the most severe, 17 (28.8%) as grade B, and 39 (66.2%) as grade A. Patients classified as grade B were older, drank more, and showed higher levels of AST and alkaline phosphatase when compared with individuals classified as grade A. Genotypes A and D were predominant, and no significant differences with respect to genotype distribution were observed. Analysis of the hematological parameters showed that patients classified as Child's grade B had lower levels of platelets and higher levels of prothrombin time than those classified as Child's grade A. The profile of the patients with cirrhosis, including an extended number of individual characteristics, provides useful information, however, only a prospective study could evaluate definitively if liver disease is influenced by these factors. Future studies would benefit from the analysis of the impact of genotypes on liver disease, particularly genotypes A and D, the most predominant genotypes in northern Portugal. J. Med. Virol. 83:71–77, 2011. © 2010 Wiley‐Liss, Inc.
Molecular epidemiology of human papillomavirus genotype in women with high‐grade squamous intraepithelial lesion and cervical cancer: Will a quadrivalent vaccine be necessary in Thailand?
Authors: Sukasem Chonlaphat , Pairoj Wantanich , Saekang Nipa , Pombubpha Hiranyaratsami , Srichunrasami Chutatip , Pongtippan Atcharaporn , Junyangdikul Pairoj , Chantratita Wasun
Published: November 2010

This study was designed to investigate the distribution of human papilomavirus (HPV) genotypes among a group of patients with high‐grade squamous intraepithelial lesion (HSIL) or worse cytology. Consequently, the genotype‐specific HPV infection in a group of HSIL and invasive cervical cancer (ICC) samples was described. Specimens were collected prospectively from 132 women referred for colposcopic examination. All the women underwent Papanicolaou (Pap) smears and colposcopies and some also underwent cervical excision procedure biopsy. The HPV genotype was determined using the INNO‐LiPA assay. Among the 132 genotyped samples, 90.91% (120/132) were diagnosed HSIL, whereas 9.09% (12/132) were ICC. From the overall prevalence of HPV in the patients, 77.27% (102/132) and 22.72% (30/132) of cases had single and multiple genotype infections, respectively. The most common cases with statistical significance were high‐risk HPV (HR‐HPV) infections in 128 samples (96.97%), whereas, four individuals (3.03%) barely were low‐risk HPV (LR‐HPV) infected, P < 0.0001, χ2. The most prevalent genotypes were frequently HPV‐16 (65/167; 38.92%, followed by HPV‐58 (25/167; 14.97%), HPV‐18 (18/167; 10.78%), HPV‐33 (13/167; 7.19%), and HPV‐68 (11/167; 6.59%). In addition, HPV‐11 (2/132; 1.51%) and HPV‐6 (1/132; 0.76%) also were observed in this study, which confirmed the high distribution of HR‐HPV among women with HSIL and ICC. HPV‐58; a unique high‐risk HPV, is prevalent in a group of HSIL and ICC cases. These data also contribute evidence that HPV‐16, ‐18, ‐58, ‐33, and ‐68 genotypes are high‐risk and high distribution among women with HSIL and ICC. Therefore, HPV‐58, HPV‐33, and HPV‐68 should be considered for development of the next vaccine generation in Thailand. J. Med. Virol. 83:119–126, 2011. © 2010 Wiley‐Liss, Inc.
Transcriptional analysis of immune‐related genes in dendritic cells from hepatitis B surface antigen (HBsAg)‐positive transgenic mice and regulation of Fc gamma receptor IIB by HBsAg‐anti‐HBs complex
Authors: Yao Xin , Wang Xuan‐yi , Zhao Chao , Sun Shu‐hui , Meng Zhe‐feng , Zhang Ji‐ming , Xu Jian‐qing , Xie You‐hua , Yuan Zheng‐hong , Wen Yu‐mei
Published: November 2010

To study the gene expression profiles in dendritic cells (DCs) from a hepatitis B surface antigen (HBsAg) positive host, transcriptional analysis of bone marrow ‐derived DCs from a lineage of HBsAg transgenic mice (#59) was compared to DCs from normal mice. Among the immune‐related genes, 12 were up‐regulated, and 14 were down‐regulated in transgenic mice relative to those of normal mice. The up‐regulated genes include genes encoding immunoglobulin, histocompatibility 2 (K region), and several complement component genes, while the down‐regulated genes include the TAP1 (transporters associated with antigen processing gene‐1), interferon induced gene (Ifi203), chemokine (C‐X‐C) ligands and leukocyte‐immunoglobulin‐like genes, Lck‐interacting transmembrane adaptor genes and histocompatibility 2 (Q region and T region). Since an immunogenic complex containing HBsAg‐anti‐HBs has been used as a therapeutic vaccine for clinical trial in chronic hepatitis B patients, DCs from #59 were incubated with immunogenic complex compared to those incubated with HBsAg alone. The immune‐related six genes up‐regulated with immunogenic complex treatment were Fcgr2b, Cxcl2, Fth1, Clec4n, Lilrb4, and Dbh, with Fcgr2b (Fc gamma receptor IIB) being the highest up‐regulated gene. Interestingly, levels of Fcgr2b were found up‐regulated in patients with chronic hepatitis B undergoing immunogenic complex immunization, which returned to baseline when immunization was discontinued. In conclusion, by transcriptional analysis, immunogenic complex induced up‐regulation of Fcgr2b expression both in dendritic cells from an HBsAg transgenic mouse model and peripheral B cells from patients with chronic hepatitis B, which indicates that Fcgr2b is one of the key molecules up‐regulated by immunogenic complex. J. Med. Virol. 83:78–87, 2011. © 2010 Wiley‐Liss, Inc.