bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival
Authors: Greither Thomas , Grochola Lukasz F. , Udelnow Andrej , Lautenschläger Christine , Würl Peter , Taubert Helge
Published: June 2009

Pancreatic cancer is the eighth most common cancer and has an overall 5‐year survival rate lower than 10%. Because of their ability to regulate gene expression, microRNAs can act as oncogenes or tumor‐suppressor genes and so have garnered interest as possible prognostic and therapeutic markers during the last decade. However, the prognostic value of microRNA expression in pancreatic cancer has not been thoroughly investigated. We measured the levels of miR‐155, miR‐203, miR‐210, miR‐216, miR‐217 and miR‐222 by quantitative RT‐PCR in a cohort of 56 microdissected pancreatic ductal adenocarcinomas (PDAC). These microRNAs were chosen as they had previously been shown to be differentially expressed in pancreatic tumors compared to normal tissues. The possible association of microRNA expression and patients' survival was examined using multivariate Cox's regression hazard analyses. Interestingly, significant correlations between elevated microRNA expression and overall survival were observed for miR‐155 (RR = 2.50; p = 0.005), miR‐203 (RR = 2.21; p = 0.017), miR‐210 (RR = 2.48; p = 0.005) and miR‐222 (RR = 2.05; p = 0.035). Furthermore, tumors from patients demonstrating elevated expression levels of all 4 microRNAs possessed a 6.2‐fold increased risk of tumor‐related death compared to patients whose tumors showed a lower expression of these microRNAs. This study provides the first evidence for an oncogenic activity of miR‐155, miR‐203, miR‐210 and miR‐222 in the development of pancreatic cancer as has been reported for other tumor types. Furthermore, the putative target genes for these microRNAs suggest a complex signaling network that can affect PDAC tumorigenesis and tumor progression.
Timp‐2 binding with cellular MT1‐MMP stimulates invasion‐promoting MEK/ERK signaling in cancer cells
Authors: Sounni Nor Eddine , Rozanov Dmitri V. , Remacle Albert G. , Golubkov Vladislav S. , Noel Agnes , Strongin Alex Y.
Published: June 2009

Both invasion‐promoting MT1‐MMP and its physiological inhibitorTIMP‐2 play a significant role in tumorigenesis and are identified in the most aggressive cancers. Despite its antiproteolytic effects in vitro, clinical data suggest that TIMP‐2 expression is positively associated with tumor recurrence, thus emphasizing the wide‐ranging role of TIMP‐2 in malignancies. To shed light on this role of TIMP‐2, we report that low concentrations of TIMP‐2, by interacting with MT1‐MMP (a specific membrane receptor of TIMP‐2), induce the MEK/ERK signaling cascade in fibrosarcoma HT1080 cells which express MT1‐MMP naturally. TIMP‐2 binding with cell surface‐associated MT1‐MMP stimulates phosphorylation of MEK1/2, which is upstream of ERK1/2, and the ERK1/2 substrate p90RSK. Consistent with volumes of literature, we confirmed that the activation of ERK stimulated cell migration. Both the transcriptional silencing of MT1‐MMP and the inhibition of MEK1/2 reversed the signaling effects of TIMP‐2/MT1‐MMP while the active site‐targeting MMP inhibitor GM6001 did not. Our data suggest that both the interactions of TIMP‐2 with MT1‐MMP, which activate the pro‐migratory ERK signaling cascade,and the conventional inhibition of MT1‐MMP's catalytic activity by TIMP‐2, play a role in the invasion‐promoting function of MT1‐MMP. The TIMP‐2‐induced stimulation of ERK signaling in cancer cells explains the direct, as opposed to the inverse, association of TIMP‐2 expression with poor prognosis in cancer.
Hexabromocyclododecane decreases the lytic function and ATP levels of human natural killer cells
Authors: Hinkson Natasha C. , Whalen Margaret M.
Published: June 2009

This study investigates the effect of hexabromocyclododecane (HBCD) on the lytic function of human natural killer (NK) cells and on ATP levels in NK cells. NK cells are capable of lysing tumor cells, virally infected cells, and antibody‐coated cells. HBCD is a brominated cyclic alkane used primarily as an additive flame retardant. If HBCD interferes with NK cell function, this could increase risk of tumor development and/or viral infection. NK cells were exposed to various concentrations of HBCD for 24 and 48 h and 6 days before determining lytic function and ATP levels. ATP levels and lytic function were also determined in NK cells that were exposed to HBCD for 1 h followed by 24 and 48 h, and 6 days in HBCD‐free media. The results indicated that exposure of NK cells to 10 µm HBCD for 24 h causes a very significant decrease in both NK cell lytic function and ATP levels (93.5 and 90.5%, respectively). Exposure of NK cells to 10 µm HBCD for 1 h followed by 24 h in HBCD‐free media showed a progressive and persistent loss of lytic function (89.3%) as well as a decrease in ATP levels (46.1%). The results indicate that HBCD exposures decreased lytic function as well as ATP levels. However, a decrease in lytic function was not necessarily accompanied by a similar decrease in ATP. Importantly, these results also indicate that a brief (1 h) exposure to HBCD causes a progressive loss of lytic function over a 6 day period. Copyright © 2009 John Wiley & Sons, Ltd.
AM–FM techniques in the analysis of optical coherence tomography signals
Authors: Pitris Costas , Kartakoullis Andreas , Bousi Evgenia
Published: June 2009

The subtle tissue changes associated with the early stages of malignancies, such as cancer, are not clearly discernible even at the current, improved, resolution of optical coherence tomography (OCT) systems. However, these changes directly affect the spectral content of the OCT image that contains information regarding these unresolvable features. Spectral analysis of OCT signals has recently been shown to provide additional information, resulting in improved contrast, directly related to scatterer size changes. Amplitude modulation–frequency modulation (AM–FM) analysis, a fast and accurate technique for the estimation of the instantaneous frequency, phase, and amplitude of a signal, can also be applied to OCT images to extract scatterer‐size information. The proposed technique could make available an extremely valuable tool for the investigation of disease characteristics that now remain below the resolution of OCT and could significantly improve the technology's diagnostic capabilities. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Successful weaning after plasma exchange for polyneuropathy related to POEMS syndrome
Authors: Wu Shang‐Gin , Kuo Ping‐Hung , Yang Pan‐Chyr
Published: June 2009

Respiratory failure due to polyneuropathy associated with POEMS syndrome (Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is unusual. In this report, we describe a 47‐year‐old male patient with polyneuropathy related to POEMS syndrome who suffered from hypercapnic respiratory failure due to progressive weakness of the respiratory muscles. His respiratory muscle strength significantly improved after plasma exchange and was extubated successfully. To our knowledge, this is the first case of POEMS syndrome with aggressive polyneuropathy that was successful treated by plasma exchange and our experience provides insight regarding the optimal management of such patients. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.
DFT/TD‐DFT investigation on Ir(III) complexes with N‐heterocyclic carbene ligands: Geometries, electronic structures, absorption, and phosphorescence properties
Authors: Liu Tao , Xia Bao‐Hui , Zheng Qing‐Chuan , Zhou Xin , Pan Qing‐Jiang , Zhang Hong‐Xing
Published: June 2009

Iridium(III) complexes with N‐heterocyclic (NHC) ligands including fac‐Ir(pmb)3 (1), mer‐Ir(pmb)3 (2), (pmb)2Ir(acac) (3), mer‐Ir(pypi)3 (4), and fac‐Ir(pypi)3 (5) [pmb = 1‐phenyl‐3H‐benzimidazolin‐2‐ylidene, acac = acetoylacetonate, pypi = 1‐phenyl‐5H‐benzimidazolin‐2‐ylidene; fac = facial, mer = meridional] were investigated theoretically. The geometry structures of 1–5 in the ground and excited state were optimized with restricted and unrestricted DFT (density functional theory) methods, respectively (LANL2DZ for Ir atom and 6‐31G for other atoms). The HOMOs (highest occupied molecular orbitals) of 1–3 are composed of d(Ir) and π(phenyl), while those of 4 and 5 are contributed by d(Ir) and π(carbene). The LUMOs (lowest unoccupied molecular orbitals) of 1, 2, 4, and 5 are localized on carbene, but that of 3 is localized on acac. The calculated lowest‐lying absorptions with TD‐DFT method based on Perdew‐Burke‐Erzenrhof (PBE) functional of 1 (310 nm), 2 (332 nm), and 3 (347 nm) have MLcarbeneCT/ILphenyl→carbeneCT (MLCT = metal‐to‐ligand charge transfer; ILCT = intraligand charge transfer) transition characters, whereas those of 4 (385 nm) and 5 (389 nm) are assigned to MLcarbeneCT/ILcarbene→carbeneCT transitions. The phosphorescences calculated by TD‐DFT method with PBE0 functional of 1 (386 nm) and 2 (388 nm) originate from 3MLcarbeneCT/3ILphenyl→carbeneCT excited states, but those of 4 (575 nm) and 5 (578 nm) come from 3MLcarbeneCT/3ILcarbene→carbeneCT excited states. The calculated results showed that the carbene and phenyl groups act as two independent chromophores in transition processes. Compared with 1 and 2, the absorptions of 4 and 5 are red‐shifted by increasing the effective π‐conjugation groups near the Ccarbene atom. We predicated that (pmb)2Ir(acac) is nonemissive, because the LUMO of 3 is contributed by the nonemissive acac ligand. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010
Ontogeny of the androgen receptor expression in the fetal and postnatal testis: Its relevance on Sertoli cell maturation and the onset of adult spermatogenesis
Authors: Rey Rodolfo A. , Musse Mariana , Venara Marcela , Chemes Héctor E.
Published: June 2009

From fetal life to adulthood, the testis evolves through maturational phases showing specific morphologic and functional features in its different compartments. The seminiferous cords contain Sertoli and germ cells, surrounded by peritubular cells, and the interstitial tissue contains Leydig cells and connective tissue. Sertoli cells secrete anti‐Müllerian hormone (AMH), whereas Leydig cells secrete androgens. In the fetal and early postnatal testis, Leydig cells actively secrete androgens. Sertoli cells are morphologically and functionally immature—e.g., they secrete high levels of AMH—and germ cells proliferate by mitosis but do not enter meiosis. During infancy and childhood, Leydig cells regress and testosterone secretion declines dramatically. Sertoli cells remain immature and spermatogenesis is arrested at the premeiotic stage. At puberty, Leydig cells differentiate again, and testosterone concentration increases and provokes Sertoli cell maturation—e.g., down‐regulation of AMH expression—and germ cells undergo meiosis, the hallmark of adult spermatogenesis driving to sperm production. An intriguing feature of testicular development is that, although testosterone production is as active in the fetal and early postnatal periods as in puberty, Sertoli cells and spermatogenesis remain immature until pubertal onset. Here, we review the ontogeny of the androgen receptor expression in the testis and its impact on Sertoli cell maturation and the onset of pubertal spermatogenesis. We show that the absence of androgen receptor expression in Sertoli cells underlies a physiological stage of androgen insensitivity within the male gonad in the fetal and early postnatal periods. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.
Passage marker excretion in red kangaroo (Macropus rufus), collared peccary (Pecari tajacu) and colobine monkeys (Colobus angolensis, C. polykomos, Trachypithecus johnii)
Authors: Schwarm Angela , Ortmann Sylvia , Wolf Christian , Streich W. Jürgen , Clauss Marcus
Published: June 2009

Ruminants are characterized by an efficient particle‐sorting mechanism in the forestomach (FRST) followed by selective rechewing of large food particles. For the nonruminating foregut fermenter pygmy hippo it was demonstrated that large particles are excreted as fast as, or faster than, the small particles. The same has been suggested for other nonruminating foregut fermenters. We determined the mean retention time of fluids and different‐sized particles in six red kangaroos (Macropus rufus), seven collared peccaries (Pecari tajacu) and three colobine monkeys (Colobus angolensis, C. polykomos, Trachypithecus johnii). We fed Co‐EDTA as fluid and mordanted fiber as particle markers (Cr, Ce). Mean (±SD) total tract retention time for fluids, small and large particles was 14±2, 29±10 and 30±9 hr in red kangaroos, 26±2, 34±5 and 32±3 hr in collared peccaries and 57±17, 55±19 and 54±19 hr in colobine monkeys, respectively. Large and small particles were excreted simultaneously in all species. There was no difference in the excretion of fluids and particles in the colobine monkeys, in contrast to the other foregut fermenters. In the nonprimate, nonruminant foregut fermenters, the difference in the excretion of fluids and small particles decreases with increasing food intake. On the contrary, ruminants keep this differential excretion constant at different intake levels. This may be a prerequisite for the sorting of particles in their FRST and enable them to achieve higher food intake rates. The functional significance of differential excretion of fluids and particles from the FRST requires further investigations. J. Exp. Zool. 311A: 647–661, 2009. © 2009 Wiley‐Liss, Inc.
Effects of ectopic expression of human telomerase reverse transcriptase on immortalization of feather keratinocyte stem cells
Authors: Xu Yulin , Yu Minli , Wu Fabai , Sun Jianguo , Wood Chris , Hattori Masa‐Aki , Wang Jinfu , Xi Yongmei
Published: June 2009

Normal somatic cells possess a finite life span owing to replicative senescence. Telomerase functions as a potential regulator of senescence in various cells. Expression level of human telomerase reverse transcriptase (hTERT) is correlated with telomerase activity and cellular immortalization. In this study, we investigated the effects of ectopic expression of hTERT on proliferation potential of chicken feather keratinocyte stem cells (FKSCs). We established FKSCs transduced with hTERT catalytic subunit fused with EGFP marker gene (hTERT‐EGFP‐FKSCs). hTERT‐EGFP‐FKSCs had the great potential of proliferation in vitro and expressed kerainocyte stem cell markers integrin β1 and CD49c. Keratin 15 and keratin 19, as native FKSCs, were also detected in hTERT‐EGFP‐FKSCs. By the analysis of fluorescent RT‐PCR, western blotting and TRAP assay, hTERT‐EGFP‐FKSCs were positive for telomerase activity, in comparison with native FKSCs showing no telomerase activity. We demonstrated that ectopic expression of hTERT could result in immortalization of FKSCs. Tumorigenecity of hTERT‐EGFP‐FKSCs were examined by soft agar assay and transplantation into NOD‐SCID mice. Results showed that hTERT‐EGFP‐FKSCs sustained the cellular characteristics of native FKSCs and had no transforming activity. In vivo differentiation multipotentials of hTERT‐EGFP‐FKSCs were confirmed by transplantation into developing chicken embryos and in situ hybridization analysis. These data provide a novel framework for understanding human telomerase activity in different species and suggest a new insight for manipulating hTERT for therapeutic purposes in treating tissue injury and aging. J. Exp. Zool. (Mol. Dev. Evol.) 312B:872–884, 2009. © 2009 Wiley‐Liss, Inc. [This article was published online on 23 June 2009. An error was subsequently identified and the article was corrected on 8 September 2009.]
ERK activation is involved in tooth development via FGF10 signaling
Authors: Cho Kyoung‐Won , Cai Jinglei , Kim Hyun‐Yi , Hosoya Akihiro , Ohshima Hayato , Choi Kang‐Yell , Jung Han‐Sung
Published: June 2009

The tooth is one of the ectodermal organs that develop from epithelial–mesenchymal interactions during embryonic development. An understanding of the underlying molecular mechanisms would improve our knowledge of the growth factors that regulate cell proliferation and differentiation. One of the related aspects is mitogen‐activated protein kinase (MAPK) signaling in tooth differentiation. The extracellular‐signal regulated kinase (ERK)/mitogen‐activated protein kinase kinase (MEK) cascade plays a pivotal role in many of the essential cellular processes underlying embryonic development, including responses to major developmental changes. However, the role of the ERK pathway in molar development is unclear. This study investigated epithelial patterning and tooth growth in the mouse embryo by monitoring ERK and fibroblast growth factor (FGF) signaling. ERK, MEK, and phosphatase and tensin homolog (PTEN) were activated at different levels and locations in the developing tooth at E13.5 to E16.5 and PN2. ERK was activated in the inner dental epithelium and cervical loop, while PTEN was activated in the outer dental epithelium. In addition, only ERK was activated in secretory ameloblast at PN2. To further define the pathways involving FGF and ERK, tooth germs were cultured in the presence of compounds to inhibit MAPK/ERK‐mediated signaling. Western blot analysis indicated that pERK2 was strongly activated in the tooth germ. Moreover, the activation level of pERK1 was dramatically increased by exogenous FGF10 alone and by combined treatment with FGF10 and U0126. The reported results will improve our understanding of the unique developmental processes of the dental epithelium and tooth growth, and will help to elucidate the fundamental mechanisms of ERK signaling underlying tooth development. J. Exp. Zool. (Mol. Dev. Evol.) 312B:901–911, 2009. © 2009 Wiley‐Liss, Inc.
Mainstreaming the rights of persons with disabilities in national development frameworks
Authors: Mwendwa Teresa Njoroge , Murangira Ambrose , Lang Raymond
Published: June 2009

Development practitioners and governments continue to grapple with how best to ensure the participation of socially excluded and marginalised groups in the development of poverty reduction strategy plans and national development programmes. This paper analyses the challenges involved in ensuring that persons with disabilities and their representative organisations are effectively included in such initiatives, using examples from recent practices in Uganda. It concludes by making some tentative recommendations on how such initiatives can be genuinely inclusive. Copyright © 2009 John Wiley & Sons, Ltd.
Disability, development and the dawning of a new convention: A cause for optimism?
Authors: Kett Maria , Lang Raymond , Trani Jean‐Francois
Published: June 2009

This policy arena focuses on a significantly under‐represented subject in international development journals—disability. This is timely, as the United Nations Convention of the Rights of Persons with Disabilities recently came into force in May 2008. As a result, there is a growing awareness among policy‐makers and development practitioners of the need to comprehensively address disability issues in their core activities. Persons with disabilities have long been subjects of international aid, so why has there been so little focus on mainstreaming disability within international development, and so little attention to development within disability circles? This editorial, and the papers presented in the policy arena, draw out the key issues around these themes that emerged from a major conference—poverty, discrimination and lack of access—held in Addis Ababa, Ethiopia in May 2008 and looks at the trajectory of links between disability and development and asks what is the significance of convention and how will it take the field forward. Copyright © 2009 John Wiley & Sons, Ltd.
The effect of adding Crabtree's catalyst to rhodium black in direct hydrogen isotope exchange reactions
Authors: Schou Søren Christian
Published: June 2009

A new catalytic system based on rhodium black using Crabtree's catalyst as an additive for direct hydrogen isotope exchange in aromatic compounds has been investigated. The level of deuterium incorporation can be improved from for example 16 to 93%. The new catalyst mixture tolerates a variety of solvents. Copyright © 2009 John Wiley & Sons, Ltd.
Hyperossification in miniaturized toadlets of the genus Brachycephalus (Amphibia: Anura: Brachycephalidae): Microscopic structure and macroscopic patterns of variation
Authors: Clemente‐Carvalho Rute B.G. , Antoniazzi Marta M. , Jared Carlos , Haddad Célio F.B. , Alves Ana C.R. , Rocha Henrique S. , Pereira Gabriela R. , Oliveira Davi F. , Lopes Ricardo T. , dos Reis Sergio F.
Published: June 2009

Species of the genus Brachycephalus, have a snout‐vent length of less than 18 mm and are believed to have evolved through miniaturization. Brachycephalus
ephippium, is particularly interesting; because its entire skull is hyperossified, and the presacral vertebrae and transverse processes are covered by a dorsal shield. We demonstrate in this paper that, at the macroscopic level, a completely hyperossified skull and dorsal shield occur only in B. ephippium, but not in B. ferruginus, B. izechsohni, B. pernix, B. pombali, B. brunneus, B. didactylus, and B. hermogenesi. An intermediate condition, in which the skull is hyperossified but a dorsal shield is absent, occurs in B. vertebralis, B. nodoterga, B. pitanga, and B. alipioi. The microscopic structure of hyperossification was examined in skulls of B. ephippium and B. pitanga, revealing a complex organization involving the presence of Sharpey fibers, which in humans are characteristic of periodontal connections. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.
Living in fast‐flowing water: Morphology of the gastromyzophorous tadpole of the bufonid Rhinella quechua (R. veraguensis group)
Authors: Aguayo R. , Lavilla E.O. , Vera Candioti M.F. , Camacho T.
Published: June 2009

We describe the bufonid gastromyzophorous tadpoles of Rhinella quechua from montane forest streams in Bolivia. Specimens were cleared and stained, and the external morphology, buccopharyngeal structures, and the musculoskeletal system were studied. These tadpoles show a combination of some traits common in Rhinella larvae (e.g., emarginate oral disc with large ventral gap in the marginal papillae, labial tooth row formula 2/3, prenarial ridge, two infralabial papillae, quadratoorbital commissure present, larval otic process absent, mm. mandibulolabialis superior, interhyoideus posterior, and diaphragmatopraecordialis absent, m. subarcualis rectus I composed of three slips), some traits apparently exclusive for the described species of the R. veraguensis group (e.g., second anterior labial tooth row complete, lingual papillae absent, adrostral cartilages present), and some traits that are shared with other gastromyzophorous tadpoles (e.g., enlarged oral disc, short and wide articular process of the palatoquadrate, several muscles inserting on the abdominal sucker). In the context of the substantial taxonomic and nomenclatural changes that the former genus Bufo has undergone, and despite the conspicuous morphological differences related to the presence of an abdominal sucker, the larval morphology of R. quechua supports including it in the genus Rhinella and placing it close to species of the R. veraguensis assemblage. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.
The lissamphibian humerus and elbow joint, and the origins of modern amphibians
Authors: Sigurdsen Trond , Bolt John R.
Published: June 2009

The origins and evolution of the three major clades of modern amphibians are still a source of controversy, and no general consensus exists as to their relationship to the various known Paleozoic taxa. This may indicate that additional character complexes should be studied to resolve their phylogenetic relationship. The salamander elbow joint has been fundamentally misinterpreted in previous morphological descriptions. In caudates and anurans, both the radius and ulna (fused in anurans) articulate with the characteristically large capitulum (radial condyle), although part of the ulnar articulating surface fits into to the smooth trochlear region. The salamander “ulnar condyle” of previous descriptions is in fact the entepicondyle. The condition seen in batrachians (i.e., salamanders and frogs) may be a lissamphibian synapomorphy because the elbow region of the primitive fossil caecilian Eocaecilia resembles those of frogs and salamanders. In addition to the large and bulbous capitulum, all lissamphibian humeri lack an entepicondylar foramen, and possess a distally pointing entepicondyle, a low and rounded ectepicondyle, and an elongated shaft. These characters are identified in key fossil forms to assess the support for the different hypotheses proposed for the evolutionary origins of lissamphibians. Temnospondyli is the only group of early tetrapods that shows a progressive evolution of lissamphibian traits in the humerus and elbow joint. Furthermore, among Paleozoic taxa, the dissorophoid temnospondyl Doleserpeton annectens is the only taxon that has the full set of humeral features shared by all lissamphibians. These results add support for the theory of a monophyletic origin of lissamphibians from dissorophoidtemnospondyls. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.
The relationship between genotypic sensitivity score and treatment outcomes in late stage HIV disease after supervised HAART
Authors: Castor Delivette , Vlahov David , Hoover Donald R. , Berkman Alan , Wu Ying Feng , Zeller Barbara , Brechtl John , Hammer Scott M.
Published: June 2009

This study investigated the effect of resistance testing quantified through a genotypic sensitivity score (GSS) on virologic, immunologic, and clinical responses among patients with late stage HIV‐1 disease receiving supervised highly active antiretroviral therapy (HAART). Newly admitted patients received drug resistance testing (n = 198) and then HAART supervised by residential health‐care facilities nurses. After initiating a resistance testing‐informed HAART regimen, patients were followed for HIV‐1 RNA suppression (<50 copies/ml), mean change in CD4+ T‐cells, new AIDS defining category C opportunistic conditions and death. GSS was constructed using the HAART regimen prescribed after resistance testing and data derived from IAS‐USA consensus mutations table with modification. Regressions with generalized estimating equations for robust estimation of standard errors and Cox proportional hazards regression estimated independent associations between GSS and treatment responses. After adjusting for adherence, initial log10 HIV‐1 RNA levels, and other covariates, patients with a GSS ≥3 had significantly greater HIV‐1 RNA suppression (adjusted odds ratio (AOR) 2.32; 95% CI 1.14, 4.75). HIV‐1 RNA levels were lower among patients with ≥95% adherence, but the effect of GSS on viral suppression was not modified by adherence. Self‐rated health status, and baseline CD4+ T‐cell counts independently predicted HIV‐1 RNA suppression. GSS did not predict mean change in CD4+ cells/mm3 (236 vs. 233, P = 0.92), occurrence of new AIDS defining category C conditions or death. These data support resistance testing‐guided therapy as an independent predictive factor to improve virologic responses in treatment‐experienced patients. J. Med. Virol. 81:1323–1335, 2009. © 2009 Wiley‐Liss, Inc.
Clearance of serum HBsAg and anti‐HBs seroconversion following antiviral therapy for chronic hepatitis B
Authors: Borgniet Olivier , Parvaz Parviz , Bouix Cécile , Chevallier Philippe , Trépo Christian , André Patrice , Zoulim Fabien
Published: June 2009

In this study, we have analyzed the evolution of serum HBsAg levels in 16 patients with chronic hepatitis B who showed an HBsAg seroconversion following antiviral therapy. The data showed that the clearance of serum HBsAg is slower than that of serum HBV DNA, which may reflect a slow kinetics of clearance of infected hepatocytes. Interestingly, HBsAg was detectable for a longer time using the Architect assay than with the Bio‐Rad assay. As viremia suppression is achieved in most patients under therapy with the new generation of nucleoside analogs, these data suggest that the quantitative monitoring of serum HBsAg may represent a novel tool for the assessment of antiviral therapy efficacy. J. Med. Virol. 81:1336–1342, 2009. © 2009 Wiley‐Liss, Inc.
Cytomegalovirus and Epstein–Barr virus coinfection in three toddlers with prolonged illnesses
Authors: Ito Yoshinori , Shibata‐Watanabe Yukiko , Kawada Jun‐ichi , Maruyama Koichi , Yagasaki Hiroshi , Kojima Seiji , Kimura Hiroshi
Published: June 2009

Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) usually cause primary and latent infections during childhood; thus, coinfection with these viruses occurs occasionally in children. However, its clinical impact has not been established, and may be underestimated. Three cases of coinfection involving these two viruses in toddlers are described: a 14‐month‐old male with infectious mononucleosis, an 18‐month‐old female with hemophagocytic lymphohistiocytosis, and a 13‐month‐old female with acute hepatitis. All three patients had prolonged illnesses. Serial serological testing and quantitation of viral DNA for CMV and EBV using peripheral blood from the patients suggested primary infections with both viruses. In all three cases, the viral load of EBV and CMV in the early stage of disease exceeded 6.4 × 103 and 8.8 × 102 copies/ml of whole blood, respectively, suggesting that the viruses were associated with the clinical condition. Recognizing that coinfection with these viruses may modulate the clinical course of disease is important. J. Med. Virol. 81:1399–1402, 2009. © 2009 Wiley‐Liss, Inc.
Seroprevalence, risk factors, and hepatitis C virus genotypes in groups with high‐risk sexual behavior in Croatia
Authors: Cavlek Tatjana Vilibic , Margan Ira Gjenero , Lepej Snjezana Zidovec , Kolaric Branko , Vince Adriana
Published: June 2009

The seroprevalence, risk factors and genotypes of hepatitis C virus (HCV) in groups with high‐risk sexual behavior (persons with multiple sexual partners, men who have sex with men, commercial sex workers and their clients and persons with sexually transmitted diseases) in seven Croatian cities were analyzed. A total of 821 participants without history of injecting drug use were included in the study. Anti‐HCV prevalence among risk groups varied from 2.9% to 8.5% with an overall prevalence of 4.6% (95% CI = 3.2–6.1) compared with 0.5% (95% CI = 0.0–1.5) in controls (pregnant females; OR = 9.66; 95% CI = 1.32–70.7). HCV‐RNA was detected in 73.1% anti‐HCV positive patients. Three of the seronegative cases (2.1%) were also found to be HCV‐RNA positive (“window period”). Genotype 1 was most commonly detected (55.6%). The most prevalent subtypes were 1a (38.9%) and 3a (38.9%). Sociodemographic characteristics (age, gender, marital status and level of education) were not associated with anti‐HCV seropositivity. Among sexually transmitted disease markers, a higher seroprevalence of HCV infection was found in subjects with a history of HBV infection (10.5% vs. 3.8%, P = 0.002) and gonorrhea (13.2% vs. 4.2%, P = 0.011). No other factors reflecting risk sexual behavior such as sexual orientation, number of sexual partners and number of risk behaviors were associated with HCV seroprevalence. J. Med. Virol. 81:1348–1353, 2009. © 2009 Wiley‐Liss, Inc.
IgA antibodies against the Epstein‐Barr nuclear antigen1 as a valuable biomarker for the diagnosis of nasopharyngeal carcinoma in Tunisian patients
Authors: Ayadi Wajdi , Karray‐Hakim Héla , Feki Lamia , Khabir Abdelmajid , Boudawara Tahia , Ghorbel Abdelmonem , Daoud Jamel , Frikha Mounir , Hammami Adnane
Published: June 2009

Serological tests for Epstein‐Barr virus (EBV) have been used for many years as diagnostic predictors of nasopharyngeal carcinoma. It has been shown previously that the conventional immunofluorescence assay has a limited diagnostic value, especially in young patients from North African area. In the search for more reliable immunoglobulin (Ig) G or IgA antibody markers for the diagnosis of nasopharyngeal carcinoma, immunoblot analysis was performed using a full spectrum of EBV proteins. Sera were collected from 108 patients with nasopharyngeal carcinoma and three control groups composed of 18 patients with lymphoma, 18 other patients with autoimmune diseases and 55 healthy EBV carriers. It was observed that the IgA Epstein‐Barr nuclear antigen 1 (EBNA1), IgA early antigen (EA)‐p138 and IgG EA‐p138 antibodies represent the most specific anti‐EBV responses in either young or older patients with nasopharyngeal carcinoma which yield higher positive rates compared to the three control groups. Since the IgA EBNA1 response showed the highest sensitivity value for the detection of nasopharyngeal carcinoma, a novel enzyme‐linked immunosorbent assay (ELISA) was established using a GST‐EBNA1 protein expressed in bacteria, containing the P‐threonine EBNA1 subtype cloned from DNA EBV sequence of C15 xenograft cells. Detection rates were 85.7% and 94.9% in young and older patients with nasopharyngeal carcinoma respectively, while only 3.6%, 11.1%, and 16.6% in healthy EBV carriers, patients with lymphoma and patients with autoimmune diseases, respectively. Thus, IgA EBNA1 ELISA may be useful for early diagnosis and mass screening of nasopharyngeal carcinoma in Tunisia even in young patients. J. Med. Virol. 81:1412–1421, 2009. © 2009 Wiley‐Liss, Inc.
Differences in viral kinetics between genotypes 1 and 2 of hepatitis C virus after single administration of standard interferon‐alpha
Authors: Toyoda Hidenori , Kumada Takashi , Kiriyama Seiki , Sone Yasuhiro , Tanikawa Makoto , Hisanaga Yasuhiro , Kanamori Akira , Atsumi Hiroyuki , Takagi Makiko , Nakano Satoshi , Arakawa Takahiro , Fujimori Masashi
Published: June 2009

Hepatitis C virus (HCV) kinetics were determined after a single administration of standard interferon (IFN) according to the HCV genotype that affects the response to antiviral therapy with IFN/peginterferon. A total of 208 patients were investigated. All patients received a single administration of 6 megaunits of standard IFN‐alpha. HCV RNA concentration was measured before, and at 24, 48, 72, and 120 hr after administration. Changes in HCV RNA concentration were compared between genotypes. The patient group consisted of 132 patients with genotype 1B, 58 with genotype 2A, and 18 with genotype 2B. In the comparison between genotypes 1 and 2, the reduction in HCV RNA concentration after a single IFN administration was less marked in patients with genotype 1B at both 24 and 48 hr after administration (P < 0.0001). In contrast, an increase in HCV RNA concentration during 24–48 or 24–72 hr after a single administration was comparable between genotypes 1 and 2. In the comparison between genotypes 2A and 2B, the reduction in HCV RNA concentration after a single administration was more marked in patients with genotype 2A, despite the similar rate of sustained virologic response to peginterferon and ribavirin combination therapy. The results of the study indicate that the rapid decrease in HCV RNA concentration observed during IFN or peginterferon therapy in patients with genotype 2 appeared to be due to the difference in sensitivity to IFN. Within genotype 2, HCV genotype 2A was more sensitive to IFN than genotype 2B. J. Med. Virol. 81:1354–1362, 2009. © 2009 Wiley‐Liss, Inc.
Genetic characterization of Chinese measles vaccines by analysis of complete genomic sequences
Authors: Zhang Yan , Zhou Jianhui , Bellini William J. , Xu Wenbo , Rota Paul A.
Published: June 2009

The complete genomic sequences of two Chinese measles vaccine viruses, Shanghai‐191 (S‐191) and Changchun‐47 (C‐47), were determined and compared to the sequences of other measles vaccine strains as well as the prototype measles strain, Edmonston wild‐type (Edwt). Compared to Edwt, S‐191 and C‐47 had 49 and 43 nucleotide changes, respectively. These differences were found at 52 nucleotide positions that were not found in other vaccine strains. Phylogenetic analysis of the all of the available genomic sequences for measles vaccines showed that S‐191 and C‐47 were most closely related to the Leningrad‐4 strain. S‐191 and C‐47 shared conserved vaccine virus‐specific amino acid changes in the phosphoprotein (P), V, C, matrix (M), and hemagglutinin (H) that could represent important targets for future studies aimed at understanding the molecular basis of attenuation. In addition, S‐191 and C‐47 had several unique amino acid changes including 13 positions that differed from Edwt. This is the first comparison of the complete genomic sequences of Chinese measles vaccines to the sequences of other vaccine strains. J. Med. Virol. 81:1477–1483, 2009. © 2009 Wiley‐Liss, Inc.
Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo
Authors: Becerra Aniuska , Warke Rajas V. , Martin Katherine , Xhaja Kris , de Bosch Norma , Rothman Alan L. , Bosch Irene
Published: June 2009

We used gene expression profiling of human primary cells infected in vitro with dengue virus (DENV) as a tool to identify secreted mediators induced in response to the infection. Affymetrix GeneChip analysis of human primary monocytes, B cells and dendritic cells infected with DENV in vitro showed strong induction of monocyte chemotactic protein 2 (MCP‐2/CCL8), interferon gamma‐induced protein 10 (IP‐10/CXCL10) and tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL/TNFSF10). The expression of these genes was confirmed in dendritic cells infected with DENV in vitro at mRNA and protein levels. A prospectively enrolled cohort of DENV‐infected Venezuelan patients was used to measure the levels of these proteins in serum during three different periods of the disease. Results showed significant increase of MCP‐2, IP‐10, and TRAIL levels in patients infected with DENV during the febrile period, when compared to healthy donors and patients with other febrile illnesses. MCP‐2 and IP‐10 levels were still elevated during the post‐febrile period while TRAIL levels dropped close to normal after defervescense. Patients with primary infections had higher TRAIL levels than patients with secondary infections during the febrile period of the disease. Increased levels of IP‐10, TRAIL and MCP‐2 in acute DENV infections suggest a role for these mediators in the immune response to the infection. MCP‐2 was identified in this work as a new unreported and important dengue‐related protein and IP‐10 was confirmed as a novel and strong pro‐inflammatory marker in acute disease. J. Med. Virol. 81:1403–1411, 2009. © 2009 Wiley‐Liss, Inc.
Adenovirus type 3 outbreak in connecticut associated with a novel variant
Authors: Landry Marie L. , Lebeck Mark G. , Capuano Ana W. , McCarthy Troy , Gray Gregory C.
Published: June 2009

An adenovirus outbreak occurred in New Haven, Connecticut in 2006–2007. Molecular typing revealed a twofold increase in adenovirus type 3 infections. Restriction enzyme analysis (REA) indicated that the CT outbreak was largely due to a marked increase in the novel Ad3a51 strain. This outbreak represents the first detection of Ad3a51 in the United States. While most infections were mild, children under 3 were at increased risk for severe disease and one patient with underlying disease died. J. Med. Virol. 81:1380–1384, 2009. © 2009 Wiley‐Liss, Inc.
Human T‐lymphotropic virus type 1 (HTLV‐1) genetic typing in Kakeroma Island, an island at the crossroads of the ryukyuans and Wajin in Japan, providing further insights into the origin of the virus in Japan
Authors: Eguchi Katsuyuki , Fujii Hidefumi , Oshima Kengo , Otani Masashi , Matsuo Toshiaki , Yamamoto Taro
Published: June 2009

Peripheral blood samples were collected from 23 human T‐lymphotropic virus type‐1 (HTLV‐1) carriers residing in Kakeroma Island, Japan (Kagoshima Prefecture, Oshima County, Setouchi Town), one of the most highly endemic areas in Japan. The samples were subjected to amplification by PCR and sequencing of the Long Terminal Repeat in order to reconstruct a phylogenetic tree of HTLV‐1 isolates. Restriction Fragment Length Polymorphism (RFLP) analysis of env region was also conducted for subgrouping of HTLV‐1. Although one sample could not be amplified by PCR, and three more could not be sequenced due to the existence of conspicuous nonspecific bands or repeated sequences, the phylogenetic analysis revealed that the remaining 19 isolates obtained from Kakeroma Island belonged to either the Transcontinental or the Japanese subgroups of the Cosmopolitan subtype, one of the three major subtypes. The RFLP data corresponded closely with the typing data throughout the sequencing. The proportion of the Transcontinental subgroup among the isolates was 26.3% (5 of 19) by sequence analysis and 27.3% (6 of 22) by RFLP. Unlike in Taiwan, China and Okinawa, the Japanese subgroup was dominant in Kakeroma Island. The analysis would also suggest that the Japanese subgroup seems not to have derived from the Transcontinental subgroup, but rather that the Transcontinental subgroup came to Japan first and was followed later by the Japanese one. J. Med. Virol. 81:1450–1456, 2009. © 2009 Wiley‐Liss, Inc.
Use of stored dried blood spots for retrospective diagnosis of congenital CMV
Authors: Atkinson Claire , Walter Simone , Sharland Mike , Tookey Pat , Luck Suzanne , Peckham Catherine , Griffiths Paul
Published: June 2009

The diagnosis of congenital cytomegalovirus infection cannot be made with certainty in children presenting after the perinatal period, unless stored early samples are available for diagnostic testing. This has led to uncertainty in confirming the overall contribution of CMV to hearing loss and neurodevelopmental impairment. The use of dried blood spots (DBSs) to retrospectively diagnose infection in children with compatible symptoms may be helpful diagnostically although there are ongoing uncertainties regarding the stability of viral DNA in cards, the risk of contamination between cards, and sensitivity and specificity in a clinical setting. This report aims to address these areas and evaluate the use of DBS testing in our hands in the United Kingdom to date. Results from testing artificially prepared cards and cards from three populations of children suggest a high specificity for congenital CMV infection and a good sensitivity for cases where sensorineural hearing loss is caused by congenital CMV. J. Med. Virol. 81:1394–1398, 2009. © 2009 Wiley‐Liss, Inc.
Lower cellular immune responses to influenza A (H3N2) in the elderly
Authors: Jia Na , Li Chris , Liu Yun‐Xi , Richardus Jan H. , Feng Dan , Yang Hong , Dang Rong‐Li , Ma Yong‐Hong , Xu Xiao‐Ning , Cao Wu‐Chun
Published: June 2009

Influenza epidemic is an important cause of severe illness in the elderly. Age‐dependent morbidity of influenza in the elderly is associated with weakened immunity. The baseline age‐related memory T cell activity in Chinese persons who are exposed to influenza virus through natural infection, are associated with the protective response to the virus after vaccination, thus providing important pre‐vaccination information. A cohort from the general population was established at the end of an influenza season in an area where influenza occurs regularly, and followed for 24 weeks. The subjects had no vaccination history for 5 years. Memory T cell responses were evaluated using a set of peptides spanning the influenza A (H3N2) entire proteome in a gamma interferon (IFN‐γ)‐enzyme‐linked immunospot (ELISPOT) assay, prior to the next influenza season. Changes of hemagglutination inhibition (HI) antibody titers were also evaluated. IFN‐γ+ T cell responses against influenza peptides were significantly lower in subjects of 60 years and older. Although the age‐related decline of cellular immune response was clear, no significant association of antibody titers with age was found. The pre‐vaccination baseline of memory IFN‐γ+ T cell immunity state in elderly Chinese was significantly lower than in people younger than 60 years. Measurement of the ex vivo cellular immune responses to influenza should be incorporated into the evaluation of protective immunity in elderly persons. J. Med. Virol. 81:1471–1476, 2009. © 2009 Wiley‐Liss, Inc.
Monitoring of herpes simplex virus DNA types 1 and 2 viral load in cerebrospinal fluid by real‐time PCR in patients with herpes simplex encephalitis
Authors: Schloss Lottie , Falk Kerstin I. , Skoog Eva , Brytting Maria , Linde Annika , Aurelius Elisabeth
Published: June 2009

A quantitative polymerase chain reaction (PCR) assay was evaluated retrospectively on 92 cerebrospinal fluid (CSF) samples from 29 patients with herpes simplex virus (HSV) encephalitis with the aim to study if the concentration of HSV genomes can be used as a prognostic marker and for monitoring of antiviral therapy. The results were compared to those obtained previously by nested PCR, and the numbers of HSV genomes/ml were evaluated in correlation to patient outcome and treatment. The aims were to compare the sensitivity of a conventional nested PCR to a quantitative PCR, to investigate the range of HSV genome concentration in initial samples and to evaluate possible relationships between the HSV DNA concentrations in CSF, neopterin levels, and outcome of disease. The 29 initial samples contained between 2 × 102 and 42 × 106 HSV genomes/ml. There was no apparent correlation between the amount of HSV DNA in the initial samples and income status, initial neopterin levels, or prognosis. The number of HSV genomes/ml declined after treatment in all patients, but HSV DNA was still detectable after day 20 in 3 out of 16 patients. A long duration of genome detectability was found to correlate with poor outcome. There was no difference in sensitivity between the nested PCR and the quantitative PCR. While the quantitative PCR is more rational than a nested PCR, the quantitation of HSV genomes does not seem very useful as a prognostic marker in HSV encephalitis. J. Med. Virol. 81:1432–1437, 2009. © 2009 Wiley‐Liss, Inc.
Effects of preharvest application of antagonistic yeast combined with chitosan on decay and quality of harvested table grape fruit
Authors: Meng Xianghong , Tian Shiping
Published: June 2009

BACKGROUND: Decay caused by fungal pathogens is responsible for significant economic loss of grape fruit in vineyards worldwide. However, postharvest treatment is not advisable for this fruit owing to its thin waxy pericarp and succulent flesh, which are easily damaged. Therefore preharvest treatment even at 1 day before harvest has been considered as a promising method to control postharvest decay of table grape fruit in storage. Integrative effects of preharvest application of Cryptococcus laurentii combined with low‐concentration chitosan on decay and quality of table grape fruit during storage were investigated in this study.

RESULTS: Spraying of antagonistic yeast combined with chitosan before harvest significantly reduced natural decay of fruit stored at 0 °C. Preharvest treatment stabilised polyphenol oxidase activity, increased peroxidase and phenylalanine ammonia‐lyase activities and decreased superoxide dismutase activity compared with control fruit. There was a higher ratio of soluble solid content to titratable acidity in treated fruit than in control fruit during storage. In addition, preharvest treatment affected the total phenolic content in fruit during storage.

CONCLUSION: The results suggest that integrative application of C. laurentii and low‐concentration chitosan before harvest may be a promising technology to control decay of table grape fruit in storage. Copyright © 2009 Society of Chemical Industry